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Europe Under Pressure: Gearing Up for a Year of Regulatory Convergence


In the last year regulatory authorities sharpened their focus on gathering more data and on achieving transparency and harmonization. Erick Gaussens reviews 2015 and looks at companies’ need to respond to converging demands in 2016.

During the past year, regulatory authorities have sharpened their focus on gathering more data and on achieving transparency and harmonization. Erick Gaussens takes stock of 2015 and of companies’ need to be able to respond at the enterprise level to converging demands in 2016.

It’s been another big year for life sciences companies, as guidances, major policy developments, and new ways of sharing data with regulatory authorities have come at them thick and fast. Patient safety, data transparency, and centralisation remain regulatory authorities’ key areas of focus. During 2015, regulators have sought to move the life sciences industry further along the path to those areas across all facets of the business: regulatory, pharmacovigilance, clinical, and manufacturing.

The authorities want not only more and more data for use in safeguarding patient populations but also the streamlining of the ways the information gets received and managed, and that at least is good news in terms of simplifying processes for companies. However, each one of those initiatives places the onus on companies to do more than simply tick the regulatory compliance box. Companies must respond to regulators’ broader and deeper demands by way of more-comprehensive and holistic regulatory information management (RIM) solutions and processes. They must give greater emphasis to the governance of data-who owns it, how it gets managed, and how it gets validated-and to strategies that integrate information from all of the key functions: regulatory, pharmacovigilance, clinical, manufacturing, and marketing. Without such an approach, each new and added initiative from the regulators both now and in the future will place an unnecessary burden on systems and processes.

IDMP progress

Perhaps the biggest incentive for companies to get their RIM processes and systems in order is the advent of the Identification of Medicinal Products (IDMP). During much of 2015, companies were anticipating that IDMP implementation would be on 1 July 2016. But as the date drew closer, it became evident that the deadline was unrealistic. The European Union’s (EU’s) IDMP task force established subgroups to present workable recommendations for the IDMP, and a proposal for an iterative approach was made. Since then, the European Commission has accepted a phased approach to implementation. The approach is defined as a preparation phase between now and the end of June 2016, followed by a transition phase. The first iteration will focus on product and substance information, with further standards to come.

Experience based on the eXtended EudraVigilance Medicinal Product Dictionary has taught the European Medicines Agency (EMA)-and, hopefully, the industry as well-the danger of rushing from the publication of guidances to implementation. The iterative approach and the longer timelines give the industry some breathing space to develop comprehensive processes, good data governance methods, and well-integrated information systems. However, that additional time has to be used productively if companies are to avoid slipping into another poorly planned response.

Once internal data management and processes are in place, companies can turn their focus to the guidances. The first edition of the substance implementation guide is imminent, though further editions with additional annexes will follow. An implementation guide for vocabularies is expected in January or February 2016. Implementation guides for medicinal products and pharmaceutical products, however, have been delayed because of the large number of comments received during the ballot period.

The IDMP ultimately will have industrywide implications, which requires involvement by all parts of the business. For example, projects that will make use of the IDMP include (1) the Open Medicine Project, which will use IDMP data to improve cross-border health-care delivery; (2) medicinal product dictionary systems for health care, which will use IDMP data; (3) electronic prescribing-a major European initiative; and (4) efforts to clarify and harmonize terms and concepts for herbal medicines. Those diverse informatics projects underscore the potential scope of the IDMP and, by extension, explain why the standards are so comprehensive.

More data but more streamlined

The regulators remain keenly focused on improving the oversight of pharmacovigilance activities, with a view to increasing transparency and harmonising the ways information is received while also continuously improving patient safety.

As of June of next year, the use of a repository for periodic safety update reports (PSURs) will become mandatory-irrespective of the submission procedure. The purpose of the PSUR repository is to harmonise safety information across Europe and deliver data transparency. The introduction of a PSUR repository and the eSubmission Gateway that companies will use to access the repository will be new for all marketing authorisation holders (MAHs), which is why it is advisable that companies take time to prepare by assessing their business processes and carefully studying guidances issued about use of the gateway.

The need for streamlined processes is further underscored with the simultaneous introduction of the Individual Case Safety Report (ICSR) database. The database is currently being audited, after which MAHs will have six months before it becomes mandatory to use the database. The advantage is that MAHs will have to report only to the EMA, with the exception of a continued requirement to report to the German and UK regulatory authorities. However, to improve safety oversight, MAHs will be required to submit more data-including information on nonserious cases, from which drug reactions related to their products are not permitted to be excluded. In addition, ICSR reporting will affect signal detection processes by requiring companies to check their ICSRs against those that will be available in the EMA database. That’s another process layer that companies will have to prepare to handle.

