Stability program expiration dating

The statistical interpretations are there is a 5% chance that the extrapolation is below 90% at f = 26 and there is a 5% chance that a further measurement at / = 26 months will yield a result below y 89% of nominal. Every batch in the stability program is subjected to this procedure the batch that yields the shortest shelf-life sets the expiration date. Possible solutions are as follows ... 

Current Good Manufacturing Practices [135] establish the requirements for maintaining a stability program and require that most pharmaceutical dosage forms have an established expiration date supported by test data [134]. There are few allowable exceptions. 

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. 

Abridged marketed product stability programs should be submitted to FDA in a prior-approval supplement, but usually not until after the approved expiration dating period has been confirmed through satisfactory stability data on the first three production batches. 

Failure to complete registration stability studies Failure to include each marketed product in the stability program Stability data not evaluated as part of the annual product review Stability results do not support expiration dating period Batches evaluated under QA requested studies released before sufficient data were available Stability data do not support proposed changes... 

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. 

Generally, a considerable waiting period is required to obtain data to establish the expiration date of a drug at shelf temperature (as most of the marketed products are relatively stable). The accelerated stability study, based on the study of rate of degradation in several storage conditions, is frequently used to circumvent this time limitation. Stability programs proposed by the FDA as part of the NDA submission are described below. 

Obtaining a kinetic date to ensure product stability may not be essential. The design of the accelerated stability program may have taken into consideration certain assumed factors (order of reaction and heat of activation). Thus, the result of the program may be the acceptance of a stable product and an estimated limited expiration date based on observation. 

Phase IV occurs after product approval and launch and the typical stability studies are focused on the marketed product stability program. These studies are conducted to assure that the product continues to meet the stability requirement for the approved expiration date. Therefore, these studies are conducted at the label storage conditions only. However, if new strengths, packages, or formulations are being developed, these studies would be conducted at accelerated storage conditions also. 

The objective for a stability program is to determine the expiration date of the product in its respective package(s). It is also to determine the proposed storage statement recommended for the product for it to continue to meet all the requirements of quality, purity, strength, and safety in the marketplace. The label storage statement must include storage precautions, if appropriate, for the pharmacists and the patients. 

The results of such stability testing shall be used in determining appropriate storage conditions and expiration dates. The written program shall be followed and shall include ... 

A formal testing program should be established to assess the stability characteristics of APIs. The results of such testing should be used to determine appropriate storage conditions and retest or expiration dates. The testing program should be ongoing and include ... 

An adequate number of batches of each API should be tested at suitable intervals to determine an appropriate retest or expiration date. This generally includes samples from the first three commercial size batches, but fewer batches may be appropriate in the initial testing program if data from previous studies or from literature show that the API is stable for at least two years. For those biotechnological/biologic and other APIs having shelf-lives of one-year or less, stability samples should be obtained and tested monthly for the first three months, and at three-month intervals thereafter. 

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