Cell Therapy Manufacturing: Regulations and Facilities

WRT&A1

Cell Therapy Manufacturing:

Regulations and Facilities

William R. Tolbert, Ph.D.BIOCOM Meeting – August 11, 2005

WRT&A2

Roadblocks to Commercial Cell Based Products

Regulatory Issues Basic Science Product Development Manufacturing Development –

Manufacturing Facilities Paradigm for Delivery of Patient-

Specific Products Potential for Allogeneic Products

(Immunogenicity )

WRT&A3

Somatic Cell TherapyAutologous

Donor/Recipient

Cell

Cell

Cell

In Vitro Manipulation

Allogeneic

Recipient

Cell

Cell

In Vitro ManipulationCord Blood Donor

WRT&A4

How are Cell-Based Products Different?

Potential for adventitious agents in starting material - possible lack of adequate methods for testing or removal.

Requirement for “aseptic processing”

Inability to effectively “sterilize” the product and often implantation must occur before testing is complete.

WRT&A5

21 CFR Part 1271“A Line in the Sand”

Regulated As

HCT/P’s under Section 351 of PHS Act

(Biologics or Devices -Must prove safety and

efficacy)

HCT/P’s under Section 361 of PHS Act

(Only for prevention of communicable disease –

No proof of efficacy)

· More than minimally manipulated

· Intended for Non-Homologous Use

· Systemic effect dependent upon metabolic activity (Allogeneic, except close relative)

· Clinical effect is systemic or dependent upon the metabolic activity of the cells for its primary function

· Combined with a device, drug or biologic

· Generally, HCT/P’s recovered, processed, stored, or distributed by methods not intended to change tissue function or characteristics

· Minimally manipulated, homologous use, metabolic tissue for self or close blood relative, or for reproductive use

WRT&A6

Regulatory Requirements for HCT/P’s

“A Line in the Sand”

cGMPs Biologics cGTPs

cGTPs cGTPs cGTPs

QSRs Biologics cGTPs

Tissue CellularTherapeutic

TissueEngineering(Combination of Cells and Device)

Requirements

Premarket Approval

351 PHS Act , FD&CIND, IDE, BLA, PMA

Marketing NotificationFD&C 361 PHS Act

WRT&A7

Challenges for Basic Science

Source of Cells or Tissues Maintenance of Pluripotency

Embryonic Stem Cells Adult Stem Cells

Control of Differentiation Target Cell / Tissue Type

Measure of Therapy / Product Potency Patient Immune Rejection

WRT&A8

Challenges for Product Development

Cell Characteristics Attached vs. Suspension Population Doubling Media/Supplements

Potency Assays Flow Cytometry

Time to Implantation Fresh or Frozen

WRT&A9

Challenges for Manufacturing Development

Aseptic Processing – Required for Cell Therapy http://www.fda.gov/cder/guidance/5882fnl.htm

Variability of Biological Components Autologous vs. Allogeneic Adventitious Agents

HIV, HCV, HBV, CMV, etc. Commercial Capacity

Scale Up Scale Out Multiple Plants

WRT&A10

Manufacturing Facilities

Capacity Issues Patient-Specific vs. Allogeneic Processing Time Quarantine Issues

Aseptic Processing for All Steps Labor Intensive High Level of Support Requirements Scheduling Issues

WRT&A11

Open vs. Closed Manufacturing Systems

FDA Cleared or Approved Sterile Tube Connecting Device (STCD) – Tubing Welders Developed for the Blood industry.

STCDs may be used for interconnecting sterile bag systems for cell and gene therapy applications.

WRT&A12

Example Facility

Standard Cell Therapy Unit 150 ft2, 2 Operators Capacity 25 to 100

Products / Year Clinical Facility

6 Units – 5,000 ft2 (18%) Capacity 150 – 600

Products / Year Commercial Facility

24 Units – 25,000 ft2 (15%)

Capacity 600 – 2,400 Products/Year

UnfinishedArea169

16.0' x 39.8'

Women's Toilet154 15.8'x7.2'

Men's Toilet153 15.8'x7.3'

QC Laboratory125

18.0' x 20.5' QC Micro127

13.0' x 10.0'

Media Testing126

13.0' x 10.0'

Pat

ient

/Don

or S

tora

ge

Cor

rido

r 10

0 2

5.0'

x 8

.5'

SurrogateCulture

13417.0' x 29.5'

Gown 1309.5' x 4.0'

ReadySupplies -

KitAssembly

1319.5' x 25.0'

GownDegown

1337.5' x 9.8'

ProductionSupport A 132

15.5' x 9.8'

JanitorCloset 12810.0' x 8.5'

Flow Cytometry129

18.0' x 11.5'

29.5

' x 9

.0'

Mec

h R

oom

A23

.5' x

3.5

'

11210.5' x 8.0'

100A 21.5' x 4.0'

SterilityTesting121R

10.3'x10.0'

Gown1216.0'

x 10.0'

10410.5' x 15.5'

10210.5' x 11.5'

Reception103

13.0' x 9.5'

10813.5'x7.7'

100A

56

.2' x

3.5

'

100C21.5' x 5.7'

Exit100B6.5'

x12.3'

100E 100.5' x 6.0'

2 ft. 6.0 in. x 18 ft. 6.0 in.

