Appendix A Template Form referred to in Chapter 15 - FacilityEquipment

Form A

237A. Gee (ed.), Cell Therapy, DOI 10.1007/b102110,C© Springer Science+Business Media, LLC 2009

Appendix B Template Form referred to in Chapter 15 - FacilityEquipment

Form B – Equipment Discard

239

240 Appendix B

Appendix C Template Form referred to in Chapter 15 - FacilityEquipment

Form C – Quality Control of Laboratory Scales

241

Appendix D Template Form referred to in Chapter 15 - FacilityEquipment

From D – Sample Policy New Equipment Qualification

243

Appendix E Template Form referred to in Chapter 15 - FacilityEquipment

From E – Sample QC SOP Quality Control Procedure for Scale

245

246 Appendix E

Index

Note: The letters ‘ f ’ and ‘t’ following the locators refer to figures and tablesrespectively.

AAABB, see American Association of Blood

Banks (AABB)AABB Cell Therapy Standards

accreditation, 93–94Accreditation Program Policy Manual,

93, 94development, 88–89

CLIA 1988 (Clinical LaboratoryImprovement Amendments), 88

SPC, 88SPU, 88Standards for a Blood Transfusion

Service, 88Standards for Cellular Therapy Product

Services, 88–89highlights of third edition, 94–95history/evolution, 87–88quality systems approach, 89–90

HPC, 89reference standards, 90

from 1991 to 2007, AABBinvolvement, 89t

transparency in settingorganizations/expertise represented, 93treview/change/approval of technical

standards, 91 fStandards for Cellular Therapy Product

Services, 901st edition of Standards for Cellular

Therapy Product Services, 92 fvalidation of assessments, 94

7-AAD, 208, 222, 232tAastromReplicellTM system, 62 f

AATB, see American Association of TissueBanks (AATB)

Advanced cell therapies, 32–33AHCTA, see Alliance for Harmonisation of

Cellular Therapy Accreditation(AHCTA)

Alliance for Harmonisation of CellularTherapy Accreditation (AHCTA),29

American Association of Blood Banks(AABB), 29

American Association of Tissue Banks(AATB), 187

American Society for Blood and MarrowTransplantation (ASBMT), 98

Antilymphocyte globulin (ALG), 51ASBMT, see American Society for Blood and

Marrow Transplantation (ASBMT)Aseptic technique, 111, 123t, 124, 129, 144,

154, 210Australian Commonwealth, 39Australian Health Ministers’ Council, 42Australia, regulatory system for cell and tissue

therapiesassessment of manufacturing process, 46current regulation of biological

therapies, 40autologous medicines, 41batch-based pharmaceuticals, 40cell-based vaccine, 41clinical indication, 41experimental cell and tissue-based

therapies, 42extemporaneously compounded, 41fresh components of blood, 41

247

248 Index

Australia, regulatory system for cell and tissuetherapies (cont.)

gene therapies, 41hematopoietic progenitor cell for

myocardial regeneration, 41human blood and tissues, 41for medicines and devices, 40premarket approval, 41product assessment, 41therapeutic goods, 42Therapeutic Goods Act, 40

development, 42Australian Health Ministers’

Council, 42cell and tissue therapies, definition, 42regulatory framework for cell and tissue

therapies, 42experimental cell and tissue-based

therapies, 42Good Manufacturing Practices (GMP), 38regulators, 38regulatory agencies, 38regulatory process, 41regulatory profession, 38therapeutics industry, 37

Autologous graft, 28

BBaldrige National Quality Program, 121Baxter Oncology Isolex 300i clinical magnetic

cell separator, 59Baylor College of Medicine, CAGT

cold storage room, 74CPF, 71–76

barcoding systems, 76CoA, 71documentation of equipment

performance, 76gowning room, 72ICCBBA, 76main corridor, 72 fmanufacturing suite, 74 fnitrogen storage banks, 75 fnon-campaign-style manufacturing, 75receiving area, 72 f

floorplan of existing CAGTcell processing facility, 69 fvector production facility, 70 f

manufacturing processes, 74new CAGT facilities, 77variety of products, 68VPF

Beckman-Coulter AcT-diff2TM hematologyanalyzer, 59

Beckman-Coulter FC500 5-color cytometer, 59Beckman J-6 M centrifuges, 59Biologics license applications (BLAs), 229BLAs, see Biologics license applications

