Manufacturers, for example, conduct stability tests to determine degradation pathways and shelf lives as well as storage settings for their products. Depending on the product type and intended application, tests and bioassays for purity, identification, potency, quality, and safety are performed.

During a stability study, materials are stored at varying temperatures and humidity levels and samples are taken at predetermined time intervals and subjected to a battery of tests, which may include an identification test, assay, physical tests, microbiological limits, and preservative effectiveness testing, all of which are performed using adequately validated methods and/or recognized compendia methods. Acceptance criteria are established before the study begins, and if a product fails to meet standards at any stage throughout the study, it may be halted and restarted after reformulation or other changes.

Testing Stages

Stability testing is performed at every stage of a biologic's life cycle. These tests have been classified into six stages by experts, ranging from early stages of development through late-stage follow-up testing.

1. Initial stage stress and expedited drug substance testing (Stage 01)
2. Stability on pre formulation batches (Stage 02)
3. Scale-up batches are subjected to stress testing (Stage 03)
4. For registration purposes, accelerated and long-term testing is required (Stage 04)
5. Ongoing stability testing (Stage 05)
6. Stability testing follow-up (Stage 06)

The data gathered during testing is dependent on the level of development. Long-term testing, for example, is used to determine shelf life, while accelerated testing is used to assess product degradation pathways and create stability-indicating analytical procedures. Prototype testing is used to characterize a product or formulation in its early phases. Stability tests are also carried out after a freeze-dried product has been reconstituted.

Stability Program Regulations and Regulatory Expectations

CQAs identify the features or features relevant to product quality in the Quality by Design (QbD) approach. CQAs are features that have an impact on the safety and efficacy of medicinal medicines. Release testing must be used to determine acceptable limits or product requirements. Stability studies of DS and DP are carried out at various stages of the drug development process, from preclinical through final product approval, with the size of the studies varying according to the stage of development. The development of analytical procedures, the establishment of acceptance criteria, forced deterioration studies, DS and DP method validation, and stress tests are among the first analytical development efforts. Stability studies may be undertaken in the early stages under expedited conditions that are limited, and without a completely established set of analytical procedures. The Quality Assurance (QA) group approves CTMs for clinical use based on a set of acceptance criteria (such as specifications).

GMP requirements must be followed for completed pharmaceutical goods beginning with the registration batches once a product has progressed to Phase III development and preparation for product registration. To achieve the defined commercial requirements for identity, purity, potency, and quality of the end product, registration batches and commercial items meant for distribution to patients must undergo extensive release testing by QC. After receiving approval, the QC group (or a "Qualified Person" [QP] in European Union pharmaceutical regulation) performs release testing of the registration batches and issues a Certificate of Analysis (CoA). It is then officially released and signed-off by the QA group for market distribution.

CTM stability testing typically includes physical characterizations such as X-ray powder diffraction (XRPD) tests for crystallinity and polymorph form, as well as tests for looks, identification and quantification (assay), impurities, dissolution (for solid dosage forms), moisture, and extra physical characterizations such as X-ray powder diffraction (XRPD) tests for crystallinity and polymorph form. The product specifications include a list of these testing. To guarantee that drug quality standards are maintained during the stability studies, they must be used to evaluate the identity, physical form (color, size, and crystallinity), purity (chemical and chiral purity), water content, performance (dissolution) and microbiological activity.

Storage of Stability

In humidity stability chambers, stability samples are held at a constant temperature. These chambers must be managed within ±2 oC and ±5% RH for chambers operated at 25 °C/60% RH, 30 °C/65% RH, and 40 °C/75% RH, according to the ICH Q1A (R2) regulation. The temperature is kept at 5 oC ± 3 oC (2 to 8 oC) with ambient humidity (monitored but not controlled). Sensors for continuous temperature and relative humidity monitoring are installed in these chambers. These records are kept on computers or in chart recorders with backup power.

Any pharmaceutical product requiring registration and commercialization must have a strong and science-based stability program. Restrictions in this field are well-established; nevertheless, how the regulations are applied and interpreted differs between companies and localities. The International Conference on Harmonization (ICH) harmonizes the major areas to assist businesses in adopting a uniform strategy.

Do you want to understand more about Stability Testing in Pharma? Join us at the Stability Studies Especially for Biologics & ATMPs MasterClass on 19th to 20th May, 2022. 

By Fazmi Zakam, Junior SEO Executive, GLC Europe, Colombo Office, Sri Lanka.