BZEm

PT

27.5

' x 8

.0'

Radioisotope Lab123L

15.5' x 10.0'

BlastogensisLab 150

10.5'x10.0'

1236.0'

x 10.0'

Released Materials122

23.0'x10.0'

RetainSamples

121L7.5'x10.0'

MechRm B1205.8'

x11.2'

100D12.5' x 6.2'

1119.0'x12.3'

1109.0'x12.3'

10913.5'x12.3'

10713.5'x11.8'

10613.5'x11.8'

10513.5'x7.5'

5.0'

x1.5

'4.

0'x1

.5'

6.5'

x3.0

'

10110.5' x 11.5'

1199.5' x 9.0'

11811.5' x 9.0'

Women 11615.0' x 6.0'

Men 11515.0' x 6.2'

Res

troo

m 1

1712

.7' x

6.0

'

Break / Conference114

21.5' x 12.3'

11310.5' x 8.0'

PT

Stairs7.5' x 5.0'7.5'

x9.0'

4.5'x6.0'

69.0'x5.3'

K

K

K

BZGown Corridor Rm 162 49.0' x 6.0'

Production Support B 160 52.0' x 8.0'P

rodu

ctio

n D

166

19.

0' x

8.0

'

Pro

duct

ion

E16

7 1

9.0'

x 8

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Pro

duct

ion

C16

5 1

9.0'

x 8

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Pro

duct

ion

B16

4 1

9.0'

x 8

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R

Duc

tR

D

uct

R

Duc

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R

Duct

Pro

duct

ion

A16

3 1

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x 8

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R

Duc

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Duct

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PT PT PT

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F16

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x 8

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PT

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CellIrradiation

123R7.5'x10.0'

14.0

' x 6

.0'

Degown161

9.0'x6.0'

K

6.0'x13.0'Gown

Toilet

Sin

k ToiletUrinal

Sin

k

Women's Lockers156

15.7'x12.8'

Men's Lockers155

15.8'x12.8'

Toilet

Em

ProductRelease/Package

1589.5'x15.0'

Ship -Receive

1599.5'x13.8'

PT

PT

K

Mechanical Room C151

25.5' x 11.2'

QuarantineStorage

15217.5' x 20.5'

Patient

Receive

Donor

Receive

Clean Closet157 9.5'x4.2'

Em

Room Layout and Dimensions

Total Facility Dimensions 163.0'x80.0'

PT

PT

WRT&A13

UnfinishedArea 169

Women's ToiletMen's Toilet

153

Lab

orat

ory

Cas

ewor

k

FlowCytometer

QC Laboratory125

QC Micro127

Media Testing126

Pat

ient

/Don

or S

tora

ge

Cor

rido

r 10

0

SurrogateCulture

134

Gown 130

ReadySupplies -

KitAssembly

131

GownDegown

133

ProductionSupport A 132

JanitorCloset 128

Flow Cytometry129

Mec

h R

oom

A

112

100A

SterilityTesting121R

Gown121

104

102 Reception103

108

100A

100C

Exit100B

100E

2 ft. 6.0 in. x

18 ft. 6.0 in.

