What Are The 5 Main Types of Regulatory Variations?
- Type IA are minor changes which have minimal impact on the Quality, Safety & Efficacy of the medicinal product or ‘Do and tell’ variations which do not require prior approval and can be implemented up to 12 months prior to notification.
- Type IAIN are also minor changes; however, they require immediate notification to the competent authority on implementation.
- Type IB variations are minor changes that are not extensions or classified in the guideline referred to in article 4 of the regulation. They require approval from the competent authority before implementation.
- Type II variations are major changes which may have a significant impact on the Quality, Safety & Efficacy of the medicinal product. They require prior approval before implementation.
- Extension applications. These include additional strengths, pharmaceutical forms or routes of administration.
Critical Areas
There are a number of key areas that have been identified as having the most issues identified on validation. These include administrative issues linked to the application form, associated annexes and documentation and the classification of the variation. The content of the electronic application form (eAF) is one of the most common causes of invalidation of submissions. Common issues that are picked up on validation of the eAF are:- Incorrect Scope applied or incorrect scope classification. The scope must reflect all changes included in application. For grouped variations, each scope listed must be identified by its classification number and detailed.
- Identification as to whether it is a single or grouped variation
- Only the presentations impacted should be listed under section 2
- Incorrect Implementation date for variations included. The type of change determines the implementation date and therefore the date will vary depending on the change.
- Incorrect classification of the variation
- Present and proposed table is not clear and concise for all changes. This table can be included as part of the eAF or as an Annex, again all changes should be reflected, including product information and editorial changes
- ASMF number and version number not referenced
- Annexes are incorrectly selected throughout the form
- Incorrect Fees
- Invalid or missing QP declarations/GMP certificates/Manufacturing Licences
- Incorrect or missing Letters of Authorisation
- Editorial changes are not listed or not described sufficiently
- The final sign off on the form should be by the person authorised by the MAH
- Classification Guideline:
- Conditions and documentation not ticked
- Dossier Content:
- Documentation indicated as required on the classification guidance not present
- Insufficient or inadequate supporting documents provided
- Only EN versions of Product information provided, no languages provided
- No word document versions (Clean and Tracked) of the updated product information provided in the ‘Working Documents’ folder