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SUPAC Guidelines

Scale-Up and Post-Approval Changes (SUPAC) guidance documents provide a framework for classifying manufacturing changes and determining regulatory filing requirements.

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SUPAC Guidance Documents

SUPAC-IR

Immediate Release Solid Oral Dosage Forms

Guidance for scale-up and post-approval changes for immediate release solid oral dosage forms including tablets and capsules.

Change Levels

Level 1- Unlikely to affect product
Annual Report
Level 2- Could affect product
CBE-30
Level 3- Likely to affect product
Prior Approval

SUPAC-MR

Modified Release Solid Oral Dosage Forms

Guidance for extended release and delayed release solid oral dosage forms with additional considerations for release-controlling mechanisms.

Change Levels

Level 1- Unlikely to affect release
Annual Report
Level 2- Could affect release
CBE-30
Level 3- Likely to affect release
Prior Approval

SUPAC-SS

Sterile Aqueous Solutions

Guidance for non-complex sterile solutions including parenteral products with special considerations for sterility assurance.

Change Levels

Level 1- Minor sterility impact
Annual Report
Level 2- Moderate sterility impact
CBE
Level 3- Major sterility impact
Prior Approval

SUPAC-IR Change Matrix (Examples)

Components & Composition

Delete or reduce colorant/flavor
Level 1AR
Change in technical grade of excipient
Level 2CBE
Change in release-controlling excipient
Level 3PAS

Manufacturing Site

Same campus, same equipment
Level 1AR
Different campus, same equipment/SOP
Level 2CBE
Different site, different equipment
Level 3PAS

Batch Size

Up to 10x scale change
Level 1AR
Greater than 10x scale change
Level 2CBE
Scale change with process modification
Level 3PAS

Manufacturing Equipment

Same design and operating principle
Level 1AR
Same operating principle, different design
Level 2CBE
Different operating principle
Level 3PAS

SUPAC Assessment Workflow

SUPAC Change Evaluation Process

Step-by-step process for evaluating and filing manufacturing changes per SUPAC guidelines

Step 1 of 80 completed
1

Identify Change Type

Typical Duration: 1-2 days

Determine the specific type of post-approval change being proposed from the SUPAC categories.

Key Requirements
  • Components and composition
  • Site changes
  • Batch size (scale-up/down)
  • Manufacturing equipment or process

Reference Documents

SUPAC-IR Guidance

Scale-Up and Post-Approval Changes: Immediate Release Solid Oral Dosage Forms

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SUPAC-MR/MR Guidance

Scale-Up and Post-Approval Changes: Modified Release Solid Oral Dosage Forms

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Filing Types

AR - Annual Report

Include in next annual report. Implement immediately.

CBE-0 - Changes Being Effected

Implement at time of submission to FDA.

CBE-30 - Changes Being Effected (30)

Wait 30 days after submission to implement.

PAS - Prior Approval Supplement

Must receive FDA approval before implementing change.

Important Notes

  • •SUPAC is FDA-specific guidance
  • •EU has separate variation system
  • •Multiple changes may require higher level filing
  • •Consider stability implications

Related Resources

Variations GuideFDA GuidelinesModule 3: Quality
VariationsBack to Post-Approval OverviewDossier Masterclass