1
00:00:15,882 --> 00:00:17,083
>> Rachel Evans:
Hello, everyone.

2
00:00:17,150 --> 00:00:18,718
My name is Rachel Evans,

3
00:00:18,785 --> 00:00:20,587
and I'm a regulatory
affairs specialist

4
00:00:20,653 --> 00:00:22,822
for the Office of Research
Support and Compliance

5
00:00:22,889 --> 00:00:25,091
at the National Institutes
of Health.

6
00:00:25,158 --> 00:00:28,495
So, I'm going to go over
a little introduction to CGMP.

7
00:00:32,699 --> 00:00:34,667
So, what is CGMP?

8
00:00:34,734 --> 00:00:38,571
So CGMP stands for current
good manufacturing practices,

9
00:00:39,272 --> 00:00:43,843
and per the FDA,
CGMP provides systems

10
00:00:43,910 --> 00:00:47,113
which assure proper design,
monitoring, and control

11
00:00:47,180 --> 00:00:50,150
of manufacturing processes
and facilities.

12
00:00:50,817 --> 00:00:53,686
So, the overall
goal to have CGMP

13
00:00:53,753 --> 00:00:56,856
is to make sure any product,
whether it's drug or biological,

14
00:00:57,357 --> 00:00:59,692
is safe for human
or veterinary use.

15
00:01:00,727 --> 00:01:04,130
And what makes CGMP unique

16
00:01:04,197 --> 00:01:06,866
is that it's a highly
regulated industry,

17
00:01:06,933 --> 00:01:10,336
and it's typically regulated by
different government agencies,

18
00:01:10,403 --> 00:01:12,539
such as FDA, EMA,

19
00:01:13,406 --> 00:01:16,843
even country-specific
government agency as well.

20
00:01:19,979 --> 00:01:24,217
So, the regulatory aspect,
who falls under CGMP?

21
00:01:24,284 --> 00:01:28,121
So, it's typically any facility
manufacturing drug products

22
00:01:28,188 --> 00:01:30,857
and biological products for
human and veterinary use,

23
00:01:31,424 --> 00:01:34,828
compounding pharmacies
such as 503B,

24
00:01:34,894 --> 00:01:37,330
phase two products, and
phase three products.

25
00:01:38,164 --> 00:01:40,366
And even though
they're not technically

26
00:01:40,433 --> 00:01:43,203
supposed to follow all of CGMP

27
00:01:43,269 --> 00:01:45,004
depending on what kind
of products you make

28
00:01:45,071 --> 00:01:46,673
and if it's patient specific,

29
00:01:47,273 --> 00:01:51,344
503A compounding pharmacies
as well as phase ones

30
00:01:51,411 --> 00:01:54,781
are still recommended to
meet CGMP wherever possible.

31
00:01:56,382 --> 00:01:58,585
And who's the
regulatory authority?

32
00:01:58,651 --> 00:02:01,054
So, again, it depends,
really, on your country.

33
00:02:01,120 --> 00:02:05,158
So, for U.S., it would be your
local state as well as the FDA,

34
00:02:05,225 --> 00:02:06,926
or Food and Drug Administration.

35
00:02:07,894 --> 00:02:12,499
For E.U., it would be EMA,
so European Medicines Agency.

36
00:02:13,166 --> 00:02:16,569
And then Japan would also PMDA,

37
00:02:16,636 --> 00:02:19,172
or Pharmaceuticals and
Medical Devices Agency.

38
00:02:20,173 --> 00:02:22,609
And another ting
to consider with GMP

39
00:02:22,675 --> 00:02:25,678
is if your product is
shipped internationally,

40
00:02:25,745 --> 00:02:27,847
whether it's coming
from the United States

41
00:02:27,914 --> 00:02:29,716
and going to the E.U.,

42
00:02:30,550 --> 00:02:34,220
you will be inspected by
multiple government agencies.

43
00:02:37,524 --> 00:02:39,726
So what are these regulations?

44
00:02:39,792 --> 00:02:43,229
Each regulatory agency also
has specific regulations

45
00:02:43,296 --> 00:02:45,298
and even provide
guidance documents

46
00:02:45,365 --> 00:02:48,468
to kind of help you understand
what the regulations are.

47
00:02:48,535 --> 00:02:51,104
So, for GMP, the big one
that everybody uses,

48
00:02:51,170 --> 00:02:52,839
whether it's Europe.

