[Code of Federal Regulations]
[Title 21, Volume 4]
[Revised as of April 1, 2002]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR211.84]

[Page 123]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 211--CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS--Table of Contents
 
    Subpart E--Control of Components and Drug Product Containers and 
                                Closures
 
Sec. 211.84  Testing and approval or rejection of components, drug product containers, and closures.

    (a) Each lot of components, drug product containers, and closures 
shall be withheld from use until the lot has been sampled, tested, or 
examined, as appropriate, and released for use by the quality control 
unit.
    (b) Representative samples of each shipment of each lot shall be 
collected for testing or examination. The number of containers to be 
sampled, and the amount of material to be taken from each container, 
shall be based upon appropriate criteria such as statistical criteria 
for component variability, confidence levels, and degree of precision 
desired, the past quality history of the supplier, and the quantity 
needed for analysis and reserve where required by Sec. 211.170.
    (c) Samples shall be collected in accordance with the following 
procedures:
    (1) The containers of components selected shall be cleaned where 
necessary, by appropriate means.
    (2) The containers shall be opened, sampled, and resealed in a 
manner designed to prevent contamination of their contents and 
contamination of other components, drug product containers, or closures.
    (3) Sterile equipment and aseptic sampling techniques shall be used 
when necessary.
    (4) If it is necessary to sample a component from the top, middle, 
and bottom of its container, such sample subdivisions shall not be 
composited for testing.
    (5) Sample containers shall be identified so that the following 
information can be determined: name of the material sampled, the lot 
number, the container from which the sample was taken, the date on which 
the sample was taken, and the name of the person who collected the 
sample.
    (6) Containers from which samples have been taken shall be marked to 
show that samples have been removed from them.
    (d) Samples shall be examined and tested as follows:
    (1) At least one test shall be conducted to verify the identity of 
each component of a drug product. Specific identity tests, if they 
exist, shall be used.
    (2) Each component shall be tested for conformity with all 
appropriate written specifications for purity, strength, and quality. In 
lieu of such testing by the manufacturer, a report of analysis may be 
accepted from the supplier of a component, provided that at least one 
specific identity test is conducted on such component by the 
manufacturer, and provided that the manufacturer establishes the 
reliability of the supplier's analyses through appropriate validation of 
the supplier's test results at appropriate intervals.
    (3) Containers and closures shall be tested for conformance with all 
appropriate written procedures. In lieu of such testing by the 
manufacturer, a certificate of testing may be accepted from the 
supplier, provided that at least a visual identification is conducted on 
such containers/closures by the manufacturer and provided that the 
manufacturer establishes the reliability of the supplier's test results 
through appropriate validation of the supplier's test results at 
appropriate intervals.
    (4) When appropriate, components shall be microscopically examined.
    (5) Each lot of a component, drug product container, or closure that 
is liable to contamination with filth, insect infestation, or other 
extraneous adulterant shall be examined against established 
specifications for such contamination.
    (6) Each lot of a component, drug product container, or closure that 
is liable to microbiological contamination that is objectionable in view 
of its intended use shall be subjected to microbiological tests before 
use.
    (e) Any lot of components, drug product containers, or closures that 
meets the appropriate written specifications of identity, strength, 
quality, and purity and related tests under paragraph (d) of this 
section may be approved and released for use. Any lot of such material 
that does not meet such specifications shall be rejected.

[43 FR 45077, Sept. 29, 1978, as amended at 63 FR 14356, Mar. 25, 1998]

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