CPG Sec. 480.300 Lack of Expiration Date of Stability Data

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CPG Sec. 480.300 Lack of Expiration Date of Stability Data
BACKGROUND:
*The CGMP regulations (21 CFR 211.137) have required that drug products packaged since September
29, 1979, bear an expiration date which is supported by appropriate stability data, with limited
exceptions. OTC drug products which have no dosage limitation and which are stable for at least three
years as demonstrated by appropriate data are exempt from the requirement to bear an expiration
date. Homeopathic drugs, while required to have a limited evaluation of stability, are also exempt from
the requirement to bear an expiration date. Additionally, allergenic extracts that are labeled "No U.S.
Standard of Potency" are exempt from the requirements to be labeled with an expiration date and the
performance of stability studies.*
Section 211.166 requires a firm to have a written stability program, the results of which are to be used
in determining appropriate storage conditions and a product's expiration date and specifies what must
be included in the stability program.
In addition, the USP requires that the labels of all pharmacopeial dosage forms bear an expiration date.
REGULATORY ACTION GUIDANCE:
Appropriate division offices within the Office of Pharmaceutical Quality Operations (OPQO) are
authorized to issue *Warning Letters without Office of Compliance, HFD-300*, review under the
following circumstances:
1. 	A non-compendial drug product intended for internal use does not bear an expiration date and
is not exempt by regulations.
Charge: 501(a)(2)(B), 21 CFR 211.137.
2. 	A prescription drug product for which it has been determined that stability studies do not exist.
Charge: 501(a)(2)(B), 21 CFR 211.166
Examples of the wording to be used in a *warning letter* are as follows:
501(a)(2)(B) Your product, (name of product), is adulterated in that the controls used for the
manufacture, processing, packing, or holding of this drug product are not in conformance with current
good manufacturing practice regulations (Title 21, Code of Federal Regulations, Parts 210 and 211).
Specific Violations are:
There is no assurance that the product meets applicable standards of identity, strength, quality, and
purity at the time of use in that it does not bear an expiration date (211.137).
You have not performed stability testing of your product and therefore are unable to appropriately
determine storage conditions designed to assure the stability of your drug product (211.166).

NOTE: If appropriate, misbranding [502(g)] may be charged when a USP drug product intended for
internal use does not bear an expiration date and is not exempt by regulations. Example of the wording
to be used in a *warning letter*:
502(g) The article (name of the drug product) is misbranded in that it purports to be a drug, the name of
which is recognized in an official compendium and the label fails to bear an expiration date as prescribed
therein.
All other cases should be referred to the Office of Compliance, *HFD-300*, or as identified in *CPG
7132a.04 (See Sec. 480.100) or* specific compliance programs, in the usual manner.
*Material between asterisks is new or revised*
Issued: 1/16/84
Revised: 9/4/87, 3/95