49
00:02:52,906 --> 00:02:56,175
Japan, or even the U.S.,
it's typically Annex One.

50
00:02:57,577 --> 00:03:01,447
And that one spells
out a lot of the way

51
00:03:01,514 --> 00:03:04,751
to interpret the regulations,
as well as give you guidance

52
00:03:04,817 --> 00:03:07,086
on where to start in
building your processes

53
00:03:07,153 --> 00:03:09,122
as well as constructing
your facilities

54
00:03:09,188 --> 00:03:10,790
and what requirements you need.

55
00:03:11,457 --> 00:03:13,426
Additional resources
-- because in GMP,

56
00:03:13,493 --> 00:03:15,094
we don't ever just use one --

57
00:03:15,695 --> 00:03:21,200
we also refer to USP, PDA,
which is a great resource

58
00:03:21,267 --> 00:03:23,503
because they provide
technical reports,

59
00:03:24,270 --> 00:03:25,805
ISO, PICS,

60
00:03:25,872 --> 00:03:29,108
and then ICH also provides
good recommendations on GMP.

61
00:03:31,911 --> 00:03:35,448
So, what kind of requirements
are listed in these documents?

62
00:03:36,549 --> 00:03:42,522
It's actually focuses on a lot
of different areas of aspect,

63
00:03:42,589 --> 00:03:45,425
so you typically would
have a quality manual.

64
00:03:45,491 --> 00:03:46,893
And it goes into
different things

65
00:03:46,960 --> 00:03:49,762
like what type of product
you're manufacturing,

66
00:03:50,263 --> 00:03:53,766
facility design,
including controls,

67
00:03:53,833 --> 00:03:57,203
how you're able to maintain
those specific requirements

68
00:03:57,270 --> 00:04:00,006
to have and manufacture
your product,

69
00:04:01,474 --> 00:04:03,743
the personnel and the
gowning requirements,

70
00:04:04,243 --> 00:04:06,179
flow patterns to how
people and materials

71
00:04:06,245 --> 00:04:08,848
are going to move through
the different spaces,

72
00:04:08,915 --> 00:04:11,217
what kind of equipment
and materials you need,

73
00:04:11,985 --> 00:04:13,987
your cleaning processes.

74
00:04:14,053 --> 00:04:17,156
And cleaning processes can
also include validated methods

75
00:04:18,358 --> 00:04:20,493
on your specific
cleaning agents,

76
00:04:20,560 --> 00:04:22,595
routine cleaning,
cleanings of equipment.

77
00:04:24,197 --> 00:04:27,133
Documentation is
another big aspect

78
00:04:27,200 --> 00:04:31,104
that is highly regulated,
which are records and reports.

79
00:04:31,704 --> 00:04:34,507
And then you have your
different quality systems

80
00:04:34,574 --> 00:04:37,210
or of your environmental
monitoring systems

81
00:04:37,276 --> 00:04:40,980
or your document systems are
all part of the requirements

82
00:04:41,047 --> 00:04:43,716
and are regulated
by regulatory agencies.

83
00:04:45,184 --> 00:04:49,155
Another thing that we do pretty
often in GMP is testing.

84
00:04:49,222 --> 00:04:53,059
So a lot of things to
validate and also prove

85
00:04:53,126 --> 00:04:54,694
that your facility is
in a state of control,

86
00:04:54,761 --> 00:04:56,896
you do a lot of
different testing.

87
00:04:56,963 --> 00:04:59,198
And a lot of the
ways that we come up

88
00:04:59,265 --> 00:05:00,800
with what kind of
equipment we use,

89
00:05:00,867 --> 00:05:04,270
cleaning, how we
document certain way

90
00:05:04,337 --> 00:05:07,740
is typically done via a
risk-based approach.

91
00:05:10,543 --> 00:05:13,479
So why would we even have
all of these requirements?

92
00:05:14,814 --> 00:05:17,016
Well, the main goal is
to protect the product

93
00:05:17,083 --> 00:05:18,251
and, in certain cases,

94
00:05:18,317 --> 00:05:20,920
some personnel from
being contaminated

95
00:05:20,987 --> 00:05:22,655
or even harming a
potential patient,

96
00:05:22,722 --> 00:05:23,990
because a lot of our product

97
00:05:24,057 --> 00:05:27,060
that we manufacture
go directly to a patient,

98
00:05:27,126 --> 00:05:31,030
and a lot of patients
have the understanding

99
00:05:31,097 --> 00:05:32,632
that what they're receiving,

100
00:05:32,699 --> 00:05:35,568
whether it's an IV
or chemotherapy drugs

101
00:05:35,635 --> 00:05:38,504
or over-the-counter medicine,
is safe for them to use.

