As per SUPAC (Scale-Up and Post-approval Changes) guideline,
Post-approval changes in the batch size from the pivotal/pilot scale bio-batch material to larger or smaller production batches call for submission of additional information in the application. Here we discuss about immediate release solid oral dosage forms.
Scale-down below 100,000 dosage units is not covered by this guidance. All scale-up changes should be properly validated and, where needed, inspected by appropriate agency personnel. There are two level changes:
Level 1 Changes
Change in batch size, up to and including a factor of 10 times the size of the pilot/bio-batch, where:
1) the equipment used to produce the test batch(es) is of the same design and operating principles;
2) the batch(es) is (are) manufactured in full compliance with CGMP's; and
3) the same standard operating procedures (SOP's) and controls, as well as the same formulation and manufacturing procedures, are used on the test batch(es) and on the full-scale production batch(es).
Required Documentation for Level 1 Changes
- Chemistry Documentation: Application/compendial release requirements. Notification of change and submission of updated batch records in annual report. One batch on long-term stability reported in annual report.
- Dissolution Documentation: None beyond application/compendial release requirements.
- In Vivo Bioequivalence: None.
- Filing Documentation: Annual report (long-term stability data).
Level 2 Changes
Changes in batch size beyond a factor of ten times the size of the pilot/bio-batch, where:
1) the equipment used to produce the test batch(es) is of the same design and operating principles;
2) the batch(es) is (are) manufactured in full compliance with CGMP'S; and
3) the same SOP's and controls as well as the same formulation and manufacturing procedures are used on the test batch(es) and on the full-scale production batch(es).
Required Documentation for Level 2 Changes
- Chemistry Documentation: Application/compendial release requirements. Notification of change and submission of updated batch records.
- Stability testing: One batch with three months accelerated stability data and one batch on long-term stability.
- Dissolution Documentation:
- For immediate release product: Case B testing. (Multi-point dissolution profile in the application/compendial medium at 15, 30, 45, 60, and 120 minutes or until an asymptote is reached for the proposed and currently accepted formulation.)
- For extended release product: In addition to application/compendial release
- requirements, multipoint dissolution profiles should be obtained in three
- other media, for example, in water, 0.1N HCl, and USP buffer media at pH
- 4.5, and 6.8 for the changed drug product and the biobatch or marketed
- batch (unchanged drug product). Adequate sampling should be performed,
- for example, at 1, 2, and 4 hours, and every two hours thereafter until
- either 80% of the drug from the drug product is released or an asymptote is
- reached. A surfactant may be used with appropriate justification.
- In Vivo Bioequivalence: None.
- Filing Documentation: Changes being effected supplement; annual report (long-term stability data).
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