Regulatory Requirements for Product Stability Testing

One of the crucial part of product development is product stability testing. It is conducted throughout a product’s life cycle. Stability is a part of a bio-therapeutic quality target product profile, and the results help analysts in understanding how important the critical quality attributes (CQSs) of both product and drug substance are influenced under particular conditions of storage, light, pH, relative humidity, temperature and other factors. Stability tests are conducted by manufacturers to ascertain degradation pathway and determine storage conditions and shelf lives of the product. For example, bioassays and tests concerned to safety, potency, quality, identity and purity are done depending on the intended use and product type.

Testing Stages

Every stages of biologics’ life cycle consist of stability testing. These tests have been divided into six stages by experts covering development from early stages to late stage follow up testing:

Stage 1 – Early stage stress and accelerated testing with drug substances

Stage 2 – Stability on pre-formulation batches

Stage 3 – stress testing on scale-up batches

Stage 4 – Long-term and accelerated testing for registration purposes

Stage 5 – Ongoing stability testing

Stage 6 – Follow up stability testing

The data which is gathered at the time of testing depends on the stage of development. For example, accelerated testing is done to evaluate product degradation pathways and enhance stability indicating analytical methods, and shelf life is decided during long term testing. In the early stages, prototype testing is done to characterize a formulation or product. After reconstitution of freeze-dried product, stability tests are also done.

In use stability testing is analysed in a European Medicine Agency note for guidance. In use testing is used for multidose products (e.g. inhaled biologics, multidose vials, pen injectors), that are at risk of physicochemical degradation, microbial contamination and proliferation due to the repeated closing and opening of their container closure systems.

Regulatory requirements

Product stability testing is needed by numerous regulatory agencies. The ICH synchronized tripartite guidelines on stability testing are ICH Q5C, which is particularly for biologics, and Q1A-Q1E documents. Q1A is the parent guideline for stability testing of all pharmaceuticals. It discusses batch selection, stress testing, storage conditions, testing frequency, and other topics. 21 CFR 211.166 also discusses stability testing for finished drug products.

Various other organizations like the Association of Southeast Asian Nations and the World Health Organization have come out with stability testing guidelines for both active pharmaceutical ingredients (APIs) and finished products; however, few of them apply only to conventional (small-molecule) drug products. Few emerging markets that are outside the ICH region (e.g. South Korea, China and Brazil) have their own country specific stability requirements.

Join this session by expert speaker Dr. David Lim, Ph.D., RAC, ASQ-CQA, on Establishing a Product Stability Testing Program to understand the regulatory requirements and good practices to establish a product stability program. Know how to present FDA-compliant practices in adequately implementing regulatory requirements for expiration dating and stability testing program depending upon product types.

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