Significant Changes in Stability sample analysis

As per ICH “significant change” the changes occur in the drug product during the stability study in Accelerated condition (ACC). 

 In general, “significant change” for a drug product is defined as:

1. A 5% change in assay from its initial value; or failure to meet the acceptance criteria for potency when using biological or immunological procedures; 

2. Any degradation product’s exceeding its acceptance criterion; 

3. Failure to meet the acceptance criteria for dissolution for 12 dosage units. 

4. Failure to meet the acceptance criterion for pH; 

5. Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g., color, phase separation, re-suspendibility, caking, hardness, dose delivery per actuation); however, some changes in physical attributes (e.g., softening of suppositories, melting of creams) may be expected under accelerated conditions;     

An ANDA applicant should submit 6 months of accelerated stability  data and 6 months of long-term stability data at the time of submission.However, if 6 months of accelerated data show a significant change or failure of any attribute, the applicant should also submit 6 months of intermediate data at the time of submission.

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.

Case Study:

For Assay: As per above guidance if 5% change in assay from initial then it is significant change,

 e.g. if initial assay is 96.2% and 03 months ACC (40°C/75% RH) assay is 101.3% (different in assay from initial assay is 5.1%), the said result is investigated through OOT and no laboratory error is identified.

Based on above guidance significant change in assay is confirmed, Is it right to start intermediate study in all 3 batches?

As per my view , here no needs to start intermediate condition stability study, we should justify with consultation of Regulatory affairs.