>> GOOD MORNING, EVERYONE, WELCOME BACK. IT'S A LITTLE WARMER THIS MORNING. GOOD, GOOD. SO THE LOGISTICS FOR TODAY ARE THE SAME AS YESTERDAY. I WON'T GO OVER THEM, IF YOU HAVE QUESTIONS SEE ME DURING THE BREAK. IF YOU HAVEN'T SIGNED IN WE WILL ASK YOU TO SIGN IN AT SOME POINT A BREAK ESPECIALLY. IF YOU ARE SPEAKING SIGN IN SO WE KNOW THAT YOU'RE HERE. FOR FOLKS WHO HAVE NOT GIVEN PUBLIC COMMENT, IF YOU WANT TO AGAIN THERE'S TIME YOU NEED TO SIGN UP BY 10 A.M. WE DON'T KNOW HOW MUCH TIME YOU'LL HAVE, WE WON'T KNOW UNTIL EVERYBODY SIGNS UP BUT WE HAVE TIME FOR EVERYBODY IF YOU HAVE NOT GIVEN PUBLIC COMMENT TO DO SO. SO WITH THAT WE WILL START WITH TOPIC 4 WHICH IS NOTIFICATION AND ADVERSE EVENT REPORTING. TOPIC 4. WE HAVE ASKED STAKEHOLDERS TO HELP WITH FEEDBACK ON THE FOLLOWING QUESTIONS. WILL NOTIFICATION BE ADEQUATE TO PROVIDE FDA LABORATORIES PROVIDERS PATIENTS AND OTHER MEMBERS OF THE PUBLIC A COMPREHENSIVE LIST OF WHAT TESTS ARE CURRENTLY AVAILABLE FOR SPECIFIC INTENDED USE? WOULD IT BE SUFFICIENT TO ALLOW LABORATORY NETWORKS MORE THAN ONE LABORATORY UNDER THIS CONTROL OF THE SAME PARENT ENTITY THAT OFFER THE SAME TEST IN MULTIPLE LABORATORIES THROUGHOUT THEIR NETWORK TO SUBMIT A SINGLE NOTIFICATION FOR A TEST? ARE THERE CERTAIN TYPES OF LDTs WHICH THE AGENCY SHOULD NEITHER ENFORCE REQUIREMENTS FOR REGISTRATION AND LISTING NOR REQUEST NOTIFICATION IN LIEU OF REGISTRATION AND LISTING. AND HOW CAN FDA LEVERAGE OTHER INFORMATION IN THE MINE THETY TO REDUCE THE INFORMATION COLLECTION ASSOCIATION -- ASSOCIATED WITH NOTIFICATION FOR LABORATORIES OBTAINING SUFFICIENT INFORMATION TO INFORM THE LTD CLASSIFICATION AND PRIORITIZATION PROCESS. WE WILL START WITH PUBLIC COMMENT ON THIS TOPIC. >> THANK YOU. I'M ELAINE LYON, MOLECULAR DIRECTOR OF PHARMACOGENOMICSES AT (INAUDIBLE) LABORATORIES. A LEADER IN INNOVATIVE LABORATORY RESEARCH AND DEVELOPMENT, (INAUDIBLE) OFFERS OVER 3,000 TESTS WITH OVER 1500 LABORATORY DEVELOPED PROCEDURES DESIGNED PERFORMED AND VALIDATED USING THE MOST CURRENT RELEVANT SCIENTIFICALLY VERIFIED INFORMATION. I ALSO SERVE AS 2014 PRESIDENT OF THE ASSOCIATION OF MOLECULAR PATHOLOGY, WHICH REPRESENTS OVER 2300 PHYSICIANS DOCTORAL SCIENCES AND MEDICAL TECHNOLOGISTS WHO SPECIALIZED EXPERTISE IN ASPECTS OF MOLECULAR DIAGNOSTICS. ANALYTICALLY VALID LTD SHOULD BE USED IN CLINICAL PRACTICE. HOWEVER THE FDA IS NOT THE APPROPRIATE AGENCY TO REGULATE SUCH TESTING SERVICES AND ANY CONCERN BUSINESS THE TEST VALIDITY SHOULD BE ADDRESSED BY MODERNIZING KLIA. LTK IS A MEDICAL SERVICE AND PERFORMANCE PROFESSIONAL SERVICES WE PROMOTE AND ENSURE PATIENT SAFETY USING PROFESSIONAL JUDGMENT AT EVERY STEP OF THE PROCESS FROM SAMPLE RECEIPT THROUGH SIGNING THE LABORATORY REPORT. MOLECULAR PATHOLOGY PROFESSIONALS ARE QUALIFIED TO OFFER THESE SERVICES BECAUSE WE HAVE COMPLETED EXTENSIVE CLINICAL TRAINING AND BOARD CERTIFIED BY RECOGNIZED PROFESSIONAL BOARDS. THIS FRAMEWORK MOLECULAR PATHOLOGY PROFESSION ABILITY TO PRACTICE MEDICINE. CLINICAL LABORATORIES ARE NOT MANUFACTURED AND SHOULDN'T BE EXPECTED THE SAME REPORTING REQUIREMENTS. THE RISK IS MITIGATED DIFFERENTLY THAN IVD KIT. COMPLYING WITH THE MDR REQUIREMENTS CONSUME SIGNIFICANT RESOURCES WITHOUT AN ACCOMPANYING GAIN TO PATIENT CARE OR SAFETY. THIS IS AN EXAMPLE OF THE FDA FRAMEWORK AND APPROPRIATELY SUPER IMPOSING MANUFACTURING REGULATIONS ON MEDICAL PRACTICE. LABORATORY DIRECTORS ARE MEDICALLY AND LEGALLY RESPONSIBLE FOR THE ENTIRE LABORATORY PROCESS WHETHER OR NOT THE TEST FDA CLEARED OR PRODUCT. THE MDR REQUIREMENTS MANUFACTURERS MUST REPORT TO THE FDA INFORMATION THAT REASONABLY SUGGESTS THAT ADVICE MAY HAVE CAUSED OR CONTRIBUTED TO DEATH OR SERIOUS INJURY OR TO HAVE (INAUDIBLE) LIKELY TO CAUSE OR CONTRIBUTE TO A DEATH OR SERIOUS INJURY. IF THE MALFUNCTION WERE TO REOCCUR. OUR,EXPERIENCE IN PERFORMING THOUSANDS OF LABORATORY TESTS OVER MANY YEARS SUGGEST THE RISK IS CAUSING OR CONTRIBUTING TO DEATH OR SERIOUS INJURY IS EXCEEDINGLY LOW. COMPLIANCE WITH THE REQUIREMENT TO NECESSITATE LABORATORY DEVELOPING POLICIES PROCEDURES AND INFRASTRUCTURE FOR ANALYZING REPORTING PROP TENIAL EVENTS THE COST OF THESE ACTIVITIES ARE HIGH BUT THE LIKELIHOOD IS SURVEILLANCE WOULDN'T YIELD REPORTABLE EVENTS. I SUPPORT AMP PROPOSAL LIMITING APPLICATION TO HAVE MKR REQUIREMENTS TO LABORATORIES THAT RECEIVED APPROVAL FOR HOLLIESK LDPs,. THOSE DEFINED HIGH RISK BY AMP DIFFERENT FROM WHAT'S CLASSIFIED IN THIS FRAMEWORK. PROPOSED FRAMEWORK WOULD DUPLICATE REGULATIONS ALREADY IN PLACE REQUIRING LABORATORIES TO NOTIFY THE FDA WHICH TEST IS REDUNDANT AND CURRENTLY SUBMIT LISTS OF TESTS TO CM AND CLIA AND PARTICIPATE IN THE GTR AT THAT TIME NIH AS WELL AS PUBLIC DATABASES. FURTHER UNDER THE RECENTLY ENACTED LABORATORY REQUIRED TO PROVIDE PRICING DATA ON EACH TEST PERFORMED TO CMS. THE FDA SHOULD CONSIDER EXCESSING EXISTING HHS AGENCIES REGISTRIES IN LIEU OF REQUIRING LABS TO COMPLETE AN ENTIRELY NEW NOTIFICATION PROCESS. THANK YOU AGAIN FOR THE OPPORTUNITY TO COMMENT. >> GOOD MORNING. THANK YOU FOR LETTING ME SPEAK I AM LAWYER IN PRIVATE PRACTICE. MY NAME IS MIRI PENDERGAST AND THE VIEWS I -- MARY PENDERGAST AND THE VIEWS ARE MY OWN. I DON'T ENVY THE FDA FOR HAVING TO THINK THROUGH THESE VERY CONTENTIOUS AND CHALLENGING ISSUES. AND WHEN THE DUST SETTLES AFTER THE LITIGATION THE LEGISLATION AND YOU'RE ALLOWED TO GO FORWARD I ENCOURAGE YOU TO DO SO BY REGULATION IF YOU'RE ALLOWED. I THINK THAT THE BEST LONGEST AND MOST SUCCESSFUL FDA PROGRAMS HAVE BEEN DONE THROUGH REGULATION AND THAT GUIDANCE DOCUMENTS. IT GIVES YOU AN OPPORTUNITY TO BE VERY FLEXIBLE, IT GIVES YOU AN OPPORTUNITY TO EXPLAIN YOURSELF THROUGH THE PREAMBLES TO THE PROPOSED AND FINAL RULES, IT REQUIRES LEVEL OF DETAIL THAT IS OFTEN MISSING IN GUIDANCE DOCUMENTS. AND BECAUSE ITS CONTROLS OR REGULATES BOTH REGULATOR AND REGULATED IT GIVES EVERYBODY THE SAME SET OF STANDARDS UPON WHICH THEY MUST BEHAVE AND IT INSPIRES I THINK MORE COMPLIANCE BY INDUSTRY. FINALLY IF IT GIVES THE OPPORTUNITY TO ENFORCE WHATEVER REGULATIONS ARE STANDARDS YOU MIGHT HAVE IN A MUCH MORE SIMPLE MANNER. MY SECOND POINT, I THINK YOUR PROPOSAL TO USE A NOTIFICATION SYSTEM AS OPPOSED TO REGISTRATION AND LISTING IS A GREAT IDEA. I THINK IT SHOWS REGULATORY FLEXIBILITY AND I ENCOURAGE THAT REGULATORY FLEXIBILITY IN ALL ASPECTS YOU ARE WORKING ON TODAY. MY THIRD POINT, I THINK THAT THE MEDICAL DEVICE REPORTING SYSTEM DOES NOT GRAFT WELL ON TO WHAT CLINICAL LABORATORIES DO. IN PREPARATION FOR TODAY, I LOOKED AT THE MEDICAL DEVICE REPORTS FOR THE TESTS OR TEST SYSTEMS, THAT ARE CURRENTLY APPROVED BY THE FDA. AND THEY DO NOT PROVIDE THE INFORMATION OR THE ACCOUNTABILITY THAT WE NEED. THE MEDICAL DEVICE REPORTS SUBMITTED TODAY ALWAYS SAY IT IS A MALFUNCTION, THEY NEVER ACKNOWLEDGE THAT THERE WAS POTENTIAL HARM CAUSED TO ANYONE BY GETTING THE WRONG RESULTS. VALIDITY SHOULD BE THE TOUCH STONE FOR WHAT YOU DO AND I THINK LABORATORIES SHOULD BE HELD RESPONSIBLE AND HOLD THEMSELVES RESPONSIBLE ANY AND EVERY TIME THEY GIVE SOMEONE THE WRONG ANSWER ABOUT WHAT A SPECIMEN SHOWS OR REVEALS. SO I ENCOURAGE YOU TO THINK ABOUT HOW YOU CAN HAVE A SYSTEM TO REPORT ANALYTICAL VALIDITY BUT THAT'S WHERE THE CLINICAL LABORATORIES OBLIGATION SHOULD END. I THINK IF THEY GIVE THE WRONG ANSWER THEY SHOULD HAVE TO REPORT. IF THEY GIVE THE RIGHT ANALYTICAL ANSWER THEN THEY HAVE FULFILLED THEIR DUTY AND IT'S UP TO THE DOWNSTREAM USERS TO REPORT IF FOR EXAMPLE THE ANALYTICAL RESULT WAS CORRECT THAT THE PHYSICIAN MADE A MISTAKE SO I THINK THERE COULD BE A BRIGHT LINE DRAWN THERE. THANK YOU VERY MUCH. >> THANK YOU SO MUCH. WE'RE GOING TO MOVE ON TO OUR PANEL DISCUSSION. IF OUR PANELISTS COULD MAKE THEIR WAY UP. AND WE'LL START WITH MARIA GIOVANNI, MODERATOR OF THE SESSION. >> THANK YOU. GOOD MORNING. MY NAME IS MARIA GIOVANNI, I'M THE MODERATOR FOR SESSION 4 FOR THE PANEL DISCUSSION. MY ROLE AT NIH IS I'M AT THE NATIONAL INSTITUTES OF ALLERGY AND INFECTIOUS DISEASES AND DIRECTOR OF THE OFFICE OF GENOMICS AND ADVANCED TECHNOLOGIES AND I COORDINATE A LOT OF THE DIAGNOSTIC ACTIVITIES FOR THE INSTITUTE FOR INFECTIOUS DISEASES. AND I'M PLEASED TO BE HERE. I THINK WHAT WE'RE GOING TO DO TODAY IS THAT I'LL LET THE FIVE PANEL MEMBERS INTRODUCE THEMSELVES VERY BRIEFLY AND THEN START WITH THE QUESTIONS. JUST LIKE THE OTHER PANELS I WANT TO REMIND EVERYONE THAT THE REAL GOAL TODAY IS TO HAVE A DISCUSSION BY THE PANEL MEMBERS WITH THE IMPETUS OF THE QUESTIONS TO REALLY HAVE A CONSTRUCTION FEEDBACK ON THE FRAMEWORK AND THE NOTIFICATION GUIDANCE AS IN THE GUIDANCE AND IS IN APPENDIX A AND B FOR THE FDA. SO WE HAVE FOUR QUESTIONS, WE HAVE ABOUT 30 MINUTES TO GET THROUGH THEM. LET'S BEGIN. I WILL JUST START WITH CLEM MCDONALD, INTRODUCE YOURSELF AND GO DOWN THE LINE PLEASE. >> I'M CLEM MCDONALD DIRECTOR OF LISTER HILL SENTENCER NATIONAL LIBRARY OF MEDICINE. >>TY I'M CHRIS NEWTON WHICH HE, CARDIOLOGIST AT -- CHEH, CARDIOLOGIST AT MASS GENERAL HOSPITAL I'M A CARDIOVASCULAR GENETICIST, I'M HERE BOTH AS CLINICIAN BUT ALSO VOLUNTEER FOR THE AMERICAN HEART ASSOCIATION THAT DEALS WITH THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASE AND STROKE. >> I'M JAN NOWAK, PATHOLOGIST FROM ILLINOIS, I WORK AT NORTH SHORE UNIVERSITY HEALTH SYSTEM WHICH IS A MODEST SIZE HEALTHCARE SYSTEM OF FOUR HOSPITALS ON THE NORTH SIDE OF CHICAGO. I DIRECT THE MOLECULAR DIAGNOSTICS LABORATORY AT EVAN SON HOSPITAL, A LARGE TEACHING HOSPITAL, THAT'S WHAT YOU SHOULD BE THINKING OF WHERE I USE LDTs AND HAVE BEEN FOR A LONG TIME. I'M HERE AS A REPRESENTATIVE OF THE AMERICAN MEDICAL ASSOCIATION. >> GOOD MORNING. I'M WENDY RUBINSTEIN, I'M A SENIOR SCIENTIST AT NIH, I AM AT THE NATIONAL CENTER FOR BIOTECHNOLOGY INFORMATION WHICH IS PART OF THE NATIONAL LIBRARY OF MEDICINE. I DIRECT THE NIH GENETIC TESTING REGISTRY, MY TRAINING AND EXPERIENCE IS AS AN INTERNIST, A CLINICAL GENETICIST AND MOLECULAR GENETICIST. >> MY NAME IS CARRIE WELL, I'M BOARD DIRECTOR MEMBER FOR THE NATIONAL SOCIETY OF GENETIC COUNSEL ALREADY AND STUDY COORDINATOR AT JOHNS HOPKINS. >> GREAT. THANK YOU VERY MUCH. SO LET'S GET STARTED. SO THE VERY FIRST QUESTION IS AND WE HEARD IT BEFORE BUT I WILL REPEAT, WILL NOTIFICATION BE ADEQUATE TO SIDE FDA LABORATORIES PROVIDERS AND OTHER MEMBER OF PUBLIC A COMPREHENSIVE LIST OF WHAT TESTS ARE CURRENTLY AVAILABLE FOR SPECIFIC INTENDED USE. UNLESS YOU HAVE I HAVE A VOLUNTEER TO START FROM THE DISCUSSION PANEL, I WILL -- WOULD YOU LIKE -- OKAY VOLUNTEER, GO AHEAD. THANK YOU. >> I HAD TO CAREFULLY STUDY THE DRAFT THAT CAME OUT ON NOTIFICATION AND MDR BECAUSE THOSE ARE NOT THE KINDS OF -- I HAD TO DELIBERATELY STUDY THE DRAFT GUIDANCE NOTIFICATION IN MDR BECAUSE I'M NOT FAMILIAR WITH THOSE THINGS SO MY THOUGHTS AS THEY EVOLVED OVER THE LAST COUPLE OF DAYS AFTER HAVING READ THAT, ONE IS AS I UNDERSTAND IT, FDA IS GONE TO THE TROUBLE OF ESTABLISHING A MECHANISM FOR NOTIFICATION THAT WOULD NOT REQUIRE ANY FEES AND THAT'S ALWAYS APPRECIATED. HOWEVER THE ALTERNATIVE TO THAT IS REGISTRATION WHICH WOULD REQUIRE -- WHICH WOULD BE REQUIRED ONCE A TEST HAS TO GO THROUGH PRE-MARKET APPROVAL. SO IN MY OWN LABORATORY JUST IN VISITING HOW THIS WOULD WORK, WHERE WE DO A GOOD INFECTIOUS DISEASE TESTING I FOCUS ON ONCOLOGY TESTING. OUR VOLUME OF ONCOLOGY TESTING, I CAN TELL YOU THAT WE TEST MAYBE 130 NON-SMALL CELL LUNG CANCERS A YEAR, 150 COLON CANCERS FROM OUR ENTIRE SYSTEM, OUR LABORATORY IS CONSIDERED FAIRLY ACTIVE AND FAIRLY TYPICAL OF MOLECULAR DIAGNOSTICS LABORATORY WE DO, I ESTIMATED HERE 12 LDTs MOST OF THESE WOULD BE CATEGORIZED AS MEETING UNMET NEEDS BECAUSE THERE IS NO FDA APPROVED METHOD TO DOs THINGS. IF I INCLUDE I PLUS USE THESE TESTS AND PERFORM ON PSYCHOLOGY SMEARS, WHICH I DO, FOR THAT INDICATION I HAVE 24 LDTs, WE DO ALL THIS TESTING WITH 1.5 FTE SO MYSELF AND ONE AND A HALF MED TECH THAT DO THIS TESTING. TO HAVE GO THROUGH THE NOTIFICATION PROCESS WOULD BE WOULD BE ADMINISTRATIVE BURDEN TO GO TO MY ADMINISTRATION AND SAY I NEED EXTRA HELP TO DO THIS, ON TOP OF THAT, WE FACE THE PROSPECT THAT ONCE FDA APPROVED VERSION OF THESE TESTS BECOME AVAILABLE THEY NEED TO GO THROUGH THE OTHER PROCESS OF REGISTRATION AND IT'S GOING TO BE COSTLY. THE NET RESULT WILL BE AS WELL SHOULD WE BE DOING THIS. SO THAT'S MY CONCERN THERE. SECONDLY, YESTERDAY DR. GUTMAN WHEN HE WAS TALKING ABOUT THE ELEMENTS THAT GO INTO THE PACKAGE INSERT FOR A TEST NOTED ALL THIS -- MOST OF THE IMPORTANT INFORMATION IS ALREADY COLLECTED BY KLIA. ON TOP OF THAT, UNDER KLIA THROUGH THEIR LABORATORY ACCREDITATION PROGRAM COLLECTS ALL OF THIS INFORMATION. I HAVE BEEN A TEAM LEADER ON LABORATORY INSPECTIONS AND MATERIAL THAT'S GIVEN TO THE TEAM LEADER TO THE INSPECTION TEAM, WE SEE ALL THE TESTS THAT A LABORATORY DOES, WE KNOW THEIR TEST VOLUME, WE KNOW THE INSTRUMENTS THAT THEY'RE USING THROUGH THE PROFICIENCY TEST PROGRAM, THEY ALSO COLLECT THE DIFFERENT METHODOLOGIES THAT ARE USED, WHETHER THE TESTS ARE FDA APPROVED, WHETHER THEY'RE NOT FDA APPROVED, WHAT THE INDICATIONS FOR TESTING ARE IN THAT LABORATORY, ALL THAT INFORMATION IS THERE. AND IT'S ALL DONE IN A CONTEXT OF A QUALITY ASSURANCE PROGRAM THAT HAS TO BE DEMONSTRATED. SO WHEN I GO TO LABORATORY I KNOW ALL OF THOSE THINGS. I'M A LITTLE BIT -- I UNDERSTAND WHAT FDA IS TRYING TO COLLECT HERE BUT IF YOU CALL ME NEXT MONDAY I PROBABLY HAVE ALL THIS INFORMATION JUST BY PARTICIPATING IN THESE PROGRAMS. I CAN TELL YOU HOW MANY LABORATORIES ARE DOING PROFICIENCY TESTING FOR IHC. I CAN TELL YOU THERE ARE ABOUT 600 LABORATORIES IN THE COUNTRY THAT ARE DOING FISH OR IN SITU HYBRIDIZATION FOR HER 2. I CAN TELL YOU HOW MANY LABORATORIES ARE DOING EGFR TESTING AND THE REASONS THEY DO IT. ALL THIS INFORMATION IS THERE. AND SO MAYBE THIS MORE RELATES TO THE FOURTH QUESTION, ARE THE RESOURCES AVAILABLE THAT FDA CAN USE. I SERIOUSLY RECOMMEND THAT FDA TALK TO KLIA AND CAT ABOUT UTILIZING THE INFORMATION THAT IS ALREADY COLLECTED. I'LL STOP THERE. >> GREAT. THANK YOU. SO LET'S GO WITH DR. MCDONALD. >> SO I COME FROM A DIFFERENT PERSPECTIVE. I'M AN INTERNIST AND I HAVE BEEN AROUND LABORATORIES FOR 40 YEARS. I'M CHAIRMAN OF THE LUNG COMMITTEE, WE HAVE A CHALLENGE TRYING TO UNDERSTAND WHAT THE TEST IS, FROM THE NON-PACKAGE INSERTED TEST, IT CAN BE VERY DIFFICULT TO KNOW WHAT THEY REALLY ARE. SO MAYBE TO ANSWER THE FIRST QUESTION, ONE OF THE THING THAT'S VALUABLE IN THE PACKAGE INSERT IS HOW IT'S REPORTED AND ANOTHER THING THAT'S VALUABLE IS THE ACCURACY AND WHAT OTHER THINGS ARE CROSS REACT WITH THE TEST. I'M NOT SAYING YOU SHOULD USE THOSE TO. THE POINT OF OTHER SYSTEMS CHECKING DATA, YOU WILL HEAR ABOUT GTR, HELT-7 HAS COME PEND YUM OF LAB TESTS MASTER TEST FILE WHICH IS ADOPTED WIDELY BY THE LARGE COMPANIES BECAUSE YOU CAN SEND IT TO YOUR CUSTOMERS AND THE LIKE. I HAVE FOUR COPIES OF THE KEY PART HERE. THAT'S -- IT OVERLAPS SO I THINK IT WOULD BE A GOOD IDEA TO HARMONIZE THE CONTENTS OF SOME OF THESE THINGS SO WHERE THEY OVERLAP ONE COULD SPECIFY THIS IS THE SAME AS THAT AND FIND AUTOMATIC WAY TO MOVE THE DATA BUT LABORATORIES ARE TYPICALLY BUILDING COMPENDIUMS, SOME OF THE ARE VERY COMPLETE AND RICH AND YOU CAN TELL WHAT'S GOING ON, SOME ARE NOT. I'LL STOP WITH THAT. >> GO AHEAD. WE'LL MOVE RIGHT DOWN. THANK YOU. >> FULLY SUPPORTIVE OF THE FDA REVISITING ITS ENFORCEMENT DISCRETION HISTORY OVER LDTs AND WE'RE SUPPORTIVE OF REGULATING HIGH RISK TEST OR AT LEAST EXAMINING HIGH RISK TESTS, WE DON'T THINK KLIA CURRENTLY HAS BEEN ASSESSING THE CLINICAL VALIDITY. SPECIFICALLY NOTIFICATION IS UPSTREAM TO FDA RISK ASSESSMENT AND PRIORITIZATION OF REVIEW, WE THINK IT'S CRITICAL TO HAVE A NOTIFICATION PROCESS THAT INFORMS THAT. CURRENTLY THERE ARE NOT WELL CURATED LISTS OF LDTs THE NOTIFICATION PROCESS WOULD FEED INTO THAT SO WE HAVE A BETTER UNDERSTANDING OF THE BROAD SCOPE OF LDTs, AHA WOULD CONSIDER NOTIFICATION ELEMENTS ARE RELATIVELY MINIMAL, I THINK WE HAVE HEARD MUCH INFORMATION IS ASSEMBLED FOR KLIA PROCESSES SO IT IS OR IT ISN'T BURDENSOME IF THE INFORMATION IS THERE, WE THINK THAT IN ORDER TO BETTER INFORM FDA RISK ASSESSMENT PRIORITIZATION, INCLUDING SCIENTIFIC LITERATURE THAT SUPPORTS THE CLINICAL VALIDITY OF THE TEST IS IMPORTANT TO INFORM RISK ASSESSMENT PROCESS. >> GREAT. THANK YOU. >> I'LL RESPOND TO THIS QUESTION. SPECIFICALLY AND THEN I HAVE MORE GENERAL COMMENTS. MY COMMENTS ARE NOT SO MUCH ABOUT WHETHER OR NOT TO MOVE FORWARD WITH NOTIFICATION MORE IN THE PRACTICAL ASPECT OF NOTIFICATION AND HOW IT MIGHT WORK. I SEE TWO PURPOSES IN THE COLLECTION. I SEE TWO PURPOSES IN THE COLLECTION OF DATA BY FDA WITH RESPECT TO NOTIFICATION. FIRST TO CATALOG ALL TESTS IN USE. AFTER CATALOGING THEM FDA CAN DECIDE WHICH TEST TO POSSIBLY EXERT REGULATORY AUTHORITY. THE SECOND PURPOSE IS TO COLLECT THE DATA TO SUPPORT THE EXPERT PANELS IN THEIR -- PROVIDING INFORMATION SURROUNDING RISK SO THE COLLECTION HAS TO BE ADEQUATE FOR THAT PURPOSE AS WELL. SO FOR THE FIRST PURPOSE COLLECTING OR CATALOGING INFORMATION ABOUT ALL LDTs, THAT DEPENDS ON THE DEFINITION OF THE TEST AND IN MAKING SURE TO COLLECT AT LEAST INFORMATION ON THE MINIMAL ELEMENTS OF THAT DEFINITION. AND THAT WOULD MEAN SUCH THINGS AS BRINGING IN INFORMATION ABOUT THE METHOD, ANOLYTES, SPECIFIC ANOLYTES SO FORTH THAT NEED TO BE SPECIFIED. AND ONE OF THE OTHER QUESTIONS HERE IS WHETHER THE TEST PERFORMANCE LOCATION ACTUALLY IS PART OF THE DEFINITION OF THE TEST SO WE'LL GET TO THAT. SO WE DID HEAR YESTERDAY ABOUT WHAT HAPPENS IF A TEST IS TWEAKED. AND THAT PERTAINS TO HOW YOU DEFINE THE TEST. SO YOU CAN'T NECESSARILY SAY WHAT CONSTITUTES THE NEW TEST UNLESS YOU HAVE THAT FIRST DEFINITION THEN YOU UNDERSTAND WHICH ELEMENTS OF TWEAKING CHANGES AND THEN MANDATE NEW NOTIFICATION. SO LET ME MAKE INTRODUCTORY COMMENTS ABOUT REGISTRY AT THIS POINT. THE NIH GENETIC TESTING REGISTRY OR GTR IS A FREE ONLINE RESOURCE THAT PROVIDES A CENTRALIZED LOCATION FOR COMPREHENSIVE GENETIC TEST INFORMATION THAT IS VOLUNTARILY SUBMITTED BY TEST PROVIDERS. SEVERAL PRESENTERS AT THIS MEETING HAVE MENTIONED SECRETARY ADVISORY COMMITTEE ON GENETIC SOCIETY AND GENETICIST DRAFT GUIDANCE ON LDTs, GTR ALSO HAD GENETICISTS AND CALLS FOR TEST REGISTRY BY STAFF PHS IN ADDITION TO STAKEHOLDERS. A 2008 REPORT RECOMMENDED THAT A PUBLICLY AVAILABLE WEB-BASED REGISTRY BE DEVELOPED TO ENHANCE TRANSPARENCY GENETIC TESTING AND ASSIST EFFORTS IN REVIEWING THE CLINICAL VALIDITY OF LABORATORY DEVELOPED TESTS. G PTR FOUND A HOME AT NIH BASED ON INTEREST BY OFFICE OF THE DIRECTOR, THE NATIONAL CENTER FOR BIOTECHNOLOGY, WHICH IS PART OF NLM TASKED WITH DEVELOPING GTR BASED ON NCBI EXPERTISE AND DATA COLLECTION AND MANAGEMENT OF MOLECULAR AND LITERATURE RESOURCES SUCH AS GEN BANK AND PUBMED. THEN THERE WAS HA PERIOD OF DIVERSE STAKEHOLDER INPUT THAT WAS FOLLOWED BY GTR DEVELOPMENT AND THE WEBSITE WAS LAUNCHED IN FEBRUARY 2012 ON RARE DISEASE DAY BY NIH DIRECTOR DR. FRANCIS COLLINS. SO GTR HAS HAD ABOUT TWO AND A HALF OR THREE YEAR CHANCE AT THIS POINT TO COLLECT DATA IN ADVANCE G TR HAS 431 PARTICIPATING LABORATORIES ACROSS THE WORLD FROM 39 COUNTRIES THEY REGISTERED 25,000 TESTS. FDI MENTIONED THAT BECAUSE FDA IS INTERESTED IN NON-U.S. LABS THAT PROVIDE TESTS IN THE U.S. SPECIFICALLY TO THE U.S. LABS 226 LABS HAVE REGISTERED 11,700 SOME ODD TESTS. THE FOCUS OF GTR INCLUDES MOLECULAR CYTOGENETICS, BIOCHEMICAL TESTS FOR HERITABLE CONDITIONS AS WELL AS TESTS ON SOMATIC TISSUES SUCH AS TUMOR TESTS. WE HAVE PHARMACOGENETIC TESTS AND COMPLEX PANELS. THE SCOPE DOES NOT CURRENTLY INCLUDE TESTS FOR NON-HUMAN SAMPLES AND THAT'S THE BULK OF TESTING FOR INFECTIOUS DISEASES. THE ENTIRE GTR DATABASE CONTAINS A GRAND TOTAL OF 16 TESTS FOR WHICH FDA APPROVAL CLEAR STATUS IS REPORTED. SO WE HAVE TAKEN A VERY GRANULAR APPROACH TO DATA COLLECTION SUCH AS FOR METHODOLOGY DOWN TO THREE LEVELS, FOR GENES VARIANTS CHROMOSOMES PROTEINS ANOLYTES FOR OTHER DATA ELEMENTS, GTR HAS FIELD FOR ANALYTICAL VALIDITY, TARGET POPULATION, AND CLINICAL UTILITY. THESE ARE GATHERED IN EXPLICIT MANNER. THE GTR TESTS ARE PERFORMED FOR OVER 5,000 VERY WELL SPECIFIED CONDITIONS. THE DATA -- I WANT TO EMPHASIZE THE IMPORTANCE OF EXPLICIT DATA COLLECTION FOR THE CONDITIONS WHICH THE TEST IS PERFORMED. NCBI NEEDED TO BUILD A RESOURCE CALLED MEDGEN TO SUPPORT DATA COLLECTION FOR GTR AS WELL AS FOR CLINICAL VARIATION BECAUSE OF THE IMPORTANCE OF CAPTURING THAT GRANULARITY IN DISEASES, THAT CAN LATER SUPPORT BASICALLY LUMPING OR SPLITTING DISEASES AND INDICATIONS FOR WHICH YOU'RE INTERESTED. I WON'T GO TOO MUCH LONGER BUT I DO WANT TO EMPHASIZE IF REASON I TALK GRANULARITY IS THAT THE TYPES OF THE DATA HAVE TO BE RELEVANT TO THE RISK OF THE PATIENT AND BASED ON THE TEST RESULTS, AND HOW THEY'RE ACTED UPON, OR NOT ACTED UPON THOSE ARE THE IMPORTANT ELEMENTS. OF THE 14 SEVERAL LIST THAT AREN'T RELEVANT TO THE RISK COLLECTION. WE HEARD YESTERDAY TEST FOR THYROID CANCER COULD MEAN A TEST FOR PAPILLARY THYROID CANCER, FOLLICULAR THYROID CANCER INDIVIDUALLY OR ALL OF THE ABOVE. AND THE DATA COLLECTION NEEDS TO OCCUR IN THE MANNER THAT CAN SUPPORT THAT. THAT'S PROBABLY NOT AZIMUTH PROBLEM FOR COMMON DISEASE THAT WE ALL CAN SAY OFF THE TIP OF OUR TONGUES BUT FOR THE MANY RARE CONDITIONS THAT ARE IN CATALOGS LIKE OMIM THAT ARE PHENOTYPES CATEGORIZED BY THE HUMAN PHENOTYPE ONTOLOGY, ORPHAN ACT AS WELL, THOSE ARE NOT INTEGRATED WITH ELECTRONIC MEDICAL RECORDS. SO NCBI ALONG WITH NLM WAS VERY ENGAGE PRODUCING A CATALOG FROM THE TOP TO THE BOTTOM SUPPORTED IN ELECTRONIC MEDICAL RECORD. >> THANK YOU. WE CAN COME BACK TO THAT IN QUESTION 4. CARRIE, PLEASE. >> I THOUGHT OF THIS QUESTION A LITTLE BIT HOW THIS INFORMS THE PUBLIC AND THE PATIENTS AND PROVIDERS. SO WHEN I WAS THINKING ABOUT THIS I WAS THINKING ABOUT MORE WHAT THIS LOOKS LIKE IN INFORMING THOSE PEOPLE. SO I'M THINKING THIS IS A TYPE OF DATABASE SO MY ANSWER IS IT MAY OR MAY NOT BE ADEQUATE. THERE'S A LOT OF GREAT DATA OUT THERE THAT WOULD BE HELPFUL FOR PHYSICIANS AND PATIENTS. BUT ALSO AS WENDY MENTIONED THERE ARE RESOURCES THAT ARE ALREADY OUT THERE THAT PROVIDERS ARE USING. SO YOU'RE NOT NECESSARILY GOING TO GUARANTEE PATIENTS GO TO YOUR WEBSITE, WHY IS IT GOING TO BE BETTER? RIGHT NOW THERE ARE TWO GENETIC PROVIDERS USE A LOT AND ONE IS GTR, THE OTHER IS GENE TESTS WHICH EXISTED PRIOR TO GTR EXISTENCE. LOOKING UP NUMBERS AND I DON'T KNOW IF THESE ARE UP TO DATE, LISTED OVER 43,000 TESTS AND GTR AS WENDY LISTED, 25,000 AND I DON'T KNOW THE DIFFERENCE BETWEEN THOSE THINGS EXCEPT THE GTR IS A NEWER DATABASE SO THAT ACCOUNTS FOR SOME OF THE DIFFERENCE. BUT I CAN TELL YOU FROM A PROVIDERS STANDPOINT, PROVIDERS TEND TO HAVE PREFERENCES WHICH OF THESE TWO DATABASES THEY PREFER TO USE. ONE IS NOT NECESSARILY BETTER THAN THE OTHER BUT THEY ARE SET UP DIFFERENTLY. SO IF YOU HAVE A THIRD DATABASE, WHO IS TO SAY PATIENTS -- PROVIDERS ARE GOING TO GO TO THAT DATABASE. SO THERE HAS TO BE SOME SORT OF WAY OF MERGING THESE TO MAKE IT EASIER TO HAVE EVERYTHING IN ONE PLACE, THAT WOULD BE GREAT BECAUSE YOU CAN SOMETIMES GET DIFFERENT INFORMATION FROM THE TWO DATABASES THAT EXIST RIGHT NOW. I WOULD ALSO SAY THAT HOW ARE YOU GOING TO LIST DAILY CHANGES THAT ARE OCCURRING IN GENETICS. PEOPLE TALKED ABOUT H THIS AND WHAT DEFINES AN LDT, ARE YOU GOING TO CHANGE EVERY TIME REAGENT CHANGES AND HOW THE FDA KEEPS UP WITH THOSE CHANGES AND MAKE SURE THE PUBLIC AND PATIENT AND PROVIDERS ARE AWARE OF DAILY CHANGES. YOU HAVE TO THINK ABOUT THAT AS WELL. AS DR. NOWAK SPOKE TO THIS POTENTIALLY COULD LIMIT TESTING AVAILABILITY BECAUSE THERE MAYBE LABS WHO CHOOSE TO NO LONGER OFFER A TEST BECAUSE THERE'S AN FDA AVAILABLE OPTION AND IT'S TOO BURDENSOME TO GO THROUGH THE REGULATORY PROCESS. IF THAT'S THE CASE YOU CAN LIMIT AVAILABILITY FOR TESTING OF PATIENTS. SOMETHING TOUCHED ON BUT NOT SPOKEN ABOUT THAT MUCH IS INSURANCE COVERAGE AND INSURANCE COVERAGE DOES NOT NECESSARILY COVER THINGS THAT ARE OUT OF NETWORK PREFERRED LABS SO CERTAIN PREFERRED LABS ARE NO LONGER OFFERING A TEST BECAUSE THERE'S AN FDA APPROVED OPTION ACROSS THE COUNTRY AND THE LAB DECIDES TO NO LONGER OFFER THAT TEST. HOW ARE YOU GOING TO GIVE THAT INFORMATION. IS THERE A WAY ON THIS POTENTIAL DATABASE THAT LISTS WHAT ENSURES COVER THIS TEST NOW THAT IT'S AN APPROVED OPTION. I DON'T THINK THERE'S A GUARANTEE BECAUSE THE FDA APPROVES A TEST THAT'S COVERED BY INSURERS SO THAT'S SOMETHING TO KEEP IN MINE AS WELL, ESPECIALLY WHEN YOU THINK ABOUT POTENTIAL WHAT'S OUT THERE AND AVAILABLE TO PATIENTS. I THINK IT'S IMPORTANT TO KEEP IN MIND WHAT THIS REGULATION IS FOR AND PREVENT HARM TO MAKE SURE IT'S NOT CAUSING HARM AND NOT CAUSING OVERBURDEN AND ADDING YET ANOTHER DATABASE THAT THERE'S MORE THINGS THAT NEED TO BE SUBMITTED TO THAT PROVIDERS WHICH ONE IS MOST ACCURATE WITH THE MOST UP TO DATE AND WHICH TO USE. >> THANK YOU. BEFORE WE MOVE ON TO QUESTION TWO WOULD ANY PANEL MEMBERS QUICKLY LIKE TO MAKE A COMMENT BEFORE WE MOVE ON? IT LOOKS LIKE YES. GO AHEAD. >> REGARDING DR. MCDONALD'S CONCERN IDENTIFYING MOLECULAR TESTS, I SUSPECT SOME OF THE PROBLEMS ARE HISTORICAL WHEN THE CPT CODES WERE METHOD LOGIC AND ONE REALLY USE THE CODES TO IDENTIFY THE PARTICULAR TESTS. BUT I THINK THAT'S CORRECTED. WE NOW HAVE ANOLYTE SPECIFIC CPT CODES AND MAJOR EFFORT BY CPT TO IDENTIFY WHAT TEST IS BEING DONE AND IT'S PUSHED BY THE PAYERS AND MAYBE THAT WILL ADDRESS SOME OF THE PROBLEMS THAT HE'S ENCOUNTERED IN THE PAST. REGARDING WHAT DR. RUBINSTEIN AND TERRY TALKED ABOUT, WE HAVE TO REMEMBER THAT LDTs ARE NOT JUST GENETIC TESTS, WHETHER HEREDITARY OR SOMATIC, THERE'S OTHER TESTING GOING ON IN LABORATORY WHETHER IT'S FLOW CYTOMETRY, IMMUNOHISTOCHEMISTRY, SPECIAL STAINS, INFECTIOUS DISEASE TESTING, THESE ARE -- THERE ARE LDTs EVERYWHERE. SO WHILE GENETIC TEST REGISTRY CAN BE USEFUL FOR PART OF THAT, THAT'S A LOT OF STUFF GOING ON THAT THAT DOES NOT ADDRESS. WHILE YOU DID MENTION WENDY THAT YOU DO THE GTR DOES INCLUDE SOMATIC TESTING ON TUMORS FOR EXAMPLE, I'M NOT SURE IT CAPTURES THE TESTS THAT WE DO. THOSE TARGETED THERAPIES. I SUSPECT MOST LABORATORIES THAT DO THESE KINDS OF TESTS HAVE NOT REGISTERED THOSE KINDS OF TESTS WITH THE GTR. YOU'RE TALKING ABOUT THE VARIANTS OF UNKNOWN SIGNIFICANCE CAPTURING THOSE THINGS FORTUNE BAR. >> A LITTLE FOLLOW-UP. CBD HELPS A LITTLE BIT, THAT'S NOT ALL YOU NEED TO KNOW, IS IT QUANTITATIVE OR QUALITATIVE? WHAT IS IT CONFUSED BY, NONE OF THAT COMES FROM THE CPT CODE. WE GET THESE GLOSSY SOMETIMES, THEY'RE LIKE IT'S A CAR. BUT YOU DON'T KNOW MUCH MORE ABOUT IT. IT'S NOT UNIVERSALLY FOR SURE. THERE'S VERY GOOD LOCALLY DEVELOPED TESTS I'LL DESCRIBE. >> WENDY. >> I WOULD AGREE WITH JAN THAT GTR DOES NOT COVER THE FULL SCOPE OF LDTs THAT ARE OUT THERE, IT'S NOT ITS PURPOSE. WE COULD INCLUDE INFECTIOUS DISEASE, IT'S DISCUSSED BUT NOT ON THE CURRENT RADAR SCREEN. SO GTR WOULD BE POTENTIALLY USED TO SUPPLEMENT INFLAMMATION AND REDUCE THE BURDEN COLLECTION BY REDUCING DUPLICATIVE EFFORTS. THIS COULD NOT SUFFICE TO BE A SOUL MEANS OF PREVENTING INFORMATION. >> I'M NOT SURE WHICH LDTs YOU'RE MENTIONING THAT ARE FOR -- I WOULD SAY THE THOROUGHNESS OF GTR IS CERTAINLY FAR FROM COMPLETE AND THE TEST NOT ALL THE TESTS ARE REGISTERED BECAUSE IT IS A VOLUNTARY REGISTRY. I DID HAVE ONE CLARIFYING POINT ABOUT GENE TESTS AS YOU CORRECTLY SAID, GTR WAS SEATED BY THE INFORMATION IN GENE TESTS AND THE DIFFERENCES BETWEEN THE NUMBER OF TESTS THAT ARE LISTED WHEN I USE NUMBERS FOR GTR, I'M SOLELY REFERRING TO REGISTER TESTS, THOSE ARE THE MOST THOROUGHLY DESCRIBED TESTS, AGREGESERRED TESTS REFLECTED FROM THE LEGACY DATABASE THEY WERE LAST UPDATED PROBABLY TWO YEARS AGO. SO WE'RE REMOVING MANY OF THOSE, SOME OF THOSE REMOVED SOME NOT UPDATED IN GENE TESTS EITHER. GENE TEST IS NOT INCLUDE THE GRANULARITY, I WOULD THINK THE FDA IS INTERESTED IN. >> SO WE SHOULD MOVE ON, WE CAN GET BACK TO THAT IN QUESTION FOUR. LET'S MOVE TO QUESTION 2. QUESTION 2 IS WOULD IT BE SUFFICIENT TO ALLOW LABORATORY NETWORKS IE MORE THAN ONE LABORATORY UNDER THE CONTROL OF THE SAME PARENT ENTITY THAT OFFER THE SAME TESTS IN MULTIPLE LABORATORIES THROUGHOUT THEIR NETWORK TO SUBMIT A SINGLE NOTIFICATION FOR THE TEST. AT THIS TIME CAN WE START WITH CAROLINARY. WE'LL MOVE THIS WAY. THANK