102
00:05:41,607 --> 00:05:45,445
So how do GMP facilities
meet regulatory requirements?

103
00:05:45,511 --> 00:05:47,513
So the big one is
quality assurance.

104
00:05:48,247 --> 00:05:51,551
So quality assurance
actually reviews separate

105
00:05:52,618 --> 00:05:55,088
from the operational team
to ensure that all

106
00:05:55,154 --> 00:05:58,691
SOPs, procedures, protocols,
and requirements are met.

107
00:05:59,826 --> 00:06:03,429
They also overall monitor
how the facility is behaving,

108
00:06:03,496 --> 00:06:05,198
how the personnel is behaving,

109
00:06:05,264 --> 00:06:07,533
as well as the
overall operations

110
00:06:07,600 --> 00:06:09,902
and reviewing of all
of the different batches.

111
00:06:11,404 --> 00:06:14,307
And another tool that
quality assurance uses

112
00:06:14,373 --> 00:06:16,743
is routine audits
and inspections.

113
00:06:16,809 --> 00:06:19,746
So not only do CGMP
facilities get inspected

114
00:06:19,812 --> 00:06:24,450
by different government agencies
or state departments, they --

115
00:06:25,218 --> 00:06:28,821
the quality assurance team,
or even a third-party vendor,

116
00:06:28,888 --> 00:06:33,259
will come out and audit
different systems within GMP

117
00:06:33,326 --> 00:06:34,927
on a frequent basis.

118
00:06:36,162 --> 00:06:39,098
And the whole point of all of
these quality assurance

119
00:06:39,165 --> 00:06:42,301
inspections and audits
are just to demonstrate control

120
00:06:42,368 --> 00:06:45,004
over the different processes
and the facility.

121
00:06:47,507 --> 00:06:49,475
So on the screen,
I have a little bit

122
00:06:49,542 --> 00:06:51,511
of a facility
organizational chart.

123
00:06:51,577 --> 00:06:55,214
This is very high level,
but this kind of shows

124
00:06:55,281 --> 00:06:58,718
you how CGMP facilities
are structured.

125
00:06:58,785 --> 00:06:59,919
So at the head,

126
00:06:59,986 --> 00:07:02,855
you have your manufacturing
authorization holder,

127
00:07:02,922 --> 00:07:04,524
or the facility owner.

128
00:07:05,525 --> 00:07:08,261
To the right of them, or
directly underneath them,

129
00:07:08,327 --> 00:07:11,798
is the head of operations.
And underneath them,

130
00:07:11,864 --> 00:07:13,499
you typically have
your production manager,

131
00:07:13,566 --> 00:07:15,535
quality control.

132
00:07:15,601 --> 00:07:17,203
Depending on what kind
of processes you have,

133
00:07:17,270 --> 00:07:19,172
you might have
additional staff there.

134
00:07:20,006 --> 00:07:23,543
And then of course, separate,
which is by the dotted line,

135
00:07:23,609 --> 00:07:25,144
is quality assurance.

136
00:07:25,211 --> 00:07:28,714
So now they're more separate to,
again, have a non-biased view,

137
00:07:29,348 --> 00:07:32,418
because they don't have direct
interactions with operations,

138
00:07:33,085 --> 00:07:36,422
as well as they have the
authority to stop the line

139
00:07:36,489 --> 00:07:39,325
in case there is a potential
risk to the product.

140
00:07:41,093 --> 00:07:44,897
Documentation --
a big part of GMP

141
00:07:44,964 --> 00:07:47,133
is our documentation practices.

142
00:07:47,633 --> 00:07:49,702
So if it was not documented,
it didn't happen,

143
00:07:49,769 --> 00:07:51,470
which is our main slogan.

144
00:07:52,738 --> 00:07:55,675
It is highly important to
have everything documented

145
00:07:55,741 --> 00:07:59,879
and documented appropriately
since all of our documents

146
00:07:59,946 --> 00:08:01,981
for GMP become official records.

