Transcript Biologic Product Sterility Regulations

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
include…those 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 C B
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materials and drug products
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
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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 <71> or other method
that is adequately validated
► §610.12(g) Exceptions
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