Interview questions on accelerated stability testing or studies from ICH (as per Q1A R2 and Q1B step 5) and FDA guidance. Stability studies ensuring product quality, safety, and efficacy throughout the period are considered prerequisites for the acceptance and approval of any pharmaceutical product. Studies are required to be conducted in a planned way, these rules issued by ICH, WHO, and or other agencies.
Why accelerated stability testing is essential:
- Throughout products, chemicals start to degrade, resulting in a lower concentration of active drugs in the dosage form.
- Due to the formation of toxic substances during the degradation of active pharmaceutical drugs.
Is significant change applies only for accelerated storage condition or is it applicable for long-term study:
According to our ICH guidelines, significant changes apply to accelerated storage conditions to answer this question. However, if significant changes occur in long-term storage conditions, the product is not considered stable, and the organization cannot apply to the agency.
ICH guidance says if long-term studies are conducted at 25°C ± 2°C and 60% and ± 5% relative humidity. The significant change occurs during six months of testing at the accelerated storage conditions. Additional testing at the intermediate storage condition should be conducted and evaluated against significant change criteria.
The initial application should include a minimum of six months of data from a 12-month study at the intermediate storage condition. It is about the applicability of significant changes.
How many API Lots are required to manufacture three batches of each strength of a proposed drug product:
According to ICH guidelines, there should be two API Lots to manufacture three batches of each strength of a proposed drug product.
Suppose the minimum of two Lots is not used to manufacture three batches of the drug product. FDA will consider it a significant deficiency and will refuse to receive the NDA application.
Tell about various storage conditions for stability and time points:
- Short-term Accelerated stability:
For testing accelerated conditions, time points are (0, 3, 6 months) and one additional time point should be covered, and then storage conditions are 40 degrees Celsius ± 2°C temperature and 75% ± 5 %. Relative humidity.
2. Intermediate accelerated stability testing:
Time points are 0, 6, 9, and 12 months and storage conditions are 30°C ± 2°C and 65% and ±5 RH.
3. long-term conditions:
Time points are (0, 3, 6, 9, 12) for first-year; and every six months over the second year, e.g. (18, 24, 36 months) and storage conditions are 25 degrees Celsius ± 2 degrees Celsius and 60% ± 5%.
if one out of the three batches is stored under accelerated conditions shows a significant change in what should be done:
According to ICH guidance, if accelerated data show a significant change or failure of any attribute in one or more batches, an applicant should submit intermediate data for all three batches. In addition, the submission should contain a failure analysis. That is a discussion concerning the observed failures.
If any significant change occurs between zero and six months, in that case, long-term data needs to be used for analysis. Six months of intermediate data are required at the time of an NDA submission, and further 12 months of data to be amended later on six months.
Intermediate data is required for evaluation at filing, including zero and six months’ time points if intermediate data fails. in this case, no extrapolation of shelf life or retest date is allowed. Long-term data alone will take over shelf life or retest determination of the sample storage requirements.
how long three pilot-scale batches need to be stored before destruction, which was submitted as a part of an NDA:
In general NDA Submission batch, samples should be
stored for one year after approval of the NDA, and samples of the drug product used for bio covalent studies must be stored for five years after approval of the NDA.