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Year : 2013  |  Volume : 137  |  Issue : 4  |  Page : 817-819

WHO Expert Committee on Biological Standardization, 58 th Report

439 Civil Supplies Godown Lane Kamalakshipuram Vellore, TN, 632 002, India

Date of Web Publication17-May-2013

Correspondence Address:
T Jacob John
439 Civil Supplies Godown Lane Kamalakshipuram Vellore, TN, 632 002
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Source of Support: None, Conflict of Interest: None

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How to cite this article:
John T J. WHO Expert Committee on Biological Standardization, 58 th Report. Indian J Med Res 2013;137:817-9

How to cite this URL:
John T J. WHO Expert Committee on Biological Standardization, 58 th Report. Indian J Med Res [serial online] 2013 [cited 2021 May 7];137:817-9. Available from:

WHO Expert Committee on Biological Standardization, 58 th Report , WHO Technical Report Series No. 963 (World Health Organization, Geneva) 2011. 244 pages.

ISBN 978-92-4-120963-2

The Expert Committee on Biological Standardization was established in 1947 and in periodic meetings it advises WHO (and through WHO the biomedical community) on a selected range of key international developments affecting the quality, safety and efficacy of vaccines, biological therapeutics, blood products and in vitro diagnostics. The scope of the Expert Committee is broad and covers all biological prophylactics, therapeutics and diagnostics in everyday medical practice and in research, development and manufacture. Authoritative, evidence-based and standardized recommendations emanate from the Expert Committee which consists of a large number of global experts from many countries, organizations and disciplines.

The 58 th Report briefly describes and updates developments in a number of items, their biological standardization, moving from biological to chemical reference materials, development of tools for assessing implementation of WHO standards, nomenclature of biological medicines, regulatory evaluation of "biosimilars" and WHO Blood Regulators Network. It includes chapters on manufacture and quality control of biologicals including a number of vaccines cell substrates, in vitro diagnostic devices, quality and safety of antisera and transmissible spongiform encephalopathies. Detailed recommendations on Japanese encephalitis (JE), influenza and meningococcal vaccines are provided in three annexes.

Recommendations on inactivated JE vaccines for human use are comprehensive. The virus strains used in vaccines include Nakayama, Beijing-1, Beijing-3 and SA14-14-2. The classical mouse brain substrate is increasingly being replaced by vaccine-quality Vero cells and primary hamster kidney cells (confined to Chinese products). Pages 21 and 57 to 115 contain detailed recommendations of biological standardization of inactivated JE vaccines - ranging from pre-clinical to finished product; these details are essential both for manufacturers and National Regulatory Authorities alike. In Annex 1 there are detailed recommendations for manufacturing; non-clinical evaluation (studies on immunogenicity, active protection, passive protection and toxicology); clinical evaluation (clinical studies, immunogenicity, safety, and post-licensure investigations); and the role and responsibilities of National Regulatory Authorities. These recommendations are timely and essential for India for two reasons: India's own inactivated JE vaccine is under indigenous development and the Government of India has introduced JE vaccination in all JE-prone districts in India. However, we use the live attenuated SA-14-14-2 strain vaccine made in China. We will have to wait for recommendations on biological standardization on live JE vaccine in a future Technical Report from WHO. Indian National Regulatory Authority can provide much needed guidance on this from its own journey during and after the registration of this vaccine in India since 2005.

The recommendations for post-licensure investigations are currently highly relevant for India. On vaccine effectiveness the Report states: "Because it is not feasible to study the protective efficacy … before licensure, it is highly desirable … to assess its effectiveness by disease surveillance after its introduction into a vaccination programme". This recommendation ought to be put in practice with quality surveillance in India. "[Coordinated] national or regional public health networks and infrastructures are necessary to ensure that cases are reliably detected". India urgently needs such a public health infrastructure. "Manufacturers should discuss arrangements for continuous disease surveillance and the potential for estimating effectiveness with the relevant national regulatory authorities…" In our case the manufacturer is in China; the vaccine is already in wide use; the onus of monitoring effectiveness (and safety and antibody persistence) thus falls on the vaccine-delivery agency, namely Immunization Division of the Government of India.