(BLAs)

CCAGT, see Center for Cell and Gene Therapy

(CAGT)CAGT, Baylor College of Medicine, see Baylor

College of Medicine, CAGTCancer Institute (UPCI) at the University of

Pittsburgh Medical Center (UPMC),The, 57

CAP, see College of American Pathologists(CAP)

CBER, see Center for Biologics Evaluationand Research (CBER)

Cell Processing Facility (CPF), 68, 69f, 70,71–76, 163, 173

Cellular Products Laboratory/Gene TherapyLaboratory (CPL/GTL), 57, 61

Center for Biologics Evaluation and Research(CBER), 4, 230

Center for Cell and Gene Therapy (CAGT), 64,67–77

Center for Devices and Radiological Health(CDRH), 4

Centers for Medicare and Medicaid Services(CMS), 94

Certificate of Analysis (CoA), 71, 158CFR, see Code of Federal Regulations (CFR)CGMP, see Current Good Manufacturing

Practice (cGMP)“CGMP for Phase 1 Investigational Drugs,”

FDA, 147Chemistry, Manufacturing, and Control

(CMC), 10–13Circular of Information (COI), 226Class 100 biological safety cabinet, 68,

147, 148Cleaning procedures

automatic disinfectant dilutionsystem, 137 f

changeover procedures, 143choices, 135–138complete cleaning of production suite,

138 fequipment cleaning, 141–142

documentation, 142schedules and practices, 138–140

cleaning schedule, example, 139tfactors, impact on efficacy of, 140

Index 249

staff, 137validation of cleaning, 140–141

virus, replication-competent, 141Clinical Laboratory Standards Institute

(CLSI), 187CLSI, see Clinical Laboratory Standards

Institute (CLSI)CMC, see Chemistry, Manufacturing, and

Control (CMC)CMC section, 10, 22, 232, 233CoA, see Certificate of Analysis (CoA)COBE R© 2991 cell washer, 59Code of Federal Regulations (CFR), 4,

157, 187COI, see Circular of Information (COI)College of American Pathologists (CAP), 130,

132, 171, 187CPL/GTL, see Cellular Products Labora-

tory/Gene Therapy Laboratory(CPL/GTL)

current Good Manufacturing Practices(cGMP), 15–17, 51, 59, 88,187, 231

DDesign of new GMP facility

central monitoring and alarm system, 82construction of space, 80 ffiling space, 83floorplan of the new Baylor GMP

facilities, 80 fgamma irradiator, 83nitrogen bank facility, 83space constraint, 79

Design Qualification (DQ), 171–172Digression, regulation of therapeutic goods in

Australia, 39–40Division of Manufacturing and Product Quality

(DMPQ), 57DLI, see Donor Lymphocyte Infusion (DLI)DMF, see Drug Master File (DMF)DMPQ, see Division of Manufacturing and

Product Quality (DMPQ)Donor Lymphocyte Infusion (DLI), 29DQ, see Design Qualification (DQ)Drug Master File (DMF), 229, 230

EEBMT, see European Group for Blood and

Marrow Transplantation (EBMT)2004/23/EC Directive, 28e-learning, advantages, 128

See also Staffing, training/competencyElectronic Submissions Gateway (ESG), 235

Endosafe R© PTSTM system, 207Endotoxin, 11, 21, 167, 207, 208, 209, 211,

222, 224, 234Environmental monitoring

“academic” GMP and GTP, 146–147air handling, 148–150

electronic counters, 149 fchangeover procedures, 151

worksheet for room changeover, 152 fdatabases, 154–155

trending of environmental monitoringdata, 154 f

elements of, 148GMP, 146GTP, 145–146interpretation of data, 151–153

antibiotics, use of, 153difficulty, 153standard policy, 153

monitoring frequencysurface monitoring, 151

recording sheet for, 150 fregulations, 145

Title 21 of the U.S. Code of FederalRegulations (21CFR), 4, 109, 145,157, 182, 183t, 187, 216

