HCT/P Contamination Prevention and Biologic Product Sterility Regulations Applicable to PBSCs

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HCT/P Contamination Prevention and Biologic
Product Sterility Regulations Applicable to PBSCs

• Cell Therapy Liaison Meeting
• June 16, 2006
• Ellen F. Lazarus, M.D.
• Division of Human Tissues
• Office of Cellular, Tissue, and Gene Therapies

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HCT/P regulations addressing contamination

• Current Good Tissue Practices (CGTP)
• 21 CFR 1271.145
• You must recover, process, store, label,
  package, and distribute HCT/Ps, and screen and
  test cell and tissue donors, in a way that
  prevents the introduction, transmission, or
  spread of communicable diseases.

Applies to all HCT/Ps, including 351 products
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21 CFR 1271.150 CGTP requirements (361 products)

• You must follow CGTP requirements to prevent the
  introduction, transmission, or spread of
  communicable diseases by HCT/Ps (e.g., by
  ensuring that the HCT/Ps do not contain
  communicable disease agents, that they are not
  contaminated, and that they do not become
  contaminated during manufacturing). Communicable
  diseases includethose transmitted by bacteria,
  fungi, parasites, and TSE agents.

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Specific CGTP provisions (361 products)

• Sec. 1271.160(b)(2) Quality program must ensure
  that procedures exist for sharing information
  pertaining to possible contamination
• Sec. 1271.160(c) Facility controls to prevent
  contamination
• Sec. 1271.195(a) and (c) Environmental control
  and monitoring where conditions could be expected
  to cause contamination
• Sec. 1271.200(b) Equipment maintenance to
  prevent contamination

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Specific CGTP provisions (361 products, with
exception)

• Sec. 1271.215 Recover in a way that does not
  cause contamination
• Sec. 1271.220(a) Process in a way that does not
  cause contamination
• Sec. 1271.260(a) Control of storage areas to
  prevent contamination
• Sec 1271.265(c)(2) You must not make available
  for distribution an HCT/P that is contaminated
  or that otherwise does not meet release criteria
  designed to prevent communicable disease
  transmission

Applies to all HCT/Ps, including 351 products
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CGMP regulations addressing contamination and
sterility (IND and licensed
products)

• 211.42 - Facility design and environmental
  control
• 211.67 Equipment cleaning and maintenance
• 211.84(d)(6) - Testing and approval of
  components, drug product containers and closures
• 211.94(c) - Sterilization and depyrogenation of
  containers and closures
• 211.100 - Production and process controls
  (process validation)
• 211.110 - Sampling and testing of in-process
  materials and drug products

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CGMP regulations addressing contamination and
sterility (IND and licensed
products)

• 211.113 - Control of microbiological
  contamination
• 211.142(b) - Storage
• 211.160 - General requirements for laboratory
  controls
• 211.165 - Testing and release for distribution
• 211.165 (b) requires tests of each batch that
  should be free of objectionable microorganisms
  and
• 211.165(f) failure to meet any specification
  means rejection unless successful reprocessing
  possible
• 211.167 - Special testing requirements - requires
  sterility testing for products if purporting to
  be sterile

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Sterility provisions of the Part 610 General
Biological Products Standards (licensed
products)

• The test 610.12 (a)
• Fluid Thioglycollate Medium - inoculum incubated
  at 30 to 350C for at least 14 days
• Soybean-Casein Digest Medium same process
• Examined visually for evidence of growth on 3rd,
  4th, or 5th day, on 7th day, and last day of test
  period
• Alternate and equivalent methods also acceptable
  under 610.9 e.g., USP lt71gt or other method that
  is adequately validated
• 610.12(g) Exceptions