Stability (ICH) Quiz 7
Q: What are the requirements regarding the number of primary batches for formal stability studies of a drug substance?
A: Formal stability studies necessitate data from at least three primary batches of the drug substance.
Q: What criteria must the primary batches meet for inclusion in formal stability studies?
A: The primary batches used for formal stability studies must be manufactured at a minimum of pilot scale. They should follow the same synthetic route and employ a method of manufacture that mimics the final production process. Additionally, the quality of these batches should be representative of the material intended for production on a larger scale.
Q: What conditions should be replicated when conducting stability studies on the drug substance?
A: Stability studies should be conducted on the drug substance packaged in a container closure system identical to or mimicking the proposed packaging for storage and distribution.
Q: Why is it necessary for the primary batches to reflect the intended production process and packaging in formal stability studies?
A: Ensuring that the primary batches used in formal stability studies mirror the intended production process and packaging is critical for accurately assessing the stability profile of the drug substance. It helps replicate real-world conditions, ensuring that the stability data obtained is relevant and applicable to the final product that will be manufactured and distributed commercially.
Q: Where can one find information about specifications for a drug substance and its degradation products?
A: Specifications for a drug substance, including tests, reference to analytical procedures, and acceptance criteria, are addressed in ICH Q6A and Q6B. Furthermore, specifications for degradation products in a drug substance are discussed in ICH Q3A.
Q: What attributes of a drug substance should be tested during stability studies, according to the ICH Guideline?
A: Stability studies should encompass testing of attributes of the drug substance that are susceptible to change during storage and are likely to impact its quality, safety, and/or efficacy. These attributes may include physical, chemical, biological, and microbiological characteristics.
Q: What analytical procedures should be applied during stability studies, as ICH guidelines ?
A: Validated stability-indicating analytical procedures should be employed during stability studies to assess the various attributes of the drug substance. These procedures help ensure accurate and reliable determination of the substance’s stability profile.
Q: How does the need for replication in stability testing depend on validation studies?
A: The decision on whether and to what extent replication should be performed during stability testing hinges on the results obtained from validation studies. Replication may be necessary based on the variability observed in the analytical procedures and the reliability required for ensuring the accuracy of stability data.
Q: What is the recommended frequency of testing for long-term stability studies of drug substances?
A: For drug substances with a proposed re-test period of at least 12 months, the frequency of testing at long-term storage conditions should typically be every 3 months during the first year, every 6 months during the second year, and annually thereafter until the proposed re-test period concludes.
Q: How many time points are recommended for testing at accelerated storage conditions, and why?
A: At accelerated storage conditions, a minimum of three time points is recommended, including the initial and final time points (e.g., 0, 3, and 6 months) from a 6-month study. This recommendation ensures adequate data collection to assess the substance’s stability under accelerated conditions.
Q: Under what circumstances should increased testing be conducted at accelerated storage conditions?
A: Increased testing at accelerated storage conditions should be conducted if there is an expectation, based on development experience, that results from accelerated studies are likely to approach significant change criteria. This may involve adding samples at the final time point or including a fourth time point in the study design to capture potential significant changes.
Q: What is the recommended time point schedule for testing at intermediate storage conditions?
A: When testing at intermediate storage conditions becomes necessary due to significant changes observed at accelerated storage conditions, a minimum of four time points is recommended. This includes the initial and final time points (e.g., 0, 6, 9, and 12 months) from a 12-month study, allowing for a comprehensive assessment of stability at intermediate conditions.