Equipment (facility)prioritization and backup, 178–179

sample prioritization of equipmenttable, 179t

QC and documentation, 179–181standardized format for the

contents, 180qualification

IQ, 176–177operator qualification, 178OQ, 176–177PQ, 177–178vs. validation, 175–176

regulations and standards, 182–185equipment checks from Title 21 Code

of Federal Regulations Part 606,183t

equipment section from Title 21Code of Federal Regulations Part1271.200, 184t

equipment section from Title 21 Codeof Federal Regulations Part 58Subpart D, 182t

equipment section Title 21 Code ofFederal Regulations Part 211.63,184t–185t

retiring equipment, 181–182

250 Index

Equipment (facility) (cont.)equipment binder, 182

selection, 171–175capital budgeting, 173choosing equipment, 172–173Design Qualification (DQ), 171–172equipment qualification cycle, 172 flifespan, 173warranties and service contracts,

174–175Error Management System, 194

See also QualityESG, see Electronic Submissions Gateway

(ESG)EUD criteria, 29EUD 2004/23/EC, 27, 30, 32EUD 2006/86/EC, 30EU Directive on Quality and Safety of Tissue

and Cells, 27–30EU Medicinal Products Directive, 30–32European Committee for Standard-

ization/Information SocietyStandardization System(CEN/ISSS), 29

European Directives (EUD), 27, 28, 29, 30, 31,32, 33

European Group for Blood and MarrowTransplantation (EBMT), 29, 98

European Guide to Good ManufacturingPractice (GMP), 30

European regulatory status, situation in France,33–35

Europe, regulatory situation for academic celltherapy facilities

advanced cell therapies, 32academic cell therapy facilities, 33Environment, Public Health and Food

Safety Committee, 33EU Directive on Quality and Safety of

Tissue and Cells, 27accreditation by organizations, 29

EU Medicinal Products Directive, 30EU Directive 2001/83/EC, 30gene therapy, 30medicinal products (MP), 30somatic cell therapy, 30

legislation, 32links, 35situation in France (example), 33

“Agence de Biomedecine,” 33Agence du Medicament (French Drug

Agency), 33cell therapy facilities, 33

“Commission de Therapie Cellulaire etGenique,” 34

French hematopoietic cell transplanta-tion programs, 35

general rules for cell or tissueprocurement, 34

ISO 9001 certification, 35JACIE accreditation, 35“Produits Therapeutiques Annexes,” 34Public National Blood Bank

Agency, 33EU Tissue and Cells Directive

2004/23/EC, 28

FFACT, see Foundation for the Accreditation of

Cellular Therapy (FACT)FACT Accreditation Program, 102FACT-JACIE International Standards

for Cellular Therapy ProductCollection, Processing, andAdministration, 99, 100

FAHCT Standards for HematopoieticProgenitor Cell Collection,Processing & Transplantation, 98

First-in first-out (FIFO) system, 159Food and Drug Administration (FDA), 3, 4, 22,

30, 53, 57, 100, 109, 121, 124, 147,159, 173, 199, 221, 229

Food, Drug, and Cosmetic Act (FD&C Act), 4Foundation for the Accreditation of Cellular

Therapy (FACT), 20, 22, 29,97–105, 124, 143, 162, 187, 206,217, 231

accreditationof cord blood banks by

FACT-NetCord, 105inspector qualifications, 103tmost commonly cited standards, 104ton-site inspection, 102–104programs, 104