147
00:08:03,850 --> 00:08:08,154
We follow good documentation
practices, or GDP for short,

148
00:08:08,955 --> 00:08:13,025
and this allows us to have
all of our documents legible

149
00:08:13,092 --> 00:08:17,697
and allows someone years
from now to be able to review.

150
00:08:19,665 --> 00:08:22,902
In the United States,
we tend to have some issues

151
00:08:22,969 --> 00:08:25,137
since we do month,
date, then year.

152
00:08:26,606 --> 00:08:31,143
And if you have an inspector
from, say, the United Kingdom,

153
00:08:32,511 --> 00:08:34,213
they may get confused on

154
00:08:34,280 --> 00:08:38,050
when the batch or the
documentation happened.

155
00:08:38,117 --> 00:08:40,086
In order to prevent
any confusion,

156
00:08:41,087 --> 00:08:43,489
we recommend doing the day,

157
00:08:43,556 --> 00:08:45,691
spelled out the three
letters of the month,

158
00:08:46,292 --> 00:08:49,629
and then the year, as
there's no confusion on

159
00:08:49,695 --> 00:08:51,731
when that event occurred.

160
00:08:52,899 --> 00:08:57,203
Another thing that we practice
in GDP is the 24-hour time,

161
00:08:57,937 --> 00:09:01,140
and, again, it prevents any
type of confusion whether --

162
00:09:01,207 --> 00:09:03,776
if you have a 24-hour
facility to make sure

163
00:09:03,843 --> 00:09:06,412
that if something was
done at 6:00 a.m.,

164
00:09:06,479 --> 00:09:08,648
it's documented at
6:00 a.m. and not,

165
00:09:08,714 --> 00:09:10,783
potentially, 6:00
p.m. by mistake.

166
00:09:12,218 --> 00:09:16,389
Now outside of GDP, we also use
a lot of different tools

167
00:09:16,455 --> 00:09:18,357
for our documentation,

168
00:09:18,858 --> 00:09:20,993
and we do a lot of
different risk assessments

169
00:09:21,060 --> 00:09:22,828
to evaluate our
different methods.

170
00:09:24,263 --> 00:09:26,599
Our procedures, standing
operating procedures,

171
00:09:26,666 --> 00:09:28,968
is one of them,
are very highly --

172
00:09:29,035 --> 00:09:32,371
are very regulated as
well as to make sure

173
00:09:32,438 --> 00:09:35,608
that everything
can be followed easily.

174
00:09:39,812 --> 00:09:41,314
So besides documentation,

175
00:09:41,380 --> 00:09:43,983
we go into kind of how
the facilities are designed,

176
00:09:44,050 --> 00:09:46,285
because this is a big
thing about cleanrooms.

177
00:09:48,120 --> 00:09:51,424
So, all of our manufacturing are
done in controlled environments,

178
00:09:52,391 --> 00:09:55,695
which is, again, cleanrooms
are typically what we use.

179
00:09:56,362 --> 00:09:57,830
And a fun fact about cleanrooms

180
00:09:57,897 --> 00:09:59,999
is that they're about
10,000 times cleaner

181
00:10:00,066 --> 00:10:01,867
than an operating
room, or OR.

182
00:10:03,636 --> 00:10:07,673
And we have different grades
for the different levels

183
00:10:07,740 --> 00:10:10,743
of the cleanrooms based
on the risk to the product.

184
00:10:11,577 --> 00:10:14,447
So, grade A is considered
critical zone

185
00:10:15,047 --> 00:10:17,950
for high-risk operations,
and in the picture below,

186
00:10:18,017 --> 00:10:21,320
it's actually that biosafety
cabinet to the right.

187
00:10:22,989 --> 00:10:25,725
Grade B for aseptic
preparations,

188
00:10:25,791 --> 00:10:28,127
which is typically the
background room for grade

189
00:10:28,194 --> 00:10:32,431
A space, and that is actually
the whole room pictured below.

190
00:10:33,532 --> 00:10:36,102
And then you also
have grades C and D,

191
00:10:36,168 --> 00:10:39,905
which are typically used to
carry out less critical stages

192
00:10:39,972 --> 00:10:41,507
and the processes,

193
00:10:41,574 --> 00:10:44,844
as well as are used for
either supporting rooms

194
00:10:44,910 --> 00:10:46,512
or staging areas.

