SUPAC (Scale-Up and Post-Approval Changes) guidelines have been developed by the U.S. Food and Drug Administration (FDA) to provide guidance on the documentation and testing that pharmaceutical manufacturers should submit in the event of post-approval changes in the manufacturing procedures.
SUPAC guidelines specifically address changes in components and composition, changes in the manufacturing sites, changes in the scale-up of production, and changes in the manufacturing equipment or process.
The SUPAC guidelines are designed to streamline the process for the industry and the FDA in determining the kind of regulatory submission required for a specific post-approval change.
They are split into different documents focusing on specific dosage forms or types of changes:
SUPAC-IR: Immediate Release Solid Oral Dosage Forms
SUPAC-MR: Modified Release Solid Oral Dosage Forms
SUPAC-SS: Non-Sterile Semisolid Dosage Forms
SUPAC-T: Non-Aqueous Topical Dosage Forms
And others for specific dosage forms or requirements.
Let's dive into the details, taking SUPAC-IR as an example:
SUPAC-IR (Immediate Release Solid Oral Dosage Forms)
The guideline defines three levels of changes:
1. Level 1 Changes:
These are considered minimal risk changes.
Generally, these can be handled with an annual report to the FDA, notifying them of the changes without waiting for approval.
2. Level 2 Changes:
These are moderate risk changes.
They often require a "Changes Being Effected in 30 days" (CBE-30) notice to the FDA.
It means the change can be made 30 days after notifying the FDA, unless the FDA objects within that time frame.
3. Level 3 Changes:
These are considered major changes with a higher potential risk.
They usually require a Prior Approval Supplement (PAS).
The manufacturer must wait for FDA approval before implementing these changes.
For each type of change (e.g., component and composition changes, manufacturing site changes, scale-up changes, process changes), the guideline outlines:
Description of the change
Recommended documentation for the change (e.g., information about the manufacturing site, equipment, process)
Recommended in-vitro testing (e.g., dissolution testing, content uniformity)
Recommended in-vivo testing (e.g., bioequivalence studies)
Example: If a manufacturer of an immediate-release tablet wishes to change the type of mixer used in their manufacturing process:
The guideline will detail what kind of documentation they should provide about the new mixer.
They may be required to provide dissolution profiles of tablets made with the old mixer vs. the new mixer to ensure product performance hasn't been adversely affected.
Depending on the extent of the change, they might also be required to provide bioequivalence data.
Importance:
The SUPAC guidelines are crucial because post-approval changes can affect the safety, efficacy, and quality of a drug product.
By following these guidelines, manufacturers can ensure they are meeting regulatory requirements while still being able to innovate and make necessary changes to their processes.