YOU. >> SO I WOULD BE SUPPORTIVE OF THIS IN THE FACT THAT IT COULD REDUCE THE PAPERWORK LABORATORIES HAVE TO DO. THAT'S PART OF WHAT THE BIGGEST COMPLAINT IS WHETHER YOU HAVE THE STAFFING TO ADHERE TO ALL THE REGULATIONS. SO THE OTHER THING I WOULD KEEP IN MIND IS LDTs ARE DIFFERENT IN DIFFERENT PLACES, THERE'S A DIFFERENT MACHINES REAGENT AND THERE'S DIFFERENT PEOPLE INTERPRETING THAT DATA. SO DIFFERENT LAB DIRECTORS AT THE DIFFERENT LOCATIONS. THERE'S A HUMAN ELEMENT TO THE GENETIC TESTING. SO YOU MAY LOOK AT A RESULT AND YOU'RE GOING TO TRY TO DEPLETE IS IT CONSERVED AMONG SPECIES. DOES IT AMINO ACID. WHAT PART OF THE THE GENE IS IT IN. GENETIC TESTS THAT ARE ALL KNOWLEDGE OF A LABORATORY DIRECTOR THAT YOU'RE NOT NECESSARILY GOING TO CAPTURE WITH A PAPER THAT'S FILLED OUT. THAT IS DIRECTOR SPECIFIC AND TRAINING SPECIFIC. SO I'M NOT SURE THAT JUST HAVING ONE BLANKET APPROVAL FOR DIFFERENT LOCATIONS IS GETTING AT WHAT YOU'RE LOOKING FOR. TRYING TO MINUTEMIZE REGULATION IS A GOOD THING UNLESS HELPING IF THAT'S NOT HELPING YOU GAIN MORE INFORMATION, PERHAPS IT IS A GOOD THING. SOMETHING TO KEEP IN MIND IS THAT LDTs ARE REALLY JUST DIFFERENT WHEREIN WITHIN A LAB ONCE THEY REVALIDATE DATA OR MACHINES EVERY FEW MONTHS SO THEY'RE DIFFERENT WITHIN INSTITUTIONS. >> SO IN THE GENETIC TESTING REGISTRY, A TEST IS IN PART DEFINED BY THE LOCATION AT WHICH IT'S PERFORMED AND SO THE SAME METHODOLOGY, IN ELEMENTS OF THE TEST IF THEY'RE ALL -- SEEM TO BE THE SAME, DIFFERENT LOCATIONS, WE LOOK AT THAT AS A SEPARATE TEST DEFINED AS THE LABORATORY BETWEEN TWO DIFFERENT KLIA LICENSES. WHETHER THE FDA REQUIRES NOTIFICATION FOR BOTH TESTS IS A MATTER OF POLICY. >> LET'S MOVE THROUGH. >> IF IT'S THE SAME TESTS, IT SHOULD BE THE SAMITES, YOU HAVE TO DEPEND UPON WHO WOKE THANK YOU VERY MUCH MORN AND GOT TO THE LAB FOR THE ORDERING PERSON TO KNOW WHAT THE TEST IS. I THINK IT'S PROBLEMATIC. ONE SHOULD AIM TO MAKE THE TEST THE SAME IF IF IN DIFFERENT LABORATORIES RUN BY THE SAME GROUP AND DO IT ONCE. IF THEY'RE NOT THE SAME WE'RE DOOMED I THINK. >> THAT'S COMPLETELY IMPOSSIBLE WITH GENETIC TESTING BECAUSE THE RESULTS ARE BASED ON THE INTERPRETATION OF THE PROVIDER WHO IS INTERPRETING THEM. SO I UNDERSTAND YOUR POINT BUT IT'S NOT LIKE A CBC OR THYROID TEST, IT'S A TEST WITH A LOT OF INTERPRETATION, THAT'S PART OF IT, THAT'S NOT GOING TO BE POSSIBLE UNLESS YOU GO TO AN AUTOMATED SYSTEM WHICH YOU CAN'T GET THE LEVEL OF RESULTS FROM THAT. >> PLEASE. >> THE INTERPRETIVE COMMENT IS DEPENDING HOW YOU SLICE IT, THAT COULD BE OUTSIDE OF THE TEST RESULTS. THERE'S THE PHYSICAL TEST RESULTS. AND INTERPRETIVE PART WILL ALWAYS VARY A LITTLE BIT DEPENDING ON IN THE EXTREME THE CLINICIAN THAT SEES THE REPORT AND THAT MAY NOT BE CONTROLLABLE AS PART OF THE TEST. I RAISE THAT. SO IN WHAT WE HEARD YESTERDAY IS IT'S DIFFICULT TO DEFINE WHAT A SYSTEM IS. YOU CAN GO BY DIFFERENT KLIA NUMBERS, YOU CAN BYPASS KLIA NUMBERS. WE HEARD SOMEONE SAY YESTERDAY THEY HAVE I DON'T KNOW 10, 20 DIFFERENT KLIA NUMBERS, LABORATORIES ASSOCIATED WITH THEIR LABORATORY WITH THEIR SYSTEM AND I THINK YOU HAVE NOW INTRODUCED ANOTHER TERM, A NETWORK. WE DON'T KNOW WHAT THESE THINGS ARE. I THINK IF A TEST IS BEING PERFORMED ON A SIMILAR INSTRUMENT IS IN MULTIPLE PLACES WITHIN SOME KIND OF A SYSTEM, IF THE VALIDATION HAS BEEN DONE JOINTLY, IF YOU'RE ASSURED THAT THE POPULATION THAT'S BEING TESTED IS THE SAME, YOU CAN'T TAKE A TEST FROM A GENERAL HOSPITAL AND MOVE IT TO A CHILDREN'S HOSPITAL IT MAYBE USED FOR AN ENTIRELY DIFFERENT PURPOSE AND YOUR NORMAL VALUES WILL BE DIFFERENT. IS THE QUALITY ASSURANCE PROGRAM THAT'S IN PLACE, IS THE PROFICIENCY TESTING PROGRAM IN PLACE AT VARIOUS LOCATIONS, IF IT DEMONSTRATES THE TESTS ARE REALLY THE SAME TESTS, THEN THERE'S CERTAINLY EFFICIENCIES IN CONSIDERING THESE ONE TESTS. IF THEY'RE SUFFICIENTLY DIFFERENT THEY NEED TO BE CONSIDERED DIFFERENT TESTS SO THERE'S A LOT OF DETAILS THAT NEED TO BE ATTENDED TO BEFORE YOU CAN LUMP THINGS TOGETHER OR SPLIT THEM APART. IT HAS TO BE DONE CAREFULLY. >> YES, PLEASE. >> AJ DOESN'T HAVE ANY SPECIFIC REASON TO OPPOSE AN EFFORT TO REDUCE THE BURDEN OF REPORTING. CLEARLY THE USE OF MACHINES REAGENTS AND STANDARD OPERATING PROCEDURES WOULD BE ASSUMED TO BE REQUIRED TO BE THE SAME ACROSS MULTIPLE SITES. WHERE THE LINE IS DRAWN AS FAR AS THE ROLE OF INTERPRETATION, CLEARLY IS A POINT THAT WOULD REQUIRE CLARIFICATION. BUT IT SEEMS REASONABLE. IF THERE ARE DIFFERENT MACHINES MEANING NOT A DIFFERENT ENTITY BUT A DIFFERENT COMMERCIAL PRODUCT IT BEGS THE QUESTION WHETHER IT'S THE SAME PROCEDURE BEING IMPLEMENTED AT EACH SITE. >> GO AHEAD. >> EVEN THE DIFFERENT MACHINE, ROUTINE LABORATORIES ROUTINE TESTS, IF ONE MACHINE GOES DOWN THEY HAVE THE SWITCH TO THE OTHER THEY DON'T ASK PHYSICIANS TO ORDER A NEW TEST THEY STANDARDIZE THEM MAKE THEM ALIKE. WE HAVE TO BE CAREFUL ABOUT PROCEDURES AND PROCESSES AND BREAKING THEM BY THIS PROCEDURE. >> WOULD YOU LIKE A COMMENT? >> I SERVED FOR A PERIOD OF TIME AS A MEDICAL DIRECTOR OF A LARGE HEALTHCARE SYSTEM, WE HAD 25 DIFFERENT HOSPITALS. WE HAD LABORATORIES THAT TEACH THOSE HOSPITALS, WE HAD CORE LABORATORIES IN TWO DIFFERENT STATES AND CERTAINLY AN EFFORT WAS MADE TO STANDARDIZE INSTRUMENTATION AND WE WERE COMPARING RESULTS ON DIFFERENT INSTRUMENTS ALL THE TIME. IF A MACHINE DID BREAK HAVING THAT REDUNDANCY WAS USEFUL BUT IT REQUIRED US TO KNOW THAT THE PERFORMANCE NORMAL VALUES AND ALL THOSE THINGS WERE CONSISTENT FROM INSTRUMENT TO INSTRUMENT TO INSTRUMENT. SO I POINT THIS OUT THAT A LOT OF THIS ALREADY HAPPENS, IT HAPPENS -- THESE ARE REQUIREMENTS OF KLIA, CAP ACCREDITATION PROGRAM, THAT'S WHAT PEOPLE DO. THIS IS IN PLACE. FURTHERMORE I POINT OUT UNDER THE CAP LABORATORY ACCREDITATION PROGRAM, THEY STRUGGLE WITH THIS NOTION OF IDENTIFYING SYSTEMS AND WHEN THEY DO THEIR INSPECTIONS, THEY HAVE PARTICULAR PROTOCOLS THAT THEY FOLLOW WHEN THEY ARE INSPECTING A SYSTEM OF HOSPITALS EACH OF THE HOSPITALS NEEDS TO BE INSPECTED INDIVIDUALLY BUT IF THERE ARE COMMON PROCEDURES, COMMON THINGS, THEY DETERMINED ADEQUATE TO DO AN INSPECTION ONE PLACE FOR THE ENTIRE SYSTEM THEY USE THAT EFFICIENCY BUT THEY STRUGGLED WITH THAT, THERE MAYBE SOMETHING TO BE LEARNED FROM WHAT IT IS THEY DO. >> THANK YOU. WOULD YOU LIKE TO MAKE ONE MORE COMMENT THEN MOVE ON. >> I WOULD SAY EVEN IF YOU HAVE THE MACHINE YOU DON'T HAVE EVERYTHING THE SAME. REAGENTS COULD BE DIFFERENT. I WORKED IN NEWBORN SCREENING LABORATORY FOR A WHILE REPORTING OUT RESULTS AND SOMETIMES THE PAPER WE RECEIVED WHICH SHOULD BE THE EXACT SAME WE THINK SOMEHOW ALTERED THE RESULT AND WE GET MORE POSITIVES THAN WE NECESSARILY HAD THE WEEK BEFORE. AND THERE WAS A LOT OF TROUBLESHOOTING TO FIGURE OUT AND IDENTIFY THAT THAT'S WHAT WE THINK WENT WRONG. SO AS MUCH AS YOU CAN TRY TO KEEP THE SYSTEM THE SAME THERE ARE DIFFERENCES THAT WE CAN'T NECESSARILY ACCOUNT FOR THAT LABORATORY DIRECTORS HAVE TO HAVE THE POWER TO CHANGE THINGS SO PATIENTS ARE SAFE. AS QUICKLY AS POSSIBLE WITHOUT GOING THROUGH AND RESUBMITTING SOMETHING. GREAT. THANK YOU. THAT'S A VERY GOOD DISCUSSION SO LET'S MOVE TO QUESTION 3. ARE THERE CERTAIN TYPES OF LDTs WHICH THE AGENCY SHOULD NEITHER ENFORCE REQUIREMENT FOR REGISTRATION AND LISTENING NOR REQUEST NOTIFICATION IN LIEU OF REGISTRATION AND LISTING. AND WHY DON'T WE START NOW WITH CHRIS. >> THE AHA BELIEVES THE FDA SHOULD REQUIRE NOTIFICATION AND SHOULD NOT HAVE ENFORCEMENT DISCRETION FOR THE NOTIFICATION PROCESS. THIS IS CRITICAL AS PREVIOUSLY OUTLINED TO ALLOWING THE CATALOGING OF LDTs FOR BOTH PUBLIC AND PROVIDER, THE PAYER COMMUNITY TO UNDERSTAND. AS WELL TO INFORM THE FDA RISK STRATIFICATION EFFORTS. WE DON'T SEE HOW THE FDA CAN RISK STRATIFY LDTs IF IT HASN'T BEEN NOTIFIED. REGARDING THE REGISTRATION AND LISTING, I THINK THE FDA'S EFFORTS TO USE RISK STRATIFICATION AND PRIORITIZATION SHOULD BE ADEQUATE BUT IT REQUIRES UPSTREAM NOTIFICATION. >> THANK YOU. >> JAN TO THE RIGHT. >> I HAVE THREE THOUGHTS HERE. CERTAINLY THOSE TESTS, THOSE LDTs THAT ARE NON-TRANSPARENT, THOSE CERTAINLY NEED TO BE LOOKED AT BY P FDA THE CONVENTIONAL METHODS OF ASSURING QUALITY ASSURANCE OF TESTING AND PROFICIENCY TESTING ARE NOT AMENABLE TO THOSE KINDS OF TESTS. I THINK PRETTY MUCH EVERYONE AGREES SOMEONE NEEDS TO LOOK AT THOSE WITH SCRUTINY. IF THERE IS AN EFFECTIVE QUALITY ASSURANCE PROGRAM AND PROFICIENCY TESTING, AND THAT'S BEING FOLLOWED, THEN I WOULD THINK THAT THOSE KINDS OF TESTS WHETHER THEY'RE FDA -- CERTAINLY FDA APPROVED YOU DON'T NEED TO LOOK AT THEM FURTHER YOU ARE LOOKING AT THEM. IF THEY'RE LDTs, THAT MAYBE THINK IT IS A PLACE TO USE ENFORCEMENT DISCRETION AND SAY WE DON'T NEED TO BE LOOKING AT THESE. I THINK YOU RUN INTO A CONUNDRUM WITH THIS NOTION OF UNMET NEEDS BECAUSE YOU'RE ACKNOWLEDGING THERE THAT THE EXISTING MECHANISMS OF PROVIDING QUALITY ASSURANCE AND PROFICIENCY FOR THOSE TESTS THAT THESE EXISTING MECHANISMS THROUGH KLIA THROUGH CAP THESE ARE SOMEHOW ADEQUATE AND SETTING THESE UP AS A CARVE OUT, THAT'S A PROPOSAL, THE COMMENT THAT DR. KLINE BROUGHT UP YESTERDAY THESE ARE NOT UNMET NEEDS. THEY ARE IN FACT MET. AND BY NOT USING ENFORCEMENT DISCRETION AND NOT LOOKING AT THOSE, IS AN ACKNOWLEDGMENT THAT THE CURRENT MECHANISMS OF QUALITY ASSURANCE AND PROFICIENCY TESTING IS ADEQUATE FOR THOSE TESTS AND IT BEGS THE QUESTION, WHY IS THIS NEED UNMET. THAT'S WHAT WE SHOULD BE PURSUING. WHY ARE THESE NEEDS UNMET. I'M NOT TALKING RARE DISEASE, I'M TALKING ABOUT COMMON CANCERS, LUNG CANCER, COLON CANCER, THESE ARE MAJOR CAUSES OF MORBIDITY AND MORTALITY IN THE US. THERE ARE UNMET NEEDS. THOSE NEEDS ARE BEING MET BY LABORATORY DEVELOPED TESTS SO IF YOU ACKNOWLEDGE THOSE THINGS ARE ADEQUATELY BEING ADDRESSED WHAT CHANGES THEN IF A MANUFACTURER DEVELOP AS TEST AND TAKES IT THROUGH THE FDA. HAVE THE STANDARDS CHANGED ALL OF A SUDDEN? IT SEEMS YOU'RE ACKNOWLEDGING THAT TESTING IS GOOD AND NOW YOU'RE GOING TO FINANCIALLY PENALIZE THE LABORATORIES THAT YOU SHOULD BE -- YOU SHOULD BE APPLAUDING. FOR SATISFYING THIS UNMET NEED BUT YOU'RE GOING TO GIVE THEM A FINANCIAL PENALTY OR REWARD THAT COMES WITH THE LABORATORY DEVELOPED TEST. I DON'T LIKE THE ANALOGY OF AN UNEVEN PLAYING FIELD. BECAUSE I DON'T FEEL I'M PLAYING A GAME. THAT'S VERY UNEVEN, IT'S TILTED. SO I FEAR THAT THAT'S A CONUNDRUM FDA WILL GET INTO IF THEY ACKNOWLEDGE THESE TESTS DON'T NEED TO BE SUBMITTED UNTIL THERE'S AN FDA APPROVED TEST. SO I WOULD ADVISE CAUTION IN PROCEEDING. AND THINKING ABOUT WHETHER YOU'RE REALLY WANTING TO IDENTIFY THAT UNMET NEED. BECAUSE THEN YOU'RE SUSCEPTIBLE TO CRITICISM THAT YOU'RE USING A LOWER STANDARD FOR THOSE KINDS OF TESTS. I DON'T SEE HOW YOU CAN DO THAT. >> THANK YOU. WHEN THE DI. >> I SEE OVERLAP WITH THIS QUESTION TOPIC THREE. I SEE OVERLAP WITH THIS QUESTION WITH TOPIC 3 YESTERDAY AND MY COMMENTS ARE ABOUT THE DEFINITION OF HUMANITARIAN USE DEVICE BEING UNDER 4,000 PERSONS TESTED IN THE U.S. PER YEAR. MY COMMENT IS IN THE AGE OF NEXT GENERATION SEQUENCING THE RELATIONSHIP BETWEEN RARE DISEASE AND RARELY TESTED DISEASE NO LONGER EXISTS. AND ESSENTIALLY THAT MEANS WE'RE BECOMING ADEPT AT SCREENING FOR RARE GENETIC DISEASES. DISEASES THAT MIGHT BE SEEN ONCE OR NEVER BY GENETIC SPECIALISTS, ARE READILY PLACED ON COMPLEX NEXT GENERATION SEQUENCING PANELS. SO TO GIVE YOU AN EXAMPLE, GTR MOST COMPLEX REGISTER TEST IS TRUE GENOME TEST AND THAT HAS OVER 1500 GENES FOR OVER 1500 CONDITIONS. COMPARING THAT WITH THE NIH OFFICE OF RARE DISEASE RESEARCH LIST, THERE'S A LARGE OVERLAP BETWEEN THE CONDITIONS ON THAT PANEL AND THAT DEFINITION. SO IF ALUMINA WERE TO PERFORM 4,000 OR MORE TRUE GENOME TESTS ANNUALLY THEN NO TESTS IN THE U.S. FOR ANY OF THE RARE DISEASES ALUMINA'S PANEL WOULD QUALIFY AS A HUMANITARIAN USE DEVICE. >> KERRY. >> SO I THINK FOR PART OF THIS QUESTION I WOULD SAY TO GO BACK TO THE REASON YOU'RE THINKING ABOUT CREATING THIS REGULATION TO BEGIN WITH, AND DETERMINE WHAT THE HARMS ARE THAT ARE OUT THERE AND THINK CRITICALLY ABOUT THAT, MAKE SURE IN CONSIDERING THAT HOW THAT WILL EFFECT EVERYONE. THERE'S A LOT OF CONSIDERATIONS TO KEEP IN MIND. YOU WANT TO KEEP IN MIND FUNDING SOURCE OF LABORATORY, YOU DON'T WANT TO PROMOTE ONLY COMMERCIAL LABS AND SHUT DOWN SMALLER LABS BECAUSE OF THAT REGULATION OR STATE PUBLIC HEALTH LABS OFFERING A VALUABLE SERVICE THAT ARE BREAKING EVEN. YOU DON'T WANT TO THROW INNOVATION WHICH IS MENTIONED A LOT OR TURN AROUND TIMES YOU DON'T WANT TO CHANGE TESTING OPTIONS AND THIS COULD PUSH GENETIC TESTING MORE TOWARDS PANELS THAN SINGLE GENE TESTS BECAUSE IT'S EASIER TO REGISTER FOR A BUNCH OF DISEASES VERSUS TESTS WHICH RAISE THE COST OF HEALTHCARE MORE MONEY BECAUSE OF TESTING FOR ONE TEST. YOU WANT TO TAKE INTO ACCOUNT TRAINING OF PEOPLE WHO ARE IN THE LAB AS WELL. SO WHERE DID THE LAB DIRECTORS TRAIN, WHERE ARE THEY ACCREDITED, ALL THAT IS VERY IMPORTANT. IF YOUR CONCERN IS THERE ARE BAD LABS THAT YOU WANT TO REGULATE, ALL OF THAT IS IMPORTANT TO MAKE SURE EVERYONE IS TRAINED APPROPRIATELY IN THE LAB AND DOING THE RESULTS. GIVING THE RESULTS. YOU ALSO AGAIN WANT TO TAKE INTO ACCOUNT THE RARE DISORDERS AND I THINK THAT YOU ALSO WANT TO MAKE SURE THIS DOESN'T EFFECT TURNAROUND TIME. AN EXAMPLE MIGHT BE THAT YOU HAVE A PATIENT WITH A DISORDER THAT ONE GENE ACCOUNTS FOR 50% OF WHAT THEY HAVE AND THEY'RE NEGATIVE FOR THAT. NEW TESTS COME UP AND THERE'S MORE GENES FOR THAT CONDITION. THE PATIENT IS PREGNANT BUT THAT TEST IS NOT FDA REGULATED, ARE THEY GOING TO BE ABLE TO GET THAT TEST AND AGAIN SOME OF THE INSURANCE ISSUES CAN IT BE COVERED, ALL THOSE THINGS NEED TO BE TAKEN, IT'S NOT ONE ISSUE, IT'S A COMPLEX ISSUE TO TAKE THESE THINGS INTO ACCOUNT AND NOT SLOWING THE OPTION OF TESTING FOR PATIENTS. >> LET'S MOVE ON. >> ONE COMMENT. IF I READ THIS RIGHT THERE'S SEVEN ITEMS TO BE ANSWERED. IF YOU GET 12 TESTS OR 20 TESTS, THAT'S GOING TO TAKE 20 MINUTES OR HALF AN HOUR. YOU'RE GOING TO HAVE TO DO THAT ANYWAY FOR YOUR CUSTOMERS TO DO SOMETHING. THE HL-7 HAS A THING THAT CONTAINS THIS. THE ISSUE COMES TO HOW AT THE GRANULARITY LEVEL HOW THE SPECIAL CONDITIONS, AND YOU HAVE TO DO IT EVERY WEEK BECAUSE YOU CHANGE THE REAGENT, I THINK IT SHOULDN'T BE HARD IF THE SPREAD ISN'T TOO COMPLEX IN TERMS OF OTHER ISSUES. BUT I MUST HAVE MISREAD IT BUT IT LOOKED PRETTY SHORT. >> BECAUSE OF TIME IF THERE'S ONE BURNING COMMENT YOU CAN MAKE IT, PLEASE BEFORE WE GO TO FOURTH QUESTION. >> VERY BRIEFLY, RARE RESULTS DON'T SIMPLY APPLY TO INHERITED DISEASES, JUST IN NON-SMALL CELL LUNG CANCER THE IASLC CPA GUIDELINES ISSUES A COUPLE OF YEARS AGO RECOMMEND TESTING FOR ALL MUTATIONS IMPORTANT FOR TYROSINE KINASE THERAPY THAT OCCUR AT A FREQUENCY OF AT LEAST 1% SO WE TEST 140 NON-SMALL CELL LUNG CANCERS EVERY YEAR AND TRANSLOCATIONS IN ALK AND ROS WE FIND INFREQUENTLY. SO FOR A VERY COMMON TEST FOR A VERY COMMONLY MALIGNANCY WE'RE LOOKING FOR RELATIVELY RARE EVENTS. THAT'S ONE THING. THE SECOND COMMENT, I WANTED TO MAKE WITH ENFORCEMENT DISCRETION LOOKING FORWARD TO YOUR YOU CONSIDER SOME RESTRAINT IN BECAUSE OF TECHNICAL COMPLEXITY AND SOFTWARE COMPLEXITY. THOSE ARE TECHNICAL ISSUES AN STANDARDS NEED TO BE DEVELOPED FOR HOW THOSE INSTRUMENTS WORK AND HOW THE SOFTWARE WORKS. BUT WE'RE IN THAT PROCESS RIGHT NOW AND THOSE STANDARDS WILL BE DEVELOPED. IT MAYBE THAT FDA HAS A PLACE IN HELPING TO DEVELOP THOSE STANDARDS, OR MAYBE NOT. BUT THEY WILL BE DEVELOPED OVER THE NEXT TWO OR THREE YEARS. WE HAVE STANDARDS HOW SEQUENCING AND NGS INSTRUMENTS WORK, WE HAVE METHODS OF MONITORING THEIR PERFORMANCE AND THAT'S WHAT WE SHOULD BE GOING FOR TO PUT TOGETHER AN OVERSIGHT PROGRAM THAT LOOKS AT EACH TEST FROM BEGINNING TO END IS A BLACK BOX BECAUSE WE DON'T UNDERSTAND THE TECHNICAL VARIATION OR THE SOFTWARE VARIATION CONSIDERED ONE TEST AS ONE BLACK BOX DOESN'T MAKE SENSE AND TO DEVELOP AN OVERSIGHT SYSTEM THAT'S IMPLEMENTED OVER NINE OR TEN YEARS ALSO DOESN'T MAKE ISSUES THAT ARE RESOLVED IN THE NEXT TWO OR THREE YEARS. SO I ADVISE SOME RESTRAINT AND SOME FORE THOUGHT IN APPROACHING THAT WHOLE NGS ISSUE, JUST BECAUSE IT'S COMPLICATED DOESN'T MEAN IT'S NOT STANDARDIZED. AND IT WILL BE. >> GREAT. THANK YOU VERY MUCH. SO LET'S MOVE TO THE LAST QUESTION. HOW CAN FDA LEVERAGE OTHER INFORMATION TO REDUCE INFORMATION COLLECTED ASSOCIATED WITH NOTIFICATION TO BE LABORATORIES WHILE OBTAINING SUFFICIENT INFORMATION TO INFORM THE LDT CLASSIFICATION AND PRIORITIZATION PROCESS. I THINK WE'LL START WITH WENDY. >> THANK YOU. USING ALREADY COLLECTED INFORMATION CAN REDUCE THE BURDEN THE MOST AS LONG AS IT IS HIGH QUALITY INFORMATION THAT IS AMENABLE TO COMPUTATIONAL APPROACHES. GTR IS NOT THE ONLY DATABASE I CAN THINK OF THAT HAS COLLECTED INFORMATION. WE HEARD A FEW ALREADY DISCUSSED HERE ONE I HAVE NOT HEARD MENTIONED IS PALMETTO GBA CMS CONTRACT AND THE MCKESSON PROGRAM, THAT'S A FEDERALLY FUNDED DATA COLLECTION EFFORT. AND LABORATORIES IN THE JURISDICTION OF PALMETTO WHO SEEK COVERAGE AND PAYMENT FOR TESTS BY CMS HAVE COMMITTED INFORMATION TO PALMETTO AND MCKESSON. NCBI HAPPENED THE 14 FDA NOTIFICATION DATA ELEMENTS IN APPENDIX A OF DRAFT NOTIFICATION TO THE GTR FIELDS. AND THE GTR FIELD IS MAPPED TO ALL BUT TWO OF THE 14 ELEMENTS. THESE ARE THE MONTHLY TEST VOLUME WHICH AS I UNDERSTAND IS AN ELEMENT BEING CONSIDERED FOR CATEGORIZATION OF RISK. WHETHER THE PATIENT POPULATION INCLUDES PEDIATRIC PATIENTS. WE HAVE TARGET POPULATION BUT WE DON'T SPECIFICALLY ASK THAT. SO THESE COULD BE EASILY ADDED TO SUPPORT DATA COLLECTION FOR FDA NOTIFICATION. WE WOULD ALSO HAVE TO GO THROUGH A MORE DETAILED MAPPING PROCESS SO THAT THE MORE DETAILS OF WHAT'S IN EACH OF THOSE WE ALL ARE CALLING THE SAME THING THE SAME THING. AS I MENTION NCBICS HAS HEAD TART IN DATA COLLECTION AND IF THE COMMUNITY DESIRES, NIH WILL WORK WITH FDA TO REDUCE SUBMITTER BURDEN AND AVOID DUPLICATIVE EFFORTS BY FACILITATING THE FDA COLLECTION PROCESS. FDA AND NIH WOULD NEED TO HEAR FROM STAKEHOLDERS, ALL OF YOU, BEFORE EMBARKING ON WORK TOWARD ASSISTING DATA COLLECTION. IF YOU THINK THIS IS DESIRABLE, I BELIEVE YOU NEED TO PROVIDE PUBLIC COMMENT THROUGH THE OFFICIAL MECHANISM BUSINESS THE FEBRUARY 3RD, DEADLINE. SO ALSO TO BE CLEAR, NIH CONCEPTUALIZES THAT DATA EXCHANGE IS INITIATED THROUGH A REQUEST BY A TEST PROVIDER. BY A LABORATORY. NCBI DOES NOT PLAN TO FORWARD INFORMATION SUBMIT TO GTR WITHOUT AN EXPLICIT AUTHORIZED REQUEST FROM A LABORATORY. FOR EXAMPLE, CONDITIONS SPECIFIED FOR GTR REGISTER TESTS WOULDN'T BE AUTOMATICALLY SENT TO FDA AS SAY INDICATION FOR THE INTENDED USE. NOR STATEMENTS ABOUT CLINICAL VALIDITY OR CITATIONS THAT WE HAVE COLLECTED. NOTE HOWEVER GTR DATA IS FULL LICK PUBLIC THROUGH THE INTERACTIVE WEBSITE WHICH IS ACCESSED BY HIGH VOLUME OF DAILY USERS. THE GTR DATA SET IS AVAILABLE THROUGH XML FILES FROM THE FTP SITE. WE HAVE APIs, SO THE DATA ARE ACCESSIBLE. >> THANK YOU, KERRY. >> I THINK AS WENDY WAS TALKING ABOUT, USING THE RESOURCES OUT THERE, GENETIC TESTING REGISTRY, OTHER DATABASES MENTIONING, THERE'S A LOT OF INFORMATION THAT'S ALREADY BEEN COLLECTED. I ALSO THINK IT'S IMPORTANT TO ENGAGE PROVIDERS TO BE ABLE TO REPORT ADVERSE EVENTS, THEY MAY REPORT TO THE LAB BUT THEY MAY NOT ALWAYS TELL THE LAB SO IF THAT'S SOMETHING YOU'RE CONCERNED ABOUT THAT ADVERSE EVENTS ARE HAPPENING IN LABORATORIES ARE WE SURE LABORATORIES ARE GETTING THAT FEEDBACK? ADVERSE EVENTS ARE TRICKY WITH LABORATORY MEDICINE BECAUSE IF YOU HAVE A FALSE NEGATIVE YOU MAY NOT KNOW THE REPERCUSSIONS OF THAT RESULT FOR YEARS. AND THAT MAY BY THAT TIME NOT GET REPORTED BACK TO LAB OR TESTS MAYBE DIFFERENT AT THAT POINT. IN GENETIC METHOD SIN ADVERSE EVENTS TEND TO BE MORE LIKELY TO DO WITH THE PROVIDERS WHO IS ORDERING THE TEST AND THEIR INTERPRETATION TO THE PATIENT OF THAT RESULT SO THE RESULT MAYBE ACCURATE, BUT IT MAYBE A PROVIDER WHO DOESN'T FULLY UNDERSTAND THE RESULT. THERE'S A LOT OF GENETIC -- NON-GENETICS PROVIDERS WHO ARE NOW ORDERING GENETIC TESTING, SOME HAVE EXCELLENT TRAINING AND GENETICS THOUGH THEY HAVE TAKEN THAT UPON THEMSELVES, SOME REFER TO GENETICS BECAUSE THEY THINK THE INTERPRETATION IS ABOVE WHAT THEIR KNOWLEDGE LEVEL IS. AND THERE IS A MIDDLE GROUP OR OTHER HEALTHCARE PROVIDERS THAT MAY THINK THEY UNDERSTAND THE GENETIC TESTS BUT SOME OF THE MORE COMPLICATIONS TESTS MAYBE TRICKY, SO THERE MAYBE A VALID LABORATORY RESULT NOT NECESSARILY ARTICULATED TO THE PATIENT BECAUSE IT IS IN THAT TRICKY ZONE, REGULATING LABORATORIES ARE NOT NECESSARILY REGULATING EVERYTHING AND I KNOW THAT'S OUTSIDE OF THE FDA PURVIEW I THINK. SO JUST IN GENERAL KEEP THAT IN MINE. >> SO I WANT TO SAY WE HAVE THREE MORE MINUTES FOR THIS PANEL. QUICKLY WE HAVE TO GET THREE MORE OPINIONS. >> I JUST WANT TO SAY EVERYTHING ISN'T GENETICS THOUGH OUR BODY IS CONTROLLED BY IT SO THERE ARE LOTS OF OTHER TESTS THAT ARE IN THIS PURVIEW THAT ONE CAN'T FORGET ABOUT. AND THIS SECOND THING IS THAT THE INTENDED USE SECTION OF THE FDA IS RICHER THAN THE LABEL SAYS. THERE'S SPECIFICITY IN THERE THAT I DON'T -- THIS QUICK BROWSING OF GTR, IT ISN'T NECESSARILY IN THERE BUT IT MAY NOT APPLY GENETIC TESTS BECAUSE SPECIMENS AN QUALITATIVE QUANTITATIVE, ET CETERA SO WE SHOULDN'T LOOSE THAT. >> CHRISTOPHER. >> IT DOES SEEM THAT HOW THE FDA AND NIH ACT IS RELEVANT SO HARMONIZATION OF THE FIELD, OPT IN WHERE IF AN LDT IS GOING THROUGH THE NOTIFICATION PROCESS TO THE FDA, THEY HAVE AN OPPORTUNITY TO UPDATE THEIR SUBMISSION TO GTR. THAT WOULD SEEM A WAY TO HAVE NON-CONFLICTING INFORMATION AND SIMPLIFY THE DATA PREPARATION FOR THAT TO THE EXTENT THAT IS SIMILAR BUT SLIGHTLY DIFFERENT FIELDS, SEEMS LIKE IT WOULD BE BURDENSOME SO TO THE EXTENT THAT FDA AND NIH CAN WORK TOGETHER TO HARMONIZE THE FIELD AND DEFINITIONS THEY USE SEEMS LIKE A OPPORTUNITY TO STREAMLINE THE PROCESS. >> I THINK SERIOUS CONVERSATIONS ABILITY WHAT KLIA AND CAP CHECKS, IT'S NOT THAT EVERYBODY HAS TO BE ACCREDITED BY CAP BUT IF THEIR PROGRAM HAS ELEMENTS THAT COULD BE EXPANDED, TO OTHER KLIA APPROVED LABORATORIES, THAT MAYBE A BIG PART OF THE PROBLEM. I WANT TO TAKE A MINUTE TO TALK ABOUT MDR, WHICH IS A BIG PART OF THAT SECOND DOCUMENT, I WAS SURPRISED WHEN I READ THAT THE ADVERSE EFFECTS THAT CALL FOR THERE ARE DEAF OR SERIOUS IRREVERSIBLE INJURY. AND I THINK MOST ADVERSE EVENTS PEOPLE TALKED ABOUT YESTERDAY AND TODAY ARE NOT THOSE KINDS OF EVENTS. I VIEW THAT WHOLE THING AS ANOTHER QUALITY ASSURANCE MEASURE BUT WE HAVE THOSE MEASURES THAT START WITH DAY TO DAY MONITORING HOUR TO HOUR MONITORING HOW WELL A TEST IS PERFORMING TO TAKE INTO ACCOUNT PRE-ANALYTICAL ISSUES POST ANALYTICAL CONSIDERATIONS, CLINICAL VALIDITY PART OF THE QUALITY ASSURANCE PROGRAM I'M FAMILIAR WITH AS LABORATORY DIRECTOR AND REASON I HAVE GRAY HAIR. HAVING ADDITIONAL QUALITY ASSURANCE MEASURE THAT ASKS HOW MANY PEOPLE HAVE DIED OR HOW MANY SERIOUSLY IRREVERSIBLY MAIMED BY YOUR TESTS THAT IS A VERY BROAD MEASURE, IT'S A VERY COURSE FILTER TO ASK WHETHER TESTING IS SAFE. WHAT WE HAVE IN PLACE UNDER KLIA THROUGH CAP ACCREDITATION IS A GRANULAR QUALITY ASSURANCE PROGRAM THAT LOOKS AT ALL THESE ELEMENTS SO I THINK YOU NEED TO VIEW IT THAT WAY. WHAT ARE YOU MEASURING AND ARE YOU CAPTURING THINGS MOST PEOPLE ARE CONCERNED ABOUT. I SUSPECT THAT'S YOUR ONLY MEASURE, THEN WE'RE DILUTING OURSELVES THAT ALL THE STUFF IS DONE AND EVERYTHING IS SAFE BECAUSE WE HAVEN'T RECORDED DEATH OR SERIOUS IRREVERSIBLE INJURY, WE'RE MISSING THE BOAT. >> THANK YOU VERY MUCH. SO THANK YOU VERY MUCH. I WOULD LIKE TO THANK THE PANEL FOR AN INFORMED DISCUSSION AND ALSO LIKE TO THANK THE AUDIENCE FOR THEIR ATTENTION. THANK YOU. [APPLAUSE] >> THANK YOU, MARIA. THERE WAS A LOT THERE SO I'M GLAD WE GOT TO STAY ON TIME. WE ARE GOING TO MOVE RIGHT INTO TOPIC FIVE. AND ED ASHWOOD IS OUR FIRST SPEAKER. TOPIC FIVE IS PUBLIC PROCESS FOR CLASSIFICATION AND PRIORITIZATION. >> WE HAVE ASKED STAKEHOLDERS TO ADDRESS THE FOLLOWING QUESTIONS. HOW SHOULD FDA STRUCTURE THE ADVISORY PANEL THAT WILL BE CONVENED TO PROVIDE INPUT TO HELP FDA ALSO FEW LDT AND PRIORITIZE FOR PRE-MARKET REVIEW REQUIREMENTS. WHICH STAKEHOLDERS SHOULD BE ABLE TO PRESENT RELEVANT INFORMATION OR VIEW THE PANEL MEETINGS TO DISCUSS THE CLASSIFICATION AND PRIORITIZATION OF LDTs, WHAT FACTORS SHOULD BE CONSIDERED IN DETERMINING LDT CLASSIFICATION AND RISK. HOW SHOULD THE ADVISORY PANEL PROCESS WEIGH FACTORS PROVIDING INPUT FOR CLASSIFYING LDT AND PRIORITIZING FOR PRE-MARKET REVIEW REQUIREMENTS. AND NOW WE'LL START OUR PUBLIC COMMENT PERIOD. >> GOOD MORNING. I'M PLEASED TO HAVE THE OPPORTUNITY TO SPEAK THIS MORNING HOWEVER I NEED TO BE OPEN AN FRANK BEFORE I ADDRESS MY ASSIGNED TOPIC. I AM ABSOLUTELY OUTRAGED AT THE FDA DRAFT GUIDANCE. I BELIEVE IT'S A MISGUIDED NAIVE AND DANGEROUS OVERAGE BY REGULATORY AGENCY CHARGED WITH EBB SURING THE SAFETY AND EFFICACY OF PATIENTS. AS A PHYSICIAN FIRST AND FOREMOST I'M SICKENED BY WHAT I KNOW WILL BE ADVERSE EFFECT ON PATIENT CARE BEFORE REMARKS ON CLASSIFICATION AND PRIORITIZATION, I WANT TO SHARE AN EXPERIENCE THAT ILLUSTRATES HOW MISGUIDED THIS PROPOSED REGULATION IS. ONE OF THE LARGEST IN THE UNITED STATES. YOU ALSO KNOW ON JULY 31st OF THIS YEAR THE FDA NOTIFIED CONGRESS THEIR INTENT TO ISSUE DRAFT GUIDANCE. WHAT YOU DON'T KNOW IS THAT ON AUGUST 22ND OF 2014 SOME THREE WEEKS AFTER THE CONGRESSIONAL NOTICE, I HAD ONE OF THE MOST FRUSTRATING PHONE CALLS OF MY CAREER. IN A CONFERENCE CALL WITH THE FDA FOLKS THAT DAY IT BECAME VERY CLEAR TO ME EARLY IN THE CONVERSATION THAT THEY HAD NO IDEA ARUP WAS A NATIONAL REFERENCE LAB. THEY THOUGHT WE DID TESTS ONLY FOR PATIENTS ABOUT THE UNIVERSITY OF UTAH. THEY WERE UNAWARE THAT WE DID TESTS OUTSIDE OUR OWN HEALTH SYSTEM WHICH MEAN IT IS FDA HAD NO REAL CONCEPT OF THE INDUSTRY THEY WERE PROPOSING TO REGULATE. TRUST ME WHEN I SAY THAT THIS IS NOT ABOUT EGO. FOR ME OR MY LAB. RATHER, THIS IS THE INTEGRITY AND ADVISABILITY OF THIS GUIDANCE. THINK ABOUT IT. FOUR YEARS AFTER THE DISCUSSION BEGAN, THREE WEEKS AFTER SUBMITTING THE PROPOSED REGULATION TO CONGRESS, THE FDA STILL NOT DONE BASIC HOME WORK THAT WOULD INFORM THEM ABOUT THE INDUSTRY THEY'RE PLANNING TO STRANGLE. ADVANCES IN PATIENT CARE THEY'RE ABOUT TO STIFLE. IT AMAZES AND ANGERS ME TO THIS DAY. MORE IMPORTANTLY THOUGH IT STRIKES ME AS EXTREMELY CARELESS AND MAKES ME WONDER WHOSE BIDDING IS THE FDA DOING? HAVING SAID ALL OF THAT, I THINK IT'S A HORRIFIC IRONY CLASSIFICATION PRIORITIZATION IS A TOPIC FOR THIS WORKSHOP. CLASSIFICATION AND PRIORITIZATION ARE EXACTLY THE ISSUE HERE. IN MORE WAYS THAN ONE. LET ME START WITH THE MOST OBVIOUS. LAB DEVELOPED TESTS ARE NOT MEDICAL DEVICES. LABORATORIES ARE NOT MANUFACTURERS. PERIOD. THAT'S A GROSS MISCLASSIFICATION. HOWEVER, I KNOW THE INTENTION OF THIS TOPIC IS TO DISCUSS THE TESTS THEMSELVES. SO LET ME TAKE A MINUTE TO SHARE MY VIEWS ON THAT. IN SHORT, I DO NOT BELIEVE THAT THE FDA OR ANYONE FOR THAT MATTER, CAN CLASSIFY LAB TEST TO LOW MODERATE OR HIGH RISK CATEGORIES. ALL HAVE FALSE POSITIVES AN NEGATIVES AND FALSE RESULTS LEAD TO HARM REGARDLESS OF THE TEST. IT'S THAT SIMPLE. THE ATTEMPT TO CLASSIFY TESTS REVEALS THE FDA NAIVETY AT BEST AND IGNORANCE AT WORST. IT'S THE BROAD BUREAUCRATIC SWEEP THAT SHOCK AND HORRIFIES EVERY DOCTOR IN THE COUNTRY CHARGED WITH PATIENT CARE AND SAFETY. LIKE MANY COLLEAGUES IN LABORATORIES ACROSS THE COUNTRY, I'M A PHYSICIAN PRACTICING LABORATORY MEDICINE. I'M NOT A MANUFACTURER. THE WORK WE DO AT ARUP IS PATHOLOGY. PATHOLOGY IS A BRANCH OF MEDICINE THAT DEALS WITH LABORATORY EXAMINATION OF BODY FLUIDS AND TISSUES FOR DIAGNOSTIC OR THERAPEUTIC PURPOSES. THE LAW OF THIS LAND CLEAR, FDA IS NOT SUPPOSED TO GOVERN PRACTICE OF MEDICINE. THIS WHOLE MATTER IS CERTAINLY THE CLASSIFICATION OF LAB TEST IS COMPLETELY OUTSIDE THEIR SCOPE AND RESPONSIBILITY LET ALOPE THEIR EXPERTISE. I THINK THE PROPOSED GUIDANCE IS AN OUTRAGE, I WILL SUFFOCATE THE CONTINUED ADVANCE PIMENTS OF PATIENT CARE AND HEALTHY PATIENT OUTCOMES AND THE PROPOSED CLASSIFICATION OF LTD IN TERRIBLY UNSOPHISTICATED OVERLY GENERALIZED WAY IS MISGUIDED NAIVE AND VERY DANGEROUS. THIS WHOLE MATTER IS REP HENCABLE AND IM-- REPREHENCABLE AND I ADVISE ALL CARE WHO INVOLVED IN THE PRACTICE OF LABORATORY MEDICINE JOIN ME IN MY OUTRAGE. THANK YOU. [APPLAUSE] >> I'M