Why Do STABILITY Studies / Testing?

Stability studies are performed to ensure that pharmaceutical products will be at the acceptable level of quality throughout the period that they are available in the marketplace and fit for consumption by the consumer up to the expiry date.

ICH and FDA stability studies are essential for drug product development supporting IND/NDA/BLA submission activities. Stability programs evaluate the active pharmaceutical ingredient (API) and/or drug product (DP) (including drug packaging) under a variety of storage and environmental conditions resulting in recommended storage conditions, retest intervals and shelf lives. If the API or DP degrades or inactive products (matrices) lead to loss of efficacy, the ramifications are inappropriate activity of the drug with possible side effects or toxicities.

What are STABILITY Studies / TESTING?

Stability testing measures the variations induced by time under various physical, chemical or microbiological changes, temperature, pH, humidity, light and radiation. Stability programs typically include real-time stability storage and may include accelerated stress (relative high temperatures and/or humidity) and forced degradation studies. For example, usual practice for retained storage are analyzed typically at 3, 6, 9, 12, 18, 24, 36, 48 and 60 months, if the API or DP has a 5-year shelf life. Testing containers and closures at different orientations, either upright or inverted, determines whether the drug product can extract chemicals from the closure components or that the drug product adsorbs to the container.

Fig. 1: Details of stability studies

What are the Tests Conducted for a Stability Potency / Bioassay Study?

Test methods are carried out using validated assays for specificity, accuracy, precision, linearity and range as well as limits of detection and quantification. Marin Bio offers stability testing services with comprehensive expertise in the areas of small molecule, large molecules, proteins, DNA, RNA, and viruses for the pharmaceutical and biopharmaceutical industries. Marin Bio’s stability services focus on the delivery of quality stability data to support every stage of the product development lifecycle from inception, development, qualification/validation, through IND and NDA/BLA stages. Furthermore, Marin Bio provides a coherent, controlled and clearly documented course for all our stability studies, with precise record keeping and reporting.

The MarinBio supporting technology for these areas are:

• Cell Based Assays
• ELISA & other Antibody Based Assays
• Flow Cytometry and Cell Characterization
• Protein, Enzyme and other Biochemical Assays
• Immunoassays & RadioImmunoassays
• Mixed Lymphocyte Reaction Assays (MLR)
• PCR and qPCR

Case Study: Forced degradation study of a protein drug

Marin Bio’s example is of forced degradation of a protein drug’s effect on a cytokine-dependent cell line. For the forced degradation, the protein drug (Test Drug) was exposed to 80^oC for increasing time. The high degradation temperature of 80^oC was chosen because exposure at 60^oC did not cause significant degradation. The Reference Standard (RS) was kept at its normal temperature, 2-8^oC.

Cell-Based Assay: Cells are exposed to Reference Standard or Test Drug for 3 days, at 37^oC in a 5% CO₂, 95% air atmosphere. Read out is measured by relative luminescence using CellTiter-Glo® which measures intracellular ATP.

Figure 1, time =0, the Test Drug has an EC₅₀ similar to the Reference Standard.

Figure 2, after 3 days at 80^oC, the Test Drug shows no activity (no EC₅₀) compared to the Reference Standard.

Creativity and Pragmatism are the core to how Marin Bio works with clients!