195
00:10:50,783 --> 00:10:54,787
So, what kind of criteria
goes into making a facility

196
00:10:54,854 --> 00:10:57,923
or a cleanroom? Well,
the overall goal

197
00:10:57,990 --> 00:10:59,992
is to prevent any type
of contamination.

198
00:11:01,927 --> 00:11:06,298
You have your different grades,
which as you start with grade D,

199
00:11:06,365 --> 00:11:09,001
you slowly work your way
up to a grade A space.

200
00:11:09,935 --> 00:11:11,537
You have different pressures,

201
00:11:12,304 --> 00:11:14,640
which the room could be
either positive pressure,

202
00:11:14,707 --> 00:11:17,877
which is typically blowing
air out of the space,

203
00:11:17,943 --> 00:11:19,945
or negative, which
is sucking air in,

204
00:11:20,012 --> 00:11:23,215
and that's typically used for
any kind of infectious product.

205
00:11:24,083 --> 00:11:26,185
You have a lot of
HEPA filters in the --

206
00:11:26,252 --> 00:11:28,687
and specific placement
for the exhaust.

207
00:11:28,754 --> 00:11:30,656
So, in the image, you
see the blue arrows,

208
00:11:30,723 --> 00:11:33,059
which are HEPA filters
blowing air in.

209
00:11:33,125 --> 00:11:34,727
And you make sure
that the exhaust,

210
00:11:34,794 --> 00:11:35,995
when building a cleanroom,

211
00:11:36,062 --> 00:11:37,897
is towards the
bottom of the floor,

212
00:11:37,963 --> 00:11:40,166
so that way air can
go completely down

213
00:11:40,232 --> 00:11:44,370
and across the room, and
it allows to make sure

214
00:11:44,437 --> 00:11:46,705
that there's proper air
changes in the space.

215
00:11:48,274 --> 00:11:51,310
Another thing to consider
about building a cleanroom

216
00:11:51,377 --> 00:11:52,678
is the flow patterns,

217
00:11:52,745 --> 00:11:56,082
so how are your personnel going
to move from space to space,

218
00:11:56,148 --> 00:11:57,516
room to room,

219
00:11:57,583 --> 00:11:59,718
and also, how are materials
getting in and out?

220
00:11:59,785 --> 00:12:01,520
Are you going to use
a passthrough?

221
00:12:01,587 --> 00:12:03,122
Do you have a special room?

222
00:12:03,189 --> 00:12:05,124
Do you have a current
passthrough?

223
00:12:06,625 --> 00:12:10,629
And, again, the big thing
is what kind of product

224
00:12:10,696 --> 00:12:11,831
you're manufacturing,

225
00:12:11,897 --> 00:12:13,766
because a lot of
your specifications,

226
00:12:13,833 --> 00:12:14,967
depending on what
kind of products

227
00:12:15,034 --> 00:12:16,702
you can make in the space,

228
00:12:16,769 --> 00:12:19,705
you might be limited
on what kind of room

229
00:12:19,772 --> 00:12:21,507
you have and you designed.

230
00:12:23,409 --> 00:12:26,445
Another thing when
you're building a cleanroom

231
00:12:26,512 --> 00:12:28,414
is to think about the cleaning.

232
00:12:28,481 --> 00:12:31,851
So how are you going to be
able to maintain the space?

233
00:12:31,917 --> 00:12:35,354
Are you able to keep it sterile

234
00:12:35,421 --> 00:12:38,624
and clean of any
potential particulates?

235
00:12:40,192 --> 00:12:43,596
And the location of equipment,
especially larger equipment,

236
00:12:43,662 --> 00:12:46,198
because if you have a
large biosafety cabinet,

237
00:12:46,265 --> 00:12:49,268
you have to make sure it's
not blocking any air flow

238
00:12:49,335 --> 00:12:53,672
and it doesn't
prevent any kind of,

239
00:12:53,739 --> 00:12:56,509
as we like to call it, like,
dead zones in the space

240
00:12:56,575 --> 00:12:58,110
where air flow just
can't reach it,

241
00:12:58,177 --> 00:13:00,980
because you don't want to have
any open manipulation products

242
00:13:01,046 --> 00:13:03,048
there, because there
is no clean air

243
00:13:03,115 --> 00:13:05,451
blowing on where
you're manufacturing.