DR. HERTZBERG, MEDICAL DIRECTOR OF REFERENCE LAB TORE, A SMALLER LABORATORY ARUP, AND SOME OF THE THINGS THAT I SEE MAY WELL APPLY TO OTHER SIMILAR AUTHORITY BUT I'M REPRESENTING ONLY MY ORGANIZATION TODAY SO I NEED TO MAKE THAT CLEAR. WE ARE A PRIVATELY HELD REFERENCE LABORATORY, WE ESTIMATE THIS YEAR WILL PROBABLY PERFORM APPROXIMATELY 400,000 CANCER DIAGNOSTIC TESTS SPECIALIZED ONLY IN CANCER DIAGNOSIS. THAT TEST VOLUME COMES FROM BILLABLE UNITS OR CPT CODES, AND REPRESENTS TASKS PERFORMED ON SOMEWHERE AROUND 30 OR 35,000 PATIENTS, DO MULTIPLE TESTS ON DIFFERENT PATIENTS AND OF COURSE THE OTHER QUESTION THAT I HAVE IS EACH ONE OF THOSE BILLABLE TESTS AND LDT OR PANEL LDT AND APPLIES TO FLOW CYTOMETRY, IMMUNOHISTOCHEMISTRY, ET CETERA. IN ANY CASE, WE ARE VERY CONCERNED ABOUT THE FDA REGULATIONS AS WELL FOR MANY REASONS OUTLINED BY MANY PEOPLE SPOKE PRIOR TO MY SPEAKING. SO GO ON. MANY OF THE CONCERNS THAT ARE EXPRESSED ARE VALID AND WE UNDERSTAND WHY FDA WANTED TO COLLECT DATA. HOWEVER WE ARE CONCERNED THAT SHOULD ALL THESE REGULATIONS AS DRAFTED BE IMPLEMENTED WE WILL HAVE VERY SERIOUS DIFFICULTIES IN COMPLYING. WE PROVIDE NECESSARY SERVICE TO PATIENTS AND PHYSICIANS WHO WORK US FUNCTION AS CONSULTANTS WE PROVIDE THE CARE, WE PROVIDE IN CONSULTATION WITH THE CLINICIAN WHOSE ARE PROVIDING CARE FOR THE PATIENTS AND THE PATHOLOGIST WHOSE ARE OUR CUSTOMERS. SO WE ARE VERY CONCERNED ABOUT THIS. WE FEEL REGULATIONS AS ADDRESSED BY PANEL SPOKE PREVIOUSLY THAT EXIST PROVIDE LOT REGULATORY OVERSIGHT OF LABORATORY MEDICINE IN GENERAL. SPECIFICALLY THEY ALREADY ADDRESS ANALYTIC VALIDITY, ACCURACY COMPONENT, PERFORMANCE SPECIFICATION, CLINICAL VALIDITY AND CLINICAL UTILITY. THESE THINGS ARE NOT THE TARGET OF ENFORCEMENT DISCRETION. STILL, ALL THESE THINGS ARE VERIFIED WHEN WE REPORT OUR RESULTS OUT ON CASE-BY-CASE BASIS, WE DISCUSS CAREFULLY, WITH CLINICIANS AN PATHOLOGISTS AND FREQUENTLY DISCUSS THE RESULT OF THE LDT WE PROVIDE WE KNOW TESTS ARE IMPLEMENTING LIFE SAVING TREATMENT FOR CANCER PATIENTS. I'M NOT SURE WHY THE ENTIRE SCOPE OF KLIA PERFORMANCE SPECIFICATIONS AND LABORATORY INSPECTION ACCREDITATION ARE NOT SUFFICIENT AND WHY PERSONNEL AND ACCREDITED ORGANIZATIONS, DO NOT OR CANNOT VERIFY THE VALIDITY OF LDT. WITH THE AFORE MENTIONED PERFORMANCE SPECIFICATION, PARAMETERS. WE ALSO FEEL STRONGLY AS PEOPLE HAVE SAID, FDA REGULATIONS THIS COMMUNITY INCLUDES BUT IS NOT LIMITED TO STATE REGULATORY BODIES SUCH AS NEW YORK STATE DEPARTMENT OF HEALTH, MENTIONED YESTERDAY, OTHER FEDERAL AGENCIES, PROFESSIONAL SOCIETIES INCLUDING ASCO AND ASH, PATIENT ADVOCACY GROUPS AND PUBLISHED PEER REVIEWED ARTICLES. REGULATIONS SHOULD BE DEVELOPED IN HARMONY WITH THOSE THINGS THAT ALLOW REQUIREMENTS FOR OPTIMAL PATIENT CARE NOW IN THE FUTURE FOR ALL IN MY LABORATORY AS WELL AS OUR PATIENTS. TARGETED PROPOSAL ON SMALL LABORATORY IS SUBSTANTIAL WE IN ESSENCE PLEAT T RESOURCES NECESSARY TO SUBMIT ANY 5, 10-K DOCUMENTATION FROM THE FDA. SO I WANT TO MENTION THE IDEA OF UNEVEN PLAYING FIELD, THE EFFECT OF REGULATIONS LIKE THIS FOR LABORATORY LIKE MINE COULD MEAN THAT THERE ARE VERY FEW REMAINING REFERENCE LABORATORIES IN THE COUNTRY INCLUDING WHAT ARE OTHER HIGH QUALITY SMALL LABS LIKE MINE. REAL CONCERN IF THESE THINGS ARE IMPLEMENTED WE WILL BE DRIVEN OUT OF BUSINESS, THIS WILL BE THE LOSS OF JOBS, I'LL HAVE THE LOOK FOR ANOTHER JOB, ALL THE OTHER MY COLLEAGUES HERE WILL HAVE TO GO LOOK FOR ANOTHER JOB. THERE ARE WAYS THAT FDA CAN AMELIORATE THESE CONCERNS. IN ESSENCE, WE WOULD LIKE NOTHING BETTER THAN FOR REGULATORY DISCRETION TO BE EXERCISED FOR ALL THE TRADITIONAL LABORATORY DEVELOPED TESTS THAT WE OFFER. IF THAT CANNOT BE PROVIDED TO US, WE REALLY, REALLY NEED VERY STRONGLY THE OPTION OF REGISTERING OUR TESTS BUT NOT HAVING ANY ADDITIONAL REGULATORY BURDEN. IF THESE TESTS, THESE ARE CANCER DIAGNOSTIC TESTS ARE CLASSIFIED HIGH RISK, THE EFFECT ON US AS AN ORGANIZATION AND MANY OTHERS IN THE LABORATORY WE WERE UNABLE TO PROVIDE THE INFORMATION FDA NEEDS AND WE DON'T HAVE RESORTSES TO DO IT. -- RESOURCES TO DO IT. >> GOOD MORNING. MY NAME IS GAIL VANCE. I'M A PROFESSOR OF MEDICAL AND MOLECULAR GENETICS AND PATHOLOGY. AT INDIANA UNIVERSITY IN INDIANAPOLIS. THERE I DIRECT THE LABORATORY OF DIAGNOSTIC GENOMICS IN WHICH 99.9% OF ALL OUR TESTS ARE LDTs. HOWEVER, HERE TODAY I'M REPRESENTING THE COLLEGE OF AMERICAN PATHOLOGISTS. AS YOU HEARD FROM MY COLLEAGUES YESTERDAY, THE COLLEGE IS A PROFESSIONAL ORGANIZATION. THAT HAS MEMBERSHIP OF APPROXIMATELY 18,000 PATHOLOGISTS WITH -- WHO PRACTICE CLINICAL AND LABORATORY MEDICINE. THROUGHOUT THE NATION. AND ABROAD. IN THE SETTINGS OF COMMUNITY HOSPITALS, INDEPENDENT LABORATORY ACADEMIC MEDICAL CENTERS, FEDERAL AND STATE HEALTH FACILITIES AS WELL. CAP HAS EXTENSIVE EXPERIENCE AS A QUALITY STANDARD SETTING ORGANIZATION. AS THE CAP ACCREDITS OVER 7,000 LABORATORIES. AND PROVIDES OR ENROLLS 23,000 LABORATORIES IN PROFICIENCY TESTING PROGRAM. I LIKE TO MAKE THREE BRIEF POINTS TODAY REGARDING THE PROPOSED LDT GUIDANCE, THE ROLE OF PATHOLOGISTS. AND THE OPTIMAL RISK CLASSIFICATIONS SCHEME. FIRST WE BELIEVE THAT THE LDT CLASSIFICATION AND PRIORITIZATION SHOULD BE BASED ON RISK OF LDTs. OUR PROPOSED APPROACH AS WAS GIVEN AT A SIMILAR MEETING IN 2010, VIEWS HIGH RISK LDTs AS PRO PRYTORY ALGORITHM REQUESTS THAT REQUIRES FDA REVIEW. HOWEVER BASED ON THE LDT DRAFT GUIDANCE AS WRITTEN, WE ESTIMATE APPROXIMATELY 1,000 LDTs TO BE CONSIDERED AS COMPANION DIAGNOSTICS AND WILL BE CHASES FEWED AS HIGH RISK LDT AND REQUIRE PMA. DESPITE THE FACT THESE TESTS HAVE BEEN WELL ESTABLISHED IN MEDICAL PRACTICE AND PROMOTE STANDARD OF CARE. SECOND WE BELIEVE PATHOLOGISTS SHOULD PARTICIPATE IN CRITICAL THROUGHOUT -- SHOULD PARTICIPATE THROUGHOUT THE LDT PROCESS BECAUSE AS PHYSICIANS WE INTERACT WITH OUR CLINICAL COLLEAGUES ON A REGULAR BASIS. TO APPROVE THE DEVELOPMENT APPLICATION AND DISSEMINATION OF THESE TESTS. WE ALSO WORK WITH OUR CLINICAL COLLEAGUES TO INTERPRET THE TEST RESULT IN LIGHT OF THE PATIENTS CONDITION. WE BELIEVE THE FDA OUTIZE EXPERT PANELS TO DETERMINE RISK CLASSIFICATION AND PATHOLOGISTS SHOULD BE MEMBERS OF THOSE PANELS. WE HAVE EXPERTISE IN THE CLINICAL AND ANATOMIC PATHOLOGY LABORATORY SPECIALTIES SUCH AS MICROBIOLOGY, IMMUNOLOGY, HEMATOLOGY, GENETICS AND INFORMATICS TO NAME A FEW. FURTHER, PATHOLOGISTS HAVE A LONG HISTORY OF PRACTICING MEDICINE. BEING RESPONSIBLE FOR THE OVERALL OPERATION AND ADMINISTRATION OF THE LABORATORY INCLUDING THE TRAINING AND EMPLOYMENT OF THE PERSONNEL IN THE LABORATORY. WE WORK ON A DAILY BASIS TO ENSURE TESTS ARE ACCURATE AND FOLLOW REGULATORY GUIDELINES THROUGHOUT THE TESTING PROCESS INCLUDING THE PREANALYTIC, ANALYTIC AND POST ANALYTIC PROCESS. FINALLY, WE BELIEVE THAT IT IS IMPORTANT TO WEIGH THE FOLLOWING FACTORS IN THE RISK CLASSIFICATIONS OF LDTs. AND THESE INCLUDE CONSIDERATION OF EXISTING INTEGRATION OF THE TEST INTO MEDICAL PRACTICE, HISTORICAL PERFORMANCE, AND EXISTENCE OF PRACTICE GUIDELINES. ALSO CONSIDERATION OF ESTABLISHED CLINICAL VALIDITY AND IN MANY CASES CLINICAL UTILITY. WE ALSO BELIEVE IT IS IMPORTANT TO CONSIDER THE AVAILABILITY OF PROFICIENCY TESTING AS THIS PROVIDES AN EXTERNAL OBSERVATION AND ASSESSMENT OF THE TESTS BEING PERFORMED. I WISH TO THANK THE FDA FOR THIS OPPORTUNITY TO COMMENT ON THE LDT DRAFT GUIDANCE, THIS GUIDANCE YOU HEARD BY MY TWO COLLEAGUES THAT PRECEDED ME REPRESENTS A SEA CHANGE FOR LABORATORIES DELIVERING LABORATORY TESTING TODAY. I WOULD SUGGEST FDA CONSIDER A NEW >> MY NAME IS PAUL KIM SPEAKING AS COUNCIL TO THE COALITION FOR 21st CENTURY MEDICINE WHICH CONSISTS OF THE WORLDS AMONG MANY DIAGNOSTIC TECHNOLOGY COMPANIES CLINICAL LABS PATIENT ORGANIZATIONS AND VENTURE CAPITAL IN THE U.S., WE HAD REPRESENTATIVES SPEAK ON OTHER TOPICS. ON THIS WE START WITH AN OBSERVATION THAT THE PROPOSAL TO IMPANEL ADVISORY COMMITTEES OR AUGMENT ADDITIONAL EXISTING ONES TO CLASSIFY LDT WILL REQUIRE DETERMINATIONS ON ADVANCED DIAGNOSTICS THAT WILL BE PRECEDENT SETTING BUT MANY UNIQUE, MANY WILL BE SERVICE OR PRODUCT SPECIFIC. THAT WILL NOT LEND ITSELF TO GENERATING BROAD CATEGORICAL CLASSIFICATION OF GENERAL APPLICABILITY ONE CAN LOOK TO HISTORIC PRACTICE UNDER EXISTING DEVICE REGULATIONS TO SEE THIS COULD LEAF TO PROLIFERATION OF VERY LARGE NUMBERS OF CLASSIFICATIONS AT EACH CAPTURE SMALL NUMBERS AND IN SOME CASES SINGULAR PRODUCTS OR TEST SERVICES. GIVEN THAT UNDERLYING IMPLEMENTATION CHALLENGE FOR THE AGENCY, COALITION AGREES WITH MANY OTHER STAKEHOLDERS THIS DEMANDS EXCEPTIONAL EXPERTISE, BECAUSE OF THE NOVELTY OF MANY OF THE TEST SERVICES AND PRODUCTS, BECAUSE OF THE INNOVATION THIS COMMUNITY GENERATES, THIS IS GOING TO LEAD TO THE EXPERTISE RESIDING IN VERY SMALL NUMBERS OF INDIVIDUALS IN MANY CASES CROSS CUTTING DISCIPLINARY EXPERTISE. THAT WILL GENERATE ADDITIONAL OR UNUSUAL ACTIVITITIES FOR THE AGENCY IN CONSTITUTING ITS LDT PANELS, FOR THAT REASON WE AGREE WITH PREVIOUS SPEAKERS AN STAKEHOLDERS THAT REACHING OUT TO PROFESSIONAL SOCIETIES TO MANY STAKEHOLDER GROUPS WHO ADDRESSED TOPICS YESTERDAY AND TODAY, CREDIBLE INDEPENDENT THIRD PARTIES THAT EXIST IN THIS LANDSCAPE OF EXPERTS IT'S CRITICAL TO DO THIS AND TO THE PANEL AND POPULATE THE ADDUCESRY STRUCTURE AND THE AGENCY WILL FIND IN MANY CASES THAT THE SPONSOR COMPANIES THEMSELVES WILL HAVE THE BEST GRASP UNDERSTANDING SITUATED TO ADVISE THE AGENCY IN CLASSIFICATIONS AS WELL AS SUBSEQUENT PRODUCT SPECIFIC OR TEST SERVICE SPECIFIC DECISIONS. OBTAINING SPONSOR INPUT CONSISTENT WITH CONFLICT REQUIREMENTS WILL BE CHALLENGING BUT IT WILL BE USEFUL FOR ALL CONCERNED. TWO FAST POINTS IN CONCLUSION, WE DO CLEARLY SUPPORT ESTABLISHMENT OF POLICIES RELATING TO THIRD PARTY CERTIFICATION ADDRESSED ELSEWHERE IN THE FRAMEWORK GUIDANCE. TO EXPLORE RELIANCE UPON THESE OUTSIDE EXPERTS AND ENTITIES THROUGH CONTRACTUAL COOPERATIVE AGREEMENTS OR UNUSUAL PROCESSES SECURE USE AND RELIANCE ON EXTANT PROCEDURES, BODIES, AND BE ABLE TO MAKE USE OF THE INFRASTRUCTURE THAT EXISTS IN OUR COMMUNITIES OUTSIDE. AND FINALLY, A POINT PROCEDURALLY BY CARTS AND HORSES, AS WE MOVE QUICKLY TO IMPLEMENT THE FRAMEWORK FOR HIGH RISK TESTS OR DEVICES, IT'S REALLY IMPORTANT FOR THEM TO UNDERSTAND THEY HAVE TO BE DOING THE CONSTITUTION AND PANEL -- IMPANELMENT AND EXERCISE ADVISORY PARABLES, IN PARALLEL TO SUBMISSIONS OR TRY TO CLARIFY RESPONSES WHO ARE SUBJECT TO REGULATION. AS WITH MANY OTHER ASPECTS OF THE PROPOSED FRAMEWORK, THEY HAVE TO RESOLVE MANY ISSUES PUBLICLY THROUGH ADDITIONAL GUIDANCE AND WELL IN ADVANCE IN PHYSICIAN ENFORCEMENT DEADLINES FOR THE FRAMEWORK. THANK YOU. >> MY NAME IS TIM LYON, I PROVIDE COMMENTS FOR THE NATIONAL NON-PROFIT LYME DISEASE ASSOCIATION INCORPORATED. WE'RE A DIFFERENT LYME DISEASE GROUP THAN PRESENTED YESTERDAY BUT THERE IS A LOT OF INTEREST OR LYME DISEASE COMMUNITY. THE ASSOCIATION IS AN ADVOCACY ASSOCIATION FOUNDED BY PATIENTS AND PATIENT FAMILIES AND PROVIDES GRANTS FOR RESEARCH THAT LED TO 35 PEER REVIEW SCIENCE JOURNAL PUBLICATIONS TO DATE AND HELD 15 ANNUAL CME MEDICAL CONFERENCES FOR DOCTORS AN RESEARCHERS. WHILE THE LYME DISEASE ASSOCIATION IS ADVOCACY ASSOCIATION IT'S DIFFERENT FROM PARTICIPANTS HERE, WE DO SHARE THE SAME COMMON INTEREST OF ENSURING PATIENT ACCESS TO EFFECTIVE DIAGNOSTICS AND TREATMENTS. I WILL POINT OUT LYME DISEASE COMES UP AND NET DOTAL JUST LIKE ADDITIONAL REGULATION OF LDTs, THE ISSUES ARE NOT UNDERSTAND. I WILL PRESENT THE TYPES OF ISSUES THAT NEED TO BE ADDRESSED FOR LYME DISEASE DIAGNOSTICS, REGARDLESS OF CHANGES IN THE REGULATORY SCHEME. LYME DISEASE IS UNIQUE IN CONTROVERSY, ISSUES TO LYME DISEASE DIAGNOSTICS ARE VOCAL INDIVIDUALS WITH VESTED INTEREST IN LYME FESTS THE QUALITIES OF TESTS IS GENERALLY POOR, THE INCONSISTENT TEST QUALITY OF INFORMATION FROM GOVERNMENT AGENCIES ONE GOVERNMENT AGENCY TALKS THE GREAT QUALITY AND ANOTHER GOVERNMENT AGENCY MIGHT TELL YOU AT THE SAME TIME IT'S VERY PROBLEMATIC. AND WHAT AN AGENCY SAYS ABOUT SENSITIVITY OF THE TEST IS OFTEN VERY DIFFERENT FROM WHAT IS STATED IN NUMEROUS PEER REVIEW STUDIES. HISTORY OF EXPERTS WHICH LEADS TO CONCERN ABOUT THE COMPOSITION OF EKS PERCENT PANELS AND NEED FOR SCREENING POTENTIAL PANEL MEMBERS FOR CONFLICT OF INTEREST AND REPRESENTATION OF DIFFERENT PERSPECTIVES TO MINIMIZE BIAS. A SIGNIFICANT CONCERN IS QUALITY AND EFFICACY OF FDA CLEARED MINE TESTS ARE NOT WELL UNDERSTOOD. HOW DO YOU EVALUATE RISK IF YOU DON'T HAVE A GOOD GRASP OF TEST PERFORMANCE. ALMOST ALL FDA LYME TESTS WERE BASED SUBSTANTIAL EQUIVALENTS IN THE CASE OF LYME SETS A VERY LOW BAR. AND FOR LYME WE CAN'T EVEN IDENTIFY WHAT THE ORIGINAL PREDICATE TESTS MAY HAVE BEEN. THE BOTTOM LINE IS IN THE CASE FDA CLEARANCE HAS NOT IN ITSELF RESULTED IN QUALITY. AVERAGE SENSITIVITY EXISTING LYME TEST IS 55% BY NUMEROUS STUDIES WHILE INNOVATIVE LDT BUMPED THAT SENSITIVITY UP TO 95%. SO THIS OBVIOUSLY ALSO HAS SOME RELEVANCE TO DISCUSSION OF UNMET NEEDS AS TALKED ABOUT QUITE A BIT YESTERDAY. LABELING INFORMATION SHOULD BE EVALUATIVE SITUATION GIVEN TO PROMINENTLY INCLUDING IF NOT ALREADY PROVIDED INFORMATION ON PURPOSES FOR WHICH LYME TESTS WERE DEVELOPED, THE LIMITATIONS OF TEST, ED SENSITIVITY, AND WARNINGS ABOUT REGARDING INTERPRETATION EG AND NEGATIVE RESULT DOES NOT NECESSARILY MEAN AN INDIVIDUAL DOES NOT HAVE LYME DISEASE AND FURTHER EVALUATION MAYBE NECESSARY. ANOTHER CONCERN IS THAT THE NEED TO BE -- THERE NEEDS TO BE A BALANCE ASSESSMENT OF CONSEQUENCES OF FALSE POSITIVES AND FALSE NEGATIVES. THERE'S BEEN AN EXCESSIVE FOCUS FROM SOME PARTIES ON ADVERSE CONSEQUENCES FALSE POSITIVES WHILE MINIMIZING PATIENT TREATING PHYSICIAN CONCERNS WITH SERIOUS HEALTH CONSEQUENCES, FALSE NEGATIVES. SIMILARLY THERE HAS TO BE A REALISTIC EVALUATION OF THE POTENTIAL FOR POTENTIAL DEVELOPMENT OF ANTIBIOTIC RESISTANCE. ONE OTHER CONCERN, A FINAL CONCERN WAS AN ADVERSE EVENTS REPORTING THAT IT'S PROBLEMATIC FOR EXISTING LDTs AND EXISTING LYME TEST AND LDT SO THE ADVERSE EVENTS REPORTING SYSTEM NEEDS TO BE FIXED FOR EXISTING TESTS AS WELL AS LDTs. I AM OUT OF TIME. I THANK THE FDA FOR THE OPPORTUNITY TO PRESENT HERE TODAY. >> THANK YOU. THAT WAS OUR LAST SPEAKER FOR THE SESSION SO WE'RE GOING TO MOVE ON TO THE PANEL, SO THE FIFTH PAM CAN TAKE THE STAGE AT THIS POINT. >> I WILL TURN IT TO BARBARA OUR MODERATOR. >> GOOD MORNING, EVERYONE. MY NAME IS BASH Z ZEHNBAUER, ACTING DIRECTOR OF CENTER FOR EPIDEMIOLOGY AND LABORATORY SERVICES AT THE CDC. I'M NOT HERE TO PRESENT CDC PERSPECTIVE, I'M HERE JUST TO SAY I'M PRIVILEGED TO WORK WITH BOTH CMS AND FDA IN A TRIAGENCY AGREEMENT IN SUPPORT OF THE CLINICAL LABORATORY IMPROVEMENT ADVISORY COMMITTEE SO IT IS A TRIAGENCY OVERSIGHT. JUST TO LET FOLKS KNOW CDC PLAY AD ROLE IN THE MEMBERS OF THE DIVISION I'M CURRENTLY PART OF WROTE THE KLIA RE GOINGS 20 YEARS AGO. SO WITH THAT I'LL LET YOU KNOW WHERE WE ARE. I WANT TO THANK THE PREVIOUS PANEL WITH A GREAT SEGUE AND ALSO PUBLIC COMMENTERS FOR THIS SESSION WHO JUMP STARTED THINGS NICELY. AND MOVE TO TOPIC NUMBER 5. SO THIS IS THE ONE THAT ON RISK CLASSIFICATION AND HOW THESE WILL BE REVIEWED AND THERE'S BEEN A LOT OF DISCUSSION ALREADY THROUGHOUT THE DAYS HERE ABOUT HOW CATEGORIES ARE ASSIGNED. THERE'S GRAY AREAS, THERE'S CONCERN THAT A SINGLE ANALYTICAL ASSAY MAYBE SEVERAL DIFFERENT RISK CATEGORIES DEPENDING ON USE OF LAB RESULTS. THIS IS AN OPPORTUNITY FOR THIS PANEL EXPERTS TO PRESENT SOME PERSPECTIVES TO AID IN THIS CLASSIFICATION. I WOULD SAY AS A MINIMUM STARTING POINT WE WOULD GO WITH THE NOTIFICATION CRITERIA THE PREVIOUS PANEL IDENTIFIED, OUR TASK HERE TODAY TO SAY WHAT ELSE NEEDS TO BE DEFINED FOR DEFINING RISK AND WHO WE GO ABOUT CONVENING ADVISORY PANELS TO DO THAT. I WILL LET THE PANEL MEMBERS GIVE A BRIEF INTRODUCTION WHO THEY ARE STARTING WITH MR. FISH. >> I'M ANDY FISH, EXECUTIVE DIRECTOR OF ADVAMEDDX, LEADING MANUFACTURERS OF DIAGNOSTIC TEST, WE (INAUDIBLE) MEDICAL DEVICE MANUFACTURERS TRADE ASSOCIATION. >> CAN YOU HEAR ME? I HAVE A SOFT VOICE AND I'M HORSE. I'M DAVID FLANNERY, M.D. CLINICAL GENETICIST, I BECAME MEDICAL DIRECTOR AMERICAN COLLEGE OF GENETICS AND GENOMICS IN SPRING. AFTER 29 YEAR CAREER AT MEDICAL COLLEGE OF GEORGIA AS A FACULTY MEMBER AND CLINICAL ADMINISTRATOR. ONCOLOGY MEDICAL GENETIC AND GENOMICS IS A PROFESSIONAL ASSOCIATION FOR CLINICAL GENETICISTS INCLUDING LABORATORY GENETICISTS. >> I'M GREGORY STORCH, PROFESSOR PEDIATRICS WASHINGTON UNIVERSITY ST. LOUIS, DIRECTOR OF CLINICAL LABORATORIES ST. LOUIS HOSPITAL AND PRACTICING INFECTIOUS DISEASE SPECIALIST, I'M REPRESENTING THE INFECTIOUS DESISTS OF AMERICA. >> GOOD MORNING, I'M LEN LICKFELD, AMERICAN CANCER SOCIETY BASED OUT OF -- LICHTENFELD OUT OF AMERICAN CANCER SOCIETY IN GEORGIA. >> I'M AMY MILLER OF THE PERMIZED MEDICINE COALITION. >> WE'LL START WITH THE -- PERSONALIZED MEDICINE COALITION. >> WE'LL START WITH HOW THE ADVISORY PANEL CONVENED TO PROVIDE INPUT ABOUT CLASSIFICATION STRATEGIES BE IDENTIFIED IN CLASSIFICATION AND PRIORITIZATION. WE HEARD SOME SUGGESTIONS ALREADY FROM OUR FIRST PUBLIC COMMENTERS BUT WE'LL START WITH ANDY FISH. THANK YOU. >> I DON'T HAVE DETAILED COMMENTS, I THINK IT MAY HAVE BEEN BROUGHT UP EARLIER BUT I THINK ONE SUGGESTION WOULD BE THAT A NUMBER OF ADVISORY PANELS SHOULD BE CONVENED TO LOOK AT DIFFERENT CLINICAL AREAS, IN OTHER WORDS SPECIFICALLY FOCUS ON SPECIFIC AREAS HEALTH CONDITIONS, AS WE DISCUSSED YESTERDAY AS WELL, MUCH OF RISK CONSIDERATIONS ARE SITUATIONAL ENTIRELY RESOLVE AROUND CLINICAL USE OF A TEST, WHAT IS THE CLINICAL QUESTION AND HOW THEY'RE CONNECTED TO THE DISEASE AREA, HEALTH CONDITION AND QUESTION AND I THINK THINKING ABOUT RISK CLASSIFICATION ONLY STARTS TO MAKE SENSE WHEN YOU LOOK AT SPECIFIC DISEASE AREAS, AT LEAST THAT'S THE LEVEL YOU WANT INPUT. SO THAT'S A GENERAL SUGGESTION TO STRUCTURE PANEL IN THOSE DIFFERENT DISEASE AREAS. >> I AGREE WITH THE CONCEPT A WIDE VARIETY OF LDTs SO YOU WOULD NEED TO HAVE POTENTIALLY SUBCOMMITTEES ADDRESSING THIS. BUT IN ANY CASE, WE FEEL STRONGLY THAT THE ADVISORY PANEL SHOULD BE COMPRISED OF EXPERIENCED CLINICIANS PERFORM THESE COMPLEX LABORATORY TESTS INAND CLINICS USE RESULTS OF THOSE TESTS. I ALSO AGREE IT WOULD BE IMPORTANT TO HAVE SEPARATE ADVISORY PANELS FOR DIFFERENT CLINICAL AREAS. AS I SAID IN MY REMARKS YESTERDAY I THINK THERE ARE A NUMBER OF RELATIVELY UNIQUE CONSIDERATIONS THAT APPLY TO INFECTIOUS DISEASE LDTs THAT ARE QUITE DIFFERENT FROM CONSIDERATIONS THAT APPLY TO OTHERS, THE EXPERTISE IS QUITE DIFFERENT. THE INFECTIOUS DISEASE LDTs REQUIRE A RAPID PACE TO IDENTIFY A DIAGNOSIS QUICKLY. THERE'S A STRONG PUBLIC HEALTH COMPONENT THAT IS VERY IMPORTANT TO CONSIDER SO I THINK SPECIFIC EXPERTISE WILL BE REQUIRED AND FOR THAT REASON I DO THINK IT WILL BE IMPORTANT TO SEPARATE THE PANELS ACCORDING TO AREAS. >> I LOOK AT THIS QUESTION FROM A BROADER STANDPOINT SO I HAVE TO FOCUS IN A SENSE ON WHAT THE QUESTION IS AND THAT'S THE INITIAL PRIORITIZATION. I AGREE WITH THE PRIOR SPEAKERS. I THINK THAT THIS IS GOING TO BE A SIGNIFICANT UNDERTAKING. I HAVE BEEN INVOLVED IN OTHER SIMILAR EVENTS IN THE PAST OF SITUATIONS IN THE PAST, IT DOES REQUIRE A NUMBER OF PANELS. THOSE REALLY HAVE TO HAVE BOTH EXPERTISE AND TEST, THE EXPERTISE IN CLINICAL UTILITY AND USE OF THAT TEST. ONE THING THAT HASN'T BEEN MENTIONED IS GETTING OTHER STAKEHOLDERS WHETHER PATIENTS OR OR PUBLIC PARTICIPATES ENGAGED IN THIS DISCUSSION. ONE OF THE ISSUES THAT THE FDA CERTAINLY THE AGENCY IS WELL AWARE IS THAT THERE'S BEEN A LOT OF CONCERN ANT THE INPUT THAT COMES FROM -- ABOUT THE INPUT FROM THE PUBLIC. I THINK IT'S A STEP IN THE RIGHT DIRECTION THIS PARTICULAR ISSUE SINCE IT'S A FORMATIVE PROCESS TO DECLARE THAT THAT'S IMPORTANT AND PUBLIC MEMBERS BE ENGAGED. I WOULD NOT MINIMIZE, MY COLLEAGUES HAVEN'T MINIMIZED OR ANYBODY THIS THIS AUDIENCE MINIMIZE THAT'S A CONSIDERABLE UNDERTAKING IN ORDER TO CONVENE, TO ORGANIZE AND TO CONVENE THE NECESSARY EXPERTISE TO HELP AGENCY MOVE THROUGH THIS INITIAL PROCESS. >> I PREFACE REMARKS BY SAYING THEY'RE FOCUSEDD ON PERSONALIZED MEDICINE AND LAB TOWER TESTS THE HIGH COMPLEXITY OF MOLECULAR TESTS BUT SOMETIMES MODERATE SO PLEASE B VIEW MY REMARKS WITH THAT CAVEAT. IN TERMS OF BUILDING THE ADVISORY COMMITTEE THERE IS A CHALLENGE WITH CONFLICT OF INTEREST RULES. I KNOW THEY HAVE TO BE FOLLOWED. BUT I THINK WE NEED TO BE CREATIVE ON STRUCTURING THE ADVISORY COMMITTEES SO THAT THE RIGHT EXPERTISE IS AVAILABLE TO ANSWER THE QUESTIONS NECESSARY. FURTHERMORE IT'S ALLUDED TO THAT WE NEED TO HEAR THE DIFFERENT VOICES. SO IF YOU WILL BEAR WITH ME FOR A SECOND I WILL READ TO YOU A LIST OF A HYPOTHETICAL ADVISORY COMMITTEE FOCUSING ON PERSONALIZED MEDICINE TESTS TO DEFINE HOW YOU CHOOSE TO DEFINE THEM. NEED EXPERT IN PERSONALIZED MEDICINE. A PHYSICIAN WHO ORDERS PERSONALIZED MEDICINE TESTS, PHYSICIANS CONDUCT AND REPORT TEST RESULTS. REPRESENTATIVES FROM THE DIAGNOSTIC KIT MANUFACTURING INDUSTRY. REPRESENTATIVES FROM SOLE SOURCE OR PROPRIETARY LABS. REPRESENTATIVES FROM HOSPITAL BASE, ACADEMIC MEDICAL SENTENCER BASED, AND SMALL CLINICAL LABS. REPRESENTATIVES FROM LARGE NATIONAL REFERENCE LABORATORIES. REPRESENTATIVES FROM FDA SENTENCER FOR DRUG EVALUATION AND RESEARCH. REPRESENTATIVES FROM CDER OBVIOUSLY. AND YOURSELVES, ALSO REPRESENTATIVES FROM PHARMACEUTICAL MANUFACTURERS. PATIENTS WHO HAVE BENEFITTED FROM THESE TESTS, REPRESENTATIVES FROM KLIA, REPRESENTATIVES FROM CDC, AND NOW THEY READ THIS LIST PROBABLY A PRIVATE PAYER AS WELL. THE REASON YOU NEED TO GO THROUGH THE EFFORT TO HAVE SUCH A BROAD REPRESENTATION, THE PERSPECTIVE IS SLIGHTLY DIFFERENT BUT GETTING THE RIGHT EXPERTS FOR ALL THESE BUCKETS FOR ALL THE DIFFERENT DISEASE STATES AND WITH THE RIGHT EXPERTISE IS GOING TO BE TO BE CHALLENGING WHEN THEY HAVE TO MEET CONFLICT RULES SO WE NEED TO HAVE CREATIVITY AROUND THAT. THANK YOU. >> THANK YOU, THAT'S VERY COMPREHENSIVE AND LEADS US TO THE NEXT QUESTION WE'RE CONSIDERING. I WOULD SUPPORT THAT THE LIST YOU HAVE GIVEN HAS BEEN BOTH SIGNIFICANTLY COMPREHENSIVE AS WELL AS GENERIC ENOUGH THAT IT WOULD EXTEND TO THINGS OVER THAN PERSONALIZED MEDICINE. THANK YOU FOR THAT QUALIFIER. I THINK WITH THE ADDITION OF THE PATIENT ADVOCATE, WHICH LEN MENTIONED AND WHAT WE INCLUDE IN KLIA AS WELL BECAUSE WE WANT THAT CONSTITUENCY, LET'S MOVE TO THE SECOND QUESTION, ARE THERE STAKEHOLDERS THE PANELISTS FEEL REALLY HAVE TO BE INCLUDED AS WELL IN ADDITION TO THOSE THAT AMY JUST DESCRIBED? WE'RE THINKING NOW IN BOTH CLASSIFICATION AND PRIORITIZATION. SO I THINK THOSE ARE GOOD STARTS FOR THE CLASSIFICATION, ARE THERE GOING TO BE OTHERS THAT WOULD BE INVOLVED IN PRIORITIZATION. >> MAYBE JUST A COUPLE OF ADDITIONAL COMMENTS. I DON'T HAVE I HAVE ADDITIONAL ONE TO SUGGEST BUT I EMPHASIZE IN COLLAR THE CLINICIAN AND PATIENTS REPRESENTATIVES ON THE CLINICIAN SIDE AND I THINK AMY'S COMMENTS COVERED THIS. I THINK IT WOULD BE VERY IMPORTANT TO GET CLINICIANS FROM A RANGE OF KNOWLEDGE BASE OR EXPERIENCE WITH UNDERSTANDING THE DEVELOPMENT OF TESTS IN THE FIRST PLACE, OBVIOUSLY CLINICS COME FROM A RANGE OF EXPERIENCE SOME ARE HEAVILY INVESTED IN THE LEADING EDGE OF TEST DEVELOPMENT AND ACADEMIC MEDICAL CENTERS AND ARE VERY MUCH AWARE OF OR PERHAPS RESEARCHERS PARTICIPATE IN DEVELOPMENT OF TESTS AND CLINICAL USE WHEREAS OTHERS PERHAPS MORE COMMUNITY CARE BASED CENTERS ARE NOT PERSONALLY INVOLVED IN THE DEVELOPMENT OF TESTS AND MAY HAVE LESS A MONTH TO MONTH UNDERSTANDING OF WHERE THE LEADING EDGE OF TESTING IS GOING, IT'S IMPORTANT TO GET THAT RANGE OF EXPERIENCE, IF YOU FLIP THIS QUESTION ON ITS HEAD AND ASK WHO SHOULD NOT BE A STAKEHOLDER PRESENTING TABLE I'M NOT SURE WHAT THE ANSWER TO THAT IS. SO IN OTHER WORDS, MAYBE EVERY STAKEHOLDER HAS A STAKE THAT HAS A VIEW, SHOULD BE INCLUDED. I DON'T HAVE A SUGGESTION SOMEONE NOT INCLUDED I THOUGHT AMY'S SUGGESTION OF AN INTERESTING ONE PAYER BECAUSE THOUGH OBVIOUSLY FDA PURVIEW IS NOT DIRECTLY GO TO THE ACCORDANCES OF COVERAGE IN PAYMENT, PAYERS ARE LOOKING TO FDA'S REVIEW FOR INFORMATION TO HELP THEM MAKE DECISIONS. THAT'S COME CLEARLY IN PAYERS THAT WEIGHED IN IN FAVOR OF FDA ACTION IN THIS AREA, BECAUSE THEY'RE LOOKING TO PLAY THAT ROLE. PERHAPS HAVING THAT PERSPECTIVE WOULD BE INFORMATIVE, TO ENDORSE THAT IDEA. >> WE CERTAINLY AGREE YOU NEED WIDE INPUT TO THE ADVISORY PANEL BUT IT SHOULD BE INPUT TO THE ADVISORY PANEL NOT NECESSARILY HUGE AMORPHOUS GROUP TRYING TO DEAL WITH THIS. INPUT FROM THESE STAKEHOLDERS WOULD BE APPROPRIATE BUT NOT NECESSARILY HAVE A HUGE ADVISORY PANEL WITH EXTENSIVE NUMBERS. >> NOT SURE I HAVE THAT MUCH TO ADD ON THIS QUESTION BUT EMPHASIZE THE IMPORTANCE OF HAVING A BROAD RANGE OF LABORATORIANS REPRESENTING LABORATORIES OF DIFFERENT TYPES OF COURSE LABORATORY LANDSCAPE IS VERY COMPLEX AND WILL BE IMPORTANT TO HAVE ACADEMIC LABORATORIES NON-ACADEMIC HOSPITAL LABORATORIES, REFERENCE LABORATORIES LARGE AND SMALL, PUBLIC HEALTH LABORATORIES, ALL REPRESENTED ON THE PANELS, PARTICULARLY WANT TO EMPHASIZE THE IMPORTANCE OF HAVING CLINICS INVOLVED IN THE USE OF TEST AND THE PRACTICE OF MEDICINE, PEOPLE WHO ARE INVOLVED IN THE DOWNSTREAM APPLICATION OF TEST RESULTS, THEY PLAY AN ABSOLUTELY CRITICAL ROLE, I DO LIKE THE IDEA OF INCLUDING PAYERS, THEY HAVE AN INTERESTING PERSPECTIVE THAT SHOULD BE REPRESENTED. >> WE ACTUALLY SUPPORT THE CONCEPT OF ADDING PAYERS TO THIS GROUP, THEY DO HAVE A PERSPECTIVE ON WHAT HAPPENS. ONE INTERESTING QUESTION I'M NOT SURE A DEFINITE ANSWER IS WHAT WAS ALLUDED TO HERE BEFORE, DO YOU HAVE A PANEL OF GENERALISTS WITH SPECIALISTS ADVISING OR PRESENTING OR ENGAGED IN ANOTHER PART OF THE TABLE OR BECOME PART OF THAT DECISION MAKING. SURE WITHIN THE AUDIENCE HERE THERE ARE MANY PEOPLE WHO FEEL ONE WAY AND MANY PEOPLE WHO FEEL ANOTHER. I THINK THAT ONE OF THE INTERESTING QUESTIONS REALLY CONCERNED ME FOR SOME TIME IS WHAT ARE WE TALKING ABOUT HERE. I HEARD DISCUSSION TODAY, UNFORTUNATELY I APOLOGIZE I COULDN'T BE HERE YESTERDAY BECAUSE OF ANOTHER OBLIGATION. I HEARD DISCUSSION WHICH MAKES IT SEEM LIKE A SIMPLE SITUATION. WE HAVE A TEST WE'RE GOING TO DO THE TEST, WE'RE GOING TO GIVE THE RESULTS OF THE TEST AND EVERYTHING IS FINE AND BEING A PHYSICIAN AND BEING ENGAGED IN THAT CAMP I UNDERSTAND THAT. THERE'S ANOTHER PIECE OUT THERE WHEN YOU LOOK AT IT, AS A PHYSICIAN. YOU MAKE ASSUMPTIONS THAT BECAUSE PEOPLE SAY WHAT THEY SAY THAT IT'S CORRECT, I CALL SOMETIMES THAT CAN BECOME WHAT I CALL BOOTSTRAPPING IF YOU SAY IT OFTEN ENOUGH IT BECOMES TRUTH. WHEREAS IN REALITY THERE'S AN EVIDENCE BASE WE HAVE TO LOOK AT FOR SOME TESTS. I DON'T THINK WHEN WE TALK ABOUT SOMEONE MENTIONED TKIs, OBVIOUSLY WELL ESTABLISHED, I CAN'T SPEAK TO PROCEDURES, I'M NOT A PATHOLOGIST OR LABORATORIAN BUT THAT'S PRETTY STRAIGHT FORWARD WHEN YOU GET MORE COMPLEX ALGORITHMIC TESTS MENTIONED BEFORE IT THAT DOES REQUIRE AN UNDERSTANDING AN OVERSIGHT TO MAKE CHURCHY IS BEING CLAIMED OFFERED IN WHAT THE EVIDENCE SUPPORTS RAISES ANOTHER INTERESTING QUESTION, I GUESS THE FDA STAFF HAS STATISTICIANS HANGING AROUND BUT YOU HAVE TO HAVE THE EXPERTISE ON THE PANEL SOMEBODY WHO UNDERSTANDS WHAT IS REASONABLE EVIDENCE. , THESE DAYS IT BECOMES AN ARCANE QUESTION. ONE OTHER PIECE TO POINT, THIS IS I COME BACK TO THE ISSUE THIS IS A PRIORITIZATION PHASE NOT THE IMPLEMENTATION OR FOLLOW-UP NINE YEARS PHASE I FEEL GIVEN THE OPPORTUNITY I'M GOING TO -- I WANT TO SAY WE HAVE TO BE UNDERSTANDING, IT'S NOT WHERE WE ARE, IT'S WHERE WE'RE GOING TO BE. AND I KNOW AMY AND EVERYONE ON THE PANEL UNDERSTANDS THAT AND YOU UNDERSTAND THAT AND MANY OF THE AUDIENCE, WHAT WE'RE DEALING WITH TODAY NEIGHBOR DIFFERENT THAN WHAT WE DEAL WITH IN THE SHORT PERIOD OF TIME. AND ALREADY WE HAVE CLAIMS BEING MADE FOR SOME TESTS, I HAPPEN TO DO A FAIR AMOUNT -- I SEE A LOT OF STUFF AND I GET ASKED A LOT OF QUESTIONS. I READ IT AND SEE THE CLAIMS MADE AND THEY'RE VERY FAR AHEAD OF WHERE WE ARE. WE IMMEDIATE NEED TO MAKE SURE, AS THESE PANELS COME TOGETHER, WE BEGIN TO UNDERSTAND WE WILL SEE CUTTING EDGE WORK AND HAVE TO START THINKING ABOUT THAT BUT TO SAY GOING FORWARD IN THE FUTURE WE HAVE TO UNDERSTAND WHAT WE'RE PUTTING TOGETHER WHICH IS GOING TO BE A NEW PAIR TIME FOR NEW TESTS TO DO NEW THINGS IN THE BRAVE NEW WORLD OF PERSONALIZED