FACT-JACIE International Standardsfor Cellular Therapy ProductCollection, Processing, andAdministration, 100–101

historical background, 97–99ASBMT, 98JACIE, 98

NetCord-FACT International Standards forCord Blood Processing, Testing,Banking, Selection and Release,101–102

standards, 99–100

Index 251

GGHTF, see Global Harmonization Task Force

(GHTF)Global Harmonization Task Force (GHTF), 40GMP, see Good Manufacturing Practice (GMP)GMP facility (new Baylor), design

central monitoring and alarm system, 82construction of space, 80 ffiling space, 83floorplan of new Baylor GMP

facilities, 80 fgamma irradiator, 83nitrogen bank facility, 83space constraint, 79

Good Manufacturing Practice (GMP), 3, 15,16, 30, 38, 43, 51, 62, 62f, 109, 121,146–147, 157, 158–159, 179, 199,216

Good Tissue Practice (GTP), 61, 121, 157–158,216

regulations, 157–158See also Supply management

HHCT, see Hematopoietic cell transplant (HCT)HCT/Ps, see Human cells, tissues, and cellular

and tissue-based products (HCT/Ps)Health Insurance Portability and Account-

ability Act (HIPAA), American,122

Heating, ventilation, and air conditioning(HVAC) system, 58–59, 148

Hematopoietic cell transplant (HCT), 35, 97,98, 100

Hematopoietic peripheral blood, 28Hematopoietic Progenitor Cells (HPC), 28, 29,

31, 68, 89, 98, 102Hematopoietic Stem Cell Laboratory (HSC

Lab), 57, 59–61HeracellTM incubator, 59High-efficiency particulate air (HEPA), 52,

135, 147HIPAA, see Health Insurance Portability

and Accountability Act (HIPAA),American

HSC Lab/IMCPL, University of PittsburghCancer Institute, see University ofPittsburgh Cancer Institute, HSCLab/IMCPL

Human cells, tissues, and cellular andtissue-based products (HCT/Ps),146, 158, 187

HVAC, see Heating, ventilation, and airconditioning (HVAC) system

IICCBBA, see International Council for

Commonality in Blood BankAutomation (ICCBBA)

IDE, see Investigational Device Exemption(IDE)

IMCPL, see Immunological Monitoringand Cellular Products Laboratory(IMCPL)

IMCPL/HSC Lab, University of PittsburghCancer Institute, see University ofPittsburgh Cancer Institute, HSCLab/IMCPL

IML, see Immunologic Monitoring Laboratory(IML)

Immunological Monitoring and CellularProducts Laboratory (IMCPL),61–64

AastromReplicell System, 62 fCPL/GTL, functions, 61–62IML, 62office, laboratory, and meeting space, 63 foffice personnel and Laboratory personnel,

workflow patterns, 64 fproducts (lymphocytes/dendritic

cells/hematopoietic cell lines/tumorcells/lines/tissue cells), 62

workflow patterns, 63 fSee also University of Pittsburgh Cancer

Institute, HSC Lab/IMCPLImmunologic Monitoring Laboratory (IML),

62INDs, see Investigational new drugs (INDs)“INDs – cGMP for Phase I Investigational

Drugs,” 159Installation qualification (IQ), 175, 176–177Institutional Review Boards (IRB), 189, 217International coding and labeling system, ISBT

128, 29International Council for Commonality

in Blood Bank Automation(ICCBBA), 76

International Organization of MedicalPhysics, 181

International Society for Cellular Therapy(ISCT), 27, 29, 97

International Society for Hematotherapy andGraft Engineering (ISHAGE), 97

International Standards Organization (ISO),89, 187, 210

Investigational Device Exemption (IDE), 13,199, 216

252 Index

Investigational new drugs (INDs), 3, 51, 59,146, 159, 195, 216, 229

IRB, see Institutional Review Boards (IRB)ISBT 128 coding and labeling system, 29, 30,

76, 100, 102, 168ISCT, see International Society for Cellular

Therapy (ISCT)ISHAGE, see International Society for

Hematotherapy and GraftEngineering (ISHAGE)

ISO, see International Standards Organization(ISO)

JJACIE, see Joint Accreditation Committee of

the ISCT and the EBMT (JACIE)JCAHO, see Joint Commission for the

Accreditation of HealthcareOrganizations (JCAHO)

