Licence Variations record the changes in methods of manufacture and testing that deviate from the originally approved methods and procedures. This approval can be in the form of a Marketing Authorisation (MA) or Product Licence (PL). Variations record changes that result from changes and requirements in the regulatory framework, and changes and improvements in the manufacturing and testing operations. These all need to be submitted for assessment to the relevant Regulatory Agencies, and in most cases approval sought prior to distributing the “new” product.
The Post-Marketing Commitment of the MA holder involves ensuring the MA is kept current and up-to-date, and changes to both the MA and Drug Master File (DMF) are notified; Registration Drift must be avoided through the robust implementation of the Change Control process. Filing variations can be complex, requiring careful consideration to ensure the commercial viability of a product is not impacted. Furthermore, variations must be filed electronically in NeeS or eCTD format as per the FDA and EU regulations.
A licence variation allows an amendment to the data previously approved by the Regulatory Authorities. Changes can have minimal, no, or significant impact on the quality, safety or efficacy of the medicinal product.
Licence Variations are categorised on the severity of their impact:-
- Type IA: “Do and Tell” – a company makes a change and then tells the authorities within the next 12 months. This is generally only applicable to minor changes in the manufacturing, testing and release operation.
- Type IB: “Tell and Do” – a company must notify the authority of a change before it’s implemented.
- Type II: “Tell and Do” – are major variations that a company must submit to the Regulatory Authorities and obtain approval before implementing.
Grouped Variations – are variations grouped and filed as one submission. This can only be done when there is a clear link between the changes. Depending on the type of variation the changes need to be on the same MA or the change is identical across several MAs.
In the USA the FDA regulate similarly tiered amendments:-
- Annual Reportable (AR) – for minor changes that do not affect the safety, quality or efficacy of a product.
- Change Being Effected (CBE) – for minor changes that are required to be submitted to FDA at the time a change is made.
- Change Being Effected in 30 days (CBE30) – are required to be submitted to FDA and following the receipt of their acknowledgement letter, must wait 30 days before implementing.
- Prior Approval Supplement (PAS) – are major changes that a company must submit to FDA and obtain approval before implementing. Comparability Protocols are a subset of PAS.
How Woodley BioReg can help with Filing Variations
Woodley BioReg helps clients overcome the challenges and complications of filing licence variations, for pharmaceutical, biopharmaceutical, healthcare and over-the-counter products globally. Woodley BioReg’s extensive experience includes:
- Managing generics products
- Managing product life-cycles
- Deciding the type of variation and if these can be grouped
- Compiling and preparing the documents for submission to the FDA, EMA, or MHRA including replacement sections, forms, expert reports, letters etc.
- Filing the variation and managing it through the review and approval process including responding to Board of Health Requests for Information (RFIs).
For more help and advice on Filing Variations please contact us.