MEDICINE. I THINK THAT THAT MAYBE NOT RELEVANT TO THIS DISCUSSION BUT IS A POINT THAT HAS TO BE KEPT IN CONSIDERATION. >> SO BUILDING OFF OF WHAT LEN SAID I WOULD LIKE TO HIGHLIGHT A POINT. IT WAS STRIKING YESTERDAY HOW THERE WERE TWO BIG BUCKETS OF RESPONSES. IT'S EASY, LET'S MOVE FORWARD AND CONFUSION BY LABORATORIANS. THERE IS ALSO SOME HOSTILITY BY LABORATORIANS SO LOOKING AT THESE ADVISORY COMMITTEES, I THINK FDA MIGHT BE USED TO PEOPLE USED TO FDA. AND WE NEED TO BE SENSITIVE TO THE DIFFERENT TYPES OF LABORATORIES, THE DIFFERENT TYPES OF LABORATORY TESTS. HOW LABORATORY MEDICINE IS DONE. AND MAKE SURE THOSE VOICES ARE ENGAGED. AND ALL THE DIFFERENT DISEASE STATES BUT ALSO DIFFERENT TYPES OF TESTS THAT DO DIFFERENT THINGS. AND ARE COMMON AND ALSO CUTTING EDGE. TO LEN'S POINT WE DO NEED TO LOOK AT THE NEAR FUTURE BECAUSE AS YOU MAY HAVE NOTICED WE HAD 41 OR 46 NEW MOLECULAR ENTITIES LAST YEAR APPROVED BY FDA, FABULOUS NUMBER AND RIGHT NOW PMC IS ANALYZING THOSE TRYING TO DETERMINE HOW MANY WERE PERSONALIZED MEDICINE, IT'S SOMEWHERE BETWEEN 25 AND 40% DEPENDING HOW YOU SELECT IT OUT. SO IT'S EXCITING AND WE DO NEED TO LOOK TOWARD THAT IMMEDIATE FUTURE. >> VERY GOOD. THANK YOU. THE NEXT PIECE OF INFORMATION WE WANT TO EXAMINE AND GET INPUT ON IS WHAT FACTORS OR CRITERIA SHOULD BE CONSIDERED WHEN DETERMINING LDT CLASSIFICATION AND RISK. WE HEARD A NUMBER DISCUSSIONED BY PEOPLE GIVING PUBLIC COMMENTS AND AS I SAID, WE KNOW THAT AT LEAST THE BARE MINIMUM WOULD BE WHAT WE SEE IN THE LIST OF NOTIFICATION ELEMENTS BUT EVEN THOSE MAY NEED TO BE REFINED CONSIDERING THE DIVERSITY OF TESTS AND THE DIVERSITY OF PERFORMANCE ENVIRONMENTS THAT WE HAVE HEARD DESCRIBED, TEST METHODS ARE RAPIDLY EVOLVING, THEIR UTILITY IS VERY DIFFERENT. FOR EXAMPLE, A HUMAN SPECIMEN MAYBE USED FOR MICROBIAL GENOME IDENTIFICATION, THAT WILL PRESENT DIFFERENT CHALLENGES THAN A CULTURE. SO ARE THERE OTHER FACTORS THAT ANY OF THE PANELISTS HAVE REALLY IDENTIFIED AND PULLED OUT IN THINGS FORWARDED TO FDA TO HELP INFORM THEM GOING FORWARD. HOW DO YOU PRIORITIZE RISK TO PATIENT? >> I WILL JUMP IN. I GUESS FIRST I MAKE A COMMENT THE QUESTION FRAMED AROUND LDT CLASSIFICATION, THAT'S THE TOPIC OF THE DAY. I SUBMIT THE AGENCY CONTINUE TO THINK ABOUT RISK OF DIAGNOSTICS IN TOTAL, IN OTHER WORDS I DON'T THINK MOST CONSIDERATIONS OF RISK THERE'S A SIGNIFICANT DISTINCTION BETWEEN TEST DEVELOPMENT AND LAB AND TEST BY MANUFACTURER PUT INTO CLINICAL USE THE QUESTION WHAT'S THE RISK TO THE PATIENT GETTING AN INCORRECT RESULT. SO I THINK AS WE HAVE FOR A NUMBER OF YEARS WE URGE THE AGENCY CONTINUE TO THINK ABOUT RISK OF DIAGNOSTICS AND RISK-BASED APPROACH OF ALL DIAGNOSTICS REGARDLESS WHO DEVELOPS THEM. I WANT TO NOTE THAT DEVELOP EXTENSIVE DOCUMENT OF RISK-BASED DIAGNOSTICS A NUMBER OF YEARS AGO ON THE WEBSITE, I MENTION MUCH WILL BE RECAPITULATED IN COMMENTS WE SUBMIT TO THIS DOCKET BUT THERE'S A LENGTHY DISCUSSION AND IN A LEVEL OF DETAIL THAT I CAN'T BEGIN TO APPROACH IN REMARKS TODAY. BUT I WANT TO CALL VERY QUICKLY A FEW FACTORS THAT WE CONSIDER CERTAINLY RELEVANT AND STARTING POINT REFERENCED PREVIOUSLY IN THIS WORKSHOP IS OBVIOUSLY CLINICAL USE, IT'S LOOKING AT WHAT QUESTION IS INTENDED TO BE ANSWERED BY RESULTS OF THIS TEST AND THEREFORE THE IMPLICATIONS IF THIS RESULT IS WRONG. HOWEVER I SUBMIT ALSO THE TOTAL RISK CONSIDERATION IS FAR MORE COMPLEX THAN THAT AND ONE BASIC INNER PLAY IS LOOKING AT WHETHER THE BIOMARKER INVOLVED IS NEW OR ESTABLISHED. IN OTHER WORDS IF IT'S ESTABLISHED AS CLINICAL VALIDITY IS ESTABLISHED AND PUTTING THAT AGAINST MATRIX WHETHER THE TECHNOLOGY PLATFORM THE TEST TECHNOLOGY ITSELF IS NEW OR ESTABLISHED AS WE HAVE LAID OUT IN OUR DOCUMENT THAT LEADS YOU TO A NUMBER OF QUESTIONS THAT GO INTO THOSE FOUR BOXES HOW THE DIFFERENT FACTORS INTERPLAY. ONE THING THAT CLEARLY THINK FDA SHOULD BE CONSIDERING AS WELL IS NOT JUST RISK IN A SENSE IN A VACUUM BUT RISK MITIGATION, WHAT IS SERVICE SKILL OF USER, THERE'S A NUMBER OF ELEMENTS THAT GO INTO THINKING YES, THEY ARE RISKS BUT THEY CAN BE MITIGATED BY VARIOUS FACTORS NOT JUST THE EVIDENCE PRESENTED TO SUPPORT THE USE OF THE TEST BUT OTHER CONSIDERATIONS IN REAL WORLD USE. WE ALSO SUGGEST FDA CONTINUE TO EVALUATE APPROPRIATE PRE-AND POST MARKET BALANCE IN CERTAIN CIRCUMSTANCES. THERE ARE REASONS THAT FDA COULD LOOK FOR ADDITIONAL EVIDENCE SUBMITTED SUPPORTING USE OF THE TEST IN THE CASE OF LDT, LOOKING AT CHECKING EVIDENCE WHILE LDTs ARE IN USE, I WOULD URGE YOU TO CONTINUE THINKING PRE-AND POST MARKET BALANCE WITH REGARD TO ALL TESTS. THE LAST POINT I MAKE, NOT A FORMAL COMMENT BUT IT GOES TO THE KIND OF THIS IDEA OF RISK TOLERANCE WHICH IS THAT THE RISK OF HARM WEIGHED AGAINST BENEFIT SO YOU NEED TO BE -- ALWAYS THINKING WHAT ARE THE UNMET NEEDS AND WHERE RISK IN A SENSE AGAIN IS NOT IN A VACUUM, WEIGHED AGAINST WHAT WE'RE TRYING TO TEST AND HOW IMPORTANT THIS TEST IS TO USE EVEN THOUGH IF THERE'S CERTAIN RISK AND IF WE'RE CLEAR WHAT THE RISKS ARE IN LABELING OR RISK MITIGATION FACTORS THERE'S SOME TESTS WE WANT IN USE IF WE UNDERSTAND SOME OF THE RISKS ARE HIGH AS LONG AS THOSE ARE IDENTIFIED AND ADDRESSED. >> I WANT TO FIRST POINT OUT I'M A GENETICIST SO I ANSWER THIS FROM PERSPECTIVE OF GENETICS BUT THAT'S A SMALL SUBSET OF THIS LARGE UNIVERSE OF LDTs THAT SHOULD BE KEPT IN MIND. ACMG IS PREVIOUSLY PUBLISHED A POLICY ABOUT RISK STRATIFICATION FOR LABORATORY DEVELOPED TESTS FOR INHERITED GENETIC CONDITIONS. WE PUBLISHED THIS, I'M HAPPY TO SHARE WITH THE GROUP. THE KEY POLICY IS THAT MOST GENETIC TESTS ARE MODERATE RISK TESTS, THERE REALLY ARE NO LOW RISK TESTS IN OUR VIEW. SO MODERATE TESTS ARE NUMBER ONE DO NOT UTILIZE PROPRIETARY METHODS OR ALGORITHMS, TWO AMENABLE TO INTERLABORATORY COMPARISON, AND THREE EVALUATED BY EXTERNAL PROFICIENCY TESTING. PUBLISHED ACMG POLICY SUPPORTS BROUGHT UP IN THE FDA GUIDANCE ABOUT THE DEVELOPMENT OF A THIRD PARTY REVIEW PROCESS FOR MODERATE RISK TESTS. COROLLARY TO THAT THEN IS THAT TEST THAT DON'T MEET THOSE CRITERIA ARE HIGH RISK TESTS, AND WE FEEL THAT THE HIGH RISK TEST WOULD BE THE HIGHEST PRIORITY. >> I WANT TO SAY I SHARE THE CONCERNS EXPRESSED EARLIER, THIS MORNING, ABOUT THE DIFFICULTIES AND VALIDITY OF ESTABLISHING A RISK CLASSIFICATION. EVERY LABORATORY TEST ENTAILS RISK. I HAVE CONCERNS THIS RISK CLASSIFICATION PROCESS MAY HAVE RUN INTO PROBLEMS WITH PRACTICALITY AND VALIDITY AS WELL, NOT SURE UNLESS THE CRITERIA ARE VERY CAREFULLY SPELLED OUT WHETHER IT WOULD BE A CLASSIFICATION PROCESS THAT WOULD BE REPRODUCIBLE. SO THESE ARE ALL CONCERNS THAT I HAVE. THAT BEING SAID THE CRITERIA FOR HIGH RISK WOULD BE -- SHOULD TAKE INTO ACCOUNT THE SEVERITY OF THE DISEASE, RAPIDITY OF THE DISEASE PROCESS AND BY WHICH DECISIONS HAVE TO BE MADE. AND THE TOXICITY OF TREATMENT, THERE BY CONSEQUENCES OF MAKING A WRONG ASSESSMENT BASED ON THE DIAGNOSTIC TESTS. IN ADDITION THE AVAILABILITY OF OTHER DIAGNOSTIC CRITERIA THAT CAN BE USED TO OFFSET THE RESULTS OF A SPECIFIC TEST. I WANT TO DRAW ATTENTION TO AN EXAMPLE USED HIGH RISK TEST AND THAT'S CYTOMEGALO VIRUS IN TRANSPLANTATION. AND OUR SOCIETY DOES NOT BELIEVE THAT THIS SHOULD BE HIGH RISK TEST NOR TEST FOR OTHER VIRUSES IN TRANSPLANTATION SUCH AS EPSTEIN BAR VIRUS AN BK VIRUS. THESE ARE IN WIDESPREAD PRACTICE AT THIS POINT IN TIME, THEY BECOME ROUTINE IN THE CASE OF CMV THERE'S AN INTERNATIONAL STANDARD THAT'S USED TO FACILITATE INTERLABORATORY COMPARISON. THESE ARE USED EVERY DAY BY TRANSPLANT PHYSICIANS AND PATIENTS ARE OFTEN TESTED LONGITUDINALLY SO WE DON'T THINK THESE TESTS SHOULD BE CONSIDERED HIGH RISK. >> ONE PROBLEM THAT WE HAVE, IN ONCOLOGY IS WE HAVE A TRACK RECORD OF SOME PROBLEMS WITH SOME OF THE TESTS OFFERED TO OUR PATIENTS. I WOULD -- AND THERE HAVE BEEN PAPERS PRESENTED AT ASCO AND PUBLISHED IN THE LITERATURE, I DON'T FOLLOW THE PATHOLOGY BUT THE ONCOLOGY LITERATURE. THERE'S PROBLEMS THAT TESTS HAVE BEEN AROUND A LONG TIME. I WOULD SAY THAT SOME OF THOSE PROBLEMS HAVE TO DO IN NO SMALL PART WITH CO-OPERATOR VARIABILITY OR LAB VARIABILITY. DIFFERENCES BETWEEN LABS PERFORMING THE SAME TESTS, WHEREAS HIGH QUALITY LABS GET HIGH CORRELATION, OTHER LABS RANDOMLY CHOSEN DIDN'T HAVE HIGH CORRELATION. THE PROBLEM OF COURSE IS THAT THE RESULTS OF THOSE TESTS MAKE A HUGE DIFFERENCE, NOT ONLY IN THE TREATMENT THAT PATIENT MAY RECEIVE, BUT ALSO IN THE OUTCOME FOR THAT PATIENT. I THINK THAT AS A FIRST CUT THERE'S NO QUESTION IN OUR AREA, ON BEHALF OF OUR PATIENTS, IT SUGGEST PRIMARY CONCERN, ONE OF THEIR CONCERNS WOULD BE THAT THAT TEST IN FACT IS PERFORMED PROPERLY WHICH MAY NOT BE A FDA ISSUE, MAYBE A KLIA ISSUE, THAT THE TEST BE MEANINGFUL AND REPRODUCIBLE AND THAT SOME LEVEL THERE'S A STATISTICAL UNDERPINNING TO SUPPORT THAT TEST. THE SENSITIVITY AND SPECIFICITY. I MENTIONED AT HEARING A COUPLE OF WEEKS AGO, SITUATION THAT I RAN INTO I WON'T BELABOR THE POINT HERE, BUT SAY IN PARTICULAR VENUE I WAS ASKED A QUESTION ABOUT A BLOOD TEST FOR COLON CANCER. I QUICKLY HAD TO USE ANY INTERNET AND FOUND SENSITIVITY AND SPECIFICITY WERE LOW. SUBSEQUENT PUBLICATIONS IN A JOURNAL LEVEL SHOWING VARIATION IS MUCH MORE RELIABLE BUT THERE IS NO EVIDENCE TO SUPPORT THIS AS A COLORECTAL CANCER SCREENING TEST YET IT IS AVAILABLE. IF I'M A PATIENT, AND I AM A PATIENT AND I DO HAVE A FAMILY HISTORY OF COLON CANCER IN MY FAMILY, I WANT TO MAKE SURE IF I GET A BLOOD TEST WHICH IS AN AWFUL LOT EASIER THAN COLON OSCOPY OR ANYTHING ELSE I WANT TO MAKE SURE IT DOES WHAT IT CLAIMS IT DOES, ACCURATELY AND REASONABLY AND SOMEBODY SOMEWHERE IS WATCHING THE STORE. THAT COME FROM VERY COMMITTED PEOPLE SO I WANT TO BE EXTREMELY CLEAR TO EVERYONE IN THE AUDIENCE THAT I UNDERSTAND THAT. BUT I ALSO FEEL BECAUSE SOME OF THIS IS AS MENTIONED ALGORITHMIC AND COMPLEX GENETIC STANDPOINT, AT LEAST WE HAVE SOME REASSURANCE, SOME CERTAINTY AT SOME LEVEL, THAT THE TEST DOES WHAT THE TEST IS SUPPOSED TO DO, NUMBER ONE. AND THE TEST IS VALID TO ACHIEVE GOALS THE CLAIMS THAT ARE MADE AND WHEN WE TALK TO OUR PATIENTS AND DO THAT TEST WE'RE DOING A BENEFIT FOR OUR PATIENTS. THAT IS A HIGHER BAR THAN EXIST TODAY BUT IT'S ALSO A REASON WE HAVE THIS DISCUSSION. NOT SURE ALL THE THINGS I'M SITTING HERE LISTENING TO, HOW MUCH THE DISCUSSION WAS REALLY SENTENCERRED ON WHAT GOES ON? A TYPICAL LABORATORY, WHERE THEY HAVE DONE A TWEAK OR TEST OR MAY TAKE A PIECE OF GENETIC MATERIAL HIGH END ALGORITHMIC SIDE. IF YOU'RE GOING THE OPERATE OR NOT OPERATE ON SOMEBODY WITH CANCER, YOU HAVE EXPERIENCE WITH THAT ONE, THAT'S A REASON WE'RE HERE. PEOPLE WERE TOLD THEY DIDN'T HAVE CANCER DID HAVE CANCER AND SOME DID, IT WASN'T CORRECT. THAT DOES HAPPEN. THOSE ARE CLEAR -- YOU WANT TO GIVE A TREATMENT, TOXICITY, YOU CAN'T HAVE A TREATMENT. BECAUSE YOU HAVE PARTICULAR ABNORMALITY. THOSE ARE THE TESTS THAT RISE AT LEAST IN OUR OPINION TO A LEVEL THAT REQUIRES THIS OVERSIGHT. >> MY UNDERSTANDING THE ENTIRE FRAMEWORK IS PREDICATED ON RISK CLASSIFICATION. THOUGH SOME AS WE HAVE HEARD THINK IT'S EASY AND OBVIOUS. THAT THESE TESTS FIT INTO THIS BOX AND THESE INTO THIS ONE AND THESE INTO THIS ONE. I THINK THERE'S A LOT OF CONFUSION. ABOUT WHAT IS HIGHEST RISK AND ALSO A LOT OF CONFUSION ABOUT THAT LINE. BETWEEN WHERE THE END OF HIGHEST RISK ENDS AND THE BEGINNING OF MODERATE RISK. AND PERSONALIZED MEDICINE AGAIN. YET WE HAVE TO CLARIFY THIS BECAUSE TIME LINES OUTLINED ARE IN SOME CASES FLEXIBLE AND GENEROUS AND PRACTICAL. THEN SOMETIMES TRUNCATED. 12 MONTHS, LABORATORIES ARE VERY NEW TO FDA VISION AND SO WE'LL NEED MORE TIME. BEING VERY CLEAR ABOUT WHAT FDA THINKS IS A HIGH RISK TEST, HAVING A PUBLIC ENGAGEMENT ABOUT OTHER TYPES OF TESTS THAT MIGHT MAP TO THOSE EXAMPLES COULD BE VERY HELPFUL. WITH HIGHEST RISK AND FOCUSING ON THAT LINE BETWEEN HIGHEST RISK TESTS AND MODERATE. I THINK THAT WOULD BE A VERY USEFUL EXERCISE, AND WHEN WE THINK ABOUT THE CONCERNS OF THE COMMUNITY I THINK WE ALSO NEED TO LOOK AT HOW PERSONALIZED MEDICINE HAS ADVANCED TREATMENT AND WHAT THE RISK OF TEST NOT BEING ON THE MARKET MIGHT BE. AND THINK ABOUT THOSE THINGS AS WELL. BECAUSE WE HAVE NEW INSIGHTS INTO HOW HEALTHCARE CAN BE CONDUCTED AND THAT'S VALUABLE AS WELL. THANK YOU. >> THANK YOU. ESPECIALLY AMY FOR BRINGING THAT LAST POINT ABOUT THE RISK OF NOT HAVING A TEST DONE, NOT HAVING IT AVAILABLE, NOT PROVIDING DIAGNOSIS OR FOCUS THERAPY BECAUSE OF TEST -- A TEST CANNOT BE PROVIDED. IT GETS TO WHAT WE HEARD THE LAST COUPLE OF DAYS IS THERE'S STIFLED INNOVATION BECAUSE OF LACK OF REGULATION, STIFLED INNOVATION BECAUSE INCREASED REGULATION, SOMEWHERE THERE'S A BALANCE IN THERE, WE'LL TRY TO FIND THAT. SO THE FINAL QUESTION THAT WE'RE ASKED TO DISCUSS THIS MORNING, HOW HOW WOULD THE ADVISORY PANEL PROCESS WEIGH THE FACTORS THAT WILL DISTINGUISH AND CLASSIFY LDT BY RISK AND PRIORITIZE THEM. I THINK THAT'S LEADING US MORE TO IF WE CAN HAVE SPECIFIC CRITERIA OR BETTER DEFINE WHAT THE THRESHOLDS AND CUT OFFS ARE, HOW WOULD ADVISORY PANELS USE THOSE PROCESSES TO AID IN THIS CLASSIFICATION, THIS HAS BEEN PROVIDED BY AS ANDY MENTIONED BY A NUMBER OF OTHER ORGANIZATIONS ABOUT POSSIBLE WAYS THAT OUTSIDE THIRD PARTY GROUPS COULD HELP IN THIS PROCESS AND HANDLE THE WORKLOAD AT LEAST FOR THE LOWER RISK, BUT AS WE KNOW WE NEED A BETTER DEFINITION OF WHAT CONSTITUTES LOWER RISK. SO IF YOU WOULD, WHAT KIND OF PROCESSES DO YOU THINK THE ADVISORY PANELS SHOULD USE TO WEIGH AND PRIORITIZE THE CRITERIA THAT YOU'RE DESCRIBING HERE TODAY. >> I MAKE A SUGGESTION, MAYBE THIS IS A LITTLE BIT SOMETHING AMY WAS SAYING, IT PROBABLY WOULD BE HELPFUL IF THE AGENCY PUBLISHING AN INITIAL NOT A FORMAL GUIDANCE BUT A DOCUMENT LAYING OUT THE WAY YOU THINK RISK WOULD BE ASSESSED GENERALLY WITH REGARD TO DIAGNOSTICS. SETTING FORTH A FRAMEWORK PRINCIPLES OF RISK ASSESSMENT AND OTHER INCLUDING US HAVE WEIGHED IN ON THIS BUT IT MIGHT BE HELPFUL FOR ALL THE PANELS WHATEVER THE PANEL PROCESS IS GOING TO BE, I THINK WHAT YOU'RE LOOKING FOR INPUT IS THE SPECIFICS THAT HELP THE AGENCY WEIGH RISK IN A GIVEN DIAGNOSTIC CONTEXT. IF YOU DON'T LAY OUT A FRAMEWORK FOR RISK ASSESSMENT IN THIS CONTEXT, EVERYONE CAN USE TO FOLLOW THEN EVERYONE IS IN A DIFFERENT POSITION CONSIDERING WHAT'S HIGH RISK. THESE -- IT'S LIKE THE WORD STRATEGY, EVERYONE HAS A DIFFERENT IDEA WHAT STRATEGY IS SO IF YOU SIT DOWN TO DISCUSS STRATEGY WITHOUT DISCUSSING WHAT IT MEANS, YOU CAN HAVE A LONG CONVERSATION AND NOT GET ANYWHERE IF YOU SIT AND SAY WHAT ARE THE RISK FACTORS AND HOW RISKY IS TESTENING THIS DISEASE AREA, YOU CAN GO A LONG TIME WITHOUT RESOLVING THAT, IF YOU HAVEN'T SET UP THE INITIAL FRAMEWORK HOW YOU THINK ABOUT RISK. RISK ASSESSMENT IS A SCIENTIFIC DISCIPLINE, THERE'S PROFESSIONALS IN RISK ASSESSMENT WITHIN THE AGENCY AND EXTERNALLY, I THINK IT MIGHT BE HELPFUL TO LAY OUT THE FRAMEWORK HOW SHOULD THE PANELS THINK ABOUT RISK. AND ANYWAY, THAT GUIDES THE INPUT YOU GET AND MIGHT BE WORTH CONSIDERING DOING. >> BIT CONFUSED BY THAT ANSWER, I THOUGHT THE ADVISORY PANEL WAS SUPPOSED TO DEVELOP THE RISK CATEGORIZATIONS. AM I CORRECT ABOUT THAT? SAME WHAT THE QUESTION WAS ORIGINALLY ABOUT. SO GET INPUT FROM EVIDENCE BASED LITERATURE, OTHER THINGS LIKE THAT BUT I THINK THE CONCEPT IS FDA WANTS GUIDANCE FROM EXPERTS TO DEVELOP THE RISK. WE HAVE GIVEN AN EXAMPLE OF THAT. >> I GUESS MY POINT IS I THINK THAT IF YOU SIMPLY HAVE LOTS OF INPUT ON WHAT ARE THE RISK ELEMENTS, IT'S BACK TO THE AGENCY TO PUT THAT IN A FRAMEWORK AND SEEMS TO ME IT MIGHT BE REASONABLE FOR THE AGENCY TO PROPOSED FRAMEWORK HOW TO THINK ABOUTRYK IN THE CONTEXT OF DIAGNOSTICS AND ASK THE PANEL TO WEIGH IN ON THAT. SO ANYWAY, I REALIZE MAYBE THAT'S A LITTLE BIT CONFUSING BUT THAT WAS MY ORIGINAL THINKING. I DON'T THINK ANYONE NECESSARILY AGREE WHAT IS'S HIGH RISK. YOU SAY SOMETHING IS RISKY WITHOUT GETTING TO THE DETAILS WHY IS IT RISKY, HIGH VERSUS MODERATE. AND SO I THINK THAT YOU WANT TO KEEP AT LEAST SOME POINT YOU WANT TO KEEP FOCUS ON THAT QUESTION. >> DO YOU THINK IT'S HELPFUL TO GET MORE CLARIFICATION ABOUT HOW THE WELL DEFINED RISK CATEGORIES THAT ARE ALREADY DEFINED FOR IVDs WHAT ARE THE POSSIBLE DIFFERENCES OR CATEGORIES THAT AREN'T INCLUDED WHEN YOU THINK DIAGNOSTIC ASSAYS LDTs, ARE THERE DISTINCT GAPS, IS THAT A PLACE THAT THE PANELS COULD AID IN. >> PERHAPS UNDERSTANDING YOUR COMMENT CORRECTLY, FDA CLASSIFIES RISK FOR DIAGNOSTICS. WE HAVE LONG STANDING REGULATION ON APPROVAL FOR CLEARANCE FOR DIAGNOSTICS SO SETTING THAT FORTH AS A STARTING POINT SEEMS THE ADVISORY PANEL SHOULD BE WEIGHING IN HOW TO ADVISE ON WHETHER THAT FDA CURRENT THINKING IS ADEQUATE, DOES IT NEED TO BE FURTHER DEFINED, ELABORATED UPON AS FDA UNDERTAKES THE PROCESS OF ASSESSING BODY OF LDT, IN MY VIEW THE ESSENTIAL RISK ASSESSMENT FOR LDT IS NOT SIGNIFICANTLY DIFFERENT THAN THE RISK ASSESSMENT FOR DEVELOPMENT OF TESTS BY OF MANIERS SO YOU HAVE A RISK ASSESS -- MANUFACTURERS. YOU HAVE CATEGORIZATIONS OF EXISTING TESTS AND IT SEEMS THE PANEL PROCESS IS TO ADD ADDITIONAL PERSPECTIVE AS FDA GOES THROUGH THIS ROUND APPLYING CURRENT ROLES TO LDT. >> OTHER PANEL MEMBERS? >> MY CONCEPTION I THOUGHT THE MAIN FUNCTION OF THE PANELS WOULD BE TO CONSIDER INDIVIDUAL TESTS AND HELP FDA MAKE A RISK ASSIGNMENT FOR THOSE TESTS, BUT I DO THINK IT WOULD BE VERY IMPORTANT AT THE OUTSET TO HAVE CAREFUL DISCUSSION ON EACH PANEL OF WHAT THE CRITERIA ARE FOR RISK AND THOSE CRITERIA MAY DIFFER SOMEWHAT FROM AREA TO AREA, SO MAKING SURE THERE IS A PROPER UNDERSTANDING AND PROPER INPUT RECEIVED IN ASSIGNING THE RISK CLASSIFICATION WOULD BE VERY IMPORTANT. >> SO ONE THING THAT'S NOT SAID IS THE RISK IS IN THE EYE OF THE BEHOLDER. AND THERE MAY WELL BE PATIENTS OTHERS SITTING WITH FAMILY MEMBER WHOSE SAY ANY TEST THAT HAS DONE TO ME THAT'S GOING TO TAKE TO HELP MOVE MY CANCER DIAGNOSIS OR TREATMENT DOWN AS THEY TESTED HIGH RISK AS FAR AS I'M CONCERNED SO THAT'S AN ISSUE TO STRUGGLE WITH. AS I THINK ABOUT THIS PROCESS AND LISTEN TO THE COMMENTS MADE TODAY, ONE THING THAT -- FIRST OFFS IN NOT -- I WOULD SUSPECT THIS WILL NOT BE A FIXED IN STONE PROCESS. OBVIOUSLY I UNDERSTAND AGENCY WORKS UNDER RULES AN REQUIREMENTS, AND HAVING WORKED ON SIMILAR LARGE PANEL DETERMINATIONS WE WEREN'T BOUND BY THE SAME RULES THAT FDA ADVISORY PANEL IS BOUND BY BUT I SUSPECT YOU'RE GOING TO COME AS ANDY MENTIONED EXISTING RISK CLASSIFICATION. YOU ARE GOING TO GET SUBSTANTIAL INPUT FROM THE LABORATORY COMMUNITY WHICH IS -- YOU'RE NOT GOING TO DO DISCUSSION ONE BY ONE, YOU ARE -- IT IS GOING TO HAVE TO BE MATCHED. AND IT WILL HAVE TO BE THOUGHT THROUGH AND THE PANELS WILL HELP CONFIRM STAFF DECISIONS, THEY HAVE TO WORK TOGETHER TO MOVE THE PROCESS FORWARD AND THERE WILL BE DEEMED AUTHORITIES AS HAS BEEN THE CASE IN KLIA. THERE WILL BE DEEMED AUTHORITIES THAT CAN DEAL WITH SOME OF THE SIMPLER TESTS NOT ALL SIMPLER BUT THE SIMPLE TESTS IN VIEW OF THE MATTER HOW WE DO THE TESTS, FALL MORE INTO KLIA THAN IT DOES TO FDA. BUT IT WILL BE A WORK IN PROGRESS. I DON'T THINK -- EVERYONE WOULD LIKE TO HAVE CLEAR GUIDELINES AT THE OUTSET BUT I DON'T THINK THAT'S REALISTIC. DOESN'T REQUIRE A LOT OF COOPERATION TO MAKE THE RIGHT DECISIONS, THEY WON'T BE PERFECT. HAVING INPUT FROM GROUPS WILL DECIDE THAT. AGAIN, I COME BACK TO THE SAME POINT. DETERMINING FACTORS TO COMPLEXITY OF THE TEST, COMPLEXITY OF CLAIM MADE FOR THE TEST. AND RISK OF WHAT IT WILL DO, AGAIN, I HAVE APPROXIMATE INTERNAL MEDICINE BACKGROUND PRACTICE AS WELL. SO BUT THERE ARE A NUMBER OF ISSUES IN TERMS OF WHETHER A DOCTOR OR PATIENT AND FAMILY WORK WITH THEIR PHYSICIAN AND THEIR HEALTHCARE TEAM TO HELP MAKE CRITICAL DECISIONS. AGAIN, I SUSPECT AS ANDY MENTIONED YOU HAVE THE FRAMEWORK, THE BASIC FRAMEWORK I THINK IT WILL BE TWEAKED, A LOT OF TESTS END IN THE LOWER END CATEGORY BECAUSE THEY ARE AS I MENTION AD FAIRLY STRAIGHT FORWARD TYPES OF TESTS, GENETIC TESTS THAT WERE REFERRED TO EARLIER AS AN EXAMPLE. I THINK IT WILL HAVE TO BE FLEXIBLE. I DON'T THINK I WILL BE ABLE TO WALK IN AND JUST SAY THESE ARE THE ARBITRARY ABSOLUTE FINAL DETERMINATIONS. THIS IS A WORK IN PROGRESS AND IT'S ONE OF THOSE EVOLVING SITUATIONS. I THINK IT'S FANTASTIC THAT ADVAMED HAS A KIT FOR MANUFACTURERS HAVE GONE THROUGH THE INTELLECTUAL EXERCISE OF LINING RISK CLASSIFICATION FOR MANUFACTURED KITS. IT WOULD BE EXTREMELY HELPFUL, I THINK TO THE FDA, AND ALSO TO THE BROADER COMMUNITY IF LAB GROUPS DID THAT SAME INTELLECTUAL EXERCISE. THIS COULD BE AN OPPORTUNITY FOR FDA TO AUGMENT THE FRAMEWORK WITH THEIR VISION THEN PUT OUT FOR PUBLIC CONSUMPTION ALONG WITH A REDRAFT OF THE FRAMEWORK AND LET THE IMMUNITY THINK ABOUT THE ENTIRETY OF THE PACKAGE AS ONE. BECAUSE ALTHOUGH SOME THINK THE BOXES ARE SET, THEY'RE EASY, WE HAVE BEEN DOING IT FOR YEARS IN THE IBB WORLD, THERE IS CONFUSION ABOUT WHERE THOSE LINES ARE. BUT IF THEN OR VARIATIONS ON A PARTICULAR THEME. GOING THROUGH THE PROCESS HAVING A WELL DEVELOPED ADVISORY COMMITTEE AT THAT POINT, WOULD BE BENEFICIAL AS WE TRY TO GET TO THESE DETAILS. THESE DETAILS ARE GOING TO MATTER AS WE DEPOSITS THROUGH THE FRAMEWORK GENERALLY, STEP ONE. >> CAN I ADD, I THINK EXACTLY WHAT YOU SAID THE IF THENS, THERE MAYBE SOME FAIRLY CLEAR BUCKETS BUT THE PURPOSE OF THE ADVISORY PANEL TO TRY TO DEEM DEAL WITH THINGS THAT FALL OUT OF THE VERY CLEAR BUCKETS. THERE WILL BE THINGS THAT FALL OUT OF THE CLEAR BUCKET. SO VERY SIMPLE TEST TO PERFORM, THEY HAVE A HUGE IMPACT AND THERE ARE MAY FALL INTO A HIGH RISK CATEGORY. THAT SORTS OF THING THAT HAPPENS AS A RESULT OF THIS. >> ALL RIGHT. IF I CAN JUST SUMMARIZE BRIEFLY WHAT WE HAVE BROUGHT OUT TODAY AS IT'S CLEAR THERE'S AT LEAST SOME CONSENSUS ABOUT LIKELY NEEDS FOR MULTIPLE ADVISORY PANELS GIVEN THE DIFFERENT TYPES OF CATEGORIES OF CLINICAL AREAS AND DIFFERENT SITUATIONS, ENVIRONMENTS IN WHICH THESE LDTs ARE PERFORMED, THERE'S BUY IN FOR A BROAD REPRESENTATION OF LEVELS OF EXPERTISE AND DIFFERENT SECTORS OF THE LABORATORY TESTING COMMUNITY, BOTH THE PHYSICIANS THAT ORDER, PHYSICIANS THAT USE THEM AS WELL AS PEOPLE PERFORMING THE TEST, PAYING FOR THE TEST, PATIENTS IMPACTED BY THE TEST RESULTS. ALSO A FEELING IT WILL BE NECESSARY TO COMPLETELY DISCLOSE CONFLICTS OF INTEREST FROM THE DIFFERENT INDIVIDUALS REPRESENTING THE SECTORS SO THEY'RE THERE REPRESENTING THE GOAL OF THE ADVISORY PANEL, NOT THEIR SPECIFIC CONSTITUENCIES WHEN THEY'RE GOING THROUGH THIS CLASSIFICATION STEP. AND THAT RISK PRIORITIZATION AND ASSESSMENT IS A DIFFERENT AREA FOR NON-MANUFACTURERS OR CLINICAL LABORATORIES TO GET INTO. MORE GUIDANCE AND CLARIFICATION ON THE PART OF FDA AND THE COMMUNITY WOULD BE HELPFUL IN THAT REGARD. MAYBE PEOPLE CAN START TO DO A SELF-ASSESSMENT THEMSELVES TO FIGURE WHAT THINGS WILL FALL IN THOSE CATEGORIES. THE PANEL MEMBERS GET A CHANCE TO SAY ANY OTHER COMMENTS ON THIS TOPIC. >> THANK YOU VERY MUCH TO OUR COMMENTERS AS WELL FOR THEIR INPUT. [APPLAUSE] >> THANK YOU. WE'RE GOING TO TAKE A BREAK. BE BACK AT 10:50. CURTIS HANSON IS UP AFTER THE BREAK. >> HI, EVERYONE, WE'RE GOING TO GET STARTED WITH THE PUBLIC PEOPLE WHO REGISTERED TO SPEAK ON MULTIPLE TOPICS. WE'LL KNOW THE AGENDA FOR THE MOST PART. THERE A COUPLE OF FOLKS THAT CAN'T MAKE TO IT THE SESSION SO BEFORE LUNCH WE'LL HAVE TIME TO ADD PEOPLE WHO REGISTERED ON SITE, I'M GOING TO READ YOUR NAMES, WE MAY NOT HAVE TIME TO GET TO YOU BEFORE LUNCH BUT WILL TRY. AFTER THE PEOPLE WHO ARE ALREADY ON THE AGENDA WE'RE GOING TO TRY TO HAVE KERRY BROAD, STEPHANIE PAIN, JOSEPH M NEARY AND ANNA SPEAK BEFORE LUNCH. THOSE PEOPLE WILL HAVE FOUR MINUTES LIKE EVERYONE ELSE. AND WITH THAT I'LL TURN IT OVER TO DR. HANSON. >> THANK YOU. MY NAME IS CURT HANSON, PROFESSOR INTERIM CHAIR DEPARTMENT OF LAB MEDICINE PATHOLOGY AT MAYO CLINIC IN ROCHESTER MINNESOTA AND PRESIDENT AND CEO OF MAYO MEDICAL LABORATORIES OR MML. WHICH SERVES OVER 4,000 MEDICAL CENTERS WITH A TEST MEAN EWE THAT INCLUDES OVER 1600 LDTs THE PRINCIPLES THAT GUIDE US ARE COMMITTABILITIMENT TO PATIENT SAFETY, ROBUST QUALITY SYSTEM, CLINICALLY VALIDATED TESTING AND ACCESS TO HIGH QUALITY LAB TESTING FOR ALL PATIENTS. ALL OUR LDTs MEAT MEET THESE PRINCIPLES. I HAVE TREE SPECIFIC COMMENTS TO MAKE TODAY. NUMBER ONE, BE SURE WE KNOW WHAT PROBLEM PETITION. MAYO CLINIC REPORTS SENTINEL EVENTS RELATED TO PATIENT SAFETY SUBMITTED BY PATIENTS EMPLOYEES ANSWER PHYSICIANS AND EVALUATED BY SENTINEL EVENT OFFICE TO UNDERSTAND ROOT CAUSES AN PROPOSE SOLUTIONS. WE USE THE SAME PROCESS WITH OUR MML CLIENTS. OVER THE LAST SIX YEARS WE PERFORMED OVER 2 AND A HALF YEARS LDTS FOR MAYOR CLINIC PATIENTS WITH ZERO SENTINEL EVENTS RELATED TO DESIGN OR VALIDATION OF LDTs FORMML CLIENTS 19 MILLION HAVE BEEN PERFORMED WITH ZERO REPORTED EVENT FOR THESE FACTORS. OVER 21 MILLION LDTs AND ZERO SENTINEL EVENTS DUE TO DEVELOPMENT DESIGN OR VALIDATION. SO WHAT PROBLEMS ARE WE TRYING TO SOLVE? NUMBER TWO, THE CURRENT FDA REVIEW DOES NOT GUARANTEE THAT LAB TESTS ARE MEETING CLINICAL OR SAFETY NEEDS. CLINICAL EXAMPLES YESTERDAY WERE COMPANION DIAGNOSTIC TEST FOR ALK AND BRAF. RESTRICTED TO MONOMODIFIED FDA KITS CANCER PATIENTS WILL BE REFUSED HOPE. LET'S GET THE RIGHT TEST DESIGN, WE NEED LABORATORY PATHOLOGY INPUT EARLIER IN THESE PROCESSES. THE CURRENT PROCESS IS ALSO FAILED US AS WE TRY TO PROTECT THE HEALTH OF EMPLOYEES TESTIMONY BRAF TEST KIT DESIRES -- WE ELIMINATED ZYLIEN TO PROVIDE A SAFE ENVIRONMENT, OUR EMPLOYEES WERE DISHEARTENED TO SEE THE FDA ENDORSE SUCH UNSAFE METHODS. FDA APPROVAL DOES NOT GUARANTEE THE BEST LAB METHODS, WE NEED THE RIGHT PROTOCOLS, PLEASE USE THE LABORATORY COMMUNITY FOR INPUT. NUMBER THREE, FDA OVERSIGHT HAS POTENTIAL TO LIMIT ACCESS TO COMMUNITY HEALTHCARE. TODAY'S COMMUNICATION AND CONSULTATION BETWEEN THE PATHOLOGISTS AND CLINICIAN IS NOT LIMITED BY THE WALLS OF THE HEALTHCARE FACILITIES. JUST LAST WEEK I CONSULTED NOT ONLY WITH PHYSICIANS AT MAYO, BUT ALSO WITH PHYSICIANS IN TEXAS MICHIGAN, AND MASSACHUSETTS AND THIS MORNING FROM ALASKA. REGARDING LABORATORY TESTING. IT WAS NO DIFFERENT IN ROCHESTER OR TRAVER CITY, MICHIGAN. WE PROVIDED MEANINGFUL CONSULTATION WITH PHYSICIANS, EVEN WITH OUR PATIENTS ARE AT DISTANCE. DON'T LIMIT THIS LDT BY THIS DEFINITION. MAYO IS UNIQUE. IT IS A LARGE TERTIARY CARE CENTER, MULTIPLE RURAL HOSPITALS AND CLINICS AND MEDIUM SIZE REGIONAL HOSPITALS, AND NATIONAL AFFILIATION NETWORK AND OVER 4,000 LAB FINDS THROUGH MML. I LEARNED A LOT. LIKE POLITICS GOOD HEALTHCARE IS LOCAL. SO YOU HAVE TO CONSIDER THE COMMUNITY WITH THIS PROPOSAL. WE KNOW OUR SMALL LOCAL COUNTY HOSPITAL VERY WELL, SIX BLOCKSES FROM US THEY WON'T SEND LDTs TO US, EVERY ACADEMIC CENTER DOES SOPHISTICATED LDT FOR COMMUNITY, MEDIUM AND LARGE COMMUNITY HOSPITAL DOES OUTREACH FOR THEIR COMMUNITY. BOTH STOP COMMUNITY RELATIONSHIPS THAT EXIST BETWEEN LAB AND CLINICIANS AND BETWEEN THE CLINICAL GROUPS. PATIENT ACCESS WILL BE AFFECTED AND STOP THE GROWTH OF HEALTHCARE EXPERTISE AND KNOWLEDGE IN THOSE COMMUNITIES. DON'T DON'T FORGET COMMUNITY CARE. MAYO BELIEVES ADDITIONAL LAYERS OF REGULATORY STRUCTURE WILL NOT GUARANTEE ANSWERS REGARDLESS OF THE DIRECTION IT HAS TO BE UPDATED AND BOUNDARY SPECIFICALLY DEFINED. WE NEED TO BE CERTAIN ABOUT THE SCOPE OF THE PROBLEM THAT THE SOLUTION WILL ACTUALLY IMPROVE PATIENT CARE AND THAT WILL NOT RESTRICT ACCESS TO LAB TESTING. THANK YOU FOR THE OPPORTUNITY TO SPEAK TODAY. >> GOOD MORNING, I'M PLEASED TO BE HERE ON BEHALF OF THE INFECTIOUS DISEASE SOCIETY OF AMERICA OR IDSA. MY COMMENTS WILL FOCUS ON THE DIFFICULTY WE BELIEVE CLINICAL RANTORIES WILL FACE AND NAVIGATING THE 5, 10-K SUBMISSION PROCESS AND THE PROBLEMS THAT WILL IMPACT PATIENT CARE AND PUBLIC HEALTH AS A RESULT. MY COMMENTS QUOTH. THOSE BY OTHER IDSA REPRESENTATIVES AT THIS WORKSHOP AND WILL BE SUBMITTING WRITTEN COMMENTS THE FDA AS WELL. IDSA IS CONCERNED THAT LDT OVERSIGHT CURRENTLY PROPOSED COULD IMPEDE PATIENT ACCESS TO EXISTING STATE-OF-THE-ART TESTS AND MAY CURTAIL DEVELOPMENT OF NOVEL TESTS FOR EMERGING INFECTIOUS DISEASE. WHAT SOME SMALL CLINICAL MICROBIOLOGY LABS MAYBE IMPACTED BY THE REGULATION BECAUSE THEY MAY CURRENTLY USE FEW OR NO LDTs, OTHER MICROBIOLOGY LABS PARTICULARLY THOSE MAJOR MEDICAL CENTERS HAVE DOZENS OF LDTs SUBJECT TO OVERSIGHT. THESE ARE THE MEDICAL CENTERS THAT SPECIALIZE IN TRANSPLANTATION AND