Joint Accreditation Committee of the ISCTand the EBMT (JACIE), 29, 35, 98,99, 100, 101, 102, 104, 105, 109

Joint Commission for the Accreditation ofHealthcare Organizations (JCAHO),187

LLeukocytes, 28, 30, 31, 68Liquid nitrogen storage facility, 59–60, 142

MManufacturer’s Operating Manual, 180Manufacturing process, assessment of, 45, 46Master file

definition and types, 229–230, 230tFDA regulations/regulatory guid-

ance/standards, 231tas formal FDA submission vs. internal

document, 234–235DMF submission/contents, 234

use and content, 230–232contents/attachments, NIH cell

processing, 232tFDA regulations/regulatory guid-

ance/standards, 231twriting, cell therapy, 233–234

quality and technical issues, 233MCT, see Molecular and Cellular Therapeutics

(MCT)MCT, University of Minnesota, 52 f

aspects of facility design, 53–55“stand-alone” facility, 54

facility design, 52–53

flow (personnel, material, product, andwaste), 55 f

layout of lower level, 54 flayout of upper level, 53 foverview, 51–52products manufactured under IND, 51–52

Molecular and Cellular Therapeutics (MCT),51–55, 52f, 64

Molecular technique, 222

NNational Heart, Lung, and Blood Institute

(NHLBI), 59Natural killer (NK) cells, 51, 62NetCord-FACT International Standards for

Cord Blood Processing, Testing,Banking, Selection and Release, 98

New drug applications (NDAs), 229NHLBI, see National Heart, Lung, and Blood

Institute (NHLBI)

OOCBQ, see Office of Compliance and

Biologics Quality (OCBQ)OCGT, see Office for Cell and Gene Therapy

(OCGT)Office for Cell and Gene Therapy (OCGT), 4Office of Compliance and Biologics Quality

(OCBQ), 57OOS, see Out-of-Specification (OOS)Operational Qualification (OQ), 176–177OQ, see Operational Qualification (OQ)Out-of-Specification (OOS), 153, 203,

224–225

PPACT, see Production Assistance for Cellular

Therapies (PACT)PBR, see Production Batch Records (PBR)Production Assistance for Cellular Therapies

(PACT), 59, 169Production Batch Records (PBR), 117–118Product manufacturing

ancillary records, 210components used and processing,

flowchart, 206 fdesign of procedure, 199–203

draft SOP, 200page from batch record, sample, 202f,

203worksheets, sample, 200–201, 201 f

production monitoring, 203worksheet, sample, 204 f –205 f

product storage and release, 210–212

Index 253

QA/QC, 211release testing, 206–210

Endosafe R© PTSTM endotoxin testingdevice, 208 f

endotoxin testing, 207HLA typing, 208mycoplasma testing, PCR reaction for,

208, 209 fpotency assays, 207

Product, review/release/administrationadministration, 226

COI, 226documentation, 217–218

infectious disease status of cell/tissuedonor, 217

regulatory issues, 216–217IRB, 217“unregulated” Type 361 products, 217

release/transportation/shipment, 225–226testing for release, 218–225

certificate of analysis, example of,220 f

elements for review, 219tGram staining, 221identity testing, 222–224mycoplasma testing, 221–222OOS results, 224–225purity, 222sterility testing, 221tests for cell and gene therapy,

223t–224tType 361 products, 218viability, 222

understanding of, 215–216components, 216

Public Health Service Act (PHS Act), 4

QQCU, see Quality control unit (QCU)Quality

comprehensive quality program, 187–188designing quality management program,

188–189IRB approval, 189“Quality Systems Management,” 189

improving cellular therapy services,194–196

Error Management System, 194quality improvement projects, 195reason to document success, 196

monitoring quality systems, 189–194audit process, document, 192first/second/third-party audits, 192

focused audits, 192indicators, selection of, 191internal auditors, selection of, 193monitors or indicators, 189process audits, 192–193Quality Assurance Plan, 189system audits, 193

