Regulatory Implications of Equipment Change in Pharmaceutical Manufacturing

Changes in equipment used for manufacturing a product can have different implications depending on the market. Regulatory authorities assess these changes based on their potential impact on product quality, safety, and efficacy. Below is a comparative view of how major markets handle equipment changes:

USFDA

• Governed by 21 CFR Part 314 (ANDA) and 21 CFR Part 211 (cGMPs).
• Equipment changes are categorized under SUPAC guidance.

Risk-Based Approach:

Major Change (Prior Approval Supplement – PAS): If the new equipment alters product quality, critical process parameters (CPPs), or critical quality attributes (CQAs), prior approval from USFDA is required.

Moderate Change (Changes Being Effected – CBE/CBE-30): If the change has moderate risk (e.g., different type of mixer but same principle), FDA needs to be informed within 30 days.

Minor Change: If the equipment change has no impact, it can be reported in the annual filing.

EMA

Governed by EMA Variations Regulation (EC No. 1234/2008).

Changes are categorized into Type IA, IB, or II Variations:

• Type IA (Do-and-Tell Change): Minor change, notified within 12 months.
• Type IB (Tell-and-Wait Change): Moderate risk, approval required before implementation.
• Type II (Prior Approval Required): Significant impact on product quality; requires full evaluation before implementation.

MHRA

• Follows EMA variation categories but has a separate national approval system post-Brexit.
• Requires clear justification of impact through comparability studies and GMP compliance assessments.

TGA

Governed by the Therapeutic Goods Act 1989.

Changes classified into:

• Category 3 Variation (Minimal impact, no prior approval).
• Category 2 Variation (Moderate impact, requires TGA review).
• Category 1 Variation (High impact, requires extensive review).

Health Canada

Uses Post-Notice of Compliance (NOC) Changes Guidance.

Categorized into:

• Level I Change (Major, Prior Approval Required).
• Level II Change (Moderate, Notify and Wait for Acceptance).
• Level III Change (Minor, Annual Notification).

WHO Prequalification

Follows WHO Guidelines on Variations.

Equipment changes need a Comparability Protocol with:

• Justification for change.
• Risk assessment and impact evaluation.
• Stability and bioequivalence (if applicable).

CDSCO

Governed by Schedule M & New Drugs and Clinical Trials Rules 2019.

Equipment change must be reported in:

• Post-approval changes notification (low risk).
• Prior approval changes submission (high risk).

Key Takeaways for Equipment Change Approval

• Risk Assessment is crucial across all markets.
• Comparability Studies must demonstrate no impact on CQAs.

Regulatory Category Matters: Understanding whether it falls under major, moderate, or minor change is essential for submission strategy.

GMP Compliance: New equipment must meet GMP requirements and be validated.

Read also:

• Key Considerations for API Source Change in Formulation
• Key Considerations for Changing the Manufacturing Site of a Formulation
• Regulatory Strategies for Excipient Grade Changes Across Global Markets

Resource Person: Moinuddin syed. Ph.D, PMP®