MANAGE CRITICALLY ILL PATIENTS TO PROVIDE HIGH LEVEL CARE. HOWEVER THE SAME LABORATORIES LACK RESOURCES BOTH FINANCIAL AND ADMINISTRATIVE IN SINGLE 5, 10-K SUBMISSION LET ALONE SUBMISSIONS FOR ALL TESTS. LDTs CLASSIFY HELIX THESE LABORATORIES ARE UNABLE TO NAVIGATE THE COMPLEX PROCESS. IN IN THE FACE OF CHALLENGES IDSA BELIEVES MANY MICROBIOLOGY LABS IN LEADING U.S. MEDICAL HE WANTERS MAY CHOOSE TO STOP USING IT ENTIRELY AND MOVE TO COMMERCIAL TESTS OR REFERENCE LABORATORIES BOTH WHICH PRESENT DISADVANTAGES. FOR EXAMPLE, COMMERCIAL ASSAYS ARE NOT AVAILABLE FOR THE ENTIRE RANGE OF TESTING CURRENTLY COVERED BY LDTs, THOSE THAT ARE AVAILABLE ARE OFTEN MORE EXPENSIVE AND MAY REQUIRE INVESTMENT IN NEW INSTRUMENTS FROM MULTIPLE COMPANIES AS NO ONE COMPANY HAS THE ENTIRE MEN EWE COVERED BY LDTs, AT LEAST A PORTION OF THESE INCREASE COSTS ARE REPORTED PASSED ON TO PATIENTS. SENDING CLINICAL SPECIMENS TO LABORATORIES FOR TESTING SIGNIFICANTLY INCREASE TURN AROUND TIME TO GET RESULTS TO PHYSICIANS. RAPID DIAGNOSTICS THAT FACILITATE INITIATION OF LIFE SAVING TREATMENT ARE CRITICAL IN INFECTIOUS DISEASE CARE, A FEW HOURS DELAY SIGNIFICANTLY IMPACT PATIENT OUTCOMES. PUBLIC HEALTH RESPONSES REQUIRE RAPID IDENTIFICATION OF EMERGING INFECTIOUS DISEASE RISK AND ANY ACTIVATION OF PUBLIC HEALTH PROTOCOL ALLOW DANGEROUS INSPECTION TO SPREAD DELAYS INCURRED BY REFERENCE LABORATORIES LESS FLEXIBLE TESTING SCHEDULES MAY SLOW DETECTION OF OUTBREAKS OF INFECTIOUS DISEASE. APPRECIATES THAT FDA PROVIDES OVERSITE EXEMPTION MANUFACTURED AND USED BY HEALTHCARE FACILITY LABORATORY FOR PATIENT THAT IS BEING DIAGNOSED OR TREATED TREATED IN THAT SAME HEALTHCARE FACILITY OR WITHIN THE FACILITIES HEALTHCARE SYSTEM. HOWEVER OFTEN A LARGE INSTITUTION CLINICAL MICROBIOLOGY LAG IS NOTED BY PREVIOUS SPEAKERS MAY SERVE AS REGIONAL LABORATORY OUTSIDE OF THE SYSTEM PROVIDING NOT ONLY QUICK TURN AROUND TIME BUT VERY IMPORTANT CONSULTATIONS TO DISCUSS RESULTS. FDA MODIFY DEFINITION OF HEALTHCARE SYSTEM TO ALLOW FOR OVERSIGHT EXEMPTION OF THIS USE OF LDTs. WE APPRECIATE THE FDA INTENDS TO EXEMPT CLINICAL MICROBIOLOGY LABS FROM FDA USER FEES BUT WE RECOMMEND THAT THIS EXEMPTION BE EXTEND BED BEYOND 2017 AS USER FEES CAN ADD ANOTHER BURDEN LIMIT ACCESS TO TESTING AND THESE HIGHER COSTS ARE PASSED TO PATIENCE. WE STRESS THE MAJORITY OF CLINICAL MICROBIOLOGY LABS NEVER INTERACTED WITH FDA IT'S CRITICAL THAT FDA IMPLEMENT ROBUST MECHANISM TO PROCESSES FOR THE INDIVIDUALS TO PROVIDE THEM WITH THE NECESSARY INFORMATION GUIDANCE AND ASSISTANCE TO NAVIGATE FDA REGULATORY PROCESSES. FOR THIS OPPORTUNITY TO PROVIDE COMMENTS AND WE LOOK FORWARD TO CONTINUING TO WORK WITH THE AGENCY TO ENSURE THE EGGLATIONS ALLOW CLINICAL MICROBIOLOGY LABORATORIES TO CONTINUE TO PROVIDE PATIENTS WITH THE NEEDED HIGH QUALITY TESTING. THANK YOU. >> I'M A NERD, I WILL USE SLIDES, I APOLOGIZE IN ADVANCE. >> I'M DON KARCHER, ASSOCIATION OF PATHOLOGY CHAIRS. WE APPLAUD YOU FOR TAKING ON THE DIFFICULT AT TIMES CONTROVERSIAL ISSUE. WE APPLAUD THE SPONSORSHIP OF THIS VERY HELPFUL WORKSHOP. THE ASSOCIATE -- ASSOCIATION OF PATHOLOGY CHAIRS REPRESENTS PATHOLOGY IN SCHOOLS OF MEDICINE ACROSS THE UNITED STATES, CANADA , AND PUERTO RICO. AS SUCH WE'RE INVOLVED OBVIOUSLY IN THE DEVELOPMENT OF LDTs, USING INNOVATIONS AN DISCOVERIES MADE IN OUR DEPARTMENTS TO DEVELOP THESE CRITICALLY IMPORTANT TESTS. AND THEY ARE NEVER DEVELOPED IN A VACUUM. THESE TESTS ARE DEVELOPED FREQUENTLY AS REQUEST OF AND ALMOST ALWAYS IN CLOSE COLLABORATION WITH CLINICAL COLLEAGUES AND THEREFORE FILL GAPS IN DIAGNOSIS AND CHARACTERIZATION OF DISEASE STATES. REGARDLESS OF THE REGULATORY ENVIRONMENT, APC MEMBER DEPARTMENTS WANT TO ENSURE THINGS. FIRST INNOVATIONS THAT HEED O THE VERY IMPORTANT TESTS REMAIN UNHINDERED THE QUALITY AND RELIABILITY OF LDTs ARE MAINTAINED HIGHEST LEVELS POSSIBLE AND THEY CONTINUE TO BE WIDELY AVAILABLE TO PAID FOR PATIENT USE. FOR DECADES KLIA AND REGULATION OF LABORATORY TESTING RESULTED IN ACCURATE REPRODUCIBLE AND RELIABILITY LDTs, CLEAR GUIDELINES INCLUDES THREE REQUIREMENTS, IT'S IMPORTANT TO REMEMBER THAT POOR PERFORMANCE IN TWO OF THE THREE IMPORTANT KLIA REQUIREMENTS CAN RESULT IN CESSATION OF TESTING MANDATED CESSATION ON THE PART OF LABORATORIES REGARDING THOSE PARTICULAR ANOLYTES SO KLIA HAS LOBUS CHECKS AN BALANCES MAINTAINING QUALITY TESTS AND ALL TESTS. AS GOOD AS KLIA IS, WE RECOGNIZE THAT LDTs HAVE GROWN TREMENDOUSLY IN NUMBER AND COMPLEXITY AND RECENT YEARS. THEREFORE APC SUPPORTS THE NEED FOR A HIGHER LEVEL OF REGULATORY OVERSIGHT OF THESE TESTS, WE SUPPORT THE IDEA FDA PLAYS A ROLE IN THIS OVERSIGHT. WE SUPPORT THAT THERE BE A RISK-BASED APPROACH TO OVERSIGHT OF LDTs AT THE LAST PANEL DEMONSTRATED THE DEVIL IS IN THE DETAILS IN TERMS OF HOW RISK IS ASSESSED. AND DETERMINED. WE DO SUPPORT CONTINUED ENFORCEMENT DISCRETION FOR CERTAIN CATEGORIES OF L DTs THE DEVIL IN THE DETAILS OF THOSE. WE SUPPORT NOTIFICATION OF FDA FOR PERFORMED BY LABS AND NOTIFICATION OF POTENTIAL MALFUNCTION QUOTE UNQUOTE OF LDTs. AND WE SUPPORT PRE-MARKET REVIEW BY THE FDA OF LDT BUT ONLY HIGHEST RISK LDTs. SO WITH ALL THAT AS BACKGROUND OUR MEMBER DEPARTMENTS RECOMMEND CLEAR GUIDELINES CONTINUE TO BE THE BASIS OF QUALITY REPRODUCIBILITY RELIABILITY AND CLINICAL VALIDITY OF LDTs AS THEY CURRENTLY DO. WE DO SUPPORT THAT FOR LOW MODERATE RISK LDTs THERE SHOULD BE ADDITIONAL REGULATORY OVERSIGHT, WE RECOMMEND ONLY TWO ADDITIONAL NECESSARY REGULATORY REQUIREMENTS. ONE, NOTIFICATION OF FDA RDTs OFFERED BY LABORATORIES AND THE OTHER IS REPORTING ADVERSE EVENTS, THAT MAYBE SUSPECTED FORMAL FUNCTION OF LDT. THIRDLY WE RECOMMEND THE HIGHEST RISK LDTs RECEIVE FULL FDA REGULATORY OVERSIGHT INCLUDING MARKET REVIEW AND MOST IMPORTANTLY STRONGLY RECOMMEND DEFINITION OF HIGHEST RISK INCLUDE TWO CRITERIA, ONE CONSEQUENCES OF INCORRECT RESULT, RESULT IN SERIOUS MORBIDITY AND MORTALITY AND THESE ASSAYS USE METHODOLOGY BASED ON PROPRIETARY UNPUBLISHED OR NON-TRANSPARENT TESTING ALGORITHMS COMPUTATIONS ET CETERA, THERE BY INTERLABORATORY AND VERIFICATION OF TEST RESULTS. WE THINK IT'S VERY IMPORTANT THESE TWO CRITERIA BE MET BY TESTS ULTIMATELY DETERMINED TO BE HIGHEST RISK. AND WE THANK YOU, VERY MUCH FOR THE OPPORTUNITIES TO MAKE THESE REMARKS. >> >> >> I DIDN'T BRING SLIDES BUT I DID BRING A SKA OF BECAUSE IT'S FREEZING UP HERE. GOOD MORNING, I GREATLY APPRECIATE THE OPPORTUNITY TO SHARE WITH YOU TODAY THE OVARIAN CANCER PATIENT PERSPECTIVE ON THE NEED FOR AN EXPECTATION OF REGULATION OF LABORATORY DEVELOPED TESTS. I'M LAURA KOONTZ DIRECTOR OF POLICY OVARIAN CANCER NATIONAL ALLIANCE, WE'RE FOREMOST ADVOCACY ORGANIZATION FOR EVERYONE LIVES TOUCHED BY OVARIAN CANCER, I'M HERE TO SPEAK ON BEHALF OF THOUSANDS OF WOMEN LIVING WITH OR AT RISK OF DEVELOPING OVARIAN CANCER. OVARIAN CANCER IS A DEADLY DISEASE. THE SIMPLE REASON IS THAT'S NO EARLY DETECTION TESTS. MANY WOMEN ARE DIAGNOSED WHEN DISEASE IS ADVANCED AND TREATMENT OPTIONS ARE LIMITED. WE LOVE TO SEE TESTS REACH THE MARKET TO HELP DOCTORS DETECT OVARIAN CANCER CASES EARLY AND SAVE THE LIVES OF COUNTLESS WOMEN EACH YEAR. BUT THESE TESTS MUST BE VALIDATED TO ENSURE THAT THEY ARE SAFE, RELIABLE AND EFFECTIVE. A FEW YEARS AGO OUR COMMUNITY EXPERIENCED FIRSTHAND THE REPERCUSSIONS OF UNREGULATED VALUE DAYED LDT. EARLY 2008 LABORATORY TESTS CLAIMING TO BE OVARIAN CANCER EARLY DETECTION TEST CAME TO MARKET. AND I WOULD LIKE EACH OF YOU TO TAKE A MOMENT TO THINK ABOUT A WOMAN IN YOUR LIFE THAT YOU KNOW AND LOVE. YOURSELF YOUR MOTHER, YOUR SISTER, IMAGINE THAT IN THE FALL OF 2008, SHE WENT TO THE HOSPITAL LANE COMPLAINING PELVIC PAIN AN URINARY SYMPTOMS AN BLOATING. AND ULTRASOUND REVEALED A LUMP ON THE OVARY. HER DOCTOR USED A TEST TO DETERMINE WHETHER OR NOT THAT LUMP WAS OVARIAN CANCER. THE TEST RESULTS CAME BACK POSITIVE SO SHE UNDERWENT A COMPLETE HYSTERECTOMY INCLUDING REMOVAL OF OVARIES. GOT THE PATHOLOGY REPORT BACK ONLY TO FIND OUT THAT SHE DID NOT HAVE OVARIAN CANCER BUT BY THAT POINT IN TIME THE DAMAGE WAS DONE AND THE REPERCUSSIONS WERE REAL. EARLY MEN PAUSE, CARDIOVASCULAR AND HIGH RISK OSTEOPOROSIS. THIS ISN'T A HYPOTHETICAL EXAMPLE. THIS HAPPENED TO MANY WOMEN IN FALL OF 2008, WHEN IT WAS PUT ON THE MARKET WITHOUT INDEPENDENT VERIFICATION THAT IT WORKED DESPITE THE OBJECTIONS OF THE SOCIETY FOR GYNOWILL DODGIC ONCOLOGY AN FDA AT THE TIME. WHILE WE HEARD A FEW STORIES FROM BEHAVE WOMEN ABOUT THEIR EXPERIENCE WITH THIS TEST, WE DON'T EXACTLY KNOW THE FULL SCOPE OF HOW MANY WOMEN WERE IMPACTED BY THE TEST. THAT'S BECAUSE KLIA DOESN'T REQUIRE ADVERSE EVENT REPORTING. WHAT WE DO KNOW IS THAT MANY WOMEN WERE GIVEN TAKOUS AND INACCURATE RESULTS WITH REAL CONSEQUENCES. ULTIMATELY THE TEST WAS REMOVED FROM THE MARKET. AND NOT BEFORE MANY WOMEN WERE PUT AT RISK. WHILE THE COMMUNITY DESPERATELY WANTS A EARLY CONNECTION TEST IT'S CRITICAL THAT THE TEST IS VALIDATED TO ENSURE IT'S ACCURATE, RELIABLE, SAFE AND EFFECTIVE. WE BELIEVE THAT THE FDA PROPOSED REGULATORY FRAMEWORK GOES A LONG WAY TO ENSURING JUST THAT. FDA REGULATION WOULD REQUIRE OR WOULD CLASSIFY TEST BUSINESS RISK AND REQUIRE THAT HIGH RISK TESTS UNDERGO PRE-MARKET REVIEW TO ASSESS AN LIT INC. AND CLINICAL VALIDITY. FURTHERMORE FDA REPORTING WHICH ALLOW BAD TESTS TO BE CAUGHT QUICKLY AND GIVE COMMUNITY OUR FULL UNDERSTANDING OF THE SCOPE OF BAD TEST. FDA COMMON SENSE PROPOSAL IS REASONABLE TO PROTECT DEVELOPERS THAT'S WHAT THE PATIENT COMMUNITY EXPECTS WHEN THEY GO TO THEIR DOCTORS OFFICE AND GET A TEST THAT'S GOING TO DETERMINE THEIR RISK OF DISEASE OR TREATMENT FOR DISEASE, IT'S APPROVED IN ADVANCE. WE THINK IT'S A REASONABLE APPROACH AND LAST MONTH THE FDA APPROVED THE FIRST LDT FOR TESTING AS COMPANION FOR OVARIAN CANCER DRUG. FURTHERMORE THEY DID THIS UNDER THE DRUG AND THE TESTS WERE APPROVED UNDER ACCELERATED REVIEW. I WOULD ALSO POINT OUT THAT MOST OF THE TESTS THAT ARE USED IN OVARIAN CANCER WERE CURRENT AND MONITORING FDA APPROVED TESTS. CLEARLY THIS PATHWAY WORKS. FDA PROPOSAL ALSO INCLUDES THOUGHTFUL EXCEPTIONS THAT ALLOW INNOVATION AND PROCEED WHILE PROVIDING STRONG PATIENT PROTECTION AND ENSURE ALL TESTS ARE VALID RELIABLE SAFE AND EFFECTIVE. AND WE BELIEVE THE PATIENTS DESERVE NO LESS. THANK YOU. >> GOOD MORNING FDA STAFF AND MEMBER OF PUBLIC, MY NAME IS AMY MILLER I'M EXECUTIVE VICE PRESIDENT OF THE PERSONALIZED MEDICINE COALITION. WE REPRESENT INNOVATORS SCIENTISTS PATIENTS, PROVIDERS AND PAYERS. PMC PROMOTE UNDERSTANDING AND ADOPTION OF PERSONALIZED MEDICINE CONCEPTS SERVICES AND PRODUCTS PATIENTS AND THE HEALTH SYSTEM. WE THINK THANK FDA FOR THE OPPORTUNITY TO SPEAK WITH YOU TODAY. PERSONALIZED MEDICINE IS AN EMERGING FIELD THAT USES DIAGNOSTIC TOOLS TO IDENTIFY SPECIFIC BIOLOGICAL MARKERS, OFTEN DETERMINE WHICH MEDICAL TREATMENTS AND PROCEDURES WORK BEST WHICH THERE'S PATIENTS. BY COMBINING THIS INFORMATION INDIVIDUAL MEDICAL RECORD CIRCUMSTANCES, PERSONALIZED MEDICINE ALLOWS DOCTORS AND PATIENTS TO DEVELOP TARGETED PREVENTION AND TREATMENT PLANS. WHEN EFFICIENCIES ARE INTRODUCED, SUCH AS PROVIDING THE RIGHT TREATMENT TO THE RIGHT PATIENT AT THE RIGHT TIME, THE OVERALL HEALTH SYSTEM CAN -- HEALTHCARE SYSTEM COSTS DECREASE. IT IS FAIR TO SAY NO OTHER ISSUE AND PERSONALIZED MEDICINE POLICY HAS GARNERED MORE INTEREST OVER THE LAST DECADE THAN THE QUESTIONS OF IF, WHEN AND UNDER WHAT CIRCUMSTANCES FDA WOULD ACTIVELY REGULATE LABORATORY DEVELOPED TESTS. WE NOW HAVE A PROPOSAL TO CONSIDER AND APPROVE. WHILE SOME ACTIVELY PROPOSED FDA REGULATION OF LAB TESTS STATING THAT DEVICE REGULATION WAS NOT DESIGNED TO FIT LABORATORY MEDICINE AND SOME ACTIVELY SUPPORT IT, AND WANT THE FRAMEWORK IMPLEMENTED AS QUICKLY AS POSSIBLE, ARGUING THAT MANY IMPORTANT TESTS ARE NOT REGULATED. THE COALITION IS COMMITTING TO IMPROVING THE FRAMEWORK SO THAT PERSONALIZED MEDICINE AS A FIELD CAN ADVANCE AND IMPROVE THE QUALITY OF PATIENT CARE THUS REAPING SYSTEMIC BENEFITS. IS A START AND PMC IS PLEASED WITH THE HIGH LEVEL OF ENGAGEMENT THAT FDA HAS HAD WITH STAKEHOLDERS. AND WE ENCOURAGE FDA TO CONTINUE THAT HIGH LEVEL ENGAGEMENT. AS MANY POINTED OUT, TWO LARGE CRITICAL PIECES OF THE FRAMEWORK ARE MISSING. FIRST GUIDANCE ON LDT RISK CLASSIFICATION, AND SECOND, HARMONIZATION BETWEEN THE KLIA PROGRAM FOR LABORATORY INSPECTION AND FDA MANUFACTURING REGULATIONS. PMC CONTENDS RELEASING THESE TWO DOCUMENTS IN DRAFT, BEFORE FINALIZING THE FRAMEWORK, SINCE MOST OF THE REGULATORY STRUCTURE IS PREDICATED TON RISK CLASSIFICATION OF LDTs. FURTHERMORE RELEASING THE DODGES AS A DRAFT PACKAGE A ALLOWS A MORE ROBUST EXAMINATION OF FDA VISION AND THAT COULD LEAD TO MORE SPECIFIC POTENTIAL IMPROVEMENTS. FDA IS CURRENTLY COLLECTING PUBLIC COMMENTS ON THE DRAFT FRAMEWORK AND HAS STATED THEY ONLY INTEND TO ISSUE ANOTHER DRAFT FOR PUBLIC COMMENT IF THE CHANGES ARE SUBSTANTIAL. WE ARGUE THAT THE TWO MISSING PIECES ARE SUBSTANTIAL ENOUGH TO WARRANT ISSUE WEDNESDAY OF ANOTHER DRAFT. TO ENCOURAGE THOUGHTFUL REVIEW OF THE PROPOSED SECOND DRAFT, WE SUGGEST THAT FDA OUTLINE THE SUBSTANTIVE COMMENTS RECEIVED FROM STAKEHOLDERS AND THE AGENCY RESPONSES TO THOSE SUGGESTIONS. A CLEAR ARTICULATION OF WHY A SUGGESTION WAS ACCEPTED OR REJECTED, WOULD GREATLY AID STAKEHOLDERS AS THEY WORK WITH THE AGENCY DURING THE REVISION AND LIMITATION. WHILE FDA LIKELY TO RECEIVE TREMENDOUS PRESSURE TO FINALIZE GUIDANCE DOCUMENTS ABOUT START REGULATING LDTs, WE URGE THE AGENCY TO TAKE THE TIME NECESSARY TO GET IT RIGHT. CLASSIFICATION OF EXPECTATIONS FOR THE FIELD IS NECESSARY FOR IT TO MOVE FORWARD. IN CONCLUSION WE REQUEST THAT FDA ISSUE DRAFT GUIDANCE DOCUMENTS ON LDT RISK CLASSIFICATION, FDA CLIA HARMONIZATION WITH UPDATED DRAFT OF THE TWO EXISTING FRAMEWORK DOCUMENTS COUPLED WITH EXPLANATION WHY COMMENTS RECEIVED FROM STAKEHOLDERS WERE ACCEPTED OR REJECTED. FDA ENGAGE THE PUBLIC IN OUTREACH ACTIVITIES AS YOU HAVE DONE OVER THE LAST TWO MONTHS. THANK YOU FOR YOUR TIME. >> >> GOOD MORNING, I APPRECIATE THE OPPORTUNITY TO SHARE OUR THOUGHTS WITH THESE AUDIENCE. I AM FEDERICO MONZON, MOLECULAR POLICY PROFESSIONAL MEDICAL DIRECTOR ONCOLOGY AT INVITAE CORPORATION. ININVITAE'S MISSION IS TO BRING GENETIC INFORMATION INTO MAINSTREAM PRACTICE TO IMPROVE THE QUALITY AND HEALTHCARE FOR BILLIONS OF PEOPLE. THE FDA DRAFT GUIDANCE ON REGULATORY OVERSIGHT REPRESENTS PROGRESS WHEN COMPARED TO PRIOR PROPOSALS ESPECIALLY WITH REGARD TO THE INCLUSION OF A IMPLEMENTATION AND THE ACCEPTANCE OF LITERATURE, AND RETROSPECTIVE DATA AS EVIDENCE OF CLINICAL VALIDITY. HOWEVER, IN A NUMBER OF RESPECTS, THESE GUIDANCE THREAT PES TO SLOW RECENT RAPID INNOVATION JUST AS A PROMISE OF PERSONALIZED MEDICINE WHICH WILL SURELY BENEFIT A LARGE NUMBER OF U.S. PATIENTS START TO MATERIALIZE. IN THIS REGARD OUR PRIMARY CONCERNS ARE, ONE, SIGNIFICANT COST REDUCTION IN GENETIC TESTING IS NECESSARY TO FULLY REALIZE ITS BENEFITS TO PATIENT CARE. THIS IS POSSIBLE BY THE USE OF MULTI-ANOLYTE TESTING AND GENETIC ASSAYS WHICH PROVIDE ECONOMIES OF SCALE. HOWEVER, THE CURRENT DRAFT GUIDANCE LARGELY BASED ON THE PARADIGM OF ONE ANOLYTE TO ONE INTENDED USE DOES NOT CONTEMPLATE THESE ASSAYS. WE DO APPRECIATE FDA HOSTING A WORKSHOP TO DISCUSS NEXT GENERATION SEQUENCING PANELS AN ENCOURAGE THE AGENCY TO FULLY VET HOW IT INTENDS TO INTEGRATE MULTIPLE ANALYSIS AND PANELS BEFORE ISSUES FINAL GUIDANCE. TWO, CURRENTLY LABORATORY PROFESSIONALS PERFORM INTERPRETATION OF VARIANTS USING PRACTICE GUIDELINES ESTABLISHED BY MEDICAL ORGANIZATIONS SUCH AS THE AMERICAN COLLEGE OF MEDICAL GENETICS AN GENOMICS AND OTHERS. THE INTERPRETATION PROVIDED BY THESE HIGHLY TRAINED AND QUALIFIED PROFESSIONALS, IS PART OF THE SERVICE PROVIDED BY LABORATORY AND CANNOT BE SEPARATED FROM THE ANALYTICAL PROCESS. ANY PLAN BY FDA TO REGULATE MUST NOT EXTEND TO THE INTERPRETATION OF TEST RESULTS BY TRAINED GENETIC MEDICAL PROFESSIONALS AS THIS CONFLICTS WITH THE PRACTICE OF MEDICINE, LIMITING THEIR ABILITY TO APPLY THIS CONSENSUS GUIDELINES AND THEIR ABILITY TO PROVIDE UP TO DATE STANDARD OF CARE FOR PATIENTS. THREE, THE DRAFT GUIDANCE INDICATE AS NEW SUBMISSION IS REQUIRED FOR SIGNIFICANT MODIFICATION TO CLEAR OR APPROVED LDT. THIS WILL DRAMATICALLY SLOW THE RATE OF INNOVATION IN CLINICAL LABORATORY MEDICINE AND ESSENTIALLY FREEZE IN TIME FOR U.S. PATIENTS. FURTHER, THESE VARIANTS COULD ENCOURAGE EVENVATION TO MOVE -- INNOVATION TO MOVE OUTSIDE THE UNITED STATES. THOUGH WE FIRMLY BELIEVE THE U.S. LABORATORY INDUSTRY SHOULD TAKE THE LEAD IN IMPLEMENTATION OF PERSONALIZED MEDICINE, IN ORDER TO FULFILL OUR MISSION TO MAKE COMPREHENSIVE GENETIC TESTING MORE AFFORDABLE AND ACCESSIBLE, INVEIGH THEY WOULD LIKE TO INTRODUCE IMPROVEMENTS TO THE INTERNATIONAL MARKETS TO OUR LABORATORY LONG BEFORE THEY'RE AVAILABLE IN THE U.S. DUE TO FDA REGULATORY BURDENS. FOUR, THESE REGULATION AS PROPOSED COULD EFFECT TVLY LIMIT PATIENT ACCESS TO NEW GENETIC ASSAY REDUCING NUMBER OF LABORATORIES THAT SUSTAIN INNOVATION. IN ADDITION, THE VERY LIMITED NUMBER OF TESTS THAT WOULD FULFILL THE RARE TEST EXCEPTION AND THE ADMINISTRATIVE BURDEN IMPOSED TO LABORATORIES COULD FORCE REDUCTIONS IN TEST MENUS AND PRICE INCREASES WHICH IN ANKER RA OF DECREASING REIMBURSEMENT FOR LAB TORE TESTS, WOULD LIKELY LEAD TO AN INAPPROPRIATE CONTRACTION OF THE LABORATORY INDUSTRY. AS CURRENTLY DRAFTED FDA PROPOSED OVERSIGHT WILL HAVE UNINTENDED CONSEQUENCES THAT COULD INTERFERE WITH THE PRACTICE OF MEDICINE RESTRICT PATIENT ACCESS TO MUCH NEEDED TESTS AND STIFLE INNOVATION IN THE UNITED STATES. ALTERNATIVELY INVEIGHTY PROPOSE MODERNIZING AND IMPROVING KLIA TO OVERSEE GAPS MEDICINE IS PARAMOUNT TO FIRST DO NO HARM. THANK YOU. [APPLAUSE] >> GOOD MORNING. I'M JAMES PRESCOTT WITH LABS WE'RE A REGIONAL LABORATORY IN TENNESSEE, THANK YOU TO THE FDA FOR TAKING COMMENTS THIS MORNING. I HAVE FOUR POINTS TO MAKE. FIRST THE FDA IS PROPOSING TO IMPLEMENT A REGULAR HATORY SCHEME THAT COULD COST THE U.S. HEALTHCARE SYSTEM HUNDREDS OF MILLIONS IF NOT BILLIONS OF DOLLARS. ASIDE FROM ISOLATE OR ANECDOTAL INSTANCE IT IS FDA IS NOT PROVIDED ANY DATA REGARDING ANY HARM VERSUS BENEFIT OF THE CURRENT ENVIRONMENT OR HOW THE PROPOSED REGULATORY SCHEME MAY PROVIDE SIGNIFICANT IMPROVEMENT IN PATIENT CARE. THERE ARE THOUSANDS OF LABS IN THE U.S. THAT USE LABORATORY DEVELOPED PROCEDURES AND TENS OF THOUSANDS OF PROCEDURES IN USE. IT IS UNCLEAR HOW THE FDA CAN EFFECTIVELY PROCESS HUNDREDS OF APPLICATIONS IN EVEN THE FIRST CATEGORY OF THE PROPOSED REGULATIONS IN A REASONABLE TIME FRAME. THE FDA DATABASE SHOWS ONLY 80 NEW OR REVISED ASSAYS WERE APPROVED IN 20 146789 THE CAP PROFICIENCY TESTING SURVEYS INDICATE THAT THERE ARE 430 LABORATORY DEVELOPED PROCEDURES FOR BRAF EGFR AND KRAS FIVE TIME IT IS THE NUMBER OF ASSAYS. THE ABILITY OF FDA TO IMPLEMENT ITS SOLUTIONS WARNED. SECOND PROPOSED REGULATORY SCHEME IMPEDES USE OF NEWLY DISCOVERED MARKERS DIAGNOSTIC PROGNOSTIC AND THERAPEUTIC INFORMATION TO PATIENTS AND CLINICIANS. THE JACK 2 V 617F VARIANT DISCOVERED IN EARLY 2005 WITHIN SIX MONTHS WAS PROVIDING VALUABLE DIAGNOSTIC INFORMATION. WE ARE SEEING THE SAME PATTERN WITH (INDISCERNIBLE) VARIANT A RAPID ADOPTION BY CLINICIANS TO HELP DIAGNOSE AND PROVIDE THE PROPER TREATMENT FOR PATIENTS, THE PROPOSED REGULATORY FRAMEWORK DELAY THESE ASSAYS BY YEARS, AT POTENTIAL SIGNIFICANT COST THE PATIENTS LIVES AN WELL BEING. THIRD LABORATORIES ARE HEALTHCARE PROVIDERS, NOT MANUFACTURERS WITH WE WORK WITH PARTNER CLINICS TO PROVIDE THE TESTING THEY REQUEST TO HELP TREAT THEIR PARENTS AND OUR PATIENTS. THE PROPOSED REGULATORY FRAMEWORK REQUIRES LABS IN LONGER FOCUS ON PROVIDING QUALITY RESULTS BUT TO SPLIT FOCUS TO INCLUDE AQUA IRING MANUFACTURING EXPERTISE THAT HAS LITTLE TO DO WITH LABORATORY OPERATIONS. THERE IS DATA HOW WELL THEY PERFORM COMPARED TO FDA REVIEW TESTS. A VIDEO FOR PROFICIENCY SURVEY DATA FROM BRAF AN KRS SHOW THE LABORATORY DEVELOPED PROCEDURES PERFORM EXTRAORDINARILY WELL. WHEN COMPARED TO FDA APPROVED COMPANION DIAGNOSTIC TESTS WITH ACCURACY NEAR 100%, A SIGNIFICANT SOURCE OF INACCURACIES IS FDA CLEARED IVD TO INCORRECTLY CLASSIFY CLINICALLY IMPORTANT BRAF VARIANTS. THE SIMPLE REVIEW INSUFFICIENT TO DRAW CONCLUSIONS IT POINTS TO THE POSSIBILITY LABORATORY DEVELOPED PROCEDURES ARE MORE THAN FDA DEVELOPED IVDs. SITTING FOR YESTERDAY AND TODAY IT'S -- I HAVE UNDERSTOOD THAT BETWEEN THIS GUIDANCE AND THE CURRENT IVD REGULATIONS, THE GOAL OF THE FDA IS THAT ALL CLINICAL TESTS HAVE TO BE REVIEWED BY THE FDA. I POSIT THAT IT IS IMPOSSIBLE FOR THE FDA TO HAVE THE EXPERTISE TO JUDGE WHAT IS AN ACCEPTABLE LEVEL OF CLINICAL VALIDITY OF EVERY TEST FOR EVERY USE. THAT KNOWLEDGE IS IMPOUNDED NOT ONLY IN ENTIRE RAN COMMUNITY BUT WITHIN THE PRACTICE OF MEDICINE. THERE IS A POTENTIAL BETTER METHOD ACHIEVING THE GOALS. LABORATORIES REGULATED UNDER CLIA AND STATE HEALTH DEPARTMENTS ADDITION OF THIRD REGULATORY SCHEME SEEMS TO BE ONE OF THE MOST DISRUPTIVE METHODS TO ACHIEVE THE GOAL THAT THE FDA IS OUTLINED. THE FDA SHOULD WORK WITH CMS AND ACCREDITING DEVELOPS TO ENHANCE CLIA. THIS IS A VIABLE MUCH LESS DISRUPTIVE MECHANISM TO ACHIEVE THE FDA STATED GOAL AND FITS INTO A REGULATORY ENVIRONMENT THE LABS HAVE DEMONSTRATED COMPETENCE. THANK YOU VERY MUCH. >> GOOD MORNING, MY NAME IS PAUL RADENSKY, I REPRESENT THE COALITION FOR 21st CENTURY MEDICINE. KNOW A NUMBER OF OUR INDIVIDUAL MEMBERS AS WELL AS ONE OF MY COLLEAGUES ALREADY SPOKE DESCRIBED THE COALITION, TWO POINTS THAT I WANT TO RAISE AS BACKGROUND IS THE COALITION HAS TAKEN NO POSITION ON FDA LEGAL AUTHORITY, LEAVING THAT TO OTHERS TO LOOK INTO. THE COALITION STOOD FOR THE POSITION IT WOULD BE VAST TO REGULATORY SCHEME LIKE THIS CHEWTHROUGH RULE MAKING. THAT'S BENEFICIAL FOR THE REGULATOR AS WELL AS FOR THE STAKEHOLDERS. BUT RECOGNIZING THAT THE AGENCY HAS MOVED FORWARD THROUGH A GUIDANCE PROCESS WE ARE HAPPY TO WORK WITH THE AGENCY TO SEE HOW WE CAN BEST MAKE THIS WORK FOR ALL STAKEHOLDERS. ONE THING THAT COMES OUTS OF A DAY AND A HALF TWO DAY SESSION LIKE TODAY IS THIS IS COMPLICATED AND THERE ARE A NUMBER OF CRITICALLY IMPORTANT ISSUES THAT MUST BE AWE DRESSED, MANY THINGS THAT FDA -- ADDRESSED. MANY THINGS FDA DOES IT GETS THE FEEL THROUGH CASE BY CASE AS IT DETERMINES BY LOOKING AT DIFFERENT DRUGS OR DEVICE WHAT IS IS RIGHT FOR THOSE INDIVIDUAL DRUGS OR DEVICES. BUT FOR FRAMEWORK LIKE THIS, WE CANNOT HAVE IT START A NUMBER OF CRITICAL ISSUES ARE ADDRESSED. IT IS CRITICALLY IMPORTANT STAKEHOLDERS UNDERSTAND WITH FAIR SPECIFICITY WHAT'S REQUIRED WHAT THE DEFINITIONS WILL BE, WHAT IS ABOUT LDT VERSUS NOT LDT, WHAT THE RISK CLASSIFICATIONS ARE LIKELY TO BE. WHAT THE REQUIREMENTS ARE GOING TO BE WITH RESPECT TO QUALITY SYSTEM, WHAT THE ISSUES ARE WITH RESPECT TO PRACTICE OF MEDICINE VERSUS THE PRACTICE OF CREATING A LABORATORY TEST. ALL OF THOSE THINGS REALLY NEED TO BE FAIRLY WELL DEFINED BEFORE GUIDANCE IS FINALIZED AND NOT AS WE GO. WHY IS THAT CRITICALLY IMPORTANT? IF WE DON'T HAVE CLARITY, LABS WON'T KNOW WHAT TO DO. IF WE DON'T HAVE A SUFFICIENT AMOUNT OF TIME THEY WON'T BE ABLE TO IMPLEMENT OR CONDUCT WHATEVER STUDIES, PUT IT TOGETHER TO SUBMIT TO THE FDA. WE KNOW THAT FDA HAS PUT FAIRLY LONG TIME LINE ON THIS, BUT THAT CAN BE A SHORT TIME LINE IF FOR EXAMPLE THE RISK CLASSIFICATION COMES TO SAY YOU NEED TO SUBMIT AND THEN YOU ONLY HAVE A TWO YEAR PERIOD AT THAT POINT IN TIME. IF YOU HAVE A PMA DEVICE TO GET THE QUALITY SYSTEMS UP DURING THAT TIME. WE NEED REGULATION THAT IS RATIONAL AND FAIR, IT NEEDS TO BE REFLECTING WHAT OUR PUBLIC HEALTH CONCERNS AND NEEDS TO BE FAIR TO ALL STAKEHOLDERS INCLUDING LABORATORIES AN MANUFACTURERS. AND WHAT THE REQUIREMENTS ARE FOR THOSE DIFFERENT GROUPS. OTHERWISE WE WILL HAVE SERIOUS UNINTENDED CONSEQUENCES. THOSE UNINTENDED CONSEQUENCES ARE PATIENT SPECIFIC AS BROUGHT UP BY A NUMBER OF STAKE HOLDERS TODAY BUT ALSO INVESTORS WILL SIMPLY NOT INVEST, DEAL WITH THE FACT THERE MIGHT BE UNCERTAINTY SCIENTIFICALLY, IF THERE'S OOH LOT OF UNCERTAINTY FROM REGULATORY PERSPECTIVE THEY'RE NOT GOING TO INVEST. IN ADDITION IF THERE'S UNCERTAINTY AS TO WHERE WE NEED TO BE REGULATED AND WHAT IS OUTSIDE, I CAN TELL YOU FROM A LOT OF EXPERIENCE WE HAVE HAD DEALING WITH INSPECTOR GENERAL'S OFFICE IN DEPARTMENT OF JUSTICE, THEY DON'T UNDERSTAND AND THEY WILL NOT GET WHETHER WHEN WE HAVE AN ISSUE OF SUBSTANTIAL USE OF TEST IS OFF LABEL. TO THE INSPECTOR GENERAL'S OFFICE IF A LOT OF USE OF TEST IS OFF LABEL, PER SE SOMEONE HAS DONE SOMETHING WRONG WE GOT TO GET THIS RIGHT BEFORE THAT CAN BE ADDRESSED. I APPRECIATE THE AGENCY HAS IDENTIFIED SIX OF THE CRITICAL AREASTHEY ARE THE RIGHT CRITICAL AREAS TO FOCUS ON. WE SAY SPECIFICALLY WHAT IS THE DEVICE, QUALITY SYSTEMS THE LABELING VERSUS CLINICAL CONSULTATION AND RISK CLASSIFY CASES ARE KEY THINGS WE MUST GET FURTHER ALONG SUBSTANTIALLY FURTHER ALONG THAN WHERE WITH ARE IN DRAFT GUIDANCE BEFORE THE FDA MOVES FORWARD TO FINALIZE THE GUIDANCE. THANK YOU. >> >> >> MY THANKS TO THE FDA FOR THIS OPPORTUNITY. I'M PROFESSOR PATHOLOGY AT UNIVERSITY OF PITTSBURG, MY AREA IS TRAN PLANTATION PATHOLOGY, I HAVE BEEN PRACTICED 25 YEARS. I PRESENT THE AMERICAN SOCIETY OF TRANS PLANTATION AS A CHAIR OF THEIR TRANSPLANT DIAGNOSTICS COMMITTEE AND OUR SOCIETY HAD OVER SITE ON INTEREST OF 100,000 TRANSPLANT PATIENTS WHO ARE ON THE WAITING LIST TODAY. ON THE LIGHTER SIDE I'M FATHER OF A TEENAGE DAUGHTER WHO LET ME USE THE iPAD TODAY BUT I WILL STICK TO THESE SCRAPS OF PAPER BECAUSE THEY ARE MORE -- (INDISCERNIBLE) I'M GOING TO DIVIDE MY TALK INTO THREE CAT CATEGORIES CORRESPONDING TO LDT CALLED 3, 2, 1. (INDISCERNIBLE) THESE INCLUDE PATHS WITH THE SAME INTENDED USE AS CLEARED OR APPROVED COMPANION DIAGNOSTICS. OUR SOCIETY SUGGESTS THAT THE FDA CONSIDER GRANDFATHERING THOSE TESTS THAT ARE ALL INVALUE AT A TIMED AND PERFORMED IN FULL COMPLIANCE WITH KLIA CAP AND HEALTH DEPARTMENT REQUIREMENTS. IT IS ESSENTIAL THAT BE ALLOWED TO CONTINUE POINTED OUT BY MANY SPEAKERS, OTHERWISE THERE WOULD BE SEVERE DISRUPTION OF MEDICAL CARE. I WOULD SUBMIT THAT NEITHER PATIENT SAFETY NOR THE INTEREST OF THE COMMERCIAL STAKEHOLDERS AD VERILY AFFECTED AS LONG AS THESE ASSAYS USE COMPONENTS WHICH ARE LEGALLY MARKETED WHICH ARE NOT OFFED BEYOND LOCAL POPULATIONS AND NOT MANUFACTURED IN HIGH VOLUME. EVEN THE LOCAL POPULATION CAN BE RELAXED. I BELIEVE IN THE CASE OF -- WHICH ARE BEING OFFERED BY WELL REFUSED ACADEMIC LABORATORY, THERE'S NO REASON THESE CANNOT IMPLEMENT QA PROCESSES COMPARABLE TO THOSE OFFERED BY COMMERCIAL VENDORS. AFTER ALL MANY LDTs WERE IMPLEMENTED BEFORE ANY FDA DOES EVER BECAME AVAILABLE. NOW, WITH REGARD TO -- TO TWO LDTs, I WOULD URGE CONSIDERING THE MEMBERS OF OUR SOCIETY IN SEEKING AS AN ORGANIZATION OF PHYSICIANS, WHICH HAS HUNDRED THOUSAND PATIENTS ON THE TRAN PLANT WAITING LIST, WE HAVE SPECIAL EXPERTISE IN OPPORTUNISTIC PATHOGENS IMMUNE FUNCTION DRUG MONITORING AND RECOGNITION OF COMPLEX DRUG INTERACTIONS IN PATIENTS WHO HAVE TO FOLLOW A BOWL FULL OF PILL EVERY DAY. FINALLY WITH RESPECT TO CLASS ONE, TRANSPLANT PATHOLOGY WOULD LIKE TO STRESS THE NEED TO KEEP IN THIS CATEGORY ROUTINE PATHOLOGY USE THE FROZEN SECTIONS AND MOST IMMUNOHISTOCHEMISTRY IN SITU TECHNIQUES WHICH USE WELL CHARACTERIZED COMMERCIAL REAGENTS. THESE TESTS WERE DEVELOPED IN HOUSE TO MEET NEEDS THAT CANNOT BE REGULATED OR ECONOMICALLY BACKED BY COMMERCIAL HAVE BEEN DOORS. VENDORS. AS FOR THE TESTS OFFERED BY THE LABS I WOULD ASK THE FDA TO CONSIDER KEEPING THESE TESTS IN DISCRETION FOR THE FORESEEABLE FUTURE AND EXEMPT THEM FROM NEW REGISTRATION AND REQUIREMENTS. IN SUMMARY, THE AMERICAN SOCIETY OF TRANSPLANTATION UNDERSTANDS THAT EVERY LABORATORY HAS THE OBLIGATION TO PROVIDE WELL SUMMARIZED CLINICAL CLINICALLY EVALUATED TESTS TO ITS PATIENTS. HOWEVER, ANY NEW REGULATIONS THAT ARE IMPOSED SHOULD BE COMPLIMENTARY TOO AND WITH THOSE ALREADY IN PLACE. THE INTEREST OF SMALL LABORATORIES ACADEMIC INSTITUTIONS, PROFESSIONAL ORGANIZATIONS, AND LARGE COMMERCIAL ENTITIES MUST ALL BE KEPT IN MIND AS WE MOVE FORWARD SUCH AN APPROACH WOULD BE COST AND LABOR EFFICIENT FROM THE FDA AND THE LABORATORIES THAT IT SEEKS REGULARLY SO MY MY THANKS AGAIN FOR THIS OPPORTUNITY TO TALK. >> THANK YOU. WE HAVE SOME TIME BEFORE LUNCH, IS KERRY HERE? TAKE FOUR