SubscribeBROMI (Better Regulation of Medicines Initiative) - National Marketing Authorisation Variations in the UK
This article explains the new initiative introduced in April 2008 in the UK for variations to nationally granted marketing authorisations. The BROMI variations scheme does not extend to decentralised, centralised or mutual recognition marketing authorisations.
BROMI
In the UK, the health authority, the MHRA (Medicines Healthcare and Regulatory Agency), has been considering a risk-based approach to assessment of various regulatory activities in order to reduce the burden of regulation wherever possible. It has already rolled out initiatives for the self-certification of minor changes to labelling and patient information leaflets, and streamlined the process for obtaining copy-marketing authorisations. BROMI variations are the latest scheme to be introduced. Further work is under consideration with regard to streamlining areas of pharmacovigilance and renewals.
Regulatory Self-Certification
BROMI Variations Scheme
This initiative introduces a self-certification scheme for certain Type 1A national variations, and an expedited process for certain Type 1B and Type II variations.
The scheme has been evolved through the piloting with a small group of companies before rolling it out to all national marketing authorisations.
The MHRA receive approximately 22,000 variations each year, of which half are Type 1A variations, and of these, the majority are national marketing authorisations. From experience of the pilot scheme, it has been estimated that approximately 80% of national Type 1A variations could be self-certified in the future.
BROMI Variations Categories
There are various categories of variations under the scheme, which is based on a risk-assessment basis. The categories of variations are defined:
- Self-certification BROMI
- Type 1A BROMI
- Type 1B BROMI
- Type II BROMI
Based on the pilot scheme and historical analysis of variations the categories for the BROMI scheme have been decided. The MHRA have issued a guidance document which outlines which categories a variation will fall into. ‘BROMI Dossier Requirements for Type 1A and Type 1B UK National Notifications’ is available to download from the website, www.mhra.gov.uk. This is closely based on the European guidelines for Type 1A and Type 1B Notifications, but has been amended in terms of the conditions and documentation required. It also has been colour-coded in order to assist users to determine the relevant BROMI category and thus the requirements for each change. The coding is yellow for self-certification BROMI, blue for Type 1A BROMI and green for Type II BROMI applications.
Some changes that were previously Type 1A applications, e.g. change in the address of a Marketing Authorisation holder, or addition of secondary packaging sites, are now self-certification BROMI applications.
Similarly some categories of Type 1B variations have become Type 1A BROMI applications, e.g. minor changes to the manufacturing process of the drug substance with no changes to reagents or solvents used in the process.
Some Type II applications have become Type 1B BROMI applications, e.g. the addition of a manufacturing site for a sterile finished product, the addition of an additional distributor, or the removal of tablet markings.
BROMI Variations Procedure
All BROMI variations must be submitted through the MHRA portal. The portal is an electronic system, which allows secure direct submission of applications to the MHRA.
A correct, complete documentation package must be submitted with every application to ensure success using the BROMI guideline refereed to above.
It is vital to check that the details of the currently registered information of the Marketing Authorisation match those held by the MHRA, as this is key to ensure correct self-certification and submission of the correct category of variation application.
Self-certification BROMI applications will have an automatic acknowledgement from the portal, which will allow immediate implementation, with a formal acknowledgement letter issued subsequently. Type 1A BROMI applications will undergo a 14-day scientific validation process and Type 1B BROMI applications a 30-day assessment procedure.
The MHRA plan an ongoing audit BROMI of activity, particularly self-certification applications, with potential consequences of failure either withdrawal of an approved application or other enforcement action.
Pharmaceutical Risk-Based Assessment
BROMI Variations Benefits
The risk-based assessment means that the introduction of the category of self-certification BROMI variations will allow many of the more routine or administrative updates to a Marketing Authorisation to be carried out in a predictable timescale under industry control. This should have clear benefits in terms of manufacturing planning and stock control.
The other major benefit is the reclassification of other changes, particularly those from Type II to Type 1B changes where the documentation for such changes becomes clearly defined, and the timescale for assessment shortened from the current 90 to a 30 day timetable.
These benefits to the industry, and also the reduction of resource at the MHRA on administrative procedures, offer clear advantages to all without compromising public health protection.