BZEm

PT

Radioisotope Lab123L

BlastogensisLab 150

123Released Materials

122

RetainSamples

121L

MechRm B120

100D

111 110 109

107

106

105

101

119 118

Women 116

Men 115

Res

troo

m 1

17

Break / Conference114

113

PT

Stairs

K

K

K

BZ

CO2

Incub

Table

Com

pute

r

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

Gown Corridor Rm 162

Production Support B 160P

rodu

ctio

n D

166

Pro

duct

ion

E16

7

Pro

duct

ion

C16

5

Pro

duct

ion

B16

4

R

Duc

tR

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uct

R

Duc

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R

Duct

Pro

duct

ion

A16

3R

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Duct

R

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PT PT PT

Pro

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F16

8

PT

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Cart

Cell Counte

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Computer

SS Wire Shelving

Computer

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Ref

Com

puter6ft

Biosafety O

vr/Und

CO

2 Incubator

Ref

Com

puter6ft

Biosafety O

vr/Und

CO

2 Incubator

Ref

6ftBiosafety

6ftBiosafety

Table

6ftBiosafety

6ftBiosafety

Cell Counte

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Fre

ezer

Sta

inle

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able

Com

pute

r

StainlessT

able

Dou

ble

Doo

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efri

gera

tor

Stainless S

teel Wire

Shelving

Cart

Flow

Cytom

eter D

ouble Door

Refrigerator

LaboratoryCasework

PT

Computer

Sin

kOvr/UndMicro

Incubator

6ftBiosafety

Computer

Microscop

e

6ftBiosafety

Ovr/Und CO2

Incubator

Microscop

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Microscop

e

Microscop

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Dou

ble

Doo

r R

efri

gera

tor

LaboratoryCasework

Table

Fre

ezer

Cent

LaboratoryCasework

Lab

orat

ory

Cas

ewor

k

Sink

Laboratory

Casew

ork

Sink

6ftBiosafety

Ovr/UndMicro

IncubatorComputer

Microscop

e

- 80 C FreezerRetain Samples

- 80

C F

reez

erR

etai

n S

ampl

es

IPA

Bench

MirrorSoiledGowns

Clean

Gow

ns

K

PT

CellIrradiation

123RScintillation

CounterHarvester

6ftBiosafety

Computer

Microscop

e

Computer

Microscope

Ovr/Und CO2

Incubator

Irradiator

Degown161

IPA

Mirror

SoiledGowns

K

Gown

SS

Wire

Shelving

Bench

Toilet

Sin

k ToiletUrinal

Sin

k

Tow

els

Tow

els

Women's Lockers156

Men's Lockers155

Toilet

Cle

an S

crub

s LockersLockers

Lockers

Lockers

Lockers

Lockers

Bench

BenchDir

ty

Scr

ubs

Cle

an S

crub

s LockersLockers

Lockers

Lockers

Lockers

Lockers

Bench

BenchDir

ty

Scr

ubs

Computer

Microscope

Lab

orat

ory

Cas

ewor

k

Em

ProductRelease/Package

158

Ship -Receive

159

Fre

eze

r

StainlessT

able

PT

Cab

inet

Com

puterS

tainless Table

PT

Com

puter

Cab

inet

K

Mechanical Room C151

QuarantineStorage 152D

oubl

e D

oor

Ref

rige

rato

r

Freezer

Dou

ble

Doo

r R

efri

gera

tor

Dou

ble

Doo

r R

efri

gera

tor

Shelving

Shelving

Shelving

Class100 WS

Computer

Double Door Refrigerator


She

lvin

g

Freezer

Shelving

ComputerShelving


Car

t

Car

t

Cart

Cart

Table

Patient

Receive

Donor

Receive


Dou

ble

Doo

r R

efri

gera

tor

Dou

ble

Doo

r R

efri

gera

tor

Com

puterT

ableC

omputer

Bench

Clean

Gow

nsIPA

Mirror

Clean Closet157S

ink

Sink

Cabinet

SoiledGowns

Clean Gowns IPA

Em

Equipment Layout

CO2 CO2N2N2 N2 CO2 CO2N2

BiohazWaste

BiohazWaste

BiohazWaste

BiohazWaste

RadioWaste

RadioWaste

RadioWaste

BiohazWaste

CO2 CO2

PT

CO2

Incub

CO2

Incub

CO2

Incub

PT

Cen

tC

ent

Cen

tC

ent

Com

pute

r

WRT&A14

ReceivingRm 114

18.5' x 10.0'

Media TestingRm 159A10.0' x 9.0'

EnvironmentalMonitoringRm 159B

12.0' x 9.0'

Clean C

orridor BR

m 104 11.5' x 6.0'

Clean C

orridor B R

m 104 46.0' x 6.0'

Administration CubiclesRm 190

14.0' x 20.5'

QA ManagerOffice

Rm 17411.0' x 8.0'

Women's ToiletRm 187

12.0' x 11.7'Toilet Toilet Toilet

Men's ToiletRm 186

12.0' x 11.7'

Sink

ToiletUrinal Urinal

Sink

SinkSink

Gown / DegownRm 170

10.0' x 8.0'

SterilityTesting A Rm 172

10.0' x 23.0'

SterilityTesting B Rm 173

10.0' x 23.0'

Access C

orridor C R

m 102 101.0' x 6.0'

QC Lab 3Flow Cytometer

Rm 16812.0' x 30.0'


Rm 16212.0' x 30.0'

Patient CellIrradiation

Rm 1579.0' x 9.0'

Clean C

orridor BR

m 104 23.0' x 6.0'

Clean C

orridor B R

m 104 50.0' x 6.0'

Clean C

orridor BR

m 104 12.5' x 6.0'

Personnel Entry Rm 12018.5' x 8.5'

Acc

ess

Cor

rido

r A

Rm

100

59.