Quality Assurance Plan, 189See also Quality

Quality control (QC), 54, 131, 177,179–181, 188

Quality control unit (QCU), 188“Quality Systems Management,” 189

R“Reagent Rental” agreement, 174Regulation of Biological Therapies in

Australia, 40–42Regulation of cell product manufacturing and

delivery, US perspectivecell therapy development, history of, 3–4cGMP and Cell Product Manufacturing,

15–17CMC section, 10

chemistry and manufacturing, 12drug product, 12labeling, 12–13pharmacology/toxicology (pharm/tox)

section, 13combination products, 6–7cross-referencing, 13filing IND, 14GMP components

controlled labeling operations, 20delivery of cellular products, 21–22equipment records/calibration/cleaning,

19facility requirements, 19management systems, 19–20processing records, 18–19QA/QC program, 19release criteria principles, 20–21SOP development, 18staff training, 18validation procedures, 19

IND/GMP sliding scale, 17–18IND maintenance, 15IND process, 7

pre-IND meeting, 8–9requesting meeting, 7–8sponsor/investigator, 7submission, 9–10

regulation of cell therapies, history of

254 Index

Regulation of cell product manufacturing anddelivery, US perspective (cont.)

CBER, 5–6CDER, 6CDRH, 6

Type V Master File, 13–14U.S. Food and Drug Administration

(FDA), 4Regulatory system for cell and tissue therapies,

Australiaassessment of manufacturing

process, 46current regulation of biological therapies

autologous medicines, 41batch-based pharmaceuticals, 40biological therapeutic goods, 42biological therapies, 40cell-based vaccine, 41clinical indication, 41experimental cell and tissue-based,

41–42fresh components of blood, 41gene therapies, 41hematopoietic progenitor cell for

myocardial regeneration, 41human blood and tissues, 41premarket approval, 41product assessment, 41regulatory system for medicines and

devices, 40Therapeutic Goods Act, 40

development ofAustralian Health Ministers’

Council, 42cell and tissue therapies, definition

of, 42digression, regulation of therapeutic

goods, 39Australian Register for Therapeutic

Goods, 40biological therapies, 40Commonwealth, 39health care services, 39jurisdictions, 39medicines and medical devices, 40public subsidy, 40TGA, 39Therapeutic Goods Act, 39, 40

experimental cell and tissue-basedtherapies, 42

GMP, 38regulatory agencies, 38regulatory process, 41

regulatory profession, 38therapeutics industry, 37

SSPC, see Standards Program Committee (SPC)SPU, see Standards Program Unit (SPU)SQR-1 fill sequencer system, 58Staffing, training/competency

adult learner, 127–128assumptions about, 127methods for presentation, 128

analysis, 122competence

CLIA, competency assessmentprogram, 130 f

competency requirements, 132design of training program, 125–127

GxP manufacturing environ-ment/training policy document,126–127

development, 129checklists, 129training, 129 f

e-learning, advantages, 128evaluation, 130implementation, 130job description, 122–123

clinical production scientist, 123 frecordkeeping, personnel records, 133selection of employee, 121training regulations, 124–125

master training list, 125tperformance objective for aseptic

technique, 124Standard Operating Procedures (SOPs), 11,

18, 28, 64, 100, 109–120, 129, 136,176, 182, 194, 200, 215, 225, 233

document approvalannual review, 118–120archival of SOPs, 118document change request form, 116 fdocument distribution and availability,

117new SOPs, 115PBR, 117–118retired SOPs, 117revised SOPs, 115–116SOP sign-off page (example), 119 ftraining documentation, 118

document control, 111required elements, 111

formatting and content of SOPs, 112–113body of SOP, 113

Index 255

numbering systems for SOPs, 111–112two-letter characters, 112

types of SOPs, 110–111activities in cellular therapy

manufacturing facility, flowchart,110t

PBR, 111validation plans, 114–115writing SOPs, 113–114

Standards for a Blood Transfusion Service, 88Standards for Cellular Therapy Product

