Drug product expiration dating period

This section also concerns itself with the ability to review laboratory test procedures and laboratory instruments used. It is stressed that reserve samples of marketed products must be retained in their original containers for at least 2 years after the final distribution of a lot or at least 1 year after the drug s expiration date. In this same light, laboratory data for each batch or lot of drug should be retained for these time periods... 

Assuming a common slope with different intercepts for different batches, the expiration dating period is computed for each individual batch. The minimum of the expiration dating periods of the individual batches is the expiration dating period of the drug product. 

Since the minimum of all the expiration dating periods is the shortest shelf life among all batches, this estimate will provide a 95% confidence that the strength of the drug product will remain above the acceptable lower specification limit. 

Shelf Life (also referred to as Expiration Dating Period) — The time period during which a drug product is expected to remain within the approved shelf-life specification, provided that it is stored under the conditions defined on the container label. 

Stability studies during the IND phase provide not only assurance of the quality of clinical trial material but also the basis for the drug product development program. Stability data are used to evaluate different formulations, methods of manufacture, and container-closure systems, as well as to determine storage requirements, expiration dating periods, and specifications. 

Accelerated studies are carried out for 6 months, intermediate studies for 12 months and long-term studies for the duration of the proposed retest period for APIs and expiration dating period for drug products. 

The FDA Draft Stability Guidance defines an approved stability protocol as a detailed plan described in an approved application that is used to generate and analyze stability data to support the retest period for a drug substance or the expiration dating period for a drug product. 

State the proposed expiration dating period and storage conditions. Summarize the stability studies justifying the expiration dating period. Stability data should be submitted for the drug product in the container in which it will be marketed. 

Products without an Approved Stability Protocol Applicants who have previously performed stability studies on a drug product without an approved protocol are required to submit an appropriate protocol under a Prior Approval Supplement under 21 CFR 314.70(b) or (g) or 601.12(b) (see Section V regarding an Approved Stability Protocol). On approval of the protocol, applicants may initiate stability studies on all annual batches under the ICH long-term conditions. Data from the first three consecutive annual batches after the switch can be used to verify the current—or establish a new—expiration dating period. However, if the applicant wishes to verify product stability under the ICH conditions over a shorter time span, three production batches within 1 year, instead of three consecutive annual batches, may be studied... 

The stability protocol should include methodology for each parameter assessed during the stability evaluation of the drug substance and the drug product. The protocol should also address analyses and approaches for the evaluation of results and the determination of the expiration dating period, or retest period. The stability-indicating methodology should be validated by the manufacturer and described in sufficient detail to permit validation or verification by FDA laboratories. 

Conduct or complete the necessary studies on the first three production batches and annual batches thereafter of each drug product, container, and closure according to the approved stability protocol through the expiration dating period... 

For the purpose of approval of drug applications, stability data on pilot-scale batches should include results from microbial challenge studies performed on the drug product at appropriate intervals. In general, microbial challenge studies conducted initially, annually, and at the end of the expiration dating period are adequate. Chemical assays of preservative contents should be performed at all test points. 

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