Stability testing expiration dating period

An extension of an expiration dating period based on (1) data obtained under a new or revised stability testing protocol that has not been approved in the application or (2) full shelf life data on pilot scale batches using an approved protocol. 

To enable a clinical trial to start as soon as possible, stability testing is carried out in parallel with the clinical trial, but is initiated 3 to 6 months earlier. Three-to-six-month accelerated and real-time data, which are used to project or support the expiration dating period for the batch(es) to be used... 

A well-designed stability program meets all regulatory requirements and attains its objectives with minimal expenditure of resources. It provides all necessary data in a form that can be easily interpreted and evaluated, and distinguishes between analytical variability and instability. It specifies a testing frequency, which will provide early detection of instability and support the desired expiration-dating period. 

Rationale for bracketing and matrixing Storage conditions Container orientations Test methods Acceptance criteria Retest/expiration dating period Storage conditions for different types of protocols Clinical trial material Registration stability Annual batches Postapproval changes Special studies Test Parameters... 

Proposed or approved expiration dating period Sample requirements, based on amount needed for each test Preparer or reviewers approval signatures, including stability coordinator, laboratory head, QA, and others as appropriate... 

Conductance of the sterility test initially for all lots and at the end of the shelf-life expiration dating period for the product lot under stability testing... 

Satisfactory Data If the stability data generated on the first three annual batches after the switch to the ICH-recommended long-term testing conditions using an approved protocol, as defined above, support the previously approved expiration dating period under the non-ICH conditions, the data can be submitted in the next annual report, and the current expiration dating period can be retained. 

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. 

Batches selected for stability studies should optimally constitute a random sample from the population of production batches. In practice, the batches tested to establish the expiration dating period are often made at a pilot plant that may only simulate full-scale production. Future changes in the production process may thus render the initial stability study conclusions obsolete. 

Labeling requirements in 58.105(c) are not controversial and are the minimum to ensure against mix-up of test or control articles. The Expiration date needs to be included on the label only if one has been established. Some laboratories include a retest date on the label as a reminder of the need for periodic stability analyses. Only special storage conditions (e.g., refrigerate, protect from light, protect from freezing ) need to be included on the label. 

A reasonable interpretation of 58.113(c) should not require expiration dating of containers of article/carrier mixtures when the mixtures wiU be used on the date of preparation unless a component of the mixture has an extremely short (e.g., less than 8 hr) period of stability. This section does not require that an expiration date appear on feeders that are filled with article/ diet mixtures on the date the mixture is prepared and are presented to the test animals on that same day. 

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