5' x

6.0

'

Acc

ess

Cor

rido

r A

Rm

100

57.

5' x

6.0

'

Cle

an C

orri

dor

A R

m 1

03 3

1.0'

x 6

.0'

Cle

an C

orri

dor

A R

m 1

03 3

7.0'

x 6

.0'

Cle

an C

orri

dor

A R

m 1

03 4

4.0'

x 6

.0'

Gown Corridor B Rm 107 52.0' x 6.0'

Pro

duct

ion

4R

m 1

29 1

9.0'

x 8

.0'

Pro

duct

ion

5R

m 1

30 1

9.0'

x 8

.0'

Pro

duct

ion

3R

m 1

28 1

9.0'

x 8

.0'

Pro

duct

ion

2R

m 1

27 1

9.0'

x 8

.0'

Production Support A 133 52.0' x 11.0'

Gown Corridor A Rm 106 49.0' x 6.0'

R D

uct

R D

uct

R D

uct

R D

uct

Degown ARm 132

6.0' x 9.0'

Pro

duct

ion

1R

m 1

26 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

PT PT PT

Pro

duct

ion

6R

m 1

31 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

PTPTPT

Pro

duct

ion

10R

m 1

37 1

9.0'

x 8

.0'

Pro

duct

ion

11R

m 1

38 1

9.0'

x 8

.0'

Pro

duct

ion

9R

m 1

36 1

9.0'

x 8

.0'

Pro

duct

ion

8R

m 1

35 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

DegownB

Rm 1476.0'

x 10.0'

Pro

duct

ion

7R

m 1

34 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

PT PT PT

Pro

duct

ion

12R

m 1

39 1

9.0'

x 8

.0'

PT

R D

uct

R D

uct

R D

uct

R D

uct

PTPT R Duct

R Duct

Pro

duct

ion

16R

m 1

44 1

9.0'

x 8

.0'

Pro

duct

ion

17R

m 1

45 1

9.0'

x 8

.0'

Pro

duct

ion

15R

m 1

43 1

9.0'

x 8

.0'

Pro

duct

ion

14R

m 1

42 1

9.0'

x 8

.0'

Production Support B 148 52.0' x 11.0'

R D

uct

R D

uct

R D

uct

R D

uct

Pro

duct

ion

13R

m 1

41 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

Pro

duct

ion

18R

m 1

46 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

Pro

duct

ion

22R

m 1

53 1

9.0'

x 8

.0'

Pro

duct

ion

23R

m 1

54 1

9.0'

x 8

.0'

Pro

duct

ion

21R

m 1

52 1

9.0'

x 8

.0'

Pro

duct

ion

20R

m 1

51 1

9.0'

x 8

.0'

Gown Corridor C Rm 108 49.0' x 6.0'

R D

uct

R D

uct

R D

uct

R D

uct

Degown CRm 156

9.0' x 6.0'

Pro

duct

ion

19R

m 1

50 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

Pro

duct

ion

24R

m 1

55 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

R Duct

R Duct

Access Corridor B Rm 101 135.5' x 6.0'

Clean Corridor C Rm 105 78.0' x 6.0'

GownC

Rm 1496.0'

x 12.5'

GownB

Rm 1406.0'

x 12.5'

GownA

Rm 1256.0'

x 12.0'


11.5' x 12.5'ToiletToilet Toilet

Men's ToiletRm 115

11.5' x 12.5'

Sink

ToiletUrinal Urinal

Sink

SinkSink

Women's LockerRm 119

18.5' x 24.0'

Men's LockerRm 113

18.5' x 24.0'C

lean

Cor

rido

r A

Rm

103

19.

0' x

6.0

'

Product ReleasePackagingRm 124

18.5' x 15.0'

CleanCloset

Rm 1225.8' x 10.0'

Janitor'sCloset

Rm 1215.8' x 10.0'

Ready Supplies AKit Assembly

Rm 110 18.5' x 20.0'Release Supplies Rm 109 18.5' x 25.5'

Quarantine Supplies Rm 111 18.5' x 18.5'

Truck DockRm 116

18.5' x 20.0'

ShippingRm 118

18.5' x 10.0'

Mechanical AreaRm 123

18.5' x 24.5'

Cold Room112

9.0' x 14.0'

Car

tP

ass

Th

ru

Car

tP

ass

Th

ru



Men's ToiletRm 164

12.5' x 11.7'