MINUTES THAT WOULD BE GREAT. I THINK WE'LL HAVE TIME STEPHANIE AND (INDISCERNIBLE) BEFORE LUNCH. >> HELLO, MY NAME IS (INDISCERNIBLE) COUNSELOR AT JOHNS HOPKINS AND TODAY I'M SPEAKING THE NATIONAL SOCIETY OF GENETIC COUNSELOR, AND I USE AN iPAD SO HOPEFULLY TECHNOLOGY GOES WITH ME TODAY. THE NATIONAL SOCIETY OF GENETIC COUNSELORS RECOGNIZE ADVANCES TOWARDS PERSONALIZED MEDICINE SIGNIFICANTLY INCREASE MISAPPLICATION AND MISINTERPRETATION OF GENETIC TESTING, WE ALSO RECOGNIZE THAT AS MORE LABORATORIES OPEN THAT ARE DOORS AND GENETIC TESTING BECOMES A BOOMING BUSINESS, THERE'S THE POSSIBILITY THERE COULD BE LABORATORIES THAT PROVIDE POOR QUALITY RESULTS WHICH AFFECT PATIENT CARE. HISTORIC UTILIZATION OF GENETIC TESTS POSES LOW RISK TO PATIENTS BECAUSE TYPICALLY INVOLVED IN ORDERING TEST. TO CRITICALLY THINK ABOUT QUALITY OF LABORATORY AND GENETIC TESTS REPORT THEY GENERATED. PROVIDE WITH LITTLE OR NO GENETICS TRAINING PROVIDE TRAINING TO AND LIES THE GREATEST RISK. WHILE INCREASED OVERSIGHT AND REGULATION IS IMPORTANT, AS GENETIC TESTING ENTERS TO COMMON DISEASE AND PHARMACO GENETICS, IT CONCERNED STRINGENT REGULATION MAY IMPEDE PATIENT ACCESS TO TEST FOR RARE ORPHAN GENETIC DISEASE AND DEVELOPMENT OF TESTS FOR BROAD POPULATION. THIS MAY PROMOTE LARGER LABS OFFERING LARGER PANELS AND MAY HURT SMALLER LABORATORIES MANY WHOM MAYBE OFFERING BETTER CALL TEST. IF AS A RESULT OF THIS REGULATION LABORATORY STOP OFFERING TESTS THEY WERE PREVIOUSLY OFFERING THIS COULD INADVERTENTLY CAUSE ISSUES WITH TESTING ACCESS DUE TO LACK OF NETWORK INSURANCE COVERAGE. FOR THESE REASONS NSGC SUPPORTS RISK-BASED APPROACH REGULATION OF GENETIC TESTING, GENETIC TESTING SPECIALISTS ARE INVOLVED IN TESTING. IN TERMS OF MEDICAL DEVICE REPORTING, FOR LDTs AND ADVERSE EVENT REPORTING, BELIEVE THIS IS WILL BE CHALLENGING IN TERMS OF APPLICATION TO LDT THAT ARE MOLECULAR AND GENETIC TESTS. FOR YEARS IT HAS TRACKED EVENTS IN DELIVERY OF GENERAL THE SERVICES AS WE PURSUE LICENSES IN STATES A KEY COMPONENT IS TO PROTECT THE PUBLIC, SOMETHING WE SHOULD KEEP IN MIND WHEN IT COMES TO THIS GUIDANCE. IN ORDER TO TRANSLATE IN STATES WE NEED TO DEMONSTRATE HARM. WHAT WE FIND IS LITTLE HARM COMES FROM INVALID LAB RESULTS BUT MISAPPLICATION TECHNOLOGY OR INCORRECT IMPLEMENTATION OF VALID TEST RESULT IN THE PATIENT CARE, THE MAJOR HARM ARE FROM DELIVERY OF HEALTH SYSTEMS OUTSIDE THE FDA REGULATION, NOT IN VALID TEST RESULTS. ANOTHER KEY ISSUE IS ADVERSE EVENTS LIKELY WILL NOT BE READILY KNOWN. AND ADVERSE EVENT FROM A DRUG INTERACTION OR MEDICAL DEVICE IS ALMOST IMMEDIATE IN TERMS OF PATIENT REACTION. IF THERE IS NOT INVALID TEST RESULT OR IF THERE ISN'T A VALID TEST RESULT A FALSE NEGATIVE FOR INSTANCE, MANAGEMENT MAY DICTATE NO THERAPY AND INVALID RESULT MAY NOT BE KNOWN UNTIL LATER WHEN THE DISEASE MANIFESTS ITSELF WHICH COULD BE YEARS OR DECADES LATER. WE WOULD ALSO ADVANCES ARE ENINCURRING DAILY, NEW PANELS AND OTHER TECHNOLOGY IS BEING OFFERED BY COMPANIES AND THEY ARE CHANGING MONTHLY IF NOT MORE SO. ANY REGULATION SHOULD APPRECIATE THE INNOVATION AND SHOULDN'T IMPEDE PROGRESS THAT COULD CREATE MORE HARM THROUGH REGULATION THAN NOT. REGULATIONS NEED TO ENSURE WHATEVER THEY DO THEY DO NOT STIFLE TECHNOLOGY AND GREATLY IMPROVE HEALTH OUTCOMES. THANKS FOR THE OPPORTUNITY TO SPEAK TODAY. >> THANK YOU. IS STEPHANIE HERE? I'M GOING TO TURN OFF THE SCREEN SO YOU GUYS CAN SEE WELL. IT'S NOT ACCURATE. >> GOOD MORNING. I'M STEPHANIE ARNOLD PAGE, DIRECTOR OF POLICY COMMUNICATION AT NATIONAL COALITION OF NTD DIRECTORS. IT'S PARTNERSHIP OF PUBLIC HEALTH PROFESSIONALS DEDICATED TO PROMOTING SEXUAL HEALTH THROUGH PREVENTION OF STDs MEMBERSHIP REPRESENTS STATE, LOCAL AND TERRITORIAL DIRECTORS AND PROGRAMS IN ALL 50 STATES, SEVEN CITY, EIGHT U.S. TERRITORIES ALL PROVIDING FRONT LINE STT PROGRAMS SERVICES AN COMMUNITIES ACROSS THE COUNTRY. LAB DEVELOPED TESTS ARE A PARTICULAR CONCERN TO NCSD MEMBERSHIP AND STD PREVENTION BECAUSE OF THE ISSUE OF EXTRA GENITAL SCREENING FOR STDs, THAT IS TESTING FOR AN STD AT A NON-GENITAL SITE, NAMELY THE PHARYNX OR THE RECTUM. SCREENING OF THE EXTRA GENITAL SITES IS IMPERATIVE TO DEPREVENTION AND YET IN JEOPARDY FOR FRAMEWORK FOR LAB DEVELOPED TESTS. RESEARCH FOUND THAT ONLIER RETHRALL SCREENING FOR CHLAMYDIA AND GONORRHEA WERE CONDUCTED IN MEN WHO HAVE SEX WITH MEN, MOST BACTERIAL INFECTIONS WOULD BE MISSED. SPECIFICALLY 53% CHLAMYDIAL INFECTIONS AND 64% OF GONOCOCAL INFECTIONS WOULD BE MISSED IF URINE ORERRATE THRALL SCREENING WAS PERFORMED FOR MSM. NON-TESTING EXTRA GENITAL INFECTIONS MEAN WE MISLARGE NUMBERS OF ACTIVE INFECTIONS THAT ARE OFTEN ASYMPTOMATIC LEADING TO FURTHER SPREAD OF TWO COMMON AND INCREASING STDs. THE PROBLEM IS THAT AT A PRESENT THERE IS NOT A SINGLE DIAGNOSTIC APPROVED BY THE FDA FOR TESTING IN THIS RECTUM AND THE PHARYNX FOR CHLAMYDIA AND GONORRHEA, THE CDC RECOMMENDS ANNUAL RECTAL AND CHLAMYDIAL TESTING FOR MEN WHO HAD ANAL INTERCOURSE THE PRECEDING YEAR AND GONE RELEASE INFECTION SCREENING FOR MEN WHO HAD RECEPTIVE ORAL INTERCOURSE IN THE PRECEDING YEAR. IN ADDITION THE CDC RECOMMENDS ALL INDIVIDUALS INCLUDING HETEROSEXUALS AT RISK FOR GONORRHEA SHOULD BE SCREENED AT ALL MUCOSAL SITES INCLUDING PHARYNGEAL AND RECTAL SITES. AS WE CONTINUE TO ADDRESS GONORRHEA RESISTANCE, WE NEED TO DO AS MUCH AS WE CAN TO ENSURE ALL AT RISK POPULATIONS WERE RECEIVING APPROPRIATE SCREENING AT ANY SITE EXPOSED TO POTENTIAL INFECTION. BECAUSE OF CDC RECOMMENDATIONS AND OTHER ATTEMPTS TO SCALE UP RECTAL AND PHARYNGEAL SCREENING LABS HAVE INDIVIDUALLY VALIDATED VARIOUS DIAGNOSTIC PLATFORMS APPROVED FOR SPECIMEN TESTING FOR TESTING OTHER ANATOMICAL SITES. WITH GREAT SUCCESS AN EFFECTIVENESS. LABS LED THE EFFORT BECAUSE OF HURDLES SEEKING FORMAL APPROVE FOR THESE ALTERNATIVE SPECIMENS HAVE BEEN PROHIBITED FOR THE DIAGNOSTIC COMPANIES. NCSD STRONGLY BELIEVES THE CURRENT LAB DEVELOP TESTING FOR EXTRA GENITAL SPECIMEN IS MEETING A PROFOUNDLY IMPORTANT AND VEERLY UNMET NEED. UNDER FDA PROPOSED GUIDANCE HOWEVER, ACCESS TO THIS VITALLY NEEDS TESTED WILL BE SEVERELY LIMITED. WHILE NO FDA CLEAR OR APPROVED IVD PRODUCT AVAILABLE FOR SPECIFIC USE OF TESTING IN THE RECTUM OR THE PHARYNX, AND SOME VALIDATIONS MEET THE DEFINITION OF LBT CURRENTLY IN GUIDANCE, THEY'RE NOT BEING CURRENTLY USED IN ONE HEALTHCARE SYSTEM AS FDA CURRENTLY DEFINES IN A HEALTHCARE SYSTEM. IN DETERMINING WHETHER AN LDT IS FOR UNMET NEED NCSD SUGGESTS THE FDA ADD THE FOLLOWING: WHILE THERE'S NO FDA CLEARED OR APPROVED IVD AVAILABLE FOR THAT SPECIFIC INTENDED USE, AND THAT INTENDED USE IS SUPPORTED BY RECOMMENDATIONS CENTERS FOR DISEASE CONTROL AND PREVENTION. NCSD AS LINES ITSELF WITH COMMENTS BY THE APHL ASSOCIATION FOR PUBLIC HEALTH LABORATORIES STATING THAT THE PUBLIC HEALTH LABORATORY SYSTEM IS AN IMPORTANT PART OF THE HEALTHCARE SYSTEM. THANK YOU AGAIN FOR THIS OPPORTUNITY TO SPEAK AND NCSD HOPES ALTERING THE FRAMEWORK THE FDA WILL ENCOURAGE AND NOT HINDER THE ONLY OPTIONS FOR THOSE IN STD PREVENTION CURRENTLY HAVE TO PERFORM DESPERATELY NEEDED EXTRA GENITAL SCREENING. >> THANK YOU. NOW FROM (INDISCERNIBLE). >> THANK YOU FOR HOLDING THIS MEETING GIVE US THE OPPORTUNITY TO COMMENT TODAY. MY NAME IS VANCE SANDERBOM VICE VICE PRESIDENT OF CLINICAL AFFAIRS IN VIRGINIA. I HEARD A NUMBER OF SPEAKERS THE LAST FEW DAYS TWO TALK ABOUT -- LET ME GET THE TECHNOLOGY RIGHT HERE. SHARING DIFFERENCE STORIES ABOUT THE FDA STARTING THEIR EXERCISING THEIR ENFORCEMENT DISCRETION AUTHORITY OVER LDTs, I WOULD LIKE TO SHARE OUR EXPERIENCE WITH THE FDA AND FDA CLEARED LDT FOR A NUMBER OF YEARS AND BEGIN, THIS IS FROM A PERSPECTIVE OF A SINGLE LABORATORY THAT PERFORMS A NUMBER OF HIGH COMPLEX ALGORITHMICALLY DRIVEN TESTS IN PSYCHOLOGY SO I'M NOT IMPLYING THAT OUR EXPERIENCE CAN BE TRANSLATED TO THE SITUATION OF ALL THE PEOPLE ATTENDING THIS MEETING. AJINIA IS ONE OF THE FEW LABORATORIES THAT HAS EXTENTTIVE EXPERIENCE WITH FDA OVERSIGHT OF LDT. OUR MULTI-GENE ASSAY FOR THE EARLY STAGE BREAST CANCER WAS THE FIRST DE NOVO 5, 10 CLEARED ASSAY OF ITS KINDS IN 2007 AND WE OBTAINED FIVE CLEARANCES TO DATE. T THEY SUBMITTED THE ASSAY FOR FDA CLEARANCE IN 2006, AS IT IS OUR STRONG BELIEF THAT FIRST AN FOREMOST PHYSICIANS AND PATIENTS SHOULD BE ABLE TO RELY ON THE TEST SAFETY ABOUT EFFECTIVENESS. ALTHOUGH WE HOLD THE FIRST COMPLEXITY BASED IVD MIA CLEARANCE AGINIA STRONGLY SUPPORT IT IS PROPOSED RISK-BASED REGULATORY APPROACH. WHEN FDA BEGAN REGULATING MEDICAL ADVISERS LETs GENERALLY WERE RELATIVELY SIMPLE LOW RISK TASKS AND FDA EXERCISED ENFORCEMENT DISCRETION BY NOT REGULATING THEM. NOW, LDTs ENCOMPASS THE MOST ADVANCED MOLECULAR DIAGNOSTICS HIGHER RISK TESTS ESSENTIAL FOR SAFE EFFECTIVE USE OF CANCER THERAPIES. CRITICAL DETERMINING THE SERIOUS LIFE THREATENING DISEASES. A BAD TUMOR MARKER TEST IS AS BAD AS A BAD DRUG. WITH THE ROLE DIAGNOSTIC TESTS AND PERSONALIZED MEDICINE WE FEEL THE FDA HAS TO ACT NOW. AN ARGUMENT HEARD OVER THE LAST DAY AND A HALF IS THAT FDA OVERSIGHT WILL HAMPER INNOVATION. IN OUR 7 YEARS EXPERIENCE WORKING WITH THE FDA, THAT'S NOT BEEN OUR EXPERIENCE. BY VALIDATING ANALYTICAL AND CLINICAL VALIDITY AT THE FDA IN OUR VIEW EVALUATE DATA THAT IS OR SHOULD BE AVAILABLE FOR THE TEST -- BEFORE THE TEST HITS THE MARKET IN THE FIRST PLACE. MOST CLEARANCES WERE COMPLETED WITHIN FIVE MONTHS OF THEIR SUBMISSION. WE ALSO HEARD MANY TIMES DURING THIS MEETING, IT'S OUR EXPERIENCE THAT IT'S DIFFICULT FOR PHYSICIANS USING THE TEST RESULTS TO ASSESS THE QUALITY OF A COMPLEX LDT. AT THE END USER LEVEL THERE'S LIMITED KNOWLEDGE OF THE ANALYTICAL AND CLINICAL VALIDITY OF COMPLEX LDT. IN OUR EXPERIENCE FDA CLEARED LDTs ARE NOT FAVORED OVER THE ONES UNDER CLIA. TESTS REVIEWED BY THE FDA HAVE RESTRICTIONS RIGHTED TO THE DATA SUBMITTED IN THAT CLAIM. WITHOUT FDA EXERCISING IS OVERSIGHT OVER LDT WE BELIEVE NEW COMPLEX TESTS WILL CHOOSE TO HOME BREW EXEMPTION AND MARKET THE TEST AS LDT UNDER CLIA FOR THE WRONG REASONS. CALL SYSTEM PROCESS PLAYS AN IMPORTANT ROLE IN DECIDING WHETHER A NEW SUBMISSION IS REQUIRED. IN OUR EXPERIENCE THE FDA QUALITY SYSTEM REGULATIONS REQUIREMENTS PROVIDE A SOLID BASIS FOR ASSURING A DEVICE MODIFICATIONS ARE APPROPRIATELY EVALUATED THROUGH RISK MANAGEMENT PRIOR TO MARKETING AND THAT THE METHODS AND RESULTS OF EVALUATION ARE WELL DOCUMENTED. IN CONCLUSION, I THINK THAT WE HAVE NOT OR EVER WILL REACH CONSENSUS ON ALL LDTs DISCUSSED HERE THE LAST TWO DAY BUS MOST OF YOU WILL AGREE THAT COMPLEX HIGH RISK LDTs NEED THE FALL UNDER FDA OVERSIGHT. WE SUPPORT FDA INTENTION TO ADDRESS HIGH RISK LDTs EARLY ON IN YOUR NINE YEAR PROGRAM WHICH SHOULD IN OUR VIEW INCLUDE ALL ALGORITHMICALLY DRIVEN GENOMIC TESTS. >> WITH THAT WE'LL BREAK FOR LUNCH AND BE BACK HERE AT ONE O'CLOCK. IF YOU ORDERED LUNCH LIKE YESTERDAY, IT WILL BE OUT IN THE LOBBY. THANK YOU. WHICH WOULD BENEFIT CHILDREN IN EMERGING NATIONS. OUR CLINICAL TRIALS IN AFRICA, INDIA, AND PERU HAVE BEEN VERY SUCCESSFUL. IT IS AN INEXPENSIVE TEST AND TAKES LESS THAN TWO HOURS TO PERFORM AND PRODUCE RESULTS. WE USE SOME OF OUR OWN MONEY TO DEVELOP THIS TEST, WHICH IS VERY SENSITIVE AND SPECIFIC. THE FDA WAS EXCITED ABOUT THE TEST AND SAID THEY WOULD FAST-TRACK THE TEST. IT HAS NOW BEEN OVER FOUR YEARS, AND NOTHING HAS HAPPENED. IT SEEMS THAT I HUGE BOTTLE NECK ALREADY EXISTS. WHY ADD TO THAT? THERE ARE ALREADY EXPERTS IN CMS IN NEW YORK STATE WHO PERFORM INTENSE INSPECTIONS. WHY NOT TRUST THEM TO CONTINUE A PROGRAM THAT WORKS? WHY OVER -- WHY OVERLAP WITH AN ADDITIONAL GOVERNMENT AGENCY, WHICH WOULD ONLY ADD COST TO THE TAXPAYERS AND INCREASE INSURANCE COSTS? THIS PROGRAM WILL MAKE IT MORE DIFFICULT FOR PATIENTS AND DOCTORS TO GET THEIR DIAGNOSIS. ADDITIONALLY, INDEPENDENT LABS SUCH AS OURS WOULD NOT HAVE THE TIME OR FINANCIAL RESOURCES TO SUBMIT ALL THE TESTS TO THE FDA. LABS MAY BE FORCED TO CLOSE THEIR DOORS, LEAVING THOUSANDS OF PEOPLE UNEMPLOYED AND ABANDONING POTENTIAL LIFE-SAVING TESTING. I WOULD /HRAOEULIKE TO THANK THE ORGANIZERS FOR THE FORUM AND FOR ALLOWING US TO SPEAK. THANK YOU AGAIN. >> WE'LL MOVE ON TO THE NEXT PERSON THEN? IS LIZ HERE? >> MY NAME IS LIZ AND I'M A INVESTIGATOR -- REGULATOR CONSULTANT. I WORK PREDOMINANTLY WITH EMERGE EMERGING DIAGNOSTICS, WHICH CHOOSE THE THE LD T ROWDY -- ROUTE TO BRING THEIR PRODUCT TO MARKET. THE OPINIONS IN /THIS PRESENTATION ARE MINE. I'D LIKE TO SHARE MY EXPERIENCE WHERE CLINICAL RABBITS MET CHALLENGES. EXISTING CLEAR QUALITY SYSTEMS TO MEET THE QSR REQUIREMENTS. COMMENTS ON THE PROPOSED TIME TIMEFRAME FOR THE QSR FOR DESIGN CONTROLS. CLEAR LABS CAN FIND THE QSR CONFUSING. LIKE MOST QUALITY SYSTEMS REGULATION ARES IT DESCRIBES HOW IT CAN BE ACHIEVED AND NOT HOW TO DO IT. OFTEN THINK THEY HAVE TWO SEPARATE SYSTEMS AND THE CONCEPT OF DESIGN CONTROLS IS USUALLY -- THE INITIAL RESPONSE TENDS TO BE THAT IT'S DIFFERENT FROM THE CLI CLIIA AND TOO TIME-CONSUMING AND EXPENSIVE. I SPOKE OF THE 2010 PUBLIC MEETING ON LD TS AND COMMENTED THAT THE CLEAR REGULATIONS AND THE QSR ARE SEPARATED BY COMMON LANGUAGE. FOR EXAMPLE, VERIFICATION AND VALID /A*EATION MEAN SOMETHING DIFFERENT IN EACH SYSTEM. AND THAT THERE ARE MANY COMMON CONTROLS REQUIRED BY BOTH SYSTEMS, MAKING IT POSSIBLE FOR A CLIIA LAB TO ADDRESS THOSE. SO FOUR YEARS LATER, INTEREST STILL SEEMS TO BE WIDESPREAD CONFUSION OVER HOW THE QSR RELATES TO LD TS AND IF THE FDA WILL BE REGULATING ALL CLIIA RABBIT ACTIVITIES. IF WE LOOK AT THE ACTIVITIES OF QUALITY SYSTEM, THERE IS VERY LITTLE OVERLAP. CLIIA HAS UNIQUE REQUIREMENTS FOR SAMPLING TESTING. THE Q.^R HAS UNIQUE REQUIREMENTS FOR DEVELOPMENT OF THE LD T AND THE MANUFACTURING OF THE TEST COMPONENTS. THE TWO SYSTEMS OVERLAP IN REQUIREM TO ESTABLISH PERFORMANCE OF THE TEST SYSTEMS AND AN /HREALYTICAL AND CLINICAL VALID /A*EATION AND POST MARKET ACTIVITY SUCH AS COMPLIANT HANDLING. THE DESCRIPTION OF THE ACTIVITIES PROVIDED WAS WELL- WELL-PRESENTED IN THE RECENT FDA GUIDANCE BUT I UNDERSTAND IT BECAUSE I'M FAMILIAR WITH FDA TERMINOLOGY. AGAIN, COMMON LANGUAGE DIVIDES US. FOR EXAMPLE, MANUFACTURER, CLIIA LABORATORIES ARE CONFUSED HOW THEY WOULD IMPLEMENT THE MANUFACTURING REQUIREMENTS WHEN THERE ARE TEST COMPONENTS MANUFACTURED BY -- TESTING. HOW CAN WE MINUIMIZE OVERLAPPING CONTROLS TO CREATE A QUALITY SYSTEM THAT'S EASY TO IMPLEMENT AND MANAGE? THE CORE OF THE CLIIA QUALITY SYSTEM AND SAMPLE TESTING PROCEDURES DON'T HAVE TO CHANGE. THE QSR DOESN'T COVER THAT. EXISTING CONTROLS CAN BE USED TO SUPPORT THE QSR ACTIVITIES. FOR EXAMPLE, A DESIGN CONTROL CAN BE CONTROLLED USING THE SAME DOCUMENT CONTROL AS /AA TEST METHOD OF LS T. MOST LABORATORIES HAVE A PROT PROTOCOL TO FOLLOW AND THIS OFTEN CONTAINS SOME OF THE REQUIREMENTS IN DESIGN CONTROLS SUCH AS DEFINING THE TEST PERFORMANCE. REAGENT PREPARATION AND QUALIFICATION CLEAR TERM NOCK FOR MANUFACTURING ARE ALSO IN SE PROPERTICESSES CAN BE MODIFIED TO MEET THE QSR REQUIREMENTS. SOP'S MARKETING ACTIVITIES HAVE TO BE MODIFIED OR IMPLEMENTED TO MEET THE MORE RIGOROUS FDA REQUIREMENTS AND MEDICAL DEVICE REPORTING. I URGE THE FDA TO ENSURE THE REGULATION OF LD TS AND IN INSPECTIONS ONLY COVER QSR ACTIVITIES AND NOT CLIIA ACTIVITIES. A COMMENT ABOUT THE STAGE AND THE Q.^R. THE YEARS WE'VE BEEN DISCUSSING REGULATORY PLAYING FIELD FOR MANUFACTURERS IN CLIIA LABS. FDA OVERSIGHT WILL LEVEL THE PLAYING FIELD. DESIGN CONTROLS ARE KEY TONE SURING A ROBUST STATE EFFECT AND ANDIVE TEST AND MOST OF THE FAILURES THAT I'VE SEEN MAY HAVE BEEN AVERTED IF DESIGN CONTROLS HAD BEEN IN PLACE. THEREFORE, I URGE THE AGENCY TON DELAY THE ENFORCEMENT DESIGN CONTROLS TO HIGH-RISK TESTS AND POTENTIALLY ININTRODUCE A -- IN INDUCE A SYSTEM FOR P.M.AS. THANK YOU FOR THE OPPORTUNITY. >> THANK YOU FOR THE OPPORTUNITY TO DISCUSS WITH YOU THIS AFTERNOON A FEW COMMENTS REGARDING THE GUIDANCE DOCUMENT. MY NAME IS ROBIN STOMBL ER AER AND I'M PRESIDENT OF ALLBURN HEALTH STRATEGIES AND SPEAKING TODAY ON BEHALF OF MICROBIOLODGICS, BASED IN ST. CROWD, MINNESOTA, IS A IT PROVIDES READY-TO-USE QUALITY CONTROL MICROORGANISMS FOR ACT ACTING DEVELOPMENT, INSTRUMENT VALID /A*EATION AND ROUTINE QUALITY CONTROL TESTING OF DIAGNOSTICS A ASSAYS IN CLINICAL LABORATORIES AS WELL AS OTHER INDUSTRIES. QUALITY CONTROL IS A PROCESS USED TO ASSESS THE QUALITY AND RE/RAOEUBLT OF /AA LABORATORYS TEST RESULT. LABORATORIES USE BIOLOGICAL REFERENCE MATERIALS TO EVALUATE PERFORMANCE OF IN VITRO DIAGNOSTIC DEVICES THAT ARE UT UTILIZED IN HUMAN DISEASE DIAGNOSIS AND TREATMENT. IT IS CRITICAL TO KNOW IF THE TEST RESULT REPORTED IS VALID. VALID /A*EATION THROUGH QUALITY CONTROL WILL HELP PINPOINT POSSIBLE FAILURE IN TEST SYSTEMS SYSTEMS, METHODS, ENVIRONMENTAL CONDITIONS AND LABORATORY PERSONNEL PERFORMANCE. LD TS, LIKE OTHER LABORATORY TESTS, NEED VALID /A*EATION BEFORE RESULTS ARE REPORTED. MICROBIOLODGICS WOULD LIKE TO RAISE TWO ISSUES WITH REGARD TO THE FDA ON THE REGULATORY OVER OVERSIGHT FRAMEWORK OF LD T. FIRST, WE WOULD /HRAOEULIKE TO CLARIFY THE USE OF QUALITY CONTROL AND THE USE OF LD TS. LD TS ARE CONSIDERED HIGH- HIGH-COMPLEXITY TESTS UNDER /THE IMPROVEMENT AMENDMENTS OF 1988. LABORATORIES PERFORMING TESTS OF HIGH COMPLEXITY MUST MEET QUALITY CONTROL REQUIREMENTS TOTO ENSURE AN /HREALYTICAL VALIDITY. HIGH FLEXITY LABORATORY DIRECTOR WILL ESTABLISH AND MAINTAIN A QUALITY CONTROL PROGRAM SO THAT RELIABLE LABORATORY SERVICES ARE PROVIDED AND ANY FAILURES ARE IDENTIFIED AS THEY OCCUR. IT IS OUR UNDERSTANDING THAT THIS ROUTINE VALID /A*EATION PROCESS, USING QUALITY CONTROL, WILL NOT CHANGE FOR LD TS. HOWEVER, UNDER /THE FDA DRAFT ANCE, THERE ARE CIRCUMSTANCES WHEREBY LABORATORY DEVELOPED TESTS SHOULD BE REVIEWED FOR PERFORMANCE CHARACTERISTICS, INCLUDING AN LITICAL SPEC /TPEIFICITY AND SENSE ECISION IN DESIGN AND SENSITIVITY, THE ACCURACY AND MANUFACTURING PRIOR TO MARKETING FOR CLINICAL USE. IT WILL BE NECESSARY TO ENSURE VALIDITY OF THESE DEVICES WITH THE USE OF STANDARD /AOEUIZED BIOLOGICAL REFERENCE MATERIALS. IT IS OUR UNDERING THAT THE ROLE OF QUALITY CONTROL UNDER CLIIA AND THE USE OF STANDARD REFERENCE MATERIALS UNDER /THE FDA DRAFT GUIDANCE ARE SEPARATE AND DISTINCT. THE ROLE OF ONE IS NOT INTENDED TO USE DUPLICATE THE ROLE OF THE OTHER. IN OTHER WORDS, FDA APPROVAL OF A LABORATORY-DEVELOPED TEST WOULD NOT EXEMPT CONTROL. SECOND, AN ISSUE THAT IS NOT DISCUSSED IN THE DRAFT GUIDANCE IS THE USE OF CERTIFIED REFERENCE MATERIALS OR C /R-FPR MS, WHICH ARE HIGHLY CHARACTERIZED HOMO/OPBGENOUS AUTHENTICATED CONTROLLED MATERIAL. LABORATORIES HAVE OPTION FOR OB OBTAINING MATERIALS. BUT NOT ALL OF THESE OPTIONS ARE WELL-CHARACTERIZED OR AUTHENT AUTHENTICATED. HIGHLY EFFECT /KWREUIVE STANDARDS IN LABORATORY TESTING AS WELL AS IN RESEARCH AND DEVELOPMENT. REFERENCE MATERIAL PROVIDERS SUCH AS MICROBIOLODGICS ARE A ACCREDITED UNDER ISO 34, 2009, WHICH IS AN INTERNATIONALLY RECOGNIZED BENCHMARK TO CERTIF3 THAT THEIR STANDARDS ARE PROVEN TO BE ACCURATE. TO ASSESS THE QUALITY OF METHOD VALID /A*EATION AND TO TRACE TO AN ESTABLISHED STANDARD, THEY ARE OFTEN USED BY LABORATORIES AND MANUFACTURERS ALIKE. THEY ALSO SERVE TO MEET THE REQUIREMENTS OF ISO 17025. IS-- ISO 15189 ACCREDITED RABBIT RABBIT. PLAY PROVIDE CONFIDENCE IN RESULTS WHEN LABORATORIES ARE VALID /A*ATING AND VERIFYING PROCESS PROCESSES AND INSTRUMENTS TO LD TS. SUGGESTING THE USE OF C /R-FPR MS, WHEN APPROPRIATE WITHIN THE FDA FDA'S RISK FRAMER -- FRAMEWORK, MAY BE OF BENEFIT TO PATIENTS, LABORATORIES AND MANUFACTURERS. THANK YOU AGAIN FOR THIS OP TO PRESENT ON BEHALF OF MICROBIOLODGICS. WE LOOK FORWARD TO CONTINUING TO WORK WITH YOU IN PURSUIT OF /AEA SAFER, HEALTHIER WORLD. >> THANK YOU. AND WE'LL HAVE SHE'ILA -- IS DAVID HERE? ANNA? MAKE YOUR WAY TO THE SIDE AND GET READY, THAT WOULD BE GREAT. >> GOOD AFTERNOON. MY NAMES CAKATHERINETINEAN. I HAVE A PH.D IN HUMAN GENETICS. IN THE PAST 30 YEARS MY PROFESSIONAL CAREER HAS EN/KOPL ENCOMPASSED BEING A LABORATORY DIRECTOR AND DEVELOPING LIFE SCIENTISTS RESEARCH PRODUCTS AND DIAGNOSTICS. IN THE LAST TEN YEARS I'VE BEEN A CONSULTANT ON STRATEGY AND DEVELOPMENT OPERATIONS. MY ADVICE TO MY CLIENTS, WHEN DEVELOPING NEW CLINICAL DIAGNOSTICS PRODUCTS, IS TO INVEST IN /AA QUALITY SYSTEM AND DESIGN THEIR PRODUCTS UNDER /THE DESIGN CONTROL. THIS IS AN SENSE -- EXPENSIVE PROPOSITION FOR MANY OF THEM AS IMPLEMENTATION /UPLZ -- COMES AT A COST BOTH IN TERMS OF TIME AND CAPITAL AND MILLIONS OF DOLLARS TO THE PRODUCT DEVELOPMENT TIME TIMELINE. QUALIFICATIONS VARY SIGNIFICANTLY AND ONE /OF MY CONCERNS OF THE CURRENT DIALOGUE BETWEEN THE FDA AND LABORATORIES IS /THE QUALITY MEANS VERY DIFFERENT THINGS. MY RECOMMENDATIONS, THEREFORE, ARE THAT ONE, WE SHOULD DEVELOP A COMMON VOCABULARY THAT IS MEANINGFUL TO BOTH SIDES. THE FDA SHOULD PROVIDE TRAINING TO SPREAD THEIR QUALITY KNOWLEDGE TO THE BASE -- QUALITY KNOWLEDGE BASE TO THE LABORATORY COMMUNITY. SISTER VERSA. I THINK LABORATORIES SHOULD READ SOME OF THE FDA LITERATURE, SPECIFICALLY -- SPECIFICALLY THE CLEARANCE AND APPROVALS OF PRODUCTS THAT ARE RELEVANT. SECONDLY, I THINK WE SHOULD -- THE FDA SHOULD CHOOSE A QUALITY SYSTEM THAT FITS THE PURPOSE. MY /SREPLS THAT THE EVOLVING INTERNATIONAL ISO STANDARD MIGHT BE A GOOD HARMONIZING FOCUS AND WOULD WORK -- THEY SHOULD WORK TO IN/KRORCORPORATE THE STANDARDS AND FDA DESIGN CONTROL PRACTICES, WHERE APPROPRIATE. QSRS, ARE A LITTLE TOO CURVE CUMBERSOME FOR LABORATORIES AND /TPRA*PBFRANKLY THERE ARE NOT ENOUGH PEOPLE WITH REGULATORY EXPERTS AVAILABLE TO HELP THESE LABORATORIES IN /TS TRANSITION. I URGE THE FDA TO RECOGNIZE THAT THIS IS A SIGNIFICANT UNFUNDED MANDATE FOR LABORATORIES AND YOU SHOULD USE YOUR INFLUENCE TO RAISE THIS ISSUE WITH CMS. LABORATORIES ARE UNDER HUGE FINANCIAL CONSTRAINTS AND THIS IS EXACERBATED BY POOR RIM BURSEMENTS FOR MANY TESTS. AS TO WHY THEY SHOULD PAY FOR QUALITY IF YOU MOVE FORWARD WITH THIS. I THINK ALSO THAT THE FDA SHOULD ACKNOWLEDGE THE FACT THAT THE SCIENCE IS CHANGING RAPIDLY IN THE INHERENT GENETIC DISEASE AREA. I THINK THIS IS IN LINE WITH RECENTLY RELEASED IN TERMS OF THE ASSAYS AND THE SEQUENCING KIT. YOU SHOULD RELY ON THE EXPERTISE OF CLINICAL MEDICINE -- MEDICAL COMMUNITY TO INTERPRET THE VALID VALIDITY AND YOU SHOULD PROMOTE THE USE OF DATABASE, ET CETERA, AS /AA WAY OF IMPROVING PATIENT SAFETY. I THINK YOU SHOULD NOTE THAT DR. RUBENSTEIN EATS COMMENTS EARLIER ABOUT THE UNIFYING GENOME TEST TESTING FOR RARE DISEASES WILL MAKE TESTING FOR THESE COMMUNITIES QUITE COMMON. I THINK ALSO NUMBER FIVE, YOU SHOULD CONCEIVE THE FACT THAT THE SCIENCE FIELD IS MOVING SO QUICKLY THAT THERE IS NO WAY FOR INDIVIDUAL TESTS REQUIRING P.M.A LEVEL SUBMISSIONS TO KEEP UP WITH THESE ADVANCES. THE PLATFORMS AND THE MOREOVER, LABORATORIES CANNOT SAMPLE THEMSELVES ARE OFTEN TOO SMALL AND LIMIT ING ING TO SUPPORT THE MULTITUDE OF TESTS THAT ARE DICTATED BY CURRENT PRACTICES. AGAIN, REGULATE MANY OF THESE MULTIMUTATION TESTS AT THE LEVEL AND USE YOUR INFLUENCE WITH THE NCI AND NIH TO DEVELOP A NATIONAL REGISTRY DATABASE TO TRACK PATIENTS -- PATIENTOUT -- OUTCOME AND MONITOR PATIENT SAFETY. THANK YOU FOR THE OPPORTUNITY TO COMMENT. >> /TKPWAOFRPB. MY NAME IS JILL WO-- WAL COUGH AND I'M THE CONSULTANT OF STRATEGIES RELATED TO POLICY AND DIAGNOSTICS. I AM SPEAKING TODAY ON BEHALF OF THE COALITION FOR 21ST CENTURY MEDICINE AND I APPRECIATE THE OPPORTUNITY TO EXPRESS IS A FEW POINTS TO YOUR CONSIDERATION AND RESPOND TO THE QUESTIONS REGARDING THE APPLICATION OF THE FDA QUALITY SYSTEMS REGULATIONS TO LABORATORY DEVELOPED TESTS. THE COALITION FOR MEDICINE COMPRISES OF THE WORLD'S ON A INNOVATIVE DIAGNOSTIC COMPANIES, LABORATORIES AND PATIENT GROUPS WORKING TO SUPPORT THE APPROPRIATE REGULATORY OVERSIGHT AND REIMBURSEMENT POLICIES TO PROMOTE ONINNOVATION AND DEVELOPMENT IN THE USE OF ADVANCED PERSONALIZED DIAGNOSTIC TESTING. THE OVERARCHING POSITION IS THAT FDA MUST ADDRESS THE KEY UNRE UNRESOLVED ISSUES ESSENTIAL TO ENABLING LABS TO COMPLY -- COMPLY WITH THESE NEW REQUIREMENTS PRIOR TO FINALIZING REQUIREMENTS. THE SIGNIFICANT CHALLENGE OWE OCCURRING ARE MUCH LIKELY TO BECOME THE NEW REALITY ABSENT DETAILS OF /KPWAOEUPBS DEVELOPED WITH LABORATORY IN/PPUT BEFORE THE PROPOSED FRAMEWORK IS FINALIZED AND COMPLIANCE BEGINS. THE COALITION'S POSITION ON REGULATORY AUTHORITY AND USE OF COMMENT ROLE MAKING HAVE ALREADY BEEN CREASED SO I'D LIKE TO FOCUS ON THE QSR ISSUE. IN THE DRAFT GUIDANCE, FDA PROPOSES TO REQUIRE A VAST VARIETY OF LABORATORIES TO COMPLYWITH QSR TO PROVIDE DETAIL ON HOW THE REQUIREMENTS WILL BE APPLIED TO LD TS GENERALLY AND TO DIFFERENT LABORATORIES MORE SPECIFICALLY. WHILE THE COALITION APPRECIATES AND UNDERSTANDS THE NEEDS IN HOW A LAB MIGHT CHOOSE TO COMPLY, LABS BE ARE ALREADY SETTING REGULATIONS AND OFTEN SEEK ADDITIONAL CERTIFICATIONS, AS WE'VE HEARD MANY TIMES TODAY. IT IS ESSENTIAL THAT FDA HARMON HARMONIZE THE REQUIREMENTS AT A MORE GRANULE LAR LEVEL. IN RESPONSE TO THE QUESTIONS THAT YOU IDENTIFIED FOR THIS SEG SEGMENT OF THE WORKSHOP, I ASK THAT THE FOLLOWING SUGGESTIONS. C 21 URGES FDA TO PROVIDE A ROAD MAP AND DEFINE WITH LAB AND CMS IN/PPUT. AS /AA FIRST STEP IT IS IM/PEPERATIVE FOR THE DEVELOPMENT OF A FLEXIBLE REGULATORY SYSTEM THAT FDA CONDUCT AND PUBLISH AN EXPENSIVE SIDE-BY-SIDE COMPARISON OF REGULATIONS. ADDITIONALLY AT A MINUIMUM, FDA SHOULD PUBLISH REVISED DRAFT GUIDANCE OUTLINITHE AP AP/KAEUGTSS TO LABORATORIES THAT DEVELOP LD TS. FDA SHOULD RELY ON CLEAR REQUIREMENTS AND FDA SHOULD LIMIT THE REQUIREMENTS FOR Q.^R REQUIREMENTS FOR THE PART OF THE LAB TEST SERVICE THAT COMPRISES THE VIRTUAL DEVICE, CONSISTENT WITH THE RECOMMENDATIONS FOR THAT DEFINITION, BY WE WILL PROVIDE IN OUR WRITTEN COMMENTS. THE ADDITIONAL DRAFT GUIDANCE SHOULD PROPOSE A STRAIGHTFORWARD CROSSWALK IN -- AND OTHER MEANINGFUL TOOLS WITH MULTIPLE REGULATIONS SUCH AS FORMATS AND CHECKLISTS VERIFYING WHICH EXIST EXISTING LABORATORY VERIFICATION VERIFICATIONS WOULD BE SUFFICIENT FOR FDA PURPOSES. IN ITS IMPLEMENTATION AND ENFORCEMENT PRACTICE TO THE NEW NEWLY TAILORED QSR, FDA SHOULD MAXIMIZE THE THIRD PARTY CERTIFICATIONS BY RELYING ON AGENCIES AND THE USE OF ESTABLISHED CERTIFYING ENTITIES AS POSSIBLE. HOWEVER, NEW TRAINING FOR /EUPB INSPECTORS WILL BE ESSENTIAL. FOR ANY AREAS WHERE THERE IS CONFLICT BETWEEN FDA AND CLIIA REGULATIONS, THE AGENCY SHOULD PROVIDE SPECIFIC GUIDANCE FOR ADDRESSING SUCH CONFLICT IN THE REGULATION. FOR AREAS WHERE FDA BELIEVES THAT THE REGULATORY REQUIREMENTS ALREADY IN PRAISE ARE IN INSUFFICIENT TO COMPLY WITH SYSTEMS, SPECIFIC GUIDANCE SHOULD BE AVAILABLE. TO ENSURE THAT THE REGULATORY BURDEN IS IDENTIFIED AND SHOULD PROVIDE A CHECKLIST FOR CANCE AND THIS PROCESS THE SHOULD INCLUDE LAB INSPECTIONS. LASTLY, THE FDA SHOULD DEVELOP A PROGRAM TO ENSURE THAT IN INSPECTORS ARE TRAINED TO COVER THE INSPECTION S S IN WHICH THERE WOULD BE HEALTHY FOR BOTH CLIIA AND FDA AND LIMITED TO PART OF THE TEST SERVICE. AND WE ROOK FORWARD TO PROVIDING YOU MORE DETAIL IN OUR WRITTEN COMMENTS AND I THANK YOU VERY MUCH FOR YOUR /WEUWILLINGNESS TO WORK WITH US ON THIS AND FOR HAVING US TODAY. >> THANK YOU. >> WE'RE NOW GOING TO MOVE /OON TO DAVID -- IS HE HERE YET? IF NOT, THEN LET'S GO ON TO JOSEPH -- I'M SORRY. >> IT WAS A VERY GOOD TRY AND CERTAINLY NOT THE WORST THING THAT HAS EVER BEEN DONE TO MY I'M THE EXECUTIVE VICE PRESIDENT OF THE AMERICAN SOCIETY OF HUMAN GENETICS, THE LARGEST IN THE WORLD. WE HAVE 8,000 MEMBERS. ABOUT 75 /P-FRTS THEM IDENTIFY THEMSELVES AS RESEARCHERS. MOST OUR MEMBERS ARE IN ACADEMIC SETTINGS. ABOUT 25% OF THEM IDENTIFY THEMSELVES AS HAVING PRIMARY CLINICAL RESPONSIBIES. THEY ARE ENGAGED IN THE DEVELOPMENT OF NEW KNOWLEDGE AND TECHNOLOGY AND ALL AREAS OF GENT GENETICS, INCLUDING LD TS. OUR COMMENTS DERIVE FROM THE RECOGNITION THAT FDA IS THE STILL ACTIVELY EVALUATING THE NATURE OF GENETIC AND GENOMIC TESTS. WE WONDER WHETHER OR NOT WHETHER OR NOT -- WHETHER THE SCHEME IS PREMATURE, IN SO FAR AS THE IT'S AFFECTS GENETIC TESTING. FDA DEFINES AN LD T AS AN /EUINVI INVITRODIAGNOSTIC DEVICE INTEND FOR CLINICAL USE. WE ARE CONCERNED THAT THE MEANING OF CLINICAL USE AND THE PROCESS FOR ASSESSING INTENT ARE UNCLEAR WHEN APPLIED TO GENOMICS GENOMICS. THIS LACK OF CLARITY RAISES SUB SUB/SEUD /KWRSIDIARY CONCERNS ABOUT FDA'S VIEW OF GENOMICS AND ASUMMITSS IN PROPOSE ING ING TO REGULATE TASAS A MEDICAL PRODUCT. SOMETIMES GENOMICS INVOLVES PRODUCTS THAT ARE SUITABLE FOR FDA REGULATION, BUT OTHER TIMES IT INVOLVES THE PRACTICE OF MEDICINE, AS WE'VE HEARD ON A NUMBER OF OWE /KAEUGTSS, OR FORMS OF RESEARCH AND SCIENTIFIC SPEECH THAT LIKELY LIE OUTSIDE FDA'S REGULATORY AUTHORITY. THE PROSPECTIVE REGULATION OF GENOMICS AS /AEA MEDICAL PRODUCT ALSO RAISES A SET /OF NOT AS LARY LEGAL ISSUES THAT HAVE BEEN -- IMPLICATIONS THE GUIDANCE HAS NOT ADEQUATELY EXPLORED. OUR RECOMMENDATION IS SIMPLY THAT FDA DEFINE CLINICAL USE MORE PRECISELY. SECOND, ALTHOUGH WE RECOGNIZE THAT IT'S APPROPRIATE FOR FDA TO ENSURE THE AN /HREALYTICAL VALIDITY OF PRODUCTS THAT DETECT THE VARIANCE OF PATIENT OR RESEARCH SUBJECT MAY POSSESS, WE RECOMMEND THAT THE AGENCY NOT ATTEMPT TO REGULATE THE PROVISION OF INFORMATION THAT DERIVES FROM THOSE TESTS. THE DRAFT GUIDANCE USED DIRECTED LD TS USED IN A CLINICAL USE -- SETTING. WE APPRECIATE THE AGENCY'S EFFORTS TO CLASSIFY -- CLARIFY IMPLICATION FORS RESEARCH, BUT APPROPRIATE POLICY ON GENOMIC RESEARCH REQUIRES A MORE NUANCE NUANCEED AND DELIBERATE ANALYSIS THAN IS POSSIBLE AS SORT OF AN AFTERTHOUGHT OR AN APPENDAGE TO THE GUIDANCE. APPLICATION OF THIS DRAFT GUIDANCE TO GENOMIC RESEARCH RISKS SERIOUS UNINTENDED CON CONSEQUENCES. AN EXAMPLE IS ON PAGE 37 OF THE GUIDANCE, WHICH STATES THAT THE FDA'S INVESTIGATIONAL DEVICE EX EXEMPTION REGULATIONS WILL APPLY IF TEST RESULTS ARE RETURNED TO PATIENTS WITHOUT CONFIRMATION BY A MEDICALLY ACCEPTED DIAGNOSTIC PRODUCT OR PROCEDURE." THIS STRICT UR HOLD OF PROCESS OF RETURNING RESULTS IN THE RESEARCH SETTING WHERE CONFIRMAT CONFIRMATTRY PRODUCTS AND PROCEDURES MAY NOT EXIST. RESEARCH SUBJECTS HAVE ETHICALLY -- ETHICAL AND LEGAL PRIVACY RIGHTS TO REQUEST INFORMATION THAT RESEARCH TESTING HAS REVEALED ABOUT THEM AND POLICIES THAT LACK THE RETURN OF RESULTS COULD IMPEDE THE GENOMIC RESEARCH ENTERPRISE. SO OUR RECOMMENDATION HERE IS THAT FDA SEVER ISSUES RELATED TO RESEARCH, USES OF GENOMIC TEST TESTING FOR MORE FOCUSED CONSIDERATION AND /AA LIKELY PLATES TO DO THAT IS IN THE UPCOMING CONVERSATION ABOUT NEXT NEXGEN SEQUENCING AND GENETIC TEST BASED ON THAT PROCESS. LAST, WE BELIEVE THAT FDA IS OVERLY OPTIMISTIC IN ITS ASSUMPTION THAT IT CAN ESTABLISH CLINICAL VALIDITY FOR MOST DNA VARIANCE ON LITERATURE IN A TIME TIMELY MANNER. IN THE FORESEEABLE FUTURE, THERE SIMPLY WILL NOT HAVE NOT BE SUB SUBSTANTIVE LITERATURE THAT EXPLAINS THE MAN IS FOR MOST. SO I AM RUNNING OUT /OF TIME AND I WILL SIMPLY RECOMMEND HERE THAT FDA SUPPORT POST MARKET DATA, COLLECTION AND ANALYSIS TO HELP ESTABLISH CLINICAL VALIDITY OF GENETIC TESTS. WE LOOK FORWARD TO MAKING THE EXPERTISE OF OUR MEMBERSHIP AVAILABLE TO FDA, AS YOU WORK THROUGH THESE ISSUES. THANK YOU. >> THANK YOU, ANNA? >> HI. THANK YOU VERY MUCH FOR THE OPPORTUNITY TO SPEAK TODAY AT THE -- AT /THIS VERY IMPORTANT MEETING. MY NAME IS ANNA AND I AM SPEAKING ON BEHALF OF THE NATIONAL SUMMERTIME FOR HEALTH RESEARCH.^ A LITTLE BACKGROUND. I RECEIVED MY PH.D IN CELL BIOLOGY FROM HARVARD MEDICAL SCHOOL AND CONDUCTED RESEARCH HERE AT THE NIH. NICE TO BE BACK. OUR NONPROFIT ORGANIZATION CONDUCTS RESEARCH, SCRUTINIZES DATA AND THE LITERATURE AND THEN EXPLAINS THE EVIDENCE OF RISKS AND BENEFITS TO /SPAEURBTS -- PATIENTS AND PROVIDERS. SO I AM SPEAKING TODAY AS /AA SCIENTIST WHO APPRECIATES THE POWER OF DATA BUT WHO ALSO WANTS PATIENTS AND FIPHYSICIANS TO HAVE THE BEST POSSIBLE INFORMATION THAT THEY NEED WHEN THEY HAVE TO MAKE POTENTIALLY CRITICAL MEDICAL DECISIONS. THE FDA RELEASED THIS NEW GUIDANCE ON LABORATORY DEVELOPED TESTS BECAUSE OF EVIDENCE THAT PATIENTS WERE HARM BY FAULTY TESTS. AND SO WE WANT /TO APPLAUD THE FDA FOR THEIR PLAN TO IM/PROPROVE OVERSIGHT OF LAB TESTS AND THE NIH FOR THEIR COMMITMENT TO MEDICAL CARE. WE HAVE A FEW -- MANY OF THESE TESTS ARE USED TO DIAGNOSE THE DISEASE OR DETERMINE A COURSE OF TREATMENT. IF A TEST DOESN'T WORK CORRECT CORRECTLY, A PATIENT MAY BE EXPOSED TO RISKS FRAY TREATMENT THEY DIDN'T NEED OR NOT RECEIVE A TREATMENT THAT WOULD HAVE HELPED THEM. IN ADDITION, WHEN THE FDA START STARTED REGULATING MEDICAL DEVICES ALMOST 40 YEARS AGO, THESE TESTS WERE VERY DIFFERENT. THEY ARE NOW WIDESPREAD AND ARE THE BASIS OF SOMETIMES HIGH-RISK DECISIONS. UNDER CLIIA, TEST MAKERS DO NOT HAVE TO DEMONSTRATE CLINICAL VALIDITY. AT FDA, APPROVAL STANDARDS INCLUDE SAFETY AND EFFECTIVENESS EFFECTIVENESS. FDA REVIEW WOULD IM/PROPROVE TRANS TRANS/PAEURPPARENCY AND DATA QUALITY. AND LASTLY, CURRENT POLICIES DO NOT REQUIRE ADVERSE EVENT REPORTING OR MANUFACTURING SAFEGUARDS. FDA APPROVAL DOES. PATIENTS USING HIGH-RISK DIAGNOSTICS DESERVE THESE PROTECTIONS. OUR SENSOR HAS FREQUENTLY URGED THE FDA TO IM/PROPROVE OVERSIGHT OF MEDICAL DEVICES. WE BELIEVE IT IS ESSENTIAL THAT FDA HAVE THE AUTHORITY TO REGULATE LABORATORY DEVELOPED TESTS IN ORDER TO STIMULATE EVEN BETTER SCIENCE AND HELP ENSURE THAT PATIENTS RECEIVE THE FULL BENEFIT OF OUR GROWING SCIENTIFIC KNOWLEDGE AND JUST TO PARAPHRASE THE RECENT J"JAMA" ARTICLE BY DR. SHARP, PATIENTS TRAVEL IN AMBULANCES THAT ARE REGULATED. SO HOSPITALS THAT ARE REGULATED AND CARE USING MEDICINES THAT ARE REGULATED AND ADMINISTERED BY NURSES AND FIPHYSICIANS WHO ARE /ROEGT -- REGULATED. THAT SAME PATIENT'S LIFE OR DEATH SHOULD NOT DEPEND ON WHETHER AN UNREGULATED DIAGNOSTIC RESULT IS ACCURATE. THANK YOU. /PHRA [APPLAUSE] >> THANK YOU. IS DAVID SMALLEY HERE YET? OKAY, WE'LL MOVE /OON TO PANEL 6. IF YOU ALL COULD MAKE YOUR WAY UP, THAT WOULD BE MODERATE BID LARRY BRODY FROM NIH. AFTER THAT PANEL, THEN DAVID SMALLEY WILL PROVIDE COMMENTS AND THEN WE'LL CLOSING REMARKS FROM DR. SHARON. >> WELCOME. THIS IS THE /HRALAST PANEL. I SEE WEARY FACES OF TWO DAYS. TWO /STKAEUSZ LANGUAGE -- RONG TIME TO BE HERE. I AM LARRY BRODY AND DIRECTOR OF THE HUMAN GENOME WITH RESEARCH INSTITUTE. I ALSO RUN A RESEARCH LAB IN WHICH I'VE USED LD TS TO DEVELOP RESULTS IN PART OF RESEARCH. I WILL BE THE MORD -- MODERATOR FOR THIS AND WE WILL MOSTLY FOCUS ON THE /HRALAST 3 OF THE QUESTIONS AND I'LL START BY READING THEM. AND THEN I WILL TRY TO KEEP THE DISCUSSION GOING. THE FIRST QUESTION THAT WE WANT WANTED TO FOCUS ON WAS "ARE THERE FDA QS REQUIREMENTS DIFFERENT FROM CLIIA REQUIREMENTS?" YOU HEARD ABOUT THE RECENT COMMENTS. AND "THE FDA SHOULD CONTINUE NOT TO NORSE THOSE BY CLIIA?" AND WE COULD GO THROUGH THE TABLE FOR THOSE OF YOU WHO WANT /TO RESPOND TO THE FIRST ONE. IT LOOKS LIKE ANDREW IS READY. >> SHOULD WE INTRODUCE OURSELVES OR NOT? >> YES. WHY DON'T WE GO -- >> OKAY. >> HELLO AGAIN. MY NAME IS GAIL, THE PROFESSOR OF MEDICAL AND MOLECULAR GENT GENETICS AND PATHOLOGY AT INDIAN INDIANA UNIVERSITY AND I AM HERE TODAY REPRESENTING CAP. >> I AM ANDY, A CLINICAL PA PATHOLOGIST PRACTICING LABORATORY MEDICINE IN THE DEPARTMENT OF LABORATORY MEDICINE AT THE UNIVERSITY OF WASHINGTON. WE ARE A MODERATE REFERENCE LABORATORY THROUGHOUT THE STATE OF WASHINGTON NATIONALLY AS WELL AS INTERNATIONALLY. I ALSO AM A RESEARCHER. WE HELP TO DEVELOP NOVEL PROT YOMIC METHODS FOR PROTEINS LLY WHEN FDA-APPROVED IDD IDDS FAIL AND I AM VERY EXCITED ABOUT THE OPPORTUNITY TO WORK WITH THE FDA HOPEFULLY TO GET A PROCESS IN PLACE THAT IS NOT OVERLY RESTRICTIVE LABORATORIES. I AM HONORED TO BE HERE, THANK > I AM AT THE UNIVERSITY OF UTAH AND THE MEDICAL DIRECTOR AT THE LABORATORIES. I AM ALSO THE IMMEDIATE PAST PRESIDENT OF AM P. NOT EXACTLY SURE WHO I AM REPRESENTING TODAY. SO I THINK I'M JUST REPRESENTING MYSELF. >> GOOD AFTERNOON, AND MANY THANKS TO THE FDA FOR THE OPPORTUNITY OTO BE PART OF THIS PANEL. I'M SCOTT PATTERSON AND THE EXECUTIVE MEDICAL DIRECTOR AND MEDICAL SCIENCES. I'M A BIOKCHEMIST AND I HAD THE OPPORTUNITY TO LEAD AND FOUND THE ENGINES BIOMARKER PROGRAM FOR THE PAST THREE YEARS LED DIAGNOSTIC PARTNERSHIPS IN GLOBAL IMPLEMENTATIONS. ONE /OF MY COMMENTS ARE REALLY MY OWN AT /THIS FORUM, THAT ARE IN INFORMED BY /TTHAT EXPERIENCE AS WELL AS DISCUSSIONS WITH COLLEAGUES WITHIN INDUSTRY. THANKS FOR THE OPPORTUNITY TO BE A PART OF THE PANEL. >> I'M /SWRAOUDY WILBUR, THE CLIIA LAB DIRECTOR AT 3 LABORATORIES AND TODAY I AM REPRESENTING D /KP-FPX, WHICH IS ONE OF THE FEW LABORATORIES THAT HAS ACTUALLY TAKEN LD TS THROUGH THE PROCESS. AND I WILL BE SPEAKING ON BEHALF OF THEM AND ALSO ON BEHALF OF 21 21ST CENTURY COALITION MEDICINE. THANK YOU. >> HI. MY NAME IS MICKEY WILLIAMS, A PH.D TRAINED AS /AA MOLECULAR BIOLOGIST AND BASICALLY DEVELOPING MOLECULAR ASSAYS MOST OF MY CAREER. I WORK AT FREDERICK NATIONAL LABS FOR CANCER RESEARCH. I'VE HAD EXPERIENCE BOTH IN THE PHARMACEUTICAL INDUSTRY, FROM DEVELOPMENT OF DRUGS, AS WELL AS /K-GTS IT. AND I WOULD SAY I'VE ALWAYS BEEN ON THE RESEARCH END BUT I WORK WITH THE NCI VERY CLOSELY AND WE'RE INVOLVED IN BRINGING NEXT GENERATION SEQUENCING INTO SEVERAL LARGE NATIONAL STUDIESTH AT THE -- THAT THE NCI IS SPONSORING AND WE DO HAVE A CLI CLIIA LAB THAT IS LOCATED IN FREDERICK AT THE NATIONAL LABS, THAT IS VERY MUCH ENGAGED IN DEVELOPMENT OF THESE ASSAYS, HENCE, I AM VERY HAPPY TO BE HERE AND CONTRIBUTE TO THE DISCUSSION. >> OKAY, LET'S GO BACK TO THE QUESTION. SORRY FOR JUMPING THE GUN. THE TOP /KWREUIC WE'D LIKE TO START WITH -- ARE THE ARE THERE FDA QUALITY SYSTEM REQUIREMENTS THAT RIVER -- DIFFER FROM CLIIA AND THAT FDA SHOULD CONTINUE NOT TO NORSE FOR LABORATORIES THAT USE LD TS?" >> I JUST WANTED TO THANK YOU FOR THIS CONVERSATION. WE'RE A LITTLE BIT SURPRISED THAT IT WASN'T MORE OF /AA CONVERSATION AT /THIS PROGRAM BUT I DO WANT /TO ASSURE AEVERYONE -- EVERYBODY THAT /PWERP ABLE TO CONVERSE WITH THE FDA PRIOR TO HAVING THIS MEETING. IT WAS A WONDERFUL CONVERSATION. PART OF WHAT WE TALKED ABOUT WAS THE CONTRAST AND THE OVERLAP BETWEEN WHAT IS COVERED BY CMS AND CLIIA AND WHAT'S PRESENT IN THE QUALITY SYSTEMS REGULATIONS. HEY, WHAT'S DIFFERENT? AND HAVE YOU TALKED TO CMS AND CLIIA AND TRIED /TO FIGURE OUT WHERE IS THE OVERLAP, ET CETERA? IN FACT, THEY'VE COME UP WITH A CROSSWALK TABLE, WHICH HASN'T BEEN SHARED BUT HAS BEEN DEVELOPED AND I THINK THAT'S THE FIRST STEP, AS WE TRY TO BEGIN TO UNDERSTAND HOW THE QUALITY SYSTEM REGULATIONS ARE GOING TO AFFECT THE PRACTICE OF MEDICINE IN CLINICAL LABORATORIES. THE BIGGEST THING THAT'S THE DIFFERENCE IS THE DESIGN CONTROL AND THAT'S PRETTY COMPLICATED, ESPECIALLY FOR D -- LD TS THAT ARE BEING USED IN THE PRACTICE OF MEDICINE AND HOW /TO MAKE -- TAKE A DESIGN CONTROL WHEN SOMEBODY HAS ALREADY BEEN DESIGNED AND IMPLEMENTED IS TRICKY. THE QUESTION BECOMES HOW DO WE TAKE DESIGN CONTROL IN THE FUTURE? ONE OF THE THINGS ABOUT DESIGN CONTROL THAT'S A LITTLE BIT TRICK Y IS .MASTER RECORD REGISTRY, WHICH IS SEPARATE DID YOU -- BUT IS ANOTHER EXAMPLE OF THE DIFFERENCE BETWEEN CLIIA AND THE QSR REQUIREMENT. HOW ARE WEING ABOUT TO TAKE THE DESIGN CONTROL PROCESS IN THE FRAMEWORK OF LD TS IS A COMPLICATED QUESTION. I THINK IT'S GOING TO NEED A LOT MORE CONVERSATION. I DON'T THINK THAT WE CAN GIVE AN ANSWER TODAY, BUT I THINK THAT YOU'RE RIGHT, AFTER READING THIS STENEXTENSIVELY OVER /-THE /HRAFLAST COUPLE /OF DAYS, I THINK THAT'S THE BIGGEST DIFFERENCE AND I DON'T KNOW THAT WE HAVE A SIMPLE ANSWER. BUT I DON'T THINK IT SHOULD BE APPLIED IMMEDILY TO LD TS. IT WOULD CRUSH US. >> I'D LIKE TO COMMENT AS WELL, AND I CONCUR WITH YOU. WE REALLY DO BELIEVE THAT THERE SHOULD BE HARMONIZATION OF CLIIA AND THE FDA QSR AND IT'S NICE TO KNOW THAT THERE IS A CROSSWALK AND THAT SHOULD BE SHARED SO WE CAN ADD SOME CLARITY BECAUSE A ROT OF US ARE DEALING WITH THIS CONFUSION. THERE ARE TWO REGULATORY SYSTEMS WITH VERY DIFFERENT LANGUAGES. BUT WE DO KNOW THAT THEY OVERLAP IN SOME AREAS AND CONTRAST GREATLY AND CAP ACTUALLY DID PERFORM A /KRAUFBG ITS OWN. IT MAY OR MAY NOT BE SIMILAR TO WHAT THE FDA DID AND SOME OF THE AREAS THAT WE FEEL THAT ARE GOING TO BE DIFFICULT, IF NOT NON-APPLICABLE, INCLUDE NON- NON-CONFORMING PRODUCT, LABELING AND PACKAGING CONTROLS, DISTRIBUTION, IN/STAL /A*ESTALATION, THE DEVICE MASTER RECORD, DEVICE HISTORY RECORD AND SERVICING. >> ONE OTHER PART THAT HASN'T BEEN MENTIONED AS THE -- IS /THE PURCHASING CONTROLS AND THAT WILL TAKE TIME TO IMPLEMENT IN THE LABORATORY. AND THE SUPPLIERS THAT WE DEAL WITH MAY OR MAY NOT BE READY FOR THAT AS WELL SO THAT'S SOMETHING THAT THE LABORATORIES MAY NOT HAVE ANY CONTROL OVER. ONE OF THE DIFFICULT AREAS THAT WE'VE TRIED /TO LOOK AT /TTHIS AND SAY HOW CAN WE IM/PROPROVE GOING FORWARD AND CAN WE START SOME OF THESE DESIGN CONTROLS RIGHT NOW INTO WHAT WE'RE DOING? THE PERSONNEL REQUIREMENTS ARE EVEN DIFFERENT THAT WE'RE TRYING TO /TPEFIT IN OUR EXISTING STRUCTURE TO WHAT A DESIGN CONTROL WOULD BE AND IT IS NOW AFFECTING JOB TITLES. IT'S AFFECTING SALARIES. IT'S AFFECTING A LOT /OF THINGS LIKE THAT THAT WE DON'T EVEN KNOW HOW /TO PUT THIS TOGETHER. AND WITH THE FDA, FLEXIBLE IN SAYING OKAY, WE'RE NOT GOING TO HAVE THIS EXACT TITLE WITH THIS EXACT JOB DESCRIPTION? LET'S BE A LITTLE MORE FLEXIBLE AND FIND SOMETHING THAT COULD ACTUALLY WORK. >> I THINK I COULD ADD A SMALL AMOUNT AND THAT IS THAT AS ANN -- ANDY REFLECTED UPON THE DISCUSSION WITH THE FDA THAT THEY HAVE HAD THESE DISCUSSIONS AROUND HARMONIZATION AND THIS IS CRITICAL TO BE ABLE TO SHARE THIS WITH THE COMMUNITY SO THAT ADDITIONAL /TKAOEB CAN BE OB OBTAINED, SUCH AS WHAT ELAINE JUST RAISED AROUND TITLES SO THAT IT IS CLEAR HOW LABS ARE ABLE TO ADOPT THE APPROPRIATE COMPONENTS OF QUALITY SYSTEMS REGULATIONS SO THAT THE ELEMENTS OF DESIGN CONTROL CAN BEGIN TO BE UTILIZED. BECAUSE WE SEE THAT DESIGN CONTROL COMPONENT AS PARENT -- IMPORTANT OR THOSE HIGH-RISK DEVICES WHICH ARE MOST OF INTEREST TO US. >> AND JUST JUMPING IN RIGHT HERE. I THINK LIZ SPOKE EARLIER AND HAD A REALLY GOOD CONCEPT OF WHERE THE OVERLAP IS. ON THE A SAY END OF THINGS IS CLEARLY A LOT /OF QUALITY THAT GOES INTO DEFINING THE ASSAY, DEFINING THE REAGENCY AND THAT ARE BEING USED, QUALIFICATIONS FOR NEW LOTS. SO THERE IS OVERLAP. I THINK WITH THE INTENTION AT ARREST, AS I'M UNDERSTANDING WHAT THE FDA IS STRIVING TOWARD, AND THAT SHOULD BE WITH RESPECT -- RESPECTED WHERE IT EXISTS. MAY BE FORMALIZED AND STATED CLEARLY AND I'VE HEARD THAT MENTIONED MANY, MANY TIMES IN GUIDANCE OR WHATEVER REGULATIONS REGULATIONS. I THINK CLARITY IS VERY IMPORTANT ABOUT BECAUSE WORKING AT A COMMERCIAL DIAGNOSTICS COMPANY, WE HAD A SPRE LARGE STAFF OF PEOPLE THAT IT IS THEIR JOB TO INTERPRET THE LANGUAGE. AND FOR AN LK T, YOU'RE NEVER GOING TO BUILD THAT INFRA INFRASTRUCTURE WITHIN THE LAB. SO CLEAR GUIDANCE AND MINUIMIZING WHERE THE OVERLAP IS. I'LL TALK A LITTLE BIT ABOUT HOW WE'VE DONE THINGS AT THE NATIONAL LAB WHEN WE'RE PREPARING A TEST TO GO IN TO AP APPLICATION. AND AS FAR AS THE DESIGN CONTROL ASPECTS THAT WE FEEL ARE VERY IMPORTANT IN THE DEVELOPMENT AND DEFINING WHAT WE'RE ABOUT TO DO IS TO CLEARLY STATE OUR INTENDED USE. AND I THINK THAT UPFRONT THEN HELPS US TO UNDERSTAND THE RISKS AT ARREST IN OUR OWN MINDS, THAT THIS ASSAY IS GOING TO BRING ALONG IN THE TREATING AND DOCUMENTING THAT IN /AA WAY THAT IS CLEAR, WHAT PATIENT POPULATION IS GOING TO BE USED ON /SKWHRARBGTS DEVICE ACTUALLY IS, WHERE DOES IT START? WHERE DOES IT END? IT'S A SYSTEM, AND HAVING THAT WELL-DOCUMENTED IN /AA WAY THAT YOU CAN TRACK THAT. I MEAN, I KNOW SOME CLIIA LABS DO THIS, BUT I DON'T THINK WE ALL DO IT AT THE SAME LEVEL. AND THEN, AS FAR AS HAVING THESE INTENDED USE STATEMENTS, BEGINNING WHEN AT SAYS ARE BEING DEVELOPED, WHAT LEVEL OF SPECIFICATIONS AND AN /HREALYTICAL PERFORMANCE ARE GOING TO BE IMPORTANT TO HAVE A SUCCESSFUL A ASSAY AND DO THE MINUIMAL AMOUNT OF HARM AS POSSIBLE? AND A LOT /OF OUR ASSAYS, SPEC FISITY IS VERY IMPORTANT. WE'RE WILLING TO POTENTIALLY HAVE A LOWER SENSITIVITY IN THAT TRADE-OFF. AND AGAIN, WE DO THAT AS PART OF AN /EUINFORMAL DOCUMENTATION THAT WE'RE DOING BEFORE WE BRING IN AN ASSAY INTO OUR CLINICAL LAB. THE OTHER EXTREME AGAIN IS IN THE MANUFACTURING ASPECT QUALITY QUALITY. AND OBVIOUSLY, MOST LABORATORIES DOING LD TS ARE NOT MANUFACTURING INSTRUMENTS.^ THEY'RE NOT MANUFACTURING A LOT OF THE REAGENTS. THEY'RE BRINGING IN COMPONENTS BUT ONCE AGAIN WE HAVE WAYS TO AT LEAST FROM CLIIA PERCESPECTIVE, DEAL WITH WHAT TYPES OF REAGENTS AND HOW WE BRING A REAGENT IN /SAND QUALIFY IT FOR USE IN THE ASSAY. HOW WE ACTUALLY VALID /A*ATE OUR /SKPRUPLTS HOW OFTEN THEY ARE READY AND THE LIKE AND WHAT PERFORMANCE SPECIFICATIONS THEY FEED TO HAVE. SO I THINK THAT'S, IN MY MIND, ADEQUATE, IF WE WERE LIVING AT THE A MANUFACTURING LEVEL, ONCE AGAIN, THEN THE COST AND THE BURDEN THAT WOULD BE PUT ON TO LABORATORIES WOULD BE EXCESSIVE, I THINK. >> LET ME TAKE UP THAT POINT THAT WAS JUST TOUCHED ON BY SEVERAL OF YOU. SO GIVEN THAT WE WON'T HAVE RIGHT NOW EXACTLY WHAT WE HAVE TO DO, WE WANT /TO THINK ABOUT EX EXTRA BURDEN. ASSUME THAT ANYTHING THAT RIGHT NOW APPEARS TO OVERLAP WITH CLI CLIIA, JUST REALLY DOES OVERLAP, YOU DON'T HAVE TO DO THAT TWICE. THE FDA VERSION HAS THE CLIIA VERSION BUT THEY'RE ESSENTIALLY TWO TASTES OF VALNILLA. WHAT ADDITIONAL BURDEN COULD YOU FOE -- SEE AND ADDITIONAL COSTS IN PERSONNEL AND ECONOMIC COSTS DO YOU SEE COME OUT OF THIS, THE COMBINES, AS YOU READ THEM, SOME >> TO ME, I THINK PART OF IT IS JUST WHAT HAS BEEN BROUGHT UP BY SEVERAL PEOPLE IS FIGURING OUT HOW TO DO THIS. THAT THE PERSONNEL, AS YOU SAY, EXIST WITHIN THE MANUFACTURING ORGANIZATIONS ARE USED TO DEALING WITH THE FDA, HAVE RELATIONSHIPS WITH PEOPLE AT THE FDA. BECAUSE A LOT OF THEM HAVE COME FROM THE FDA. AND HAVE GREAT EXPERIENCE WITH THE QSRS. I WANT /TED TO POINT OUT PART OF THE ISSUE HERE BECAUSE I'M NOT SURE EVERYBODY IN THE CROWD UNDERSTANDS THIS, BUT IN OUR PHONE CALL PRE-PANEL PHONE CALL, I THINK SCOTT MENTIONED THAT THERE IS A /RLOT OF WIGGLE ROOM WITHIN THE Q.^R. IT WAS SURPRISING TO ME TO HEAR THAT SOMETHING -- COMING FROM SOMEBODY IN /AA MANUFACTURING ENVIRONMENT. BUT IT'S REALLY VERY TRUE. AND I THINK WHAT WE'RE ASKING FOR IS CLARITY. AND I WANT TO READ TO YOU JUST ONE OF THE PARAGRAPHS THAT'S ON THE HEAD PAGE OF THE FDA'S WEBSITE ABOUT QSRS AND IT SAYS " "THE FDA HAS IDENTIFIED IN REGULATIONS THE ESSENTIAL ELEMENTS THAT A QUALITY SYSTEM SHALL EM/PWOEBODY WITHOUT PRESCRIBING SPECIFIC WAYS TO ESTABLISH THESE ELEMENTS. BECAUSE THE QS REGULATION COVERS A BROAD SPECTRUM OF DEVICES AND PROCESSES, ET CETERA, IT ALLOWS SOME LEEWAY IN THE DETAILS OF A QUALITY SYSTEM ELEMENT. LEFT TO MANUFACTURERS TO DETERMINE THE NECESSAITY FOR OR THE EXTENT OF SOME QUALITY ELEMENTS AND TO DEVELOP AND IMPLEMENT SPECIFIC PROCEDURES TAILORED TO THEIR PARTICULAR DEVICES." SO GIVEN THAT LANGUAGE AND THROWING THAT OUT TO A CLINICAL LABORATORY, I THINK THERE IS GOING TO BE /AA LOT /-OF CONFUSION. AND I THINK THAT ONE OF THE THINGS THAT WE ARE ASKING IS A CHECKLIST. ACTUALLY HOW DO YOU DO THIS? WHAT ARE YOU EXPECTING TO SEE? BECAUSE OTHERWISE, THE Q.^R IS TINE, -- TINY. BUT SOMEHOW OR OTHER ALL OF THOSE CONSULTANTS AND REGULATORY PEOPLE WITHIN ALL OF THE COMPANIES TURN THAT INTO THOUSANDS OF PAGES OF THE MISSION. EXACTLY -- WHAT IS IT THAT YOU WANT FROM -- INAUDIB[INAUDIBLE] > ONE OF THE EFFICIENCIES WE DO AT THE LABORATORIES IS THAT WE PUT MULTIPLE ASSAYS ON ONE INSTRUMENT OR TRY TO STANDARDIZE OUR METHODS AS MUCH AS POSSIBLE. AND WHEN /AA MANUFACTURER, WE GET AN FDA-CLEARED CHECK FROM A MANUFACTURER, WE THEN HAVE TO TRY TO /TPEFIT IT INTO OUR EXISTING PROCESSES AS WELL. AND THEREFORE, MANY TYPES WE TAKE IT OFF-LABEL AND DO SOME CHANGES TO MAKE IT PROCESS -- OUR PROCESSES. WE HAVE TESTS THAT ARE BY THIS DEFINITION MAY BE HIGH-RISK AND WE NEED TO GET THEM THROUGH THE FDA. IF THERE ARE 50 TESTS, WE USE FIVE DIFFERENT /SKPHRAOFPLZ THE FIVE DIFFERENT PLATFORMS, THE RE REAGENTS AND THE -- EVERYTHING IS SIMILAR -- OR SOMETHING ALONG THOSE LINES. GENERALLY, UNIFORM STANDARDS THAT WE DO NOT NEED TO DO AN ENTIRE DESIGN SEG /*PMENT FROM THE ENTIRE PROCESS. WE CAN PUT THEM INTO EXTRACTION pPROCESSES AND WE KNOW THAT WE CAN USE THIS EXTRACTION WITH THIS INSTRUMENT AND CLEARLY REFERENCE BACK TO ANOTHER STUDY OR ARE WE GOING TO HAVE TO REFERENCE THAT? IT'S BEGINNING TO BE EASY FOR US TO START FROM SCRATCH TO DO FROM THE ASSAYS. IF A SENSE IT'S TOTALLY DIFFERENT FLAVORS. THRE IS A LOT /OF UNCERTAINTY AND DON'T KNOW HOW TO DO BUT IT WOULD BE VERY USEFUL AND VERY HELPFUL IF THE DESIGN CONTROL -- IF WE CAN REFERENCE BACK REAGENT STABILITY SPECIMEN STABILITY. BOTTOMLINE I WORK WITH DNA, I KNOW HOW STABLE DNA IS. NO MATTER WHAT SYSTEM I PUT IT IN /SAND WE'VE DONE SOME STUDIES BUT I CAN'T DO IT EVERY TIME. >> I WANTED TO THANK JUDY FOR BRINGING UP THE PHONE CALL AND MENTIONING THE LEGAL ROOM. ACTUALLY THE FDA TALKED ABOUT A LITTLE BIT AND RECOGNIZE THAT THERE IS WIGGLE ROOM AND IT'S ON PURPOSE BECAUSE THIS DOCUMENT IS SUPPOSED TO COVER LOTS OF MEDICAL DEVICES AND IT'S SUPPOSED TO BE THE PURPOSE. QUALITY IS GOOD. VALID /A*EATION IS ABOUT. QUALITY CONTROL IS GOOD. EVERYBODY AGREES WITH THAT. QUALITY SYSTEM REGULATION." I DON'T KNOW. I READ THIS DOCUMENT. I CONSIDER MYSELF A SLIGHTLY INTELLIGENT INDIVIDUAL. I HAVE NO IDEA WHAT QUALITY SYSTEM REGULATIONS ARE ANY GOOD AND PART OF THE REASON WE'RE ASKING FOR CLARITY IS BECAUSE LEGAL ROOM GENERATS FEAR AND UN UNCERTAINTY. ABSOLUTELY NO IDEA WHAT IS GOING TO HAPPEN WHEN SOMEBODY /TPWHAOUBGZ YOUR LAB IF YOU ARE SUPPOSED TO /ADHERE TO THIS DOCUMENT. SO I THINK /KHRAEURL -- CLARITY IS A GOOD THING. I ASK MYSELF HOW IN THE WORLD CAN YOU APPLY THIS DOCUMENT THAT IS CURRENTLY RUNNING IN THE LABORATORY, SOMEING AND WHY NOT KILL THIS, AS IT APPLIES TO CLINICAL LABORATORIES AND FIGURE OUT WHAT IS IT ABOUT DESIGN CONTROL THAT REALLY IS IMPORTANT AND WHAT DO YOU WANT TO SEE AS BEBEGIN TO DEVELOP OUR NEW LAB TESTS? SHOULD IT BE AN /EUINFORMAL DOCUMENT, OR DO YOU WANT SOMETHING THAT'S CONCRETE AND E ELABORATE AND TALKS ABOUT SPECIFIC THINGS? CONCRETENESS AND CLARITY WOULD BE GOOD. DOCUMENTS DON'T PROVIDE THAT AND I DON'T KNOW HOW /TO ANSWER THE QUESTION. AND SO I WOULD LOVE TO HAVE CLARITY. WE ASK LATER WHAT ARE THE RESOURCE THAT'S WE NEED TO THE CLINICAL LABORATORY. CLARITY I WOULD CONSIDER AS /AA RESOURCE. CLARITY AND DIRECTION. >> SO THE ANSWER IS PART OF IT IS THAT THE DOCUMENT WAS DESIGNED FOR TRADITIONAL DEVICES THAT ARE MANUFACTURED. AND IS THAT WHY WHEN YOU GO THROUGH IT, IT DOESN'T SEEM TO FIT WITH WHAT IS ACTUALLY GOING ON IN THE LD T ENVIRONMENT? >> I THINK A /RLOT OF IT DOES, RIGHT? PRODUCT IDENTIFICATION AND TRACE TRACEABILITY DEVICE MASTER RECORDS AND HISTORY RECORD, LABELING AND PACKAGE, WHICH I WOULD ARGUE THAT'S HOW WE TRANS TRANSMIT DATA IN THE PRACTICE OF MEDICINE. PURCHASING CONTROLS, WE'VE ALREADY TALKED ABOUT. WE HAVE TO EVALUATE ALL OF THE PEOPLE WE WOULD PURCHASE FROM AND TELL WHY WE PICKED THE ONE WE PICKED. A LOT /OF IT JUST DOESN'T REALLY I /TKPWGUESS -- AND IF YOU TRIED /TTO PRETEND, OKAY, MAYBE I CAN TAKE SOME OF THESE, IT IS NOT OBVIOUS HOW YOU DO IT. >> I'M SMILING A LITTLE BIT BECAUSE I WAS JUST TALKING ABOUT WHAT WE FELT WHAT I THINK CAP DID IN CROSSWALK IN THE Q.^R ELEMENTS DANT PLY. AND ANDREW AND I NOW DISAGREE BECAUSE HE THINKS SOME OF THESE ELEMENTS HE CAN INTERPRET. I INTERPRET THEM DIFFERENTLY AND SO THIS IS THE PROBLEM. YOU ARE GOING TO HAVE TWO PEOPLE WHO ARE SITTING HERE /TIN /TTHIS MEETING SIDE BY SIDE GOING THROUGH THE SAME TERMS DIFFERENTLY. SO AS YOU KNOW, CAP IS DEEMED A CREDITOR FOR CLIIA LABORATORY CHECKLISTS, WHICH SPECIAL TELL A LABORATORY HOW /TO PERFORM CLINICAL TESTING AND WE'VE BEEN ASKED OVER AND OVER AND AS YOU SEE, THESE CHECK RISS ARE MODIFIED OVER AND OVER BECAUSE THEY WANT ADDITIONAL CLARITY. THEY WANT -- THE INTEND -- INTENT IS ABOUT. THEY WANT TO COME INTO COMPLIANCE BUT THEY DON'T WANT WIGGLE ROOM OR THIS MIS MISINTERPRETATION OR AN /EUPB INSPECTOR TO COME IN AND INTERPRET IT ONE /WAWAY AND THEY HAD INTERPRET ED ED IT A DIFFERENT WAY. SO THERE IS REALLY GOING TO HAVE TO BE SOME CONCRETE LANGUAGE AND CLARITY AS WE SAID, TO HELP LABORATORIES COME INTO /KPRAOEUPBS AND THIS IS GOODING TO TAKE TIME. AND THIS IS GOING TO TAKE EDUCATIONAL MATERIALS, SEM MARS, SCREENING, ET CETERA. IT'S A HUGE BURDEN. ALSO WITHIN THE RABBIT, WE ARE GOING TO HAVE TO TRAIN OUR PERSONNEL TO COME INTO COMPLIANCE. WE'RE GOING TO HAVE TO TRAIN THEM FOR THE TERMINOLOGY. I ALREADY HAVE A QUALITY A ASSURANCE PERSON WHO PRETTY MUCH DOES ALL SHE DOES. THAT'S HER TOTAL JOB RESPONSIBILITY TO KEEP US IN COMPLIANCE WITH CURRENT FEDERAL REGULATIONS, AS WELL AS THE STATE REGULATIONS AND I TELL YOU WE ARE INSPECTED REGULARLY. WE ARE INSPECTED BY CAP, EITHER INTERNAL OR EXTERNAL INSPECTION EVERY SINGLE YEAR WE'RE INSPECT INSPECTED BY THE STATE. WE HAVE OUR OWN MEDICAL INSTITUTION. WE HAVE COMPLIANCES WE MUST MEET MEET. NG INSPECTED. SO SIFEEL THAT WE'RE CONSTANTLY AND WHEN YOU TALK ABOUT BURDENS, I REALLY DO FEAR THE IDEA OF ANOTHER INSPECTION. SO AS WE TALK ABOUT ON THE PHONE IF THERE IS SOME WAY TO /KHREFRPBLG CLIIA AND MERGE SOME OF THE INSPECTION PROCEDURES INTO ONE INSPECTION, THAT WOULD BE HELPFUL AS WELL. BUT WHEN WE TALK ABOUT BURDEN, OF COURSE, I WORRY ABOUT COST FOR RIM BURSEMENTS ARE GOING DOWN AND COSTS GOING UP. IF I HAVE TO HAVE ADDITIONAL PEOPLE, I HAVE TO HAVE ADDITIONAL SCREENING AND I HAVE TO HAVE EDUCATIONAL MATERIALS, AND I HAVE TO PREPARE FOR AN ADDITIONAL INSPECTION. SO I THINK THAT'S SOMETHING THAT NEEDS TO BE CONSIDERED X ALSO THE USER FEES. THE USER FEES ARE /STKPAPBGS WE HAVE USER FEES FOR THIS DATE AND USER FEES FOR CAP AND NOW WE'LL HAVE USER FEES FOR THE FDA AS WELL. >> DOES ANYONE ELSE ON THE PANEL WANT /TO COMMENT ON THE ADDITIONAL RESOURCES THAT WOULD BE REQUIRED TO DO IMPLEMENTATION BEFORE WE MOVE /OON TO THE NEXT TOPIC? >> YEAH. UNTIL WE HAVE CLARITY, WE REALLY DON'T HAVE A GOOD IDEA. >> I JUST WANT /TED TO FOLLOW UP ON WHAT GAIL SAID ABOUT THE THIRD PARTY, WHICH ON THE PHONE CALL MENTIONED THEY WERE TOTALLY GAME FOR THAT, TOO. I WANT TO COMPLIMENT KATHY AND AM A LITTLE BIT BIASED. THOSE CHECKLISTS ARE FANTASTIC. IT'S A DISCUSSION. YOU HAVE A DISCUSSION WITH THE INSPECT. DIN -- INSPECTOR, WHICH IS AN IN INCREDIBLE OPPORTUNITY TO LEARN FROM ONE ANOTHER AND TO MOVE FORWRD. I STRONGLY ENCOURAGE THAT KIND OF APPROACH. AND AGAIN, THIS DOCUMENT ISN'T HELPFUL. THE CHECKLIST IS. WE TALKED ABOUT TRYING TO FIGURE OUT HOW FDA /KP-T CMS ARE DIFFERENT. I THINK TO START SEEING CMS TALK MORE WITH YOU GUYS AND FIGURE OUT WHAT YOU NEED AND WHAT YOU WANT AND HAVE PRAISES WORK WITH AGENCIES TO BEGIN TO TAKE WHAT YOU NEED AND WHAT YOU WANT AND PUT IT INTO THE CLINICAL /PHAB -- /SKPRAB DO IT. I AGREE WITH GAIL. >> LAB AND. >> ONE OTHER THING THAT WOULD HELP IS WE'VE TALKED A LOT ABOUT CLINICAL LABORATORIES TRYING TO LEARN FDA AND IT WOULD BE VERY HELPFUL TO PUT THINGS TOGETHER AND MAYBE LEARN AS WELL. >> LET ME CATCH THIS THREAD. WE'RE GOING TO HAVE TO SUSPEND AND MOVE TO THE STATE WE THINK WE COULD GET AT. LET'S ASSUME WE HAVE CLARITY WITH THE CHECKLIST. WE HAVE ASSURANCE IF CAT AND CMS REQUIREMENTS ARE COVERING CERTAIN ASPECTS OF IT THAT THEY WILL NOT HAVE TO BE ESSENTIALLY DONE OVER AGAIN THE SAME THING. SO WE'VE IN/KRORCORPORATED ALL OF THAT INTO THE NEW WORLD. THE LABS ARE RUNNING LABS AND THESE ARE NOT LABS ONLINE OR MANUFACTURING TWIDEVICES COMING ONLINE. GIVEN THAT STATE /-OF THE WORLD WHERE THINGS WILL BE CLARITY, WILL NOT NON-OVERLAPPED, HOW LONG DO YOU THINK THE PERIOD HAVING THESE GUIDELINES PUT IN PLACE? WHAT IS APPROPRIATE TIME FOR -- IF YOU WERE TOLD YOU HAVE TO BE READY AND THEN THINK OF, FOR THOSE OF YOU WHO SPEAK FOR /AA LARGER COMMUNITY, MOUNTING DO YOU THINK IT WOULD TAKE? >> I ASKED THIS QUESTION AND I SAID MY RESPONSE WAS AS /HROPLONG AS IT TAKES. THIS SHOULD BE SNAG WE RUSH INTO INTO. THIS IS A NEW ELEMENT FOR LABORATORIES EXCHANGES, A SAID IN MY PUBLIC COMMENTS. IT'S A CHANGE FOR LABORATORIES. IT'S NOT THAT THEY'RE NECESSARY NECESSARILY UNWILLING TO DO SO, BUT WE NEED TO ADAPT IT TO HOW WE CURRENTLY FUNCTION AND NOT BE UNDULY BURDENSOME. SO I THOUGHT -- I THINK WE NEED THE CLARITY OF THE HARMONIZATION WHERE CLIIA AND FDA -- I MEAN THESE ARE RISK CATEGORIES. WE'RE TALKING ABOUT QSR REQUIREMENTS. ARE THOSE GOING TO APPLY TO ALL RISKS OR TO SOME AND IF SO, WHICH, A PORTION? SO THIS IS GOING TO TAKE SOME TIME, AS WAS STATED BY ONE OF THE PUBLIC COMMENTERS. MAYBE WE GET THOSE DOCUMENTS FIRST, THEN WE HAVE ADDITIONAL COMMENTS AND DISCUSSION WITH THE FDA. I DO HAVE TO COMPLIMENT THE FDA. THEY'VE BEEN VERY GOOD ABOUT TRYING TO CLARIFY THINGS FOR US. IT'S JUST THAT WE'RE NEW LEARN LEARNERS AND THAT THERE IS SOME ANXIOETY ASSOCIATED WITH IT NOT ONLY BECAUSE OF THE BURDENS THAT WE'VE ALREADY SPOKEN OF, BUT TRYING TO UNDERSTAND MASS AMOUNTS OF MATERIAL. SO I AM IN THE CAMP THAT WE'LL GO FORWARD BUT TAKE AS /HROPLONG AS WE NEED TO GO FORWARD. >> PART OF THAT IS -- INAUDIBLE [INAUDIBLE] WITH ALL OF THE VALID /A*EATION THAT'S WE'VE DONE SO FAR AND THAT THEY'VE ALREADY PERFORMING WELL, THOSE MIGHT BE EXCEPTIONAL AND MOVING FORWARD, I CAN'T REALLY GO BACK /SAND REDO UNDER DESIGN CONTROL 1500 LD TS pTHAT ARE LAB-PERFORMED. SO GOING FORWARD, THAT'S ONE OF THE MAIN QUESTIONS. THE OTHER MAIN CONCERN THAT I HAVE WITH THE DESIGN CONTROL, ET CETERA, IS WE IM/PROPROVE OUR TESTS AND KNOWLEDGE AND EVEN WITHOUT THE MEDICAL KNOWLEDGE, THERE IS A NEW REAGENT AND THERE IS SOMETHING ELSE THAT WE ARE IM IMPROVING EXISTING TESTS ABOUT ONCE EVERY WOYEARS, ET CETERA. AND SO THAT THE OTHER PART -- WHATEVER WE DO GOING FORWARD NEEDS TO BE ABLE TO BE THAT WE CAN CLICK -- QUICKLY IMPLEMENT NEW CHANGES, UPDATING TESTS, BECAUSE TRUTHFULLY, THERE IS NOT MANY FDA PRODUCTS IN MY AREA THAT -- BUT WE HAVE A COUPLE. THE COUPLE THAT WE USE /SKWRARBGTS LEAST ONE /OF THEM HAS BEEN OFF-LABEL BECAUSE WE HAVE TO PUT IT INTO WHAT WE ARE DOING. NONE OF THOSE HAVE BEEN IMPROVED EVER SINCE WE'VE STARTED THEM. AND THAT'S ONE OF THE WEAKNESSES THAT I SEE AND ONE OF THE STRENGTHS OF THE LAB DEVELOPED TESTS THAT WE'VE BEEN ABLE TO MAKE CONTINUALLY IM-- IM IMPROVEMENTS. AND I DON'T SEE HOW DESIGN CONTROL REALLY FITS THAT MODEL VERY WELL. I WOULD REQUEST THAT WE FIND SOMETHING THAT WORKS. LET'S BE OPEN AND ONINNOVATIVE AND PROGRESSIVE ABOUT THIS AND FIND A WAY THAT WILL WORK. >> I'D LIKE TO PICK /UP ON SOME OF THESE IMPORTANT COMMENTS THAT ELAINE MADE AROUND /THE USE OF XCOMPANION DIAGNOSTICS AND LIMIT LIMITED NUMBER OF THOSE THAT COMPONENTS OF WHERE MOST CONCERNED ABOUT BECAUSE WE HAVE A SINGULAR AIM WITH REGARD TO DIAGNOSTIC TESTS THAT ARE USED IN CONJUNCTION WITH THERAPEUTICS THERAPEUTICS, AND THAT IS A PATIENT'S HE WIELIGIBILITY FOR THE THERAPEUTIC BE ACCURATELY DETERMINED. AND WE FULLY UNDERSTAND THAT LABS SOMETIMES NEED TO MODIFY HOW THAT TEST IS UT RIAISED, - -- FOR VARIOUS REASONS. UT RIAISED. I DON'T MEAN TWEAKING AND I'LL GET TO /TTHAT IN A MINUTE. BUT FOR THOSE PARTICULAR ASPECTS OR PERFORMANCE CHARACTERISTICS OF THE ASSAY DUE TO ONE STAGE ALTITUDE OR SOMETHING THAT ISN'T IN THE STUDY AND I DON'T THINK IT SHOULD BE. BUT WHEN LABS HAPPEN TO MODIFY A TEST OR ADD AN ADDITIONAL TISSUE TISSUE, SUCH AS WE'VE HEARD DESCRIBED, MAY NOT BE A COMPONENT OF THE TEST THAT THE FDA REVIEWED AND AS MUCH AS WE'VE HEARD SOME COMMENTS ABOUT LIMITATIONS ACROSS THE FDA, THAT THEY CAN ONLY REVIEW THE TEST THAT'S PUT IN FRONT OF THEM. YOU HAVE TO THINK ABOUT WHAT IS THE TEST THAT IS PUT IN FRONT OF THEM FOR /AA XACOMPANION DIAGNOSTIC AND WHY IS IT IN THAT PHARMACIST -- FORMAT? BECAUSE THAT'S HOW WE'VE HAD TO UTILIZE IT IN /AA CLINICAL TRIAL TO CLINICALLY VALIDATE THAT BIO BIOMARKER THE INTENDED USE AS A XCOMPANION DIAGNOSTIC. NOW AS /AA TEST, IT'S /TPHAINTO THE BROADER POPULATION THAT CAN BE OTHER COMPONENTS, OTHER TISSUE TYPES THAT REALLY SHOULD BE TEST TESTED SO THAT PATIENTS CAN TRULY BENEFIT FROM THESE THERAPIES. SO WE BUM THE FACT THAT /R*ETS DO THESE ADDITIONAL VALID ATIONS, WHETHER THEY /BE FOR, AS /EI SAID, TISSUE TYPE. I THINK ONE OF THE COMPONENTS THAT I SEE OF DESIGN CONTROL, OR RAT -- AT ARREST SOME ELEMENTS. IF THEY WERE AVAILABLE OR UT UTILIZED IN THE LAB, WE'VE HEARD OVER /THE /HRAFLAST COUPLE /-OF DAYS HOW /RABZ HAVE OFTEN HAD TO MODIFY THESE P.M.AS IN SOME PARTICULAR MANNER. WHAT STRIKES /SPHES THAT THIS IS HAPPENING IN SO MANY INDIVIDUAL LABS. THIS DOESN'T SEEM LIKE AN OFFICIAL PROCESS. IS INTEREST A WAY THROUGH DESIGN CONTROL, THAT THAT INFORMATION -- IF IT WAS CONDUCTED IN A LAB UNDER DESIGN CONTROL SO THAT THAT INFORMATION COULD FLOW BACK MOO THE MANYA, -- P.M.A, WHETHER THAT BE HANDLED OR THE LABS HAVING PROVIDED THAT INFORMATION INFORMATION, THAT INFORMATION WOULD THEN BE AVAILABLE AND WOULDN'T HAVE TO BE EVERY SINGLE RAB THAT HAD TO MODIFY. THAT INFORMATION COULD COME BACK AND BE PART OF THE P.M.A LABEL. AND ADDRESSING THE VERY VALID CONCERN WE HAVE AS WELL WITH P.M.AS IS /THE THAT OFTEN, THE P.M.A IS SET WHEN IT'S APPROVED AND SOMETIMES IT MAY NOT BE THAT EASY TO GATHER THE INFORMATION TO CONTINUALLY IM/PROPROVE OR ADD THESE OTHER PIECES OF INFORMATION. MAYBE THIS IS AN OPPORTUNITY, THROUGH THE APPLICATION OF DESIGN CONTROL -- AND IF THOSE LABS THAT WISH TO CONDUCT THAT KIND OF WORK AND IT'S NOT THOUSANDS OF LABS THAT WE KNOW ARE PRODUCING SUCH EXCELLENT RESULTS ACROSS MANY DIFFERENT TYPES OF TESTS. BUT THOSE LABS THAT HAVE -- THAT ARE LESS -- TESTED FOR THESE CLASS 3 XCOMPANION DIAGNOSTICS, THOSE LABS -- THE TIMEFRAME WOULD BE GREAT TO IMPLEMENT THIS DESIGN CONTROL, BECAUSE I SEE THAT AS /AA WAY TO TRULY IM/PROFPROVE HOW THESE TESTS ARE USED NOT JUST IN INDIVIDUAL LABS, BUT MORE BROADLY THROUGH THE COMMUNITY AND WE SEE THAT AS A PARTICULARLY IMPORTANT COMPONENT COMPONENT. AND JUST AS I SAID, I TOUCHED PONT TWEAKS. IT'S VERY IMPORTANT. WE SOMETIMES HEAR THIS THAT FOLKS SAY "WE'VE MADE THE TESTS BETTER."^ AND BEDON'T ACTUALLY UNDERSTAND WHAT THAT MEANS BECAUSE THE TESTS THAT WE HAVE UTILIZED IN THE CLINICAL TRIAL TO CLINICALLY VALID /A*ATE THAT BI% BIOMARKER FOR PATIENT SELECTION IS SET UP ON SPECIFIC PERFORMANCE CHARACTERISTICS AND ACCEPTANCE CRY /TAOITERIA. MAKING THE TEST BETTER, WHICH MAY MEAN MAKING IT MORE SENSE SENSITIVE, WHICH /WUONE MIGHT THINK IS MAKING IT BETTER. THERE IS NO CLINICAL VALIDATION FOR THAT. IT MAY NOT BE MAKING IT BETTER. A CONCERN IS ALWAYS THAT PATIENTS BE ACCURATELY SELECTED FOR THE THERAPEUTIC. THAT'S WHY WE EMBRACE WORKING WITH THE LAB COMMUNITY AND WE HAVE TO THINK ABOUT THIS GLOBAL GLOBALLY AS WELL. HOW CAN WE ENSURE THAT THOSE TESTS ACCURATELY SELECT PATIENT? NOW, RIGHT OR WRONG, WE'VE BEEN INVOLVED IN THE -- IN BRITISHING THAT THRESHOLD, THAT CUSP FOR PATIENT SELECTION, WHICH IS RELEVANT AND WE LIVE OR DIE BY THAT FOR OUR CLINICAL TRIAL. THAT DOESN'T MEAN THAT THAT NECESSARILY IS ULTIMATELY THE MOST APPROPRIATE CUT POINT FOR EVERY POPULATION. AND AGAIN, I THINK IN /THIS IF LABS ARE INVOLVED IN /THIS HAD DESIGN CONTROL AS PART OF HOW THEY OPERATE AND THIS INFORMATION COULD FEEDBACK. MAYBE THAT'S AN OPPORTUNITY TO BE ABLE TO FURTHER OR FIND THESE ASSAYS. >> I CAN UNDER IN THE CLINICAL TRIAL SETTING WHY THIS MAKES COMPLETE SENSE AND HOW THIS INFORMATION DISSEMINATED. DO YOU SEE IT BEING PRACTICAL OR EMBRACED IN THE COMMERCIAL LAB SETTING? >> THOSE LABS THAT AREING ABOUT TO BE DOING THE WORK ALREADY ARE ARE. WE COULD HAVE THAT INFORMATION MED -- FED BACK /SAND APPROPRIATE APPROPRIATELY SENT. THE DRUG COMPANIES, THERAPIES COMPANIES ARE INVOLVED WITH OUR DIAGNOSTIC PARTNERS WOULD CERTAINLY LIKE TO SEE THAT ADDED ADDED. >> A GOOD INCENTIVE? >> YES. I THINK IT SHOULD BE SOME WAY TO WORK THIS OUT BECAUSE THEN COULD TRULY IM/PROPROVE UPON IT. >> AND I'LL JUST JUMP IN FROM A DEVELOPER OF THE ASSAYS. YOUR RESPONSE TOWARDS PERFORMANCE AND A SINGLE LAB GOES OFF AND MODIFIES THAT. IT BECOMES VERY HARD FOR THE MANUFACTURER OF THAT ASSAY TO STAND BEHIND THOSE RESULTS UNLESS THERE IS ALREADY AN INTER INTER/AOBACTION. I GOT A LITTLE BIT NERVOUS WHEN YOU SAY THAT SHOULD FLOW BACK INTO THE P.M.A. I THINK IT'S NOT -- VALUABLE INFORMATION THAT SHOULD BE DIS DISSEMINATED BUT -- INAUDIB[INAUDIBLE] FOR THE MANUFACTURE TORE TAKE THAT ON. >> THANKS FOR CLARIFYING. >> WHICH I THINK WOULD ENTAIL A NEW APPLICATION. THAT FEEDING BACK INTO THE SAME -- >> SO ONE OF THE THINGS THAT IS A VALID QUESTION THAT IS ASKED BY MANY PATHOLOGISTS IN LABS WHY COULDN'T YOU HAVE WORK WITH US IN THE DEVELOPMENT OF THE ASSAY? AND I CAN TELL YOU WE HEAR THAT FROM PATHOLOGISTS AROUND /THE WORL. AND THAT'S A /RLOT OF LABS. AND TRULY, THERE IS A WAY TO GET THAT INFORMATION, IT WOULD BE GREAT. BUT THE TIME LINES INCLUDE THAT TIME AND FAMILY.^, WHICH I THINK IS NOT IDEAL BUT IT'S PRACTICING MATIC. AND SO WE'RE OFTEN ENGAGED MORE AS THE ASSAY IS BEING IMPLEMENT IMPLEMENTED. BUT THAT DOESN'T MEAN THAT THERE CAN'T BE A MECHANISM TO /KPWAUR THAT INFORMATION TO IMPROVE THE ASSAY. >> COULD I -- >> SORRY. WE'RE TALKING ABOUT TWO DIFFERENT TIME LINES. ONE THAT'S AVAILABLE FOR THE IM IMPROVEMENT CYCLE. BUT WE DID START TALKING ABOUT THE TIME LINES FOR IMPLEMENTATION OF LD T OVERSIGHT OVERSIGHT. IF ANYONE WANTS TO TOUCH ON THAT LATTER TOP /KWREUIC BEFORE WE GO ON TO THE OTHER ONE. >> ANDY IS FIRST. >> I WANT /TED TO -- GETTING BACK TO THE TIMING QUESTION BECAUSE I THINK IT'S IMPORTANT JUST IN TERMS OF NOT ONLY QS REGULATIONS BUT P.M.A REQUIREMENTS AS WELL. I AM TRYING TO PUT THIS ENTIRE PROCESS IN PERCESPECTIVE, BOTH THE ISSUANCE OF THE DRAFT GUIDANCE, THIS MEETING THAT CONVERSATION WE'RE HAVING. AND I'M SUMMARIZING THE FOLLOWING. THERE ARE SOME BAD ACTORS OUT THERE. AND WHEN WE GO /TKPWGET THOSE BAD GUYS, THERE ISING ABOUT TO BE COLLATERAL DAMAGE. AND I THINK WHAT /YOU ARE ASKING TO US SAY IS HOW DO WE MINUIMIZE THE COLLATERAL DAMAGE? I THINK WHAT WE'VE HEARD AND KATIE YESTERDAY ONE -- SAID S LOOK AT THE LANDSCAPE AND LET'S UNDER /THE SCOPE OF THE PROBLEM, THEN UNDERSTAND THE LANDSCAPE AND THE SCOPE OF WHAT IT MEANS TO BEGIN TO BRING THESE LABORATORIES BACK INTO THE FOLD AND WHAT IT'S GOING TO DO /TO LARGE REFERENCE LABS. I THINK UNDERSTANDING WHAT IT MEANS TO PUT ALL OF THIS INTO PRACTICE IS GOING TO DEFINE A TIME LINE. AND IT MIGHT TAKE A WHILE AND THAT'S OKAY. BUT LET'S UNDERSTAND WHAT -- WHERE WE'RE GOING -- TRYING TO GET TO AND THEN DO IT AS PRACTICALLY AND AS SAFELY AS pPOSSIBLE. >> JESSICA? >> AND ONE MORE THING THAT I WANTED TO MENTION ABOUT THE CAP CHECKLIST AND I THINK ANDY SAID THAT I DO BELIEVE THAT THIS WHOLE PROCESS SHOULD TAKE AS RONG AS NEEDED. BUT ONCE THOSE REQUIREMENTS ARE ESTABLISHED AND THEY ARE PUT INTO AN /EUINSPECTION PROCESS OR CHECKLIST PROCESS, TYPICALLY WHAT CAP WILL DO, ENTER THE CHECKLIST QUESTION INTO THE APPROPRIATE CHECKLIST AND PUT IT AS WHAT'S CALLED A PHASE ONE SO THERE IS REALLY NO PENALTY THAT THE LAB IS INSPECTED UPON IT. BUT THEN THEY GET COMMENT AARY AND COME INTO COMPLIANCE WITH WHAT THE CHECKLIST WAS. SO WHAT HAPPENS WITH THOSE, ONCE THEY GO ON TO THE CHECKLIST FOR A PERIOD OF ABOUT TWO YEARS BEFORE THEY ARE REALLY THEN^-- THE LABORATORIES JUDGE UPON THEM WITH A POTENTIAL PENALTY FOR A ACCREDITATION. SO AGAIN, NOT ONLY TIME TO TAKE TO GET THIS WHOLE PROCESS TOGETHER, BUT ONCE THE PROCESS BEGINS, THERE SHOULD BE ALSO A TIME LINE FOR LETTING LABS UNDERSTAND THE REQUIREMENT OR THE INTENT OF THE QUESTION OR THE REQUIREMENT FROM THE FDA. SO TWO TIME LINES GUESS IS WHAT I AM TRYING -- >> AND GAIL, UNDER THAT PAR PARADIGM THE LAB IS ACTUALLY DOING THE WORK FOR /AA COUPLE /-OF YEARS AND THAT'S SOMEWHAT AT ODDS, AS /I UNDERSTAND THE WAY THE FDA APPROVAL -- >> RIGHT. BUT WHAT I WAS SAYING IS THAT'S WHAT WE'RE CURRENTLY DOING. THAT'S THE CLIIA AND THE CAT PROCESS. BUT IF THERE ARE ADDITIONAL QSR REQUIREMENTS AND THOSE COULD BE FOLDED INTO A SINGLE PROCESS AND THAT PROCESS HAS A CHECK RIS, THEN WE ENTER THOSE CHECKLISTS OR ADD THOSE CHECKLIST QUESTIONS AT A TIME ONCE WE ALL UNDER AND AGREE UPON THESE REQUIREMENTS. BUT THEN THERE IS A TIME LINE TO WHICH THE LAB HAS SOME ALLOWANCE ALLOWANCEY FOR THEIR PENALIZE. >> AND I AGREE. YOU MENTIONED THE WORD "YEARS" AND I AGREE. >> JUST ONE THING. I THINK WE'RE LOSING SIGHT OF THE FACT THAT WE'RE TALKING ABOUT CHECKLIST AND INSPECTION PROCESS. BUT WE'RE REALLY TALKING ABOUT SUBMISSIONS TO THE FDA. I MEAN, THAT'S THE BIG THING HERE. IT'S NOT JUST LABORATORIES CONTINUING TO DO LD TS. IT SEEMS /TTHAT THEY'RE CURRENTLY LISTED IN THE DRAFT GUIDELINES. TRADITIONALLY -- TRADITIONAL LD TS, WHERE THAT MAY BE TRUE. THERE IS A LARGE NUMBER OF LD TS THAT WILL BE CONSIDERED AS MOD MODERATE OR HIGH-RISK AND WE'LL EVENTUALLY HAVE TO SUBMIT TO THE FDA FOR APPROVAL OR CLEARANCE AS WELL. SO AND WE'RE ASKING FOR GUIDANCE FOR THAT ALSO. HOPEFULLY, THE INSPECTION PROCESS FOLLOWING THAT WILL BE MORE APPROPRIATE AS /AA CLINICAL LAB DOING ONE OF THESE TESTS. I THINK THERE IS MORE TO WHAT'S BEING ASKED OF US THAN JUST THE INSPECTION. >> OKAY. >> AND ONE OTHER THING. WHILE WE'RE TALKING ABOUT THE IN INSPECTION PROCESS. AND WHAT IT IS THAT'S BEING SUBMITTED TO THE FDA. IS /THE NEED FOR /AEA CLEAR DIVIING LINE IN WHAT'S CONSIDERED MANUFACTURING AND WHAT IS THE NORMAL RUNNING OF /AA CLINICAL LABORATORY. THAT IS STILL VERY FUZZY AND THAT NEED TO BE CLARIFIED AND THAT'S GOING TO HAVE AN IM/PABPACT ON THE TIME LINE AS WELL. >> I WANT /TED TO TOUCH ON WHAT SCOTT WAS TALKING ABOUT WHERE LABORATORIES TRY TO WORK WITH FDA-APPROVED IDD MANUFACTURERS AND TRY TO IM/PROPROVE ASSAYS AND WHETHER OR NOT THAT PROCESS IN AND OF ITSELF IS WORKING. AND UNFORTUNATELY, I DON'T THINK IT IS. AND SO WE HAVE LOTS OF EXAMPLES PUBLISHED IN LITERATURE, GOOD EXAMPLES OF CONVERSATIONS OF LABORATORIES LIKE ME SPEAKING WITH FDA APPROVED IDD MANUFACTURERS. AND IT DOESN'T GO THAT WELL GENERALLY-SPEAKING. AND THERE IS A LOT /OF LITERATURE OUT THERE THAT SAYS FDA-APPROVED DEVICES DON'T ANSWER THE CLINICAL QUESTIONS THAT THEY NEED TO, THAT LABOIES ARE TRYING TO -- THEY GET RESULTS AND FIPHYSICIANS ARE INTERPRETING THEM BASED ON GUIDELINES BUT THE LAB RESULTS FROM TWO DIFFERENT PLATFORMS ARE COMPLETELY DIFFERENT. AND AGAIN, THAT'S NOT IN THE PURVIEW NECESSARY RIOF FDA. IT IS IN THE PURVIEW OF THE PRACTICE OF MEDICINE AND UNDER UNDERSTANDING THE DIFFERENCES BETWEEN PLATFORMS IS /THE PRACTICE OF MEDICINE. I WOULD SAY. UNLESS SOMEONE HAS WORKED -- WALKED INTO THE FDA AND SAY CAN I PLEASE CLAIM EQUIVALENCE TO THIS OTHER MANUFACTURER? WHEN THEY AGREE AT THE TIME OF RELEASE YET TWO YEARS LATER DON'T, THAT AFFECTS MY PRACTICE OF MEDICINE AND THERE IS NOTHING REALLY THATA HAS THE POWER TO DO /TO CHANGE THAT NECESSARILY. AND SO WE'VE TALKED ABOUT -- LARA TALKED ABOUT OVER OVERTURE AND HOW THAT RUINED PEOPLE /A'S LIVES. AND TO MY KNOWLEDGE THERE IS ACTUALLY NO LAWSUIT OR OTHER FRAUD AGAINST A COMPANY THAT HAS OFFERED IT AS AN LD T. BUT YOU COULD LOOK AT THE UNIVERSITY OF WASHINGTON AS AN EXAMPLE WHO ACTUALLY HAD A LAWSUIT BROUGHT AGAINST THEM FOR USING AN FDA-APPROVED DEVICE. AND A WOMAN WHO DID HAVE HER UT UTERUS REMOVED BECAUSE OF RESULTS OF A LABORATORY TEST. FDA-APPROVAL OR PRE-MARKET A APPROVAL DOES NOT GUARANTEE A . GOOD FUNCTIONING TEST IN ALL THERE ARE FALSE POSITIVES AND FALSE NEGATIVES AND THAT'S JUST THE PRACTICE OF MEDICINE. TO TAKE THESE LD TS AND USE THEM IN THE CONTEXT OF OUR PATIENT CARE IS WHAT THEY'RE INTEREST FOR. SO I DON'T KNOW THAT THE P.M.AS IS NESS -- NECESSARILY GOING TO IM/PROPROVE. BUT THERE ARE WAYS TO IDENTIFY THE THINGS THAT WE'RE MISSING IN THE INSPECTION PROCESS, PARTICULARLY IN CLIIA AND TELL US WHAT WE'RE MISSING AND LET'S PUT IF IN PLACE. BUT WE NEED TO BORK, I THINK WITH CLIIA SO I WELCOME SCOTT'S THE THOUGHT ABOUT WORKING WITH LABORATORIES TO /TRAOTRY TO IM/PROFPROVE THINGS. >> YEAH. THAT'S A VERY GOOD POINT, ANDY. AND I WAS TALKING ABOUT A VERY NARROW RANGE OF DIAGNOSTICS, XAN COMPANION DIAGNOSTICS. RECOGNIZE THAT IT MAY NOT BE ALWAYS SIMPLEFOOD -- TO DO. BUT THE DATA GENERATED BY THE LABORATORY WAS ABLE TO BE BROUGHT INTO THE DESIGN HISTORY FILE OR THE P.M.A, I THINK THAT WOULD AT LEAST BE A FIRST STEP IN THAT REGARD. AS /I PREDICATED MY CLIENTS MY CONCERN IS /THE ACCURATE IDENTIFICATION OF PATIENT'S HE WILL JUST A BIT TO THERAPY AND WE KNOW THAT THE TEST THAT WE UT RIAISED TO CLINICALLY VALID /A*ATE THAT TO ACHIEVE THAT AIM IN THE PATIENT POPULATION. IT WAS PART OF THE CLINICAL TRIAL. OTHERWISE, WOULDN'T HAVE ACHIEVED THAT END. THERE ARE A NUMBER OF LABORATORY TESTS THAT ARE DEVELOPED THAT SUBSTANITUTE FOR THE P.M.A AND WHERE I'M CLEAR IS /THE PERFORMANCE CHARACTERISTICS OF THOSE ASSAYS. NOT TO SAY THEY CAN'T BE, ABSOLUTELY IDENTIFIED. IT'S JUST UNCLEAR TO US WHETHER THAT IS THE CASE AND WE DON'T KNOW THAT. AND EVEN THOUGH WE'D BE HAPPY WITH THE DIAGNOSTIC PARTNERS AND WE BELIEVE THAT THE TEST ASSAYS HAS BEEN PRODUCED AND FILED FOR PRE-MARTH APPROVAL, WE ALSO RECOGNIZE THAT WHEN IT GETS INTO THE BROADER COMMUNITY, OTHER ISSUES WILL ARISE. AND I THINK THERE NEED TO BE A MECHANISM THAT COULD ALLOW FOR THOSE TO OCCUR THAT SEEMS TO ME LIKE THE FRAMEWORK THAT'S BEEN PROPOSED AND /AA COMPONENT OF IT PROVIDES THAT OPPORTUNITY. BUT IT'S SOMETHING THAT I WOULD LIKE TO SEE US TRY TO PURSUE. AS FAR AS THE TIMEFRAME GOES, OBVIOUSLY, OUR CONCERN IS THAT WE DON'T KNOW -- ALWAYS HAVE THE ASSAYS, BUT WOULD /HRAOEULIKE TO SEE IT IN SOME KIND OF TIMEFRAME TO BRING THAT INTO BEING. IT WASN'T TOO LONG. BUT FULLY RECOGNIZING REALLY IMPORTANT CONCERNS OVER /THE RAFT COUPLE /OF DAYS. SO I THINK /HRAFS TO BE PUT INTO A TIMELINE. >> ANDY HE CECHOED THE SAME POINT. PERFECT DEVICE IN THE WRONG HAND IS NO LONG A DEVICE. AND I AM NOT SURE THIS IS AN FDA PURR VIEW AND IT MAY BE A MEDICAL PREMISE. IT SEEMS TO ME THESE KIND OF CONTROLS EITHER ON A VOLUNTEER OR A COMMUNITY BASIS, COULD BE EASILY PUT IN WITHOUT NECESSARY NECESSARILY INVOLVING A LOT /OF REGULATIONS. I DON'T KNOW IF THAT'S WHAT YOUR ORGANIZATION DOES TO A CERTAIN EXTENT. >> I THINK THAT SOME OF WHAT WE'RE TALKING ABOUT IS REALLY TRANS/PAEURPPARENCY AND THAT MAY BE LACKING IN LD TS RIGHT NOW. MAYBE THERE IS SOME WAY OF GETTING THAT INFORMATION OUT THERE. WITH AN FDA-APPROVED OR CLEARED TEST, THE SENSITIVITY AND SPEC FISITY ARE STATED. THERE IS VERY FEW TESTS THAT ARE PERFECT. THERE ARE GOING TO BE FALSE POSITIVE AND FALSE NEGATIVES, NO MATTER WHO IS APPROVED. SO MAYBE IN THAT CASE ONE OF THE THINGS THAT'S NEEDED IS TRANS TRANS/PAEURPPARENCY. I THINK IT WAS STATED THAT IT WAS 70% SENSITIVE. SO IF A FIPHYSICIAN IS USING THAT AND PAYING ATTENTION TO THE ACTUAL PERFORMANCE CHARACTER CHARACTERISTICS THAT WERE KNOWN, THEY WOULD NOT -- KNOW NOT TO USE THAT ONLY TO DETERMINE WHETHER OR NOT -- >> RIGHT ON TIME. DO YOU WANT TO HAVE A SHORT COMMENT, SOME >> I WANT TO AT /WUONE COMMENT TO WHAT'S BEEN DISCUSSED RECENTLY. BECAUSE THE FDA APPROVAL ONLY GOES SO /TPFAR AND IT'S NOT NECESSARY THAT THE TEST IS IN BAD HANDS VERSUS GOOD HAND. LIKE TO DISMISS THAT. BUT TISSUE AND PATIENT SPECIMENS ARE BIOLOGICAL SPECIMENS AND THEY'RE DIFFERENT. SO THAT'S THE PRACTICE OF MEDICINE. NOT EVERY SPECIMEN IS GOING TO BEHAVE OR PERFORM THE SAME AS THE OTHER SPECIMEN AND SO WHERE THE FDA APPROVAL OR THE LABORATORY CLIIA PROCESS ENDS, THAT'S WHERE PROFESSIONAL ORGANIZATION AND GUIDELINES BEGIN. AND I WOULD GIVE THE EXAMPLE OF THE GUIDELINES. AN FDA-APPROVED TEST BOTH FOR IH IHD AND ISA. BUT YET VARIED INTERPRETATION AMONG LABORATORIES. AND SO IT WAS PROFESSIONAL ORGANIZATIONS THAT CAME TOGETHER AND TOOK AN FDA TEST AND THEN IM IMPROVED THE PERFORMANCE OF THAT TEST THROUGH GUIDELINES. >> I WANT TO GIVE /EFREVERYONE AN OPPORTUNITY TO TAKE 30 SECOND TO SUM UP /SAND IF YOU WANT -- I'D BE HAPPY TO ADJOURN AS WELL. >> I THANK YOU FOR THE CONVERSATION. I HOPE THIS STARTS THE CONVERSATION AND I HOPE THIS ISN'T THE END OF IT BECAUSE I THINK THERE IS A /RROT TO LEARN. >> I'VE LEARNED A /RROT TODAY AND I APPRECIATE THE COMMENTS. I KNOW YOU GUYS WORKED VERY HARD ON THIS AND WE DO APPREC THIS. WE'RE ANXIOUS ABOUT THE WHOLE THING, SO YOU ARE HEARING OUR ANXIOETY AS WELL THAT WE WANT /TTO CONTINUE TO WORK WITH YOU ON IT. >> AND I AM ALL FOR IMPROVING ANY PROCESS THAT'S WE CAN THAT HELPS ME DO MY JOB BETTER. DESIGN PATROL AND LEARNING ABOUT IT. THERE ARE SOME THINGS I LIKE IT -- ABOUT IT AND THERE ARE SOME THINGS THAT I DON'T THINK ARE GOING TO BE HELPFUL BUT WILL IN INCREASE THE BURDEN. AND I WOULD SAY MAYBE BEFORE YOU ASK LABORATORIES TO DO DESIGN CONTROL, MAYBE IT'S TIME TO GO BACK /SAND REVIEW THE DESIGN CONTROL AND WHAT IS GOOD ABOUT IT AND WHAT IS SIMPLY NOT GOING TO HELP YOU MAKE A BETTER PRODUCT OR A BETTER ASSAY BUT IT'S JUST GOING TO BE MORE ADMINISTRATIVE WORK THAT IS NOT GOING TO HAVE MUCH VALUE.^ >> I THINK THAT THIS IS A GREAT TIME TO ACTUALLY HAVE THIS DISCUSSION. IT'S BEEN A RONG TIME COMING, BUT CERTAINLY CRITICAL NOW WITH EVERYBODY SPEAKING ABOUT IT IN MEDICINE. AND SO I THINK THAT THIS A APPROACH REALLY CAN HELP ENSURE THAT THAT IS ACTUALIZED IN A WAY THAT WILL HELP PATIENTS, SO THANK YOU VERY MUCH FOR BEING PART OF THE DISCUSSION. AND -- >> I AGREE. I HOPE THIS IS THE /KPWEUPBG OF THE DIALOGUE ON THIS. AND BEGINNING. I THINK IT WOULD BE VERY HELPFUL TO SET UP GUIDELINES FOR THE LABORATORIES. I THINK THERE ARE SOME FURTHER QUESTIONS. JUST TALKING TO PEOPLE HERE, THERE IS A /RLOT OF CONFUSION ABOUT HOW MANY OF THESE THINGS ARE ACTUALLY LD TS, MADE /OF MODIFICATION TO ARN EXISTING A ASSAY. ARE YOU GOING TO BE RADIOIAT ALL OF THOSE? AN ISSUE I BROUGHT UP YESTERDAY IN TALKING ABOUT OUR CLEARANCE, WHERE ALL OF THE INSTRUMENTS, INCLUDING THE LIQUID HANDLER, WAS RESISTED BY SERIAL NUMBER AND PEOPLE HAVE ASKED ME OH, YOU MEANT MOLL NUMBER AND I SAID NO, I DIDN'T MEAN MODEL NUMBER. IT WAS EVERY -- THE ONES THAT WERE USED TO DO THE CLINICAL TESTS OR THE CLINICAL VALIDATION VALIDATIONS ARE THE ONLY INSTRUMENTS THAT CAN BE USED TO DO THE TESTS, UNLESS WE RE RE/SPHESUBMIT. SO THIS KIND OF BURDEN IS GOING TO BE /AA HUGE BURDEN ON THE FDA AS WELL. >> >> I'LL GO BACK TO CLARITY. I THINK AGAIN, THAT'S ONE THING HAT YOU ARE HEARING OVER AND OVER AND OVER AGAIN. I DO LIKE TO -- THE PHASE-IN A APPROACH AND TIME /RAOEUPBZ THAT ARE TWO YEARS, THREE YEARS, WHATEVER. I THINK WITHOUT TESTING THE SYSTEM AND GETTING EXPERIENCE IN WHAT IS CHANGING AND WHAT IS THE INTENTION AND THE EXPECTATIONS WOULD BE DIFFICULT TO IMPLEMENT. SO PHASE-IN APPROACH WITH CHECK CHECKLIST AND CLARITY WOULD BE FANTASTIC. THE OTHER THING THAT I'VE HEARD THAT I WANT TO REITERATE, TOO, IS /THE INVOLVEMENT OF CMS. OBVIOUSLY, THEY HAVE SYSTEMS IN PLACE. I THINK IT'S VERY PROBLEMATIC IN A CERTAIN WAY THAT IT'S UP TO THE LOCAL INSPECTOR. AND HOW THINGS ARE INTERPRETED. BUT AGAIN, GETTING CLARITY THERE AND MORE CONSIST /*EPENCY AND MORE CONSIST /*EPENC AND WORKING CLOSELY WITH WHAT'S ALREADY IN PLACE FROM THE FDA'S PERCESPECTIVE PERSPECTIVE, WE AREN'T DUPE INDICATING OUR EFFORT IN HELPING US GET TO WHERE EVERYBODY, I THINK, WANTS TO GET US. AND THEN THE OTHER REALLY MAJOR CONTRIBUTOR QUALITY THAT I THINK NEED TO BE AT THE TABLE AND OBVIOUSLY IS VERY INTERESTING -- THIS IS THE REIMBURSEMENT. ORGANIZATIONS AND THEY SHOULD BE PAYING FOR QUALITY. AND IT'S IN THEIR BEST INTEREST, TOO,. TO BE CERTAIN THAT BEER IDENTIFYING IT AND CONTROLLING IT IN /AA WAY THAT THEY'RE SATISFIED WITH AND THAT /KPWETS INTO THE CLINICAL -- /TPHRAU[INAUDIBLE] GETS. I THINK FOR THESE TESTS DEMONSTRATING WHERE THEY OUGHT TO BE. >> I WANT TO THANK THE PANEL FOR BEING QUITE CONCISE THE ENTIRE TIME. THAT'S GREAT AND THANK YOU FOR BEING UP HERE. /PHRA[APPLAUSE] >> THANK YOU. WE HAVE A LOST WALLET. RUTH? IF YOU'VE LOST YOUR WALLET, WE HAVE IT UP HERE. SO I AM GOING TO SKIP THE BREAK AND DAVID SMALLEY IS GOING TO SPEAK AND THEN WE'LL HAVE CLOSING REMARKS FROM DR. SHARON. DO YOU WANT TO COME ON UP? >> GOOD AFTERNOON. MY NAME IS DAVID SMALLEY. I'M THE PRESIDENT OF THE LABORATORIES BASED IN TENNESSEE. I'M HERE TODAY ON BEHALF OF THE AMERICAN ASSOCIATION OF BIOAN BIOANALYSTS, OTHERWISE KNOWN AS AA /PW-FPB. WHERE I SERVE ON THE BOARD OF DIRECTORS AND I ALSO SERVED ON THE ASSOCIATION'S RK T WORK GROUP. AB IS A NATIONAL PROFESSIONAL ASSOCIATION AMONG OTHER LABORATORY PERSONNEL. IN ADDITION TO PROVIDING DIAGNOSTIC LABORATORY TESTING SERVICES RELYING ON FIPHYSICIANS EVERY DAY AND /AA NUMBER OF MEMBERS ARE ENGAGED IN THE DEVELOPMENT OF LABORATORY TESTS. THAT PROVIDE FIPHYSICIANS AND THEIR PATIENTS ACCESS TO SAFE AND EFFECT /KWREUIVE TESTS -- TESTING OPTIONS TO SUPPORT MEDICAL DECISION MAKING. SINCE 1949, AB HAS ADMINISTERED THE FULL SERVICE PROGRAMS A APPROVED BY CLIIA, THE JOINT COMMISSION AND ALL STATE AGENCY AGENCIES TO SATISFY LABORATORY PROFICIENCY TESTING REQUIREMENTS REQUIREMENTS. AA /PW-FPB'S PERCENSPECTIVE ONOVER SIGHT ON LD TS IS LARGELY THROUGH THESE LENS. AS /AA COMMUNITY, WE TALK ABOUT THE OVERSIGHT OF LD TS, PATIENT SAFETY MUST BE PARAMOUNT. THE PURPOSE IS TO OFFER PATIENTS WITH POTENTIAL TO PREVENT DISEASE, OBTAIN EARLY DIAGNOSISS AND REVIEW THE MOST ACCURATE AND BEST COURSE OF TREATMENT FOR THEIR HEALTHCARE PROVIDERS. FIPHYSICIANS MUST BE ABLE TO /RRELY ON AND TRUST THE RESULTS PROVIDE PROVIDED FROM AN LD T. AS HEALTHCARE PROVIDERS AND AS PROVIDERS OF FEDERAL AND STATE-A STATE-APPROVED PROFICIENCY TEST TESTING, AA /PW-FPB STRONGLY BELIEVES THAT A /SKPWRAEURGS NON-BURDEN PROCESS MUST BE IN PLACE TO EN ENSURE THAT TECHNOLOGY IS A ACCURATE, RELIABLE AND RE/PRAOUS REPRODUCIBLE. THE PRIMARY GOAL TO REGULATORY OVERSIGHT SHOULD BE TO AVOID POTENTIAL LIFE-ALTERING OR THREATENING IMPLICATIONS FROM AN INACCURATE OR MISLEADING TEST RESULT. A FAIR AND SOLID PROCESS IS NEEDED /TAO*T -- TO DO JUST THAT. I'D LIKE TO FOCUS MY REMARKS ON 4 KEY POINTS -- FIRST, LD TS SHOULD NOT BE REGULATED AS MEDICAL DEVICES. CLINICAL LABORATORIES ARE NOT MANUFACTUREERS IN PRACTICE OR UNDER STATUTE. THEY ARE HEALTHCARE PROVIDERS WHO OFFER TESTING SERVICES, NOT PRODUCTS. THESE SERVICES INCLUDE CONSULTATION WITH FIPHYSICIANS TO SUPPORT THE DESIGN OF NEW TESTS, CONDUCTING TESTING ON PATIENT SAMPLES AND INTERPRETING OF TEST RESULTS TO SUPPORT FIPHYSICIAN /UPBTS -- UNDERSTANDING. THESE TEST ACTIVITIES GREATLY DIFFER FROM THOSE FROM MANUFACTURERS. THE REGULATION OF LK TS SHOULD BE TRU A RISK-BASED APPROACH AND ENSURES BOTH AN /HREALYTIC AND CLINICAL VALIDITY OF ALL LK IT T TS. SUPPORTS ARE RISK-BASED PROCESS THAT WOULD FIRST ESTABLISH A CONCRETE ADVISORY AND RULE- RULE-MAKING PROCESS FOR RISK CLASSIFICATION AND INVOLVES LABORATORY SCIENTISTS, FIPHYSICIAN PHYSICIANS, CONSUMERS AND OTHER STAKEHOLDERS. THIRD, CLIIA'S ROLE SHOULD BE BETTER UNDERSTOOD AND MODERNIZE MODERNIZEED. CLIIA HAS THE BEST KNOWLEDGE AND EXPERIENCE WITH REGARD TO THE CLINICAL TESTING PROCESS AND THE REGULATES THE QUALITY OF CLINICAL LABORATORY TESTING PROCESS, QUALITY OF LABORATORY PERFORMING THE LABORATORY AND ASSESS THE TESTS THEMSELVES. AND FINALLY ANY NEW REGULATION OF LD TS SHOULD BE DONE THROUGH NOTICE AND COMMENT RULE-PAYING. THE REGULATION RAISED MANY COMPLICATED QUESTIONS TO IN INAPPROPRIATE AND DISSERVICE TO HEALTHCARE PROVIDERS, PATIENTS AND LABORATORIES TO HAVE REGULAR REGULATORY OVERSIGHT PROCESS OF LD TS IN MANY WAYS -- INAUDIBLE [INAUDIBLE] THANK YOU. >> WITH THAT, WE WILL TURN IT OVER TO DR. SHARON FOR CLOSING REMARKS. I'LL LEAVE THE DOCKET COMMENT LINK UP HERE. AND ANY QUESTIONS YOU CAN EMAIL US LATER. >> WELL, I KNOW THE WEEKEND IS UPON US, SO I WILL KEEP THIS SORT. LET ME SAY ON BEHALF OF THE FDA JUST THANK YOU TO ALL OF YOU WHO ARE HERE OR PARTICIPATED BY WEB WEBCAST FOR BEING A PART OF OUR TWO-DAY PUBLIC MEETING. IN PARTICULAR, I WANT TO THANK FOLKS WHO CAME UP /SAND PROVIDED COMMENTS AND THOSE WHO PARTICIPATED ON OUR PANELS. WE GOT VERY CONSTRUCT /KWREUIVE AND THOUGHTFUL FEEDBACK AND WE GREATLY APPRECIATE THAT. WE'RE GOING TO TAKE ALL OF THAT ALSO ENCOURAGE ALL OF YOU TO SUBMIT COMMENTS TO THE PUBLIC DOCKET, WHICH CLOSETS ON FEBRUARY 2ND. AND THAT WILL IN/TPORFORM HOW BEST TO PROCEED. ONE THING WE CAN CERTAINLY COMMIT TO AND WE WILL COMMIT TO IS TO KEEP THE DIALOGUE GOING. WE VIEW THAT THE GREATEST SUCCESS MOVINGRD IS TO HAVE CONSTRUCT /KWREUIVE DIALOGUE AND TO WORK COLLABORATIVELY TOGETHER TOGETHER. OBVIOUSLY, THERE ARE A BROAD RANGE OF PERCENTIVES, AS YOU'VE HEARD AT THE PUBLIC MEETING. THE PERCESPECTIVES KIND OF RUN THE SPECTRUM. AND AS A RESULT, AS YOU KEEP HEARING, THERE IS PROBABLY NOT A SOLUTION THAT MAKES EVERYONE HAPPY. BUT AT THE END, WHAT THIS IS BALL IS ABOUT PATIENCE AND HOW DO WE FIND THAT MOST OPTIMAL BALANCE BETWEEN ENSURING THAT THOSE TESTS, ARE GOOD TEST BUZZ WE WANT /TO MAKE /SHAOUSURE THERE IS ON A /SRAEUGS. SO WE DO HAVE NEW GOOD TESTS COMING FORWARD AND THAT PATIENTS AND PROVIDERS HAVE ACCESS TO THEM. SO AGAIN, THANK YOU VERY MUCH. HAVE A GREAT WEEKEND. /PHRA [APPLAUSE]