Glossary

1. Types of Marketing Authorisation Variations

Variations in Europe are classified into three main categories based on their impact on product safety, quality, and efficacy:

1. Type IA Variations – Minor Changes (Do Not Require Prior Approval)

• Must be notified to the regulatory authority within 12 months of implementation except for some cases where an immediate notification is required (Type IAIN).

• Examples for Type IA: Tightening of product testing limits, deletion of a manufacturing site

• Example for Type IAIN: Change in name and/or address of a marketing authorization holder

2. Type IB Variations – Minor Changes Requiring Notification & Approval

• Require prior approval before implementation.

• Approval timeframe: 30 days after validation if no objections are raised.

• Examples: Replacement of a specification attribute, change in storage conditions of the active substance or finished product

3. Type II Variations – Major Changes Requiring Full Review

• Require prior approval before implementation.

• Approval timeframe: 60 days (standard timetable), 90 days (extended timetable) or 30 days (reduced timetable).

• Examples: New therapeutic indications, safety variations based on new data, major manufacturing process changes.

2. Marketing Authorisation Variation Procedures & Timelines

Type IA (Minor Change – No Prior Approval Needed)

• Approval Required: No
• Submission Deadline: Either in a ‘Type IA annual update’ to be submitted no earlier than 9 months and no later than 12 months after the first implementation date of the Type IA variations. Alternatively, the Type IA change can also be included as part of an acceptable grouping or as part of a super-grouping variation.
• Typical Review Time: 30 days following receipt

Type IAIN (Minor Change requiring immediate notification – No Prior Approval Needed)

• Approval Required: No
• Submission Deadline: immediately
• Typical Review Time: 30 days following receipt

Type IB (Minor Change – Requires Prior Approval)

• Approval Required: Yes
• Submission Deadline: Before implementation.
• Typical Review Time: 30 days following validation.

Type II (Major Change – Requires Prior Approval)

• Approval Required: Yes
• Submission Deadline: Before implementation.
• Typical Review Time: 60 days, 90 days or 30 days, depending on timetable .

3. How to Apply for a Variation in the EU

Step 1: Identify the Variation Type – Determine if the change falls under Type IA/IAIN, IB or II.

Step 2: Prepare the Variation Application – Submit required documentation, including updated SmPC, labelling, PIL and supporting data, as applicable.

Step 3: Submit to the Competent Authority –

• EMA for centrally authorised medicines (CP).

• National Competent Authorities (NCAs) for nationally authorised medicines.

Step 4: Await Regulatory Decision & Implement Changes – Approval timelines vary by variation type.

4. Post-Approval Compliance for Variations

Pharmacovigilance Updates – Variations affecting safety information require updates to the Risk Management Plan (RMP), SmPC, labelling and PIL.

Manufacturing & Quality Control Compliance – Approved variations must be implemented in line with Good Manufacturing Practice (GMP) guidelines.

Renewals & Further Variations – Certain changes may trigger additional marketing authorisation renewals or updates.

Why Variations Are Important for Drug Safety & Compliance

• Ensure Continuous Product Quality & Efficacy – Keeps medicines up to date with the latest scientific standards.
• Improve Patient Safety – Updates to SmPC & PIL help prevent adverse drug reactions (ADRs).
• Maintain Regulatory Compliance – Prevents marketing authorisation suspension due to non-compliance.