WHO experts had been providing recommendations on pandemic influenza vaccines over several years prior to the 2009 pandemic. Although this book was published in 2011, the Expert Committee meeting was conducted in October 2007. Pages 21-22 and 117-225 are devoted to vaccines against novel and pandemic strains of influenza, in anticipation. To read the detailed recommendations in preparation for a pandemic is educational. These were undoubtedly helpful in developing and passing regulatory requirements of several vaccines against pandemic influenza in 2009. That the pandemic was milder than anticipated does not detract from the thoroughness of preparations by WHO and the Expert Committee.

Meningococcus C is prevalent in Europe and United States, but not in India. After conjugated meningococcal C vaccine became available, detailed recommendations had been made in earlier Expert Committee meetings and published in earlier Technical Reports. Two statements on page 228 are of interest to vaccinologists. Assay of functional antibody (bactericidal) elicited in response to vaccination is well established and widely accepted as a marker for protection from invasive meningococcus C disease. Therefore, it is not necessary (nor is it ethical) to conduct studies to measure the protective efficacy (in comparison with unvaccinated control) of any new vaccine. Furthermore, immune responses to carrier proteins are not much discussed elsewhere. The Expert Committee noted that immune responses are induced against carrier proteins also, but their magnitude is sub-optimal for protection by themselves.

Guidelines for cell substrates are periodically revised. The last full revision of WHO requirements for the use of animal cells as substrates for production of biological was adopted by the Expert Committee in 1996 and published in 1998 (TRS No 878). Since then, a huge volume of work has progressed and the subject is due for revision jointly by WHO and International Association for Biologicals. The present Report addressed replacement of seed stock of human diploid fibroblast MRC-5 cells. The original seed stock at population doubling level 7 (PDL-7) was established in the 1960s in the United Kingdom, from where it is released for use in the development of a number of viral vaccines. As stocks of the seed lot is depleting, a new seed lot was approved for ensuring continuity of supplies of this important cell substrate. The new seed lot will be at PDL-12. The Expert Committee has recommended the establishment of a formal monitoring programme, under the auspices of a WHO Working Group, to oversee the two major cell substrates for vaccine production, MRC-5 and WHO Vero 10-87 cell banks.

Several priority projects have been approved for continuing the agenda on WHO Biological Reference Preparations for Blood Safety-related in vitro Diagnostic Tests. As Reference Preparation batches are nearing exhaustion, replacements are recommended for anti-HBS immunoglobulin, HCV RNA, B19V DNA and anti-syphilitic Standard. New recommended Reference Preparations include several in relation to HIV 1 and 2, HBV, HCV, HTLV 1/2, Plasmodium species and Trypanosoma cruzi.

New International Reference Materials have been approved for antibiotics (Amphotericin-B and Nystatin) and toxoids (tetanus and diphtheria). Proposals under review include replacement of International Standard for monkey neurovirulence test of poliovirus Sabin type 1; Anti-measles serum for ELISA; Anti-human papillomavirus type 16 serum; Protein C concentrate; Heparin, low molecular weight; Anti-thrombin, concentrate, human; Anti-human platelet antigen 1-a; and Tissue plasminogen activator antigen in plasma. Other items covered are parathyroid hormone, recombinant, human; Tumour necrosis factor-related apoptosis-inducing ligand; and standards for stem cells.

The 58 th Report is an essential companion and reference book for all scientists involved in biomedical research in the areas of clinical diagnostics, manufacture of biological and the vaccine community - vaccinologists, vaccine trial personnel, vaccine researchers, developers and manufacturers as well as the National Regulatory Authority, Immunization Division, and National Technical Advisory Committee on Immunization.


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