Sink

ToiletUrinal Urinal

Sink

SinkSink

Surrogate Culture 1Rm 161 19.5' x 12.0'

PT



PT


PT

QC Lab 2Blastogenesis

Rm 16612.0' x 12.0'

QC MicrobiologyRm 160

25.5' x 11.5'

Radio Isotope LabRm 171

21.5' x 8.0'

K

K

K

K

K

K

K

K

K

K

K

QA DocumentVault

Rm 17511.0' x 14.5'

PurchasingManagerOffice

Rm 19711.0' x 8.0'

QA / RA / Purchasing CubiclesRm 196

27.0' x 31.5'

Medical DirectorOffice

Rm 20111.0' x 9.0'

QA ManagerOffice

Rm 19811.0' x 8.0'

Copy / FaxRm 199

11.0' x 5.0'

Production / QC / EngineeringCubiclesRm 179

29.0' x 26.0'

FacilitiesDirectorOffice

Rm 1809.0' x 10.0'

Production DirectorOffice

Rm 17814.5' x 8.5'

Copy / FaxRm 181

9.0' x 5.0'

ProductionMangersOffice

Rm 17611.5' x 8.5'


Rm 17711.5' x 8.5'

QC DirectorOffice

Rm 1829.0' x 10.0'

Training / ConferenceRm 193

20.5' x 15.5'

BreakroomRm 183

22.5' x 19.5'

HR ManagerOffice

Rm 19511.0' x 8.0'

HR AssistantOffice

Rm 19411.0' x 7.0'

IMS ManagerOffice

Rm 1849.0' x 10.0'

ComputerCenter

Rm 1859.0' x 9.0'

Plant ManagerOffice

Rm 19211.0' x 12.0'

ExecutiveAssistantOfficeRm 19111.0' x 8.0'

ReceptionRm 188

19.0' x 8.5'

Janitor's ClosetRm 189

12.5' x 6.0'

QA DirectorOffice

Rm 20011.0' x 9.0'

6.0'

x 9

.0'

6.0'

x 1

6.0'

K

K

K

E

K

6.0'

x 1

9.5'

K

K

Facility Room Layout - Total Dimensions 188.5' x 134.0'E

E

E E

R D

uct

R D

uct

PT PT PT PT PT PT

PT PT PT PT PT PT

PT

CartPassThru

RetainSamplesRm 158

6.0' x12.0'

Access Corridor A Rm 100 31.0' x 6.0'

K

PT

WRT&A15

ReceivingRm 114

18.5' x 10.0'

Media TestingRm 159A10.0' x 9.0'

EnvironmentalMonitoringRm 159B12.0' x 9.0'

Clean C

orridor BR

m 104 11.5' x 6.0'

Clean C

orridor B R

m 104 46.0' x 6.0'C

omputer

Com

puterCom

pute

rCom

puterCom

pute

r

Com

puterCom

pute

rCom

puterCom

pute

rCom

puterCom

pute

r

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

StainlessTable

Flo

wC

ytom

eter

Administration CubiclesRm 190

14.0' x 20.5'

QA ManagerOffice

Rm 17411.0' x 8.0'


12.0' x 11.7'Toilet Toilet Toilet

Men's ToiletRm 186

12.0' x 11.7'

Sink

ToiletUrinal Urinal

Sink

SinkSink

Gown / DegownRm 170

10.0' x 8.0'

SterilityTesting A Rm 172

10.0' x 23.0'

SterilityTesting B Rm 173

10.0' x 23.0'

Access C

orridor C R

m 102 101.0' x 6.0'


Rm 16812.0' x 30.0'


Rm 16212.0' x 30.0'

Patient CellIrradiation

Rm 1579.0' x 9.0'

Clean C

orridor BR

m 104 23.0' x 6.0'

Clean C

orridor B R

m 104 50.0' x 6.0'

Clean C

orridor BR

m 104 12.5' x 6.0'

Personnel Entry Rm 12018.5' x 8.5'

Acc

ess

Cor

rido

r A

Rm

100

59.

5' x

6.0

'

Acc

ess

Cor

rido

r A

Rm

100

57.

