Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.

EMA Posts new Guidance on Changing Risk-Management Plans, Manufacturing Sites

The European Medicines Agency (EMA) has posted new guidance on post-authorization changes to risk-management plans (RMPs) and manufacturing sites. EMA, which has adopted the policies in an attempt to simplify processes for marketing authorization holders, explained the implications of the guidance in two question and answer documents.

Prior to the publication of the Q&As, the 270-page document EMA maintains to provide post-authorization advice to users of the centralized procedure was lacking in details regarding how to handle changes to RMPs and certain quality-related topics. The Q&As, which form part of the EMA document and have their own sections on the regulator’s website, address this shortcoming. In doing so, EMA has moved to clarify and, in its view, simplify the process marketing authorization holders must go through to make certain changes.

The RMP Q&A is the longer of the two documents. EMA has used the text to address 12 questions, including topics such as the timing of filings for updated RMPs, changes that can be made without an additional variation and the involvement of the Pharmacovigilance Risk Assessment Committee (PRAC) rapporteur. Each of the questions and accompanying answers was published for the first time as part of the guidance, making the update one of the more substantial amendments to the post-authorization advice document.

In a statement to discuss the guidance, EMA singled out changes to its approach to complex RMP updates as being among the more significant revisions. EMA used to require filings for multiple RMP changes to be gathered into groupings. This is still the case when marketing-authorization holders are making major changes to their RMPs. In contrast, EMA will now allow multiple minor changes to be submitted as a single type IB or type II variation. EMA sees this change as freeing companies from the consequences of triggering additional type IB variation scopes.

The same intent to simplify is present in the Q&A on quality-related changes. EMA addresses four types of changes in the Q&A, namely administrative, quality, clinical and editorial. In the Q&A, EMA details the changes companies can submit under a single type II scope when introducing a new manufacturing plant for a finished product. EMA will accept changes to the production process, batch size and in-process controls “to adapt to the new manufacturing site settings” under a single type II scope. Additional scopes are needed for changes not directly tied to the new facility.

Press Release, RMP Guidance, Quality Q&A

Rasi Agrees to Waive PRIME Scientific Advice Fees for SMEs and Academics

EMA Executive Director Guido Rasi has agreed to waive the fees associated with scientific advice requests for certain products in the PRIME accelerated assessment program. The waiver applies to organizations that are perceived to be least equipped to pay, namely small and medium-sized enterprises (SMEs) and academic institutions.

Originally, EMA had intended to assess the merit of requests for reductions in the fees it charges for scientific advice requests on a case-by-case basis. However, having assessed the number of requests it is likely to receive from participants in PRIME, EMA has decided a blanket waiving of the fees is the most efficient way to ensure that financial factors do not prevent less-wealthy organizations from benefiting from its advice. Such an outcome could hinder PRIME’s ability to achieve its main goal of facilitating the fast advance of medicines to the patients who need them.

Academic organizations and companies that are registered with EMA as SMEs are in line to receive the fee exemptions. However, EMA has inserted a stipulation that prevents academic organizations from benefiting from the waiver if they are “financed or managed by private profit organisations in the pharmaceutical sector.” Academic institutions that have “operating agreements” with such an organization “concerning their sponsorship or participation to the specific research project for which a fee exemption is sought” are also outside of the scope of the waiver scheme.

The decision to waive the fees for organizations that meet these criteria was made by Rasi. In a statement to explain his reasoning, Rasi noted the aforementioned inefficiency of making fee waiver decisions on a case-by-case basis and that premarket authorization procedures such as requests for scientific advice represent a significant barrier to SMEs and particularly academic institutions. The waiver is designed to lessen these barriers for participants in PRIME, who by definition are working on medicines with the potential to address unmet medical needs. 

EMA Decision

EMA Adopts new Staffing Structure for Evaluation of Human Medicines

EMA has adopted a new staffing structure for the management of evaluation procedures for human medicines. As of 1 June, when a developer of a human medicine submits an extension application or other type of request, EMA will allocate a single procedure manager to the product being assessed.

The new model applies to type II variations, extension applications, periodic safety update reports, renewals and post-authorization measures related to centrally authorized human medicines. As part of the adoption of the model, EMA has created two new positions: procedure manager and EMA product lead (EPL). Procedure managers will “oversee all aspects of the management of regulatory procedures,” while EPLs will “build up the overall knowledge about a medicine and its therapeutic area as it moves through the different stages of its lifecycle.”

This per-product approach to the management of requests is a new way of working for EMA. Prior to the adoption of the approach, EMA put different people in charge of each procedure relating to a product. While the old approach is seen by EMA as giving it a strong procedural focus, the regulator has decided it can work more effectively under a per-product model, in part because it thinks the new approach will make it easier to handle fluctuations in the volumes of the requests it receives for different procedures.

EMA also foresees the new way of working enabling it to “improve the coordination of regulatory activities with a product, particularly where multiple regulatory procedures are run in parallel for the same product.” EMA is also looking to EPLs to support this process by facilitating discussions within and between EMA’s scientific committees. To cut the risk that the switch to per-product oversight will prove detrimental to its procedural focus, EMA is setting up process-focused communities. These groups will be made up of EMA staff who specialize in particular procedures. 

EMA Statement

Other News:

EMA has removed Genzyme’s Fabry disease drug Fabrazyme from its list of medicines affected by supply disruptions. The disruption in the supply of Fabrazyme dates back to manufacturing problems Genzyme experienced in 2009. Genzyme, first on its own and later under new owner Sanofi, took various steps to resolve the situation, but EMA has only now officially deemed the shortage to be over. EMA Notice

The United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) has alerted healthcare professionals to a recall of two batches of Santen’s Ikervis eye drops. Santen initiated the recall following the discovery of microparticles of the active ingredient, ciclosporin, during testing of samples kept under certain conditions for six months. The recall affects two batches of the product that were distributed earlier this year. MHRA Alert