Chapter 26: Reserve Samples and Retains

21 CFR 211.170 requires an appropriately identified reserve sample that is representative of each lot in each shipment of each active ingredient. The reserve sample consists of at least twice the quantity necessary for all tests required to determine whether the active ingredient meets its established specifications, except for sterility and pyrogen testing. The retention time is as follows:

• For an active ingredient in a drug product the reserve sample shall be retained for 1 year after the expiration date of the last lot of the drug product containing the active ingredient.

• For an active ingredient in a radioactive drug product, except for nonradioactive reagent kits, the reserve sample shall be retained for:

o Three months after the expiration date of the last lot of the drug product containing the active ingredient if the expiration dating period of the drug product is 30 days or less;

o Or Six months after the expiration date of the last lot of the drug product containing the active ingredient if the expiration dating period of the drug product is more than 30 days.

• For an active ingredient in an OTC drug product that is exempt from bearing an expiration date the reserve sample shall be retained for 3 years after distribution of the last lot of the drug product containing the active ingredient.

It is important that samples are appropriately identified, representative of each lot or batch of drug product, and shall be retained and stored under conditions consistent with product labeling in the same immediate container-closure system in which the drug product is marketed or in one that has essentially the same characteristics.

The FDA’s Division of Scientific Investigations (DSI) and FDA field investigators conduct inspections of clinical and analytical sites that perform bioavailability (BA) and bioequivalence (BE) testing for drug manufacturers seeking approval of a drug product.

Retention samples should be kept at the testing facility where the study was conducted. The study sponsor should provide the testing facility with a supply of the test article and the reference standard sufficient to complete the study and retain the appropriate number of dosage units as reserve samples. The study sponsor should not separate out the samples to be reserved prior to sending the batches to the testing facility. The testing facility will randomly select the reserve samples from the supply sent by the sponsor. This is to ensure that reserve samples are in fact representative of the same batches provided by the study sponsor for the testing. The testing facility should retain enough quantify to permit FDA to perform five times all of the release tests required in the application.

Samples shall consist of a sufficient quantity to permit FDA to perform five times all of the release tests required in the application or supplemental application. Each reserve sample shall be adequately identified so that the reserve sample can be positively identified as having come from the same sample as used in the specific bioavailability study. Each reserve sample shall be stored under conditions consistent with product labeling and in an area segregated from the area where testing is conducted and with access limited to authorized personnel. Each reserve sample shall be retained for a period of at least 5 years following the date on which the application or supplemental application is approved, or, if such application or supplemental application is not approved, at least 5 years following the date of completion of the bioavailability study in which the sample from which the reserve sample was obtained was used.