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 amendments in legislation and regulatory requirements, or changes implemented by manufacturers as part of process improvements. Regardless of their source, all changes must to be submitted for assessment and approval by the relevant regulatory agencies, and in most cases, approval sought prior to distributing the “new” process.
Further details are provided below:
Following product approval, MAH have post-marketing commitments that ensure the MA is kept current and up-to-date and that changes to both the MA and Drug Master File (DMF) are notified. In particular, the risk of registration drift must be avoided through the robust implementation of a change control process.
Notification of changes to regulators must be through filing variations; this can be a complex and potentially time-consuming process, requiring careful consideration to ensure the commercial viability of a product is not impacted.
A licence variation allows an amendment to the data previously approved by the regulatory authorities. Changes can have minimal 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” – These are typically administrative changes whereby a manufacturer can make a change and then tells the authorities within 12 months. This is generally only applicable to minor changes in the manufacturing, testing, and release operation.
Type IB: “Tell and do” – These types of changes are also considered to be minor changes that require the require an assessment of supporting data as they may have an impact on product safety and efficacy. Manufacturers must notify the authority of a change before it is implemented.
Type II: “Tell and do” – These are major variations that manufacturers must submit to the regulatory authorities and obtain approval before implementing. These are usually major changes that are likely to have an effect of product safety and efficacy and will require careful assessment before approval.
Grouped variations – These variations are 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 must be 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) – changes must be submitted to FDA and following the receipt of their acknowledgement letter, are required wait 30 days before implementation.
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.
Need further information?
Woodley BioReg helps clients overcome the challenges and complications of filing licence variations for pharmaceutical, biopharmaceutical, healthcare, and OTC products globally. Woodley BioReg’s extensive experience includes:
- Managing generics products
- Managing product life cycles
- Determination of the variation / amendment type and whether variations can be grouped
- Compilation and preparation of documents for submission to the FDA, EMA, or MHRA including replacement sections, forms, expert reports, letters etc.
- Publishing, submission, and management of the variation through the review and approval process including responding to Board of Health requests for Information (RFIs).