Stability program

This system includes measures and activities related to laboratory procedures, testing, analytical methods development and validation or verification, and the stability program. 

During the development phase a series of laboratory or pilot-scale batches will be subjected to this stability program. As soon as the process is scaled up to production-size batches, the first few, and at least one per year thereafter will also go on stability. Submission is only possible if the product completes a minimal combination of tests, e.g., one full-size batch for 12 months and two reduced-size batches for 6 months... 

Interpretation Active component A is so stable that a shelf-life in excess of 60 months could be assigned (it is unusual for a pharmaceutical to be approved for more than 5 years). Component B, however, undergoes hydrolysis (this fact has to be independently established, i.e., by GC/MS techniques, or equivalents). (See Fig. 4.26.) The data points cover an incomplete 24-month stability program T - 0, 3, 7, 24). The intercept is at 104.3%, an indication for over-dosing, and the slope is = 0.49 [%/month]. The... 

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 ... 

Refer the project back to the R D department for an improvement of the formula or the packaging (this can easily cost huge amounts of money and delay market introduction by years, especially if alternatives had not been thought of or had been prematurely deleted from the stability program). 

Activities encompassed by the stability program include sample storage of either development or production batches (or both), data collection and storage/retrieval, physical, chemical, and microbiological testing, document preparation of regulatory... 

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. 

QA requires the efficient analysis of many samples to support routine production release and stability programs. Methods are typically established in the analytical development group. Efficiency and convenience issues, including the speed of media preparation and the relative convenience of data handling and documentation, are important here. While compliance is important in all aspects of the pharmaceutical industry, QA functions must approach compliance perfection. Depending upon the facility, the automated apparatus may be tailored to specific methods with fixed configurations. Dissolution methods may be routine enough that a custom system, optimized for productivity, may be justified. Compliance of USP and use of industry standard apparatus is important to maintain compatibility with other company laboratories or in the case contract laboratory services are required. 

Laboratory Control System This includes laboratory test methods, stability program, and analytical method validation. 

The following principles apply to preservative effectiveness testing within a pre- and postmarketed product stability program. 

If the study outlined above in paragraph 1 was not conducted during product development, it is recommended that QA and/or the technical services groups imder-take a study to justify the cmrent specifications and the elimination of routine antimicrobial effectiveness testing within the stability program. 

Sample management and sample plans Stability program Packaging and labeling Labeling controls and approvals Package development... 

Stability data should be generated on at least three primary batches, which should be manufactured to a minimum of pilot scale by the same synthetic route and manufacturing process as the production batches. The quality of the API placed on a formal stability program should be similar to the quality of the material to be made on a commercial production scale. The container closure system must be the same or simulate the packaging proposed for storage and distribution of marketed product. 

The number of batches to be used for the stability program for a new drug product is at least three. Different batches of the drug substance should be used. 

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