Amanda E. I Proudfoot1 and Meenu Wadhwa2*
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
|
Preparation1 |
Product Code |
Status2 |
| Interleukin 1 alpha
Interleukin 1 beta Interleukin 2 Interleukin 3 Interleukin 4 Interleukin 5 Interleukin 6 Interleukin 7 Interleukin 8 Interleukin 9 Interleukin 10 Interleukin 11 Interleukin 12 Interleukin 13 Interleukin 15 Interleukin 17 Interleukin 18 M-CSF G-CSF G-CSF(pegylated) GM-CSF Leukemia inhibitory factor Oncostatin M Stem cell factor Flt 3 ligand Bone morphogenetic protein-2 RANTES MCP-1 GRO-alpha IFN alpha leukocyte IFN alpha 1 (D) IFN alpha 1/8 IFN alpha 2a IFN alpha 2b IFN alpha 2c IFN alpha n1 lymphoblastoid IFN alpha n3 leukocyte IFN alpha consensus IFN omega IFN beta IFN beta ser17 IFN beta fibroblast IFN gamma IFN gamma leukocyte IFN lambda1 TGF beta 1 TGF beta 2 TGF beta 3 Thrombopoietin TNF alpha TNF beta TRAIL |
86/632
86/680 86/500 91/510 88/656 90/586 89/548 90/530 89/520 91/678 93/722 92/788 95/544 94/622 95/554 01/420 03/200 89/512 09/136 12/188 88/646 93/562 93/564 91/682 96/532 93/574 92/520 92/794 92/722 94/784 83/514 95/572 95/650 95/566 95/580 95/568 95/574 94/786 94/754 00/572 00/574 00/576 87/586 82/587 10/176 89/514 90/696 09/234 03/124 12/154 87/640 04/166 |
1st IS
1st IS 2nd IS 1st IS 1st IS WRR 1st IS WRR 1st IS WRR WRR WRR WRR WRR WRR WRR WRR 1st IS 2nd IS 1st IS 1st IS WRR WRR WRR WRR WRR RR RR RR 1st IS 1st IS 1st IS 2nd IS 2nd IS 1st IS 2nd IS 1st IS 1st IS 1st IS 3rdIS RR RR RR BWS WRR RR RR 1st IS RR 3rd IS WRR WRR |
Human Growth Factor Standards and Reference Reagents
| Preparation1 | Product Code | Status2 |
| Basic Fibroblast Growth Factor | 90/712 | 1st IS |
| Brain-derived neurotrophic factor | 96/534 | WRR |
| Ciliary Neurotrophic Factor | 94/684 | WRR |
| Epidermal Growth Factor | 91/530 | 1st IS |
| Epidermal Growth Factor (1-52) | 91/550 | WRR |
| Hepatocyte Growth Factor | 96/564 | WRR |
| Hepatocyte Growth Factor precursor | 96/556 | 1st IS |
| Keratinocyte Growth Factor | 03/150 | WRR |
| Keratinocyte Growth Factor (24-163) | 03/148 | WRR |
| Leptin | 97/594 | 1st IS |
| Nerve Growth Factor | 93/556 | WRR |
| Neurotrophin-3 | 98/718 | RR |
| Platelet derived Growth factor BB | 94/728 | 1st IS |
| Vascular Endothelial Growth Factor 165 | 02/286 | WRR |
Murine Cytokine Standards and Reference Reagents
|
Preparation1 |
Product Code |
Status2 |
| GM-CSF | 91/658 | RR |
| Interleukin1- a | 93/672 | RR |
| Interleukin1-b | 93/668 | RR |
| Interleukin 2 | 93/566 | RR |
| Interleukin 3 | 91/662 | RR |
| Interleukin 4 | 91/656 | RR |
| Interleukin 6 | 93/730 | RR |
| Interleukin 7 | 93/740 | RR |
| Interleukin 9 | 93/504 | RR |
| Leptin | 97/626 | IS |
| TNF-a | 88/532 | RR |
Standards for Cytokine Antagonists
| Preparation1 | Product Code | Status2 |
| Etanercept | 13/204 | 1st IS |
| Infliximab | 16/170 | 1st IS |
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.
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