244
00:13:08,420 --> 00:13:11,257
So how can you make --
maintain this cleanroom?

245
00:13:11,824 --> 00:13:13,959
Typically, it's done
by routine testing,

246
00:13:14,026 --> 00:13:16,695
and this can include
environmental monitoring

247
00:13:16,762 --> 00:13:18,764
as well as your
cleaning program.

248
00:13:21,567 --> 00:13:26,338
So cleaning is actually
one of the biggest areas

249
00:13:26,405 --> 00:13:28,707
that we like to focus
in a cleanroom.

250
00:13:29,942 --> 00:13:35,014
And the biggest thing to have
is a robust cleaning program,

251
00:13:35,948 --> 00:13:38,450
because without a good
cleaning program,

252
00:13:38,984 --> 00:13:41,387
you're not preventing
any potential contamination

253
00:13:41,453 --> 00:13:46,125
of your products. So,
like the previous slide,

254
00:13:47,059 --> 00:13:49,461
designing the facility
actually considers

255
00:13:49,528 --> 00:13:51,330
how you're going to
clean the space.

256
00:13:51,997 --> 00:13:53,766
So, you don't have
any right angles

257
00:13:54,266 --> 00:13:58,938
from the wall to the floors.
Typically, it is a rounded edge

258
00:13:59,004 --> 00:14:04,410
to prevent any kind of dust
or lint from creating a film.

259
00:14:05,611 --> 00:14:08,314
You make sure that
your high-risk areas

260
00:14:08,380 --> 00:14:10,015
have no water sources

261
00:14:10,082 --> 00:14:12,785
that can potentially
contaminate the room.

262
00:14:13,485 --> 00:14:17,389
You make sure that
all of the materials

263
00:14:17,456 --> 00:14:20,025
are being able to be cleaned

264
00:14:20,092 --> 00:14:22,962
and can withstand
any cleaning agents.

265
00:14:24,897 --> 00:14:27,733
And a good rule of thumb
of how we clean the space

266
00:14:27,800 --> 00:14:32,004
is we tend to clean from
cleanest space to dirtiest,

267
00:14:32,071 --> 00:14:33,606
so that would be your
highest-risk space,

268
00:14:33,672 --> 00:14:35,774
like your grade As,
all the way through --

269
00:14:36,675 --> 00:14:38,811
you essentially clean
yourself out through --

270
00:14:38,877 --> 00:14:40,913
to a grade C or D.

271
00:14:42,982 --> 00:14:45,384
And depending on your
manufacturing properties,

272
00:14:45,985 --> 00:14:49,321
cleaning may be performed
with specific reagents.

273
00:14:49,388 --> 00:14:52,758
So, you may have to have
a bleach reagent.

274
00:14:52,825 --> 00:14:55,494
You may be able to use a
different [unintelligible].

275
00:14:55,561 --> 00:14:57,563
It really depends on
what you're manufacturing

276
00:14:57,630 --> 00:15:02,735
and what risk you have to your
staff as well as the space.

277
00:15:04,970 --> 00:15:08,374
And to determine what kind
of reagents you use,

278
00:15:08,440 --> 00:15:10,309
you do a lot of testing.

279
00:15:10,376 --> 00:15:13,345
So we typically do a
disinfection efficacy study

280
00:15:13,846 --> 00:15:17,182
to make sure that
the cleaning agents

281
00:15:17,249 --> 00:15:20,486
you selected are effective
on the microorganisms

282
00:15:20,552 --> 00:15:22,154
that you are concerned about.

283
00:15:23,422 --> 00:15:24,957
Another thing we do

284
00:15:25,024 --> 00:15:28,127
is validation of specific
cleaning processes.

285
00:15:28,961 --> 00:15:30,729
Typically, this is done

286
00:15:30,796 --> 00:15:34,366
when you have centralized
lines or equipment

287
00:15:34,433 --> 00:15:37,169
and there's a risk of
potential cross-contamination

288
00:15:37,236 --> 00:15:39,705
from batch to batch
or different products.

289
00:15:39,772 --> 00:15:43,208
So you want to make sure
that whatever cycles you use

290
00:15:43,275 --> 00:15:45,010
and whatever cleaning
process you use --

291
00:15:45,077 --> 00:15:48,614
you develop for sanitizing
in between your batches

292
00:15:48,681 --> 00:15:51,150
or your different products,
they are effective.

293
00:15:54,420 --> 00:15:56,021
So that leads us to personnel.

294
00:15:57,856 --> 00:16:01,126
Personnel are the major
contaminants in a cleanroom.

295
00:16:01,193 --> 00:16:02,728
Just sitting alone in a room,

296
00:16:02,795 --> 00:16:06,732
you shed 10,000
particles a second.

297
00:16:08,801 --> 00:16:11,437
So it is very important
for all of our staff

298
00:16:11,503 --> 00:16:14,606
to be highly trained
on all of the different

299
00:16:14,673 --> 00:16:20,045
SOPs, how the facility operates
and how to move about the space,

300
00:16:20,879 --> 00:16:22,614
to understand what
kind of equipment

301
00:16:22,681 --> 00:16:24,950
and the cleaning requirements
that there are.

302
00:16:26,151 --> 00:16:29,455
And overall, you just
want to make sure

303
00:16:29,521 --> 00:16:32,491
that your personnel understands
what they're going to walk into,

304
00:16:32,558 --> 00:16:34,093
because a lot of movement

305
00:16:34,159 --> 00:16:37,896
and the way you have to move in
a cleanroom is very specific,

306
00:16:37,963 --> 00:16:39,898
and it's very unnatural.

307
00:16:39,965 --> 00:16:44,103
So, it takes a lot of training
and different courses

308
00:16:44,169 --> 00:16:46,338
to really train yourself

309
00:16:46,405 --> 00:16:48,440
on how to move in these
spaces appropriately,

310
00:16:48,507 --> 00:16:50,876
as well as wear the
potential gowning,

311
00:16:50,943 --> 00:16:53,746
which to the image
on the screen,

312
00:16:53,812 --> 00:16:57,116
is a typical, as we like
to call it, bunny suit,

313
00:16:58,150 --> 00:16:59,852
which really only
shows your eyes.

314
00:17:01,220 --> 00:17:03,088
And you have to put this
on a specific way

315
00:17:03,155 --> 00:17:05,324
to prevent any
potential contamination

316
00:17:05,391 --> 00:17:09,461
or from you contaminating
the actual bunny suit

317
00:17:09,528 --> 00:17:11,563
before you enter
the cleanroom space.

318
00:17:12,765 --> 00:17:15,000
Another thing that's
very unique about GMP

319
00:17:15,067 --> 00:17:17,236
is we have specific
hygiene requirements

320
00:17:18,604 --> 00:17:23,308
to no fresh tattoos or open
wounds, no nail polish.

321
00:17:23,375 --> 00:17:28,414
No jewelry or earphones or
Air Pods are prohibited,

322
00:17:29,381 --> 00:17:33,018
no fake eyelashes, no makeup,
perfume, scented lotion.

323
00:17:33,919 --> 00:17:36,021
A lot of cleaners
also have a requirement

324
00:17:36,088 --> 00:17:38,290
on no smoking within
the last 30 minutes.

325
00:17:39,825 --> 00:17:44,396
And you're not allowed to even,
typically, enter the cleanroom,

326
00:17:44,463 --> 00:17:45,898
let alone sometimes
come to work,

327
00:17:45,964 --> 00:17:47,633
if you have a
respiratory infection

328
00:17:47,699 --> 00:17:50,569
or a known skin condition
such as psoriasis.

329
00:17:53,038 --> 00:17:54,973
But why does this even matter?

330
00:17:55,040 --> 00:17:57,109
This actually makes
you shed even more,

331
00:17:58,477 --> 00:17:59,711
and the whole goal
of the cleanroom

332
00:17:59,778 --> 00:18:03,015
is to limit how much you're
impacting the environment.

333
00:18:06,785 --> 00:18:10,155
So other than personnel, you
have materials to worry about.

334
00:18:10,923 --> 00:18:13,759
And this is typically
one of the second

335
00:18:13,826 --> 00:18:16,628
most common contaminants in
the -- inside the cleanroom.

336
00:18:17,963 --> 00:18:19,731
All materials
inside the cleanroom

337
00:18:19,798 --> 00:18:22,234
must be able to withstand
routine cleanings

338
00:18:22,301 --> 00:18:24,937
and are able to be
easily cleaned,

339
00:18:25,003 --> 00:18:26,605
such as stainless steel.

340
00:18:28,974 --> 00:18:31,877
Materials that are brought in
are typically individually

341
00:18:31,944 --> 00:18:34,813
wrapped and consist
of multiple bags

342
00:18:34,880 --> 00:18:38,083
to be removed at each different
grade that you go into.

343
00:18:38,984 --> 00:18:41,787
So a lot of our materials
are triple bagged,

344
00:18:42,621 --> 00:18:45,257
so every time you move
into a different room,

345
00:18:45,324 --> 00:18:50,262
you're removing a layer
from the packaging

346
00:18:50,329 --> 00:18:53,131
just to make sure
that you're reducing

347
00:18:53,198 --> 00:18:56,301
any potential contaminants from
entering inside the cleanroom.

348
00:18:57,803 --> 00:18:59,838
Any cloth items inside,

349
00:18:59,905 --> 00:19:01,807
such as wipes or
gowning materials,

350
00:19:01,874 --> 00:19:03,876
are typically low lint
and low shedding,

351
00:19:04,409 --> 00:19:07,613
so there's no cotton
or anything,

352
00:19:07,679 --> 00:19:10,182
or wool, that could
potentially make you sweat

353
00:19:10,249 --> 00:19:13,785
or shed any little, tiny fibers.

354
00:19:15,420 --> 00:19:17,089
Excess items that
are not required

355
00:19:17,155 --> 00:19:19,491
or dedicated to the
cleanroom are removed,

356
00:19:20,893 --> 00:19:25,264
and only in certain procedures
or circumstances,

357
00:19:25,330 --> 00:19:30,369
extra items may be brought in
on an as needed basis.

358
00:19:35,073 --> 00:19:38,577
So after understanding kind of
the basics about a cleanroom,

359
00:19:38,644 --> 00:19:41,413
we typically get a lot
of questions about GMP.

360
00:19:41,480 --> 00:19:45,918
So the first one is, why
are GMPs so important?

361
00:19:48,320 --> 00:19:53,525
And these GMPs are to ensure
a product is safe for use.

362
00:19:54,293 --> 00:19:59,965
So, again, our end users or
patients take these products

363
00:20:00,032 --> 00:20:03,502
with the confidence that they
are safe for them to ingest,

364
00:20:03,569 --> 00:20:06,905
or potentially, if they're
an IV or chemotherapy drug,

365
00:20:06,972 --> 00:20:09,374
can be injected
inside their veins.

366
00:20:11,276 --> 00:20:14,813
How do agencies determine
if a GMP facility

367
00:20:14,880 --> 00:20:18,584
is compliant with these --
all of these rules?

368
00:20:19,184 --> 00:20:21,687
And they do frequent
inspections,

369
00:20:22,321 --> 00:20:23,889
as well as industry is required

370
00:20:23,956 --> 00:20:26,959
to report any type of
potential contaminants

371
00:20:27,025 --> 00:20:29,628
to the regulatory agencies.

372
00:20:32,164 --> 00:20:35,400
Now if the manufacturer
is not following GMP,

373
00:20:35,467 --> 00:20:37,569
what does that mean
for the product?

374
00:20:37,636 --> 00:20:38,971
Well, in the U.S.,

375
00:20:39,037 --> 00:20:43,041
the FDA defines it as
adulterated under the law,

376
00:20:43,108 --> 00:20:45,010
and they have to be
labeled as such.

377
00:20:45,544 --> 00:20:49,581
And typically, after a product
is known to be contaminated,

378
00:20:50,115 --> 00:20:52,651
a recall is noted to the public

379
00:20:52,718 --> 00:20:55,654
and all of those products
are pulled from the shelves.

380
00:20:59,725 --> 00:21:02,127
And how do we learn
more about GMP,

381
00:21:02,194 --> 00:21:04,930
since this is a very new
concept for a lot of people?

382
00:21:06,565 --> 00:21:08,634
Well, I have some
references for you.

383
00:21:08,700 --> 00:21:13,105
The best one I can recommend
is the E.U. GMP Annex One.

384
00:21:15,340 --> 00:21:20,212
But definitely look at your
local government authority

385
00:21:20,278 --> 00:21:22,014
and see what kind of regulations

386
00:21:22,080 --> 00:21:25,684
that all GMP facilities
are required to follow.

387
00:21:27,019 --> 00:21:28,820
But thank you so much
for your time.