SUPAC - Scale-Up and Post-Approval Changes

1. SUPAC - Scale-Up and Post-Approval Changes

2. SUPAC guideline is prepared by the American Association of Pharmaceutical Scientists (AAPS) in association with the United States Food & Drug Administration (FDA) and the United States Pharmacopeia (USP). The guideline looks into manufacturing procedures, and compositional modification changes during scale-up and post-approval in drug production. In pharmaceutical technology, the transfer of a pharmaceutical product from small scale (research) to the production scale – an increase in batch size from small scale to large scale – is termed scale-up with an increase in simultaneous production outputs. In general, the process of increase in batch size is termed scale-up. This process is required for in-depth study and knowledge about the product which needs to be manufactured at a larger scale The scale-up process and the changes made after approval in the manufacturing process, equipment, composition, and change in the site are known as scale-up and post-approval changes or SUPAC. It is important to make sure that the applied process is capable enough to manufacture an appropriate quality product and as well as to know that the product after scale-up doesn’t suffer any changes in the physical and chemical properties of the product. 

3. SUPAC Guidelines SUPAC stands for Scale-up and Post Approval Changes. These guidelines state that when there is any change during the post-approval phases, such as: Manufacturing procedures or equipment, Specifications, Compositional or components change, Change in manufacturing site, Scale-up or Scale-down of batch size The above depends on anticipated or unanticipated requirements and there can be changes in the process, raw materials, equipment, manufacturing site, or batch size which may finally affect the quality attributes of the drug or finished drug product. Hence there is a need to anticipate and evaluate the effectiveness of any kind of changes on the final quality of a drug or drug product and must ensure to take appropriate investigation and submission action which has been authorized by New Drug Application (NDA), Abbreviated New Drug Application (ANDA) or by Abbreviated Antibiotic Applications (AADA’s).

4. This guidance gets together and replaces the below-mentioned scale-up and post-approval changes guide for the pharmaceutical industry: • SUPAC-IR/MR: Immediate-release tablets, capsules, soft gelatine • capsules, and modified-release oral solid dosage forms which include • delayed-release (DR) and extended-release (ER); Manufacturing • equipment addendum. • SUPAC-SS: Nonsterile semisolid dosage forms include creams, • ointments, gel, suspensions, emulsions, and Manufacturing • equipment addendum. • The post-approval changes in the drug CMC for ‘moderate’ and • ‘major’ are allowed to be submitted in the annual report. • Moderate: In case of moderate changes, the applicant must submit an addendum prior to 30 days before the supply of drug product i.e. Change being effected (CBE)-30 supplement, or in some cases, an addendum can be submitted at the time of supply i.e. CBE-0 supplement. • Major: In case of major changes, the applicant must submit and receive FDA approval of a prior approval supplement (PAS) before the distribution of the drug product.

5. The systematic aspect of SUPAC: The SUPAC guidance summaries it identifies different levels of change. Each level of change describes as per the below points: The supporting documents required by the FDA are to be filed in the NDA, ANDA, or AADA. Proposed chemistry, manufacturing, and control (CMC) assessment In-vitro dissolution analysis or in-vivo bioequivalence analysis

6. Drug products manufactured with the proposed changes are as per below: Change in components or composition Change in manufacturing site Scale up and scale down of manufacture Change in manufacturing process and equipment SUPAC guidance defines a different level of changes as per below: Proposed chemistry Manufacturing and controls tests for each level change In-vitro dissolution testing and/or In-vivo bioequivalence tests for each level of change Required documents to support filing. SUPAC guidance is important considering the scale-up process related to chemistry manufacturing and control. Scale-up is an important and expected stage of manufacturing pharmaceutical drug products which can require an increase or decrease in the batch size. It reduces the time of manufacturing, improves yield, and reduces cost.

7. FAQ What is SUPAC’s full form? SUPAC’s full form is Scale-up and Post-Approval Changes. What is SUPAC? It is not a guideline it is just a guidance document. This guidance states that when there is any change during the post-approval phases, such as manufacturing procedures or equipment, specifications, compositional or components change, change in manufacturing site, or scale-up or scale-down of batch size. What is SUPAC-IR/MR?SUPAC-IR/MR: Immediate-release tablets, capsules, soft gelatine capsules, and modified-release oral solid dosage forms which include delayed-release (DR) and extended-release (ER); manufacturing equipment addendum. What is SUPAC-SS? SUPAC-SS: Non-sterile semisolid dosage forms include creams, ointments, gel, suspensions, emulsions, and Manufacturing equipment addendum.