5' x

6.0

'

Cle

an C

orri

dor

A R

m 1

03 3

1.0'

x 6

.0'

Cle

an C

orri

dor

A R

m 1

03 3

7.0'

x 6

.0'

Cle

an C

orri

dor

A R

m 1

03 4

4.0'

x 6

.0'

Gown Corridor B Rm 107 52.0' x 6.0'

Pro

duct

ion

4R

m 1

29 1

9.0'

x 8

.0'

Pro

duct

ion

5R

m 1

30 1

9.0'

x 8

.0'

Pro

duct

ion

3R

m 1

28 1

9.0'

x 8

.0'

Pro

duct

ion

2R

m 1

27 1

9.0'

x 8

.0'

Production Support A 133 52.0' x 11.0'

Gown Corridor A Rm 106 49.0' x 6.0'

R D

uct

R D

uct

R D

uct

R D

uct

Degown ARm 132

6.0' x 9.0'

Pro

duct

ion

1R

m 1

26 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

PT PT PT

Pro

duct

ion

6R

m 1

31 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

PTPTPT

Pro

duct

ion

10R

m 1

37 1

9.0'

x 8

.0'

Pro

duct

ion

11R

m 1

38 1

9.0'

x 8

.0'

Pro

duct

ion

9R

m 1

36 1

9.0'

x 8

.0'

Pro

duct

ion

8R

m 1

35 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

DegownB

Rm 1476.0'

x 10.0'

Pro

duct

ion

7R

m 1

34 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

PT PT PT

Pro

duct

ion

12R

m 1

39 1

9.0'

x 8

.0'

PT

R D

uct

R D

uct

R D

uct

R D

uct

PTPT R Duct

R Duct

Pro

duct

ion

16R

m 1

44 1

9.0'

x 8

.0'

Pro

duct

ion

17R

m 1

45 1

9.0'

x 8

.0'

Pro

duct

ion

15R

m 1

43 1

9.0'

x 8

.0'

Pro

duct

ion

14R

m 1

42 1

9.0'

x 8

.0'

Production Support B 148 52.0' x 11.0'

R D

uct

R D

uct

R D

uct

R D

uct

Pro

duct

ion

13R

m 1

41 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

Pro

duct

ion

18R

m 1

46 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

Pro

duct

ion

22R

m 1

53 1

9.0'

x 8

.0'

Pro

duct

ion

23R

m 1

54 1

9.0'

x 8

.0'

Pro

duct

ion

21R

m 1

52 1

9.0'

x 8

.0'

Pro

duct

ion

20R

m 1

51 1

9.0'

x 8

.0'

Gown Corridor C Rm 108 49.0' x 6.0'

R D

uct

R D

uct

R D

uct

R D

uct

Degown CRm 156

9.0' x 6.0'

Pro

duct

ion

19R

m 1

50 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

Pro

duct

ion

24R

m 1

55 1

9.0'

x 8

.0'

R D

uct

R D

uct

R D

uct

R D

uct

R Duct

R Duct

Access Corridor B Rm 101 135.5' x 6.0'

Clean Corridor C Rm 105 78.0' x 6.0'

GownC

Rm 1496.0'

x 12.5'

GownB

Rm 1406.0'

x 12.5'

GownA

Rm 1256.0'

x 12.0'



Men's ToiletRm 115

11.5' x 12.5'

Sink

ToiletUrinal Urinal

Sink

SinkSink

Women's LockerRm 119

18.5' x 24.0'

Men's LockerRm 113

18.5' x 24.0'

Cle

an C

orri

dor

AR

m 1

03 1

9.0'

x 6

.0'

Product ReleasePackagingRm 124

18.5' x 15.0'

CleanCloset

Rm 1225.8' x 10.0'

Janitor'sCloset

Rm 1215.8' x 10.0'

Ready Supplies AKit Assembly

Rm 110 18.5' x 20.0'Release Supplies Rm 109 18.5' x 25.5'

Quarantine Supplies Rm 111 18.5' x 18.5'

Truck DockRm 116

18.5' x 20.0'

ShippingRm 118

18.5' x 10.0'

Mechanical AreaRm 123

18.5' x 24.5'

Cold Room112

9.0' x 14.0'

Car

tP

ass

Th

ru

Car

tP

ass

Th

ru



Men's ToiletRm 164

12.5' x 11.7'

Sink

ToiletUrinal Urinal

Sink

SinkSink


PT



PT


PT

QC Lab 2Blastogenesis

Rm 16612.0' x 12.0'

QC MicrobiologyRm 160

25.5' x 11.5'

Radio Isotope LabRm 171

21.5' x 8.0'

K

K

K

K

K

K

K

K

K

K

K

QA DocumentVault

Rm 17511.0' x 14.5'

PurchasingManagerOffice

Rm 19711.0' x 8.0'

QA / RA / Purchasing CubiclesRm 196

27.0' x 31.5'

Medical DirectorOffice

Rm 20111.0' x 9.0'

QA ManagerOffice

Rm 19811.0' x 8.0'

Copy / FaxRm 199

11.0' x 5.0'

