Guidance for new Marketing Authorisation assessment routes in the UK following Brexit: International routes
In the last of our series of posts analysing the new access routes developed in the UK, Nasos Kipentzoglou takes an in-depth look at the international routes; the Access Consortium and Project Orbis.
The consortium is a medium-sized coalition of regulatory authorities that work together to promote greater regulatory collaboration and alignment of regulatory requirements. The consortium’s goal is to maximise international cooperation between partners in the consortium, reduce duplication, and increase each agency’s capacity to ensure patients have timely access to high quality, safe and effective therapeutic products.
Access Consortium Procedure
The heads of the five agencies (UK, Australia, Canada, Singapore and Switzerland) usually meet twice a year face-to-face in the margins of international meetings or conferences to review the progress of the Access working groups and approve the work program for the upcoming year.
Currently, the Access Consortium has several working groups. Working group members have regular meetings to exchange information on regulatory issues and challenges faced by the participating regulatory agencies including issues on clinical trials, MAs, product manufacturing site inspections post-marketing surveillance, joint development of technical guidelines or regulatory standards, and collaboration on information platforms.
The Access consortium has developed 2 authorisation procedures: The New Active Substance Work Sharing Initiative and the Generic Medicines Work Sharing Initiative.
Project Orbis is a programme coordinated by the US Food and Drug Administration (FDA) to review and approve promising cancer treatments. Regulatory authorities of major countries are included such as Australia (Therapeutic Goods Administration), Canada (Health Canada), UK (Medicines and Healthcare products Regulatory Agency – MHRA), Singapore (Health Science Authority), Switzerland (Swissmedic) and Brazil (Brazilian Health Regulatory Agency).
Project Orbis provides a framework that facilitates faster patient access to innovative cancer therapies across multiple countries. The MHRA will participate fully in the scheme from 1 January 2021. While the FDA serves as the primary coordinator for application selection and review, Project Orbis Partners (POPs) may propose products for inclusion in the scheme. Each country remains fully independent of its final regulatory decision. Applications submitted to the MHRA within a Project Orbis procedure are national (Great Britain only) marketing authorisation applications and variations.
New marketing authorisation applications (MAAs) and new indication applications (variations) for oncology products are eligible for Project Orbis (PO). The selection of the products is coordinated by the FDA based on high-impact and clinically significant criteria. In general PO applications are expected to meet the criteria for FDA priority review:
- The drug is intended to treat a serious condition
- If approved, would provide significant improvement in safety or effectiveness
For the MHRA, PO submissions should also meet the qualifying criteria for the Innovation Passport within the Innovative Licensing and Access Pathway (ILAP). Inclusion in ILAP is a requirement for the participation of the MHRA as a POP.
There are several types of submissions and these are dependent on the timelines between the FDA and Participating Orbis Partners (POP).
- Applications must be submitted concurrently or near-concurrently (within 30 days) to FDA and the POPs
- Type A (Regular Orbis) allow the maximal collaboration during the review phase and the possibility of concurrent action with the FDA
- Applications submitted with a greater than 30-day delay or a regulatory action greater than 3 months or the FDA action
- Type B Orbis (Modified Orbis) allow the possibility of concurrent review with FDA but not concurrent action
- Applications where FDA has already taken regulatory action
- Type C (Written Report Only Orbis) allows FDA to share their completed review documents with POP but there is no concurrent review or action with the FDA
MHRA and the Project Orbis Procedure
Once a product or new indication has been identified for inclusion in Project Orbis, FDA will contact the MHRA to request their interest in involvement. If the request is provisionally accepted by the MHRA, the parent US Company will be advised and should provide details of the local UK affiliate to MHRA. MHRA participation is contingent on agreement with the UK affiliate and inclusion of the product/new indication in ILAP.
If the product or new indication is not already accepted for ILAP, the MHRA will arrange an Innovation Passport meeting as soon as possible after the request for inclusion in Project Orbis to confirm eligibility based on a review of the top-level clinical data. The meeting will also address practical arrangements for the submission, including the requirements for orphan products, paediatric investigation plans (PIPs) and pharmacovigilance including risk management plans (RMPs). For products and new indications already accepted in ILAP, a meeting will be arranged to discuss practical arrangements for submission.
Finally, the multidisciplinary assessment teams will assess the application collaborating with Vigilance and Risk Management of Medicines assessors for evaluation of the RMP. The assessment process will include consultation with the MHRA Expert Advisory Groups (EAGs) and the Commission on Human Medicines (CHM), as required.
Implications for manufacturers
The MHRA with the entrance of the UK in Project Orbis offers an opportunity for manufacturers to take advantage of a systematic delivery approach across multiple markets and gain early patient access whilst data continues to mature. However, manufactures should take into consideration delays to NICE delivery or data collection agreements with the Cancer Drug Fund that will be required to support cost-effectiveness. Crucially, manufacturers should take into account the Project Orbis and ILAP procedures in early clinical development to increase chances for a successful submission. Additionally, understanding the feasibility of an early marketing authorisation in the UK through Project Orbis, considering the potential NICE evaluation outcomes and the likelihood of a recommendation at an acceptable cost-effective price. The MHRA by being part of the Access Consortium coalition, routinely communicate and co-operate with other regulatory bodies across the globe. That offers a unique chance to stay up to date on technical expertise and ensures consistent, contemporary approach for evaluating and authorising the new therapeutic products.
Article published 13 April 2021.