Posted 14 April 2016
By Nick Paul Taylor
Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EMA Sets out 5-Year Strategy for Antimicrobial Monitoring Program
The European Medicines Agency (EMA) has published a draft strategy for the next five years of its program to monitor the use of antimicrobials. Over the period covered by the document, EMA plans to continue expanding the number of countries from which it gathers data with a view to ultimately covering every nation in the European Economic Area (EEA).
EMA set up the monitoring program, dubbed the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC), to improve oversight of how antimicrobials are being used in animals in the region, a key data point as the regulator works toward limiting the emergence of resistant strains. ESVAC’s first report covered 2005 to 2009 and featured data from nine countries, a figure that has increased quickly as EMA has scaled up the program. The most recent report, which EMA released in October, featured data from 26 countries.
With the EEA being made up of 31 countries, EMA is now in a position to target having data from all of the nations in the region. This is a primary objective for ESVAC’s strategy from 2016 to 2020. With Croatia, Romania and Switzerland, which is outside of the EEA but is a key partner of EMA, all set to contribute data to the 2016 report, ESVAC is set to come close to achieving its target well before the end of the period covered by its strategy document. The remaining countries account for around 5% of the food-producing animals in the region.
Efforts to increase the geographical comprehensiveness of the dataset are advancing in parallel to initiatives designed to standardize the information gathered across the region. Specifically, ESVAC is working to establish defined daily doses and defined course doses for animals, standards that go by the abbreviations DDDvet and DCDvet. By defining doses across Europe, ESVAC is aiming to support more accurate estimates of the levels of antimicrobials to which animals in each nation are exposed. ESVAC expects the improved estimates to support evidence-based policies on risk minimization.
EMA is planning to publish values for DDDvet and DCDvet in the coming months. By then, ESVAC will have begun to build a picture of how the industry and other groups have responded to its strategy document. The document is open for comment until 30 June.
Draft Strategy, Press Release
CHMP Posts Draft Revision of Guidelines on Experimental Drug Quality Documentation
EMA’s Committee for Medicinal Products for Human Use (CHMP) has proposed revisions to guidance on chemical and pharmaceutical quality documentation for investigational medical products. The draft is designed to bring the existing guideline document up to date with the changes that have occurred since it came into force in 2006.
Multiple sections are unchanged from the earlier version of the document, but the draft adds details and expands on certain points. In a discussion of drug substances, for example, the draft refers to the effect of mutual recognition agreements and EMA’s involvement in the International Conference on Harmonization (ICH). Under the proposed guidelines, applications for active substances that are already approved in one of the ICH regions or by EMA’s partners can refer to these marketing authorizations when providing information about the drug.
When making such references, EMA wants applicants to provide statements confirming that the active substance is of the same quality as the product that is approved elsewhere. In addition, filings are expected to list the name of the approved product, its marketing authorization number and the country in which it is approved, plus the identity of the organization that holds the rights to the drug. This section is entirely absent from the 2006 guidelines, which provide no details regarding how to proceed when working with a drug substance that is already approved by one of EMA’s peers.
EMA is also proposing to modify its advice on describing the manufacturing process and process controls. Currently, applications for substances that comply with the European, Japanese or United States pharmacopoeia are exempt from providing further details. EMA plans to tighten up its outlook in this regard. The revised draft allows applicants to refer to compliance with the pharmacopoeias, but also demands that the suitability of the referenced monograph to the control of the impurity profile of the active substance is discussed.
The draft is open for comment until 12 October.
In Far-Reaching Document, EMA Proposes Revisions to Sterilization Guidelines
A clutch of European regulatory committees and working groups have come together to revise EMA advice on the sterilization of medicinal products, active substances, excipients and primary containers. The draft guidelines, which would affect human and veterinary medicines, provide advice on how to choose a sterilization method.
CHMP, its veterinary counterpart, the Quality Working Party and the Biologics Working Party were all involved in the drafting of the text, resulting in a document with far-reaching implications. The text details the documents EMA expects to see in the quality dossiers of applications for the approval or variation of a sterile product. In addition, the guideline provides advice on how to select a method of sterilization.
While EMA continues to view terminal sterilization as detailed in the European pharmacopoeia as the preferred method, it is open to accepting alternatives. “It is recognized that terminal sterilization processes utilizing conditions other than the [European pharmacopoeia] reference conditions may be developed to provide satisfactory sterility assurance levels and such alternative processes may be acceptable when properly validated,” EMA wrote.
Such flexibility dates back to the antecedent of the sterilization draft, an annex to a drug development guidance document that came into force in 1999. The range of alternatives EMA is willing to consider has been tweaked, though. In a decision tree for the sterilization of aqueous products, EMA has added details regarding the use of reduced terminal heat treatment. The draft is open for comment until 13 October.
EMA Commits to Publishing Pharmacovigilance Guidance Documents Early in 2017
EMA has unveiled plans to release a clutch of pharmacovigilance guidelines by the first quarter of next year as part of its attempts to train the industry in preparation for changes to EudraVigilance. The planned documents cover the management of adverse event reporting and other tasks.
Officials plan to update regulatory advice on the reporting of adverse events through a revision to module VI of the good pharmacovigilance practices (GVPs). EMA also plans to revise module IX, a text that outlines the general requirements covering the structures and processes that are involved in signal management. The revision will detail how these structures and processes are applied in the context of pharmacovigilance in Europe.
Another two documents being worked on at EMA cover different aspects of signal detection. In an addendum to the aforementioned GVP module IX, EMA plans to cover the methodological aspects of detecting signals from spontaneous reports. The second text is intended to clarify EMA’s advice on using EudraVigilance to screen for adverse drug reactions, specifically digging into electronic reaction monitoring reports. A handful of other documents are also in the works.
EMA released the timeline for the publication of the guidelines in a broader document covering its plans for EudraVigilance training. The regulator is planning to introduce a raft of e-learning programs and webinars over the coming year.