Also on the horizon is a key initiative aimed at streamlining the rules (1) for conducting clinical trials across Europe, (2) for providing more transparency, and (3) for establishing strictly defined deadlines for the assessment of clinical trial applications. The clinical trial regulation was adopted in 2014, though compliance is not expected until later, in 2017, after the portal and database have been audited.

Integral to the clinical trial regulation are the development and maintenance of a portal and database; indeed, the application date of the legislation is linked to full functionality of the portal. The EU database will contain all of the application dossiers for the authorisation of clinical trials in Europe, information on their assessments and follow-up, and some information on results of the trials. The objective is transparency. In practical terms, that means data will, by default, be accessible to the public unless specific data must remain confidential to protect trial participants or to encourage and protect innovation. The level of transparency will enable patients to find out about current trials for medical products that might potentially treat their conditions. It also means companies will have full knowledge of what trials are taking place and will be in a position to make decisions about which products to pursue based on that information.

Beyond regulatory

The EMA also has manufacturing processes clearly in its sights as it seeks to enhance safety. As of November 2015, all medicinal products manufactured in shared facilities became subject to a strict, new EMA cross-contamination guideline. The guideline requires all multipurpose pharmaceutical manufacturers to take a thorough, risk-based approach with regard to the cleaning processes for compounds marketed in Europe. It means that acceptable daily exposure has to be assessed for every product with respect to general toxicity, carcinogenicity, immunogenicity, and reproduction toxicology.

This is a huge undertaking and affects every manufacturing facility that prepares products for the European market. And it’s by no means the only tough new manufacturing initiative aimed at improving patient safety: As of March 2016, new guidelines on the assessment of excipients will go into force, placing new obligations on companies to ensure that they have proper quality systems in place and that they can trace their supply chain and identify the material source of an ingredient, be it animal, plant, or synthetic. Companies will have to retain documentation for inspection and conduct formalised risk assessments of all excipients used-as well as of each manufacturer when an excipient is supplied by separate manufacturers.

Regulatory authorities are also focusing on the safety of cosmetics, with stricter requirements around the safety profiles of substances used in manufacturing cosmetics. In particular, regulators are concentrating on such substances as nanomaterials-in the forms of carcinogenic, mutagenic, and reprotoxic substances, and endocrine disruptors.

The European Commission is working with the Scientific Committee on Consumer Safety (SCCS) to develop opinion on substances that potentially could create concerns about consumer safety. The SCCS provides its assessment of whether a substance can be authorised, should be restricted, should be listed on an annex within cosmetics regulation EC No. 1223/2009, or should be prohibited.

Casting a wider net

Other factors affecting regulatory developments include globalization and the power of social media. The International Council for Harmonization has been undergoing major reform to expand its reach and has issued invitations to regulators around the world to join the group. The organization-which, in October 2015, changed its name to the International Council for Harmonization from the International Conference on Harmonisation-has been adapting to changes in the ways medicines get developed and regulated, and it has become eager to improve transparency between regulators, industry, and the public.

Regulators are also starting to dip their toes into social media waters. The US Food and Drug Administration has been working with a specialist informatics company to develop a data-mining platform that gathers public posts from Twitter and Facebook as part of an initiative to map safety reporting by consumers. The platform (1) singles out posts that mention both a product and an adverse event, (2) maps consumer language to the Medical Dictionary for Regulatory Activities, and (3) collects and evaluates standard product names and product event pairs for potential safety signals. So far, the research has shown that adverse events are possible to identify through social media, although the amount of information from some platforms, such as Twitter, is limited.

Thinking Big

With globalisation and the ever-expanding demand for more data and increased emphasis on harmonisation, companies can’t afford to delay management of their data and systems. As requirements intensify, as is expected in 2016-in areas ranging from clinical trials to pharmacovigilance, to manufacturing, to the all-encompassing IDMP-the emphasis must be on removing the burdens created by isolated solutions and one-off responses to regulatory requirements and instead moving towards the development of holistic RIM processes.

Those regulatory complexities are further compounded by the evolving business model, including ongoing mergers, the acquisition of product portfolios to enrich the internal pipeline, and portfolio diversification into over-the-counter products, combination products, cosmetics, and nutraceuticals. All of those trends simply add more layers of data that companies must manage.

With so many things converging on the life sciences industry, 2016 needs to be the year of process and system breakthroughs.

About the author

Erick Gaussens (egaussens@productlife-group.com) is Chief Scientific Officer at ProductLife Group.


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