Services, 89t, 90, 92 fStandards for Cord Blood Services (2001), 89Standards for Hematopoietic Progenitor Cell

Services (2000/2002), 89Standards Program Committee (SPC), 88Standards Program Unit (SPU), 88Stem- Cell TechnologiesTM, 132Story board, 196Superuser (equipment), 178Supply management

approved supplies, 160establishing system, 159–160

materials ordering and managementflowchart, 161 f

expired materials, 169formulations, 168–169GMP regulations, 158–159

CoA, 158first-in first-out (FIFO) system, 159“INDs – cGMP for Phase I

Investigational Drugs,” 159GTP regulations, 157–158parts lists, 163reagents, in-house preparation, 169receipt of supplies, 163–165

barcode and release sticker, 164 fproduction report, 165 f

regulatory requirements, 157released, 166–168

labor-intensive approach, 167–168storage, 166

high-density storage for supplies, 167 fsupply release, 166

sourcing components, 162–163specifications, 160–163worksheet, sample, 162 f

System audits, 193

TTGA, see Therapeutic Goods Administration

(TGA)Therapeutic Goods Act, 37, 39, 40

Therapeutic Goods Administration (TGA),39, 105

Tissue Processing Laboratory (TPL), 61TPL, see Tissue Processing Laboratory (TPL)Trypan blue, 222, 232tType 351 products, 146, 203, 207, 208, 216,

220, 226Type 361 products, 147, 203, 206, 207, 209,

210, 216, 217, 218, 226

UUniversity of Minnesota, MCT

aspects of facility design, 53–55“stand-alone” facility, 54

facility design, 52–53flow (personnel, material, product, and

waste), 55 flayout of lower level, 54 flayout of upper level, 53 foverview, 51–52products manufactured under IND, 51–52

University of Pittsburgh Cancer Institute, HSCLab/IMCPL

design of labs, 57–58HSC lab

Bone Marrow Transplant Program, 59current good manufacturing practice

(cGMP), 59floor plan, 60 fIND-driven projects, 59main work areas, 60processing equipment, 59testing equipment, 59–60workflow patterns for personnel,

products and waste, 61 fHVAC system, 58–59IMCPL

AastromReplicellTM System, 62 fCPL/GTL, functions, 61–62IML, 62office, laboratory, and meeting

space, 63 foffice personnel and Laboratory

personnel, workflow patterns, 64 fproducts (lymphocytes/dendritic

cells/hematopoietic cell lines/tumorcells/lines/tissue cells), 62

workflow patterns, 63 flaboratory features, 63–64

Baylor College of Medicine andMCT, 64

CAGT, 64efficient utilization of space, 64

256 Index

University of Pittsburgh Cancer Institute, HSCLab/IMCPL (cont.)

LN2 system, 63laboratory features, retain/change, 63–64products, preservation of, 58

University of Washington Gene and CellTherapy Laboratory, 112, 114, 115

US perspective, regulation of cell productmanufacturing and delivery

cell therapy development, history of, 3–4cGMP and cell product manufacturing,

15–17CMC section, 10–13

chemistry and manufacturingintroduction, 12

drug product, 12labeling, 12–13pharmacology/toxicology (pharm/tox)

section, 13combination products, 6–7cross-referencing, 13FDA, 4filing IND, 14GMP components

controlled labeling operations, 20delivery of cellular products, 21–22equipment records/calibration/cleaning,

19facility requirements, 19

management systems, 19–20processing records, 18–19QA/QC program, 19release criteria principles, 20–21SOP development, 18staff training, 18validation procedures, 19

IND/GMP sliding scale, 17–18IND maintenance, 15IND process, 7

meeting, requesting, 7–8pre-IND meeting, 8–9sponsor/investigator, 7submission, 9–10

regulation of cell therapies, history ofCBER, 5–6CDER, 6CDRH, 6

Type V Master File, 13–14

VVector Production Facility (VPF), 68–69VPF, see Vector Production Facility (VPF)

WWMDA, see World Marrow Donor Association

(WMDA)World Marrow Donor Association

(WMDA), 28