WHO International Standards and Reference Preparations for Cytokines and Growth factors

Amanda E. I Proudfoot¹ and Meenu Wadhwa^2*

¹ICIS Standards Committee Chair, and ²Cytokine & Growth Factors Section, Biotherapeutics Group, National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare products Regulatory Agency,Hertfordshire, UK

* Correspondence: [email protected]

The ability to quantify the activity of cytokines is an essential part of experimental and clinical investigation and is largely dependent upon the availability of suitable cytokine standards and reference reagents. The International Cytokine and Interferon Society (ICIS) Standards Committee was established to make recommendations regarding interferon and cytokine standards and standardization to the ICIS membership, and thereby to the international cytokine scientific community. The Committee works closely with the World Health Organization (WHO), the National Institute for Biological Standards and Control (NIBSC), the U.S. National Institutes of Health (NIH), the Biodefense and Emerging Infections Resources Repository (BEI Resources), pharmaceutical manufacturers, and regulatory agencies. The Committee includes members from several of these organizations. The role that the Committee plays as a source of information and recommendations to the ICIS membership, and to the international cytokine scientific community as a whole, is very much dependent upon suitable standards and reference materials being made available by the NIBSC. Similarly, the Standardization and Nomenclature Committee of the ICIS reviews the need for cytokine standards and their usage. With the expanding role of cytokines and growth factors in the development and manufacture of biotechnology derived products e.g., monoclonal antibodies targeting cytokines/growth factors, biosimilar medicines, cell and/or gene therapy products, the need for suitable standards is increasing. 

The accompanying Table lists WHO International Standards (IS), WHO reference reagents (WRR) and other cytokine and growth factor standards available from the NIBSC. ISs and WRRs are publicly available reference standards with defined units (International Unit for IS) established by the WHO Expert Committee on Biological Standardization. Lyophilised and formulated to ensure long term stability, they serve as ‘primary’ standards for bioactivity and for calibration of secondary reference standards. The use of IS and WRR to calibrate commercially available or laboratory made reagents including immunoassays where feasible as per WHO recommendations facilitates comparisons of data between assays, different laboratories, and individual studies allowing global harmonisation.

Table 1. Cytokine and growth factor standards and reference reagents available from the National Institute for Biological Standards and Control

 A wide range of WHO International Biological Standards and reference materials are available for the calibration of assays of therapeutic substances and immunoassays and bioassays used in basic research.  These materials are available from Standards Processing Division, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QG, UK.  The NIBSC does not charge for these materials, however there is a handling charge to cover the costs of administration, storage, and dispatch.  The handling charge is currently £120 per ampoule. A comprehensive catalogue of reference materials is available from the above address or can be accessed online via the NIBSC website (www.nibsc.org/products).

Human Cytokine Standards and Reference Reagents

 Human Growth Factor Standards and Reference Reagents

Murine Cytokine Standards and Reference Reagents

 Standards for Cytokine Antagonists

¹All preparations listed above are rDNA derived unless specified;

² IS – International Standard; WRR – WHO Reference Reagent; RR – NIBSC Reference Reagent; BWS – British Working standard; WS – Working standard

About the National Institute for Biological Standards and Control

The National Institute for Biological Standards and Control (NIBSC) is a global leader in the standardisation and control of biological medicines, playing a major role in assuring the quality of biological medicines worldwide.

NIBSC is a centre of the Medicines and Healthcare products Regulatory Agency which also includes CPRD and MHRA. The Medicines and Healthcare products Regulatory Agency is an executive agency of the Department of Health.