Production / QC / EngineeringCubiclesRm 179

29.0' x 26.0'

FacilitiesDirectorOffice

Rm 1809.0' x 10.0'

Production DirectorOffice

Rm 17814.5' x 8.5'

Copy / FaxRm 181

9.0' x 5.0'


Rm 17611.5' x 8.5'


Rm 17711.5' x 8.5'

QC DirectorOffice

Rm 1829.0' x 10.0'

Training / ConferenceRm 193

20.5' x 15.5'

BreakroomRm 183

22.5' x 19.5'

HR ManagerOffice

Rm 19511.0' x 8.0'

HR AssistantOffice

Rm 19411.0' x 7.0'

IMS ManagerOffice

Rm 1849.0' x 10.0'

ComputerCenter

Rm 1859.0' x 9.0'

Plant ManagerOffice

Rm 19211.0' x 12.0'

ExecutiveAssistantOfficeRm 19111.0' x 8.0'

ReceptionRm 188

19.0' x 8.5'

Janitor's ClosetRm 189

12.5' x 6.0'

QA DirectorOffice

Rm 20011.0' x 9.0'

6.0'

x 9

.0'

6.0'

x 1

6.0'

K

K

K

E

K

6.0'

x 1

9.5'

K

K

Facility Equipment Layout - Total Dimensions 188.5' x 134.0'E

E

E E

Towels

Towels

LaboratoryCasework

Flow

Cytom

eter L

aboratoryC

asework

Flow

Cytom

eter

LaboratoryCasework

Flo

wC

ytom

eter

S

ink

Double D

oor R

efrigerator

LaboratoryCasework

SS Wire Shelving

Computer

SS Wire Shelving

IPAWash

SoiledGowns

6ft

Bio

safe

ty

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

Cent

R D

uct

Cart

Cent

6ft

Bio

safe

ty

Cent

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

Cent

6ft

Bio

safe

ty

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

Cent Cent

6ftB

iosafety

Ovr/U

ndC

O2

Incubator

Refrig

erator

CentCent

6ft

Bio

safe

ty

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

Cent Cent

6ftB

iosafety

Ovr/U

ndC

O2

Incubator

Refrig

erator

Cent Cent

Cell Counter

Computer

SS Wire Shelving

Computer

IPAWash

SoiledGowns

6ft

Bio

safe

ty

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

CentCent

6ftB

iosafety

Ovr/U

ndC

O2

Incubator

Refrig

erator

CentCent

6ft

Bio

safe

ty

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

CentCent

6ft

Bio

safe

ty

Cent

Ovr/U

ndC

O2

Incubator

Refrig

erator

Car

t

Cent

Com

pute

r6f

tB

iosa

fety

Cent

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

Cent

6ftB

iosafety

Ovr/U

ndC

O2

Incubator

Refrig

erator

CentCent

Cell Counter

Cell Counter

Cell Counter

SS Wire Shelving

SS Wire Shelving

Computer

SS Wire Shelving

Com

pute

r6f

tB

iosa

fety

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

StainlessTable Cent

R D

uct

Cart

Cent

Com

puter

StainlessTable

6ft

Bio

safe

ty

Cent

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

Cent

Com

pute

r6f

tB

iosa

fety

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

StainlessTableCent Cent

Com

puter6ft

Biosafety

Ovr/U

ndC

O2

Incubator

Refrig

erator

StainlessTable CentCent

Com

pute

r6f

tB

iosa

fety

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or


Com

puter6ft

Biosafety

Ovr/U

ndC

O2

Incubator

Refrig

erator


Cell Counter

Computer

SS Wire Shelving

Computer

Com

pute

r6f

tB

iosa

fety

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or


Com

puter6ft

Biosafety

Ovr/U

ndC

O2

Incubator

Refrig

erator


Com

pute

r6f

tB

iosa

fety

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or


Com

puter

StainlessTable

6ft

Bio

safe

ty

Cent

Ovr/U

ndC

O2

Incubator

Refrig

erator

Car

t

Cent

Com

pute

r

StainlessTable

6ft

Bio

safe

ty

Cent

Ovr

/Und

CO

2In

cuba

tor

Ref

rig

erat

or

Cent

Com

puter6ft

Biosafety

Ovr/U

ndC

O2

Incubator

Refrig

eratorStainless

Table CentCent

Cell Counter

Cell Counter

Cell Counter

SS Wire Shelving

Bench

Mirror

