Biotherapeutic products

Biotechnology describes biological processes that have been manipulated or modified in some way through modern science.  A major industrial application of biotechnology is in the development and preparation of biological medicinal products using genetically engineered bacteria, yeast, fungi, cells or even whole animals and plants. 

Such products include cytokines, growth factors, hormones, interferons and other regulatory peptides and proteins, as well as products from novel cell lines. Some of these biological medicines were originally extracted from tissues and secretions, often of human origin and in relatively small amounts. With the advent of recombinant DNA technology, the preparation of large amounts of highly purified and characterized materials became possible, including products intentionally modified by pