Article originally published in the Food and Drug Law Journal (with permission from FDLI), August 2008

I. INTRODUCTION

Pharmacovigilance is a global public health activity that is currently undergoing a considerable amount of regulatory, social and political change. The standards expected by society have been raised following high-profile product withdrawals. Industry, regulatory authorities and consumers are now focusing on a more proactive, risk management based approach to drug safety monitoring. There has been a shift from the formulaic collection, classification and reporting of adverse event reports to a more holistic focus on any information suggesting a change in a product’s risk benefit profile.

There has also been a realization that effective pharmacovigilance must be global. Companies and regulatory authorities must receive and react to information suggesting a change in risk-benefit profile wherever it arises. The past 20 years has therefore seen a steady drive towards global harmonization of safety reporting definitions and standards.

There is, however, evidence that this shift towards international harmonization is faltering as regulatory priorities and views diverge. There are increasing differences in the way different jurisdictions interpret, implement, and follow international safety reporting standards, in particular the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)4 guidelines on adverse drug reactions and safety reporting. In Europe, for example, the regulators have fully adopted ICH guidelines. They have accepted the ICH concept that manufacturers should report only those events that the reporting physician or the manufacturer believe have a possible causal relationship with a drug. However, the United States has been slow to adopt these standards and concepts, preferring companies to report all adverse experiences, irrespective of the likelihood of a causal relationship. Even where the U.S. has proposed the adoption of ICH standards it does so with qualifications. This has resulted in significant differences in the information companies are reporting to regulators worldwide.

This can have significant practical implications for regulators, who may gain very different impressions of the scope and magnitude of an emerging safety issue. It can also affect the manner in which they treat manufacturers, either as a result of a manufacturer’s own reporting policies or those of manufacturers of products in the same class. A good example of such a circumstance arose in the context of safety concerns surrounding gadolinium contrast agents, discussed below. Different reporting practices amongst the manufacturers of these products resulted in European regulators regarding the issue as a single product concern, while the Food and Drug Administration (FDA) viewed it as a class effect.

Another threat to global harmonization of safety reporting is arising because of divergent approaches to the naming of medicinal products. Most reporting systems and standards rely on the World Health Organization (WHO) international non-proprietary name (INN) of a product as opposed to its brand name. This is because brand names can vary from jurisdiction to jurisdiction, as do prescribing and dispensing practices. Physicians in many jurisdictions prescribe and report using a product’s INN and pharmacists are often required to dispense by INN. This use of INNs is therefore necessary and also appropriate, provided regulators apply the WHO’s recommendations.

The EC has recently set an unhelpful precedent by approving two follow-on biological products, Epoetin alfa Hexal and Abseamed, with the same INN as the innovator product, Eprex/Erypro, in clear contravention of WHO guidance on drug naming. Biological products are sensitive to changes in manufacturing process and formulation and also have the potential for rare, but serious side-effects and so effective postmarketing surveillance is essential. The EC has proposed that doctors prescribe and report by brand name, and that pharmacists also dispense in that way, to overcome the problems associated with product identification. However, it is the authors’ view that such an approach will result in further threat to the harmonization of pharmacovigilance. Effective pharmacovigilance requires global harmonization of nomenclature, standards and definitions and it is unlikely that an approach relying on brand name reporting would be adopted internationally in the short term, because ICH safety reporting standards rely on the appropriate use of INNs. How can global safety monitoring and reporting work if those involved do not even speak the same language?

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Photo of Grant Castle Grant Castle

Grant Castle practices in the areas of life sciences regulatory law, with an emphasis on pharmaceutical and medical device regulation. His advice on general regulatory matters includes: adverse event and other reporting obligations, manufacturing controls, labeling and promotion, and product life cycle management.

Grant Castle practices in the areas of life sciences regulatory law, with an emphasis on pharmaceutical and medical device regulation. His advice on general regulatory matters includes: adverse event and other reporting obligations, manufacturing controls, labeling and promotion, and product life cycle management. He has also advised extensively on EC and national laws governing clinical research, data protection, and the regulatory status of borderline products. He has developed considerable expertise in coordinating regulatory projects covering jurisdictions outside of Europe, including Canada, South America, Eastern Europe, the former Soviet Union, Africa, the Near East, Japan, and Australia. His transactional work includes advice on regulatory aspects of mergers and acquisitions, licensing, and collaborative arrangements.

Photo of Brian Kelly Brian Kelly

Brian Kelly is a partner in the London Life Sciences group and also co-chair of Covington’s Global Food Industry Group. Mr. Kelly’s practice focuses on EU food and drug regulatory law, public and administrative proceedings, internal investigations, European Union law, and product liability…

Brian Kelly is a partner in the London Life Sciences group and also co-chair of Covington’s Global Food Industry Group. Mr. Kelly’s practice focuses on EU food and drug regulatory law, public and administrative proceedings, internal investigations, European Union law, and product liability and safety. The Chambers Europe Guide to the legal profession lists Mr. Kelly as part of our “world-class [regulatory and public affairs] team and describes him as a notable practitioner who is “very ambitious, thorough with a sharp intellect”. The Chambers UK Guide quotes clients saying: “his communication and work ethic stand out, he is very hard-working and dedicated when it comes to his cases.”

Mr. Kelly’s advice on general regulatory matters across all sectors includes borderline determinations, food classifications, tissue and stem cell regulation, adverse event and other reporting obligations, manufacturing controls, labeling and promotion, pricing and reimbursement/procurement, product life cycle management (foods and medicines), nanotechnology, and anti-bribery and corruption advice. Mr. Kelly has also been advising on UK and European “Brexit” related issues including tariffs.

Mr. Kelly has also advised and co-ordinated international projects on advertising/promotion, clinical research, data protection, the regulatory status of borderline products, food/cosmetic ingredient reviews and advises on regulatory aspects of corporate/commercial deals, particularly regulatory due diligence.

Mr. Kelly is also experienced in representing clients in administrative and enforcement proceedings before regulatory authorities and in the UK and EU courts.

Mr. Kelly is an honorary lecturer at University College London.