New and Updated: The Guide for the Assessment of Clotting Factor Concentrates, 3rd edition

Determining the safety and quality of therapeutic products for the treatment of hemophilia is crucial for the optimal treatment of patients. The World Federation of Hemophilia (WFH) is pleased to announce the release of the 3rd edition of the Guide for the Assessment of Clotting Factor Concentrates. The guide covers a wide range of topics related to factors that affect the quality and safety of clotting factor concentrates (CFCs), and discusses the licensing, regulation, and control of CFCs in regions with and without well-established regulatory systems. Updated to reflect the latest developments in the hemophilia treatment landscape, this third edition is a must-read for anyone concerned with the safety and supply of treatment products.

The guide introduces the reader to the key elements that contribute to the quality, safety, and efficacy of hemophilia treatment products. This topic is of particular interest to the bleeding disorders community, as hemophilia treatment products sourced from human blood have been linked to the transmission of blood-borne viruses such as the human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV and HCV), in the past. Measures designed to reduce the risk of transmission of infectious agents are based on the following principles:

  1. Selection of appropriate blood and plasma donors
  2. Screening of plasma raw materials using laboratory tests
  3. Elimination of contaminating viruses during the manufacturing process

Each of these measures is explored in great depth in The Guide for the Assessment of Clotting Factor Concentrates.

As the safety of hemophilia treatment products has increased, the focus of concern has shifted to the current serious hazard of the generation of inhibitors to clotting factors during replacement therapy. This third edition of the guide discusses in detail both advances in virus inactivation techniques and procedures that contribute to improved product safety, and the risk of inhibitor development.

The guide then reviews systems for the regulation and control of pharmaceutical medicinal products that are well established in the United States and Europe, and have greatly improved patient safety. These systems are based on arrangements including the establishment and maintenance of a system of licensing and control, the provision of standards and guidelines, the requirement for licence holders to adopt and maintain appropriate quality systems, and post-marketing surveillance of products. The approaches used in North America and Europe provide guidance for countries looking to develop their own protocols for assessing and selecting hemophilia treatment products. However, these systems are complex and some adaptation may be required in a country that is establishing its own new regulatory system. The guide stresses the minimal essential elements that should be prioritized in these cases.

The next section provides guidance for regulatory authorities in countries that have no established system for regulating plasma products, but are looking to develop procedures that ensure the safety and quality of such products. Although the guide acknowledges that establishing and maintaining such a complex regulatory system is beyond the capacity of most healthcare systems in the developing world, it maintains that it is within their capacity to develop an appropriate decision-making framework for the assessment and selection of hemophilia treatment products to improve patient safety. The guide suggests several measures that should be incorporated into the regulatory system and also describes potential pitfalls that should be avoided when developing such systems.

Finally, the guide proposes a model for the evaluation of clotting factor concentrates in countries without established regulatory agencies based on the principles outlined in previous sections. The guide discusses the key information that must be obtained from the manufacturer as well as the minimum requirements that must be met in order for a product to be considered safe for use in patients. This section describes several example scenarios of product evaluation to demonstrate the application of these principles.

The guide also features several appendices that contain useful information for the reader. Appendix 1 presents the World Federation of Hemophilia (WFH) Online Registry of Clotting Factor Concentrates and describes the information available in the registry. Highly complementary to The Guide for the Assessment of Clotting Factor Concentrates, the registry provides the details of over 100 hemophilia treatment products including many of the manufacturing details and safety characteristics discussed in the guide.

Appendix 2 offers a detailed sample questionnaire that may be used to assess whether a product should be allowed on the market. The List of Abbreviations and Glossary, in Appendices 3 and 4, respectively, provide handy quick references to some of the more complex terms and acronyms used throughout the guide. Finally, Appendix 5 lists over a dozen WFH resources that may be consulted to provide a deeper understanding of the assessment of clotting factor concentrates.

The WFH Guide for the Assessment of Clotting Factor Concentrates has long served as an essential resource for many navigating the complex issues of the safe supply of hemophilia treatment products. This third edition updates the core content, making it more relevant than ever.

Fiona Robinson, Educational Materials Manager for the WFH, wishes to thank Mark Brooker, Angela Styhler, and Georghia Michael for their contributions to this article.