IPAW

ash

Wir

e

She

lvin

g Bench

Mirror

IPA

Was

h

Wir

e

She

lvin

g

Bench

Mirror

Towels

Towels

IPAW

ash

Wir

e

She

lvin

g

Stainless Steel Wire Shelving

Sta

inle

ssT

able


Fre

ezer Cart

Cart

Loc

kers

Clean Scrubs

Lockers

Bench

Lockers

Ben

ch

Bench

Storage

Cabinet

Sink Sink

Sto

rage

Cab

inet

Com

pute

r

Computer

Computer

Com

puter

Shelving

ShelvingTab

le

Ste

el S

helv

ing S

teel Shelving

Shelving

Shelving

Freezer

Com

puterF

reezer

Pack

age

Was

teT

able

Cart

Cart

Car

tC

art

Sta

inle

ssT

able

StorageCabinet

Storage Cabinet

StainlessTable

Shelving

Car

t

Microscope

Microscope

Microscope

Microscope

Microscope

Microscope

Microscope

Microscope


Fre

ezer

Stainless Steel Wire Shelving

StainlessTable

Sta

inle

ssT

able

Com

pute

rCart

Coat Storage

CellIrradia

tor

Towels

Towels

6ftBiosafety

Ovr/UndCO2

Incubator6ft

Biosafety

6ftBiosafety

Ovr/UndCO2

Incubator

6ftBiosafety

6ftBiosafety

Ovr/UndCO2

Incubator6ft

Biosafety

6ftBiosafety

Ovr/UndCO2

Incubator

6ftBiosafety

6ftBiosafety

Ovr/UndCO2

Incubator6ft

Biosafety

6ftBiosafety

Ovr/UndCO2

Incubator

6ftBiosafety

6ftBiosafety

Ovr/UndCO2

Incubator6ft

Biosafety

6ftBiosafety

Ovr/UndCO2

Incubator

6ftBiosafety

Flow

Cytom

eter L

aboratoryC

asework

Flow

Cytom

eter

LaboratoryCasework

Flo

wC

ytom

eter

F

low

Cyt

omet

er

Sin

k

Double D

oor R

efrigerator

LaboratoryCasework

LaboratoryCasework

Mic

rosc

ope

Mic

rosc

ope

Com

pute

r

Computer

Computer

6ftBiosafety

6ftBiosafety

Ovr/UndCO2

Incubator

Ovr/UndMirco

Incubator

Microscope

Microscope

Computer

Microscope

6ftB

iosafety

6ftBiosafety

Ovr/U

ndM

ircoIncubator

IPAWash

Bench

Mirror

Micro

scope

Wir

e S

helv

ing

Wire Shelving

6ftBiosafety

Ovr/UndCO2

Incubator

ScintillationCounter

Harvester

Microscope

Refrigerator

Refrigerator

- 80 C F

reezerR

etain Sam

ples

Ref

rige

rato

r

Freezer

LaboratoryCasework

Laboratory

Casew

ork

Class 100

Sampling

StorageCabinet

Sin

k

PT PT PT PT PT PT

PT PT PT PT PT PT

PT

Loc

kers

Clean Scrubs

Lockers

Bench

Lockers

Ben

ch

Bench

IPAWash

SoiledGowns

Computer

Computer

Computer

Computer

Computer

Computer

Computer

Computer

CartPassThru

RetainSamplesRm 158

6.0' x12.0'

Ovr

/Und

Mir

coIn

cuba

tor

Microscope

Com

pute

r

6ftB

iosafety

6ftBiosafety

Ovr/U

ndM

ircoIncubator

Micro

scope

Wir

e S

helv

ing

Ovr/U

ndM

ircoIncubator

Microscope

Com

pute

r

SoiledGowns

Computer

- 80 C FreezerRetain Samples

- 80 C F

reezerR

etain Sam

ples

Computer

Microscope

Computer

LaboratoryCasework

Stainless Table

SoiledScrubs

SoiledScrubs

Access Corridor A Rm 100 31.0' x 6.0'

K

SoiledScrubs

SoiledScrubs

LockersLockers

Lockers Lockers

PT

WRT&A16

WRT&A17

Paradigm for Delivery of Patient-Specific Products

Massive Single Plant Problems with In-coming Patient Cells/Tissue Problems with Product Distribution No Real Economy of Scale

Production Units in Major Hospitals Optimum for Patient-Specific Transportation Issues Problems with Quality Oversight and Technical

Expertise; Facility Issues Multiple Regionally Located Plants

Concentrate Expertise and Quality Oversight Feasible Receiving and Shipping of Cells/Products

WRT&A18

WR Tolbert & AssociatesConsultants to the

Biopharmaceutical Industry

11483 Cypress Woods DriveSan Diego, CA 92131-3535

858-693-8163

[email protected] / www.wrtolbert.com

Documents

Cell Therapy Manufacturing: Regulations and Facilities