Sec. 420.100 Adulteration of Drugs Under Section 501(b) and 501(c) of the Act. *Direct
Reference Seizure Authority for Adulterated Drugs Under Section 501(b)* (CPG 7132a.03)
BACKGROUND:
Section 501(b) of the Food, Drug, and Cosmetic Act (the Act) deems an official drug
(i.e., a drug purported to be or represented as a drug the name of which is recognized in
an official compendium) to be adulterated if it fails to conform to compendial standards
of quality, strength or purity. Compendial tests or assay methods are used when
determining such conformance under 501(b); the standards are stated in individual
monographs as well as portions of the General Notices section of the USP/NF. Standards and
test methods have been established for such characteristics as potency, sterility,
*dissolution*, weight variation and content uniformity.
If an official drug fails to conform to one or more compendial standards of strength,
quality or purity, but plainly states on the label how it differs from the standard, then
the drug is not deemed to be adulterated under Section 501(b).
Section 501(c) of the Act deems *a drug that is not recognized in an official
compendium to be adulterated if it fails to meet the strength, purity or quality which it
purports or is represented to possess. The applicable quality standards for a drug not
recognized in an official compendium can be determined from such sources as the labeling
of the drug (or drug product), the manufacturer's written specifications, and new drug
applications. (Test methods are usually contained in the written specifications or new
drug application).*
POLICY:
Any official drug which, when tested by compendial methods, fails to conform to
compendial standards for quality, strength, or purity, is adulterated unless the
differences from such standards are plainly stated on the drug's label.
Any *drug which is not recognized in an official compendium is adulterated if its
strength differs from, or its purity or quality falls below that which it purports or is
represented to possess, when tested by scientifically sound methods.*
REGULATORY ACTION GUIDANCE:
Recommendations for regulatory action will be considered in the above instances of
adulteration. The regulatory action of choice will depend upon the circumstances of each
case.
In cases where there is a health hazard, the first choice of action should be recall,
particularly for drugs found to be non-sterile, and for narrow therapeutic range drugs
that fail potency or dissolution tests. However, where the district office has advised the
firm of such a defective product, and the firm fails to recall, seizure should be
considered. Seizure recommendations charging adulteration under section 501(c) should be
submitted to the Office of Compliance, Center for Drug Evaluation and Research (HFD-300)
(CDER).
District offices are authorized to submit seizure recommendations, charging adulteration
under section 501(b), directly to the Office of Enforcement without CDER review under the
following circumstances, provided introduction or delivery for introduction into
interstate commerce has been documented:
1. An official sample of either a compendial bulk pharmaceutical chemical or a
compendial finished dosage form has been analyzed using the compendial methods without
modification and found to fail both the original and check analyses.
2. The analyzing laboratory has certified in the transmittal memorandum that an
unmodified compendial method was used.
Note: No tolerance need be applied beyond that provided by the official compendium.
3. For sterile products, no check analysis is needed provided the compendial sterility
test was utilized without modification, the product is one that is required to be sterile,
and all relevant laboratory controls (including positive and negative) are satisfactory.
Where the analyzing laboratory deviates from the official compendial analytical
method(s), a detailed description of the deviation(s) and justification for such
deviation(s) can be submitted to CDER for review. In such cases, CDER will review only the
deviation(s) and not the choice of regulatory action or other documentation.
For seizure actions, the charges may be drafted as follows:
That the article of drug was adulterated, when introduced into and while in interstate commerce and is adulterated while held for sale after shipment in interstate commerce within the meaning of 21 U.S.C. 351(b), in that it purports to be and is represented as a drug, the name of which is recognized in an official compendium (United States Pharmacopeia) and its strength differs from, and its quality and purity falls below the standard set forth in such compendium because it fails the official (INSERT TYPE OF TEST) test.
or
That the article of drug was adulterated, when introduced into and while in interstate commerce and is adulterated while held for sale after shipment in interstate commerce within the meaning of 21 U.S.C. 351(c), in that it is a drug not subject to the provisions of 21 U.S.C. 351(b) and its strength differs from, and its purity and quality falls below that which it purports or is represented to possess because (e.g., the drug contains less than the amount of (INSERT NAME OF INGREDIENT) on the label).
It should be kept in mind that the types of adulteration found under 501(b) and 501(c)
may be indicative of a wider problem involving failure of the manufacturer to adhere to
current good manufacturing practice that should be addressed.
Issued: 10/1/80
Revised: 5/1/92