How Phase 4 Commitments and PASS Shape Drug Safety Surveillance

Introduction

After a medicine enters the market, the need for safety monitoring intensifies—not fades. To ensure ongoing evaluation of benefit-risk balance, regulatory agencies may require pharmaceutical companies to undertake post-marketing commitments (PMCs) and conduct Post-Authorization Safety Studies (PASS). These studies are a central feature of Phase 4 pharmacovigilance strategy, especially for newly approved or high-risk drugs.

What Are Post-Marketing Commitments?

Post-Marketing Commitments (PMCs) are studies or trials that a sponsor agrees to conduct after the drug is approved. They are often voluntary but may be tied to future regulatory decisions such as label revisions or continued market access.

What Are Post-Authorization Safety Studies (PASS)?

PASS are required by regulators to evaluate specific safety concerns identified pre- or post-approval. These may be non-interventional or interventional studies and must adhere to strict protocols.

Types of PASS

• Voluntary PASS: Conducted by MAH for internal decision-making or publication
• Imposed PASS: Mandated under legislation (EU: Regulation EC No. 726/2004)

Why Are PASS Important?

• Risk confirmation: Validate safety signals from spontaneous reports
• Population-specific risk: Study vulnerable groups (e.g., elderly, pregnant, renal-impaired)
• Long-term outcomes: Evaluate effects not captured in Phase 3 (e.g., cancer risk, organ toxicity)

Regulatory Requirements

FDA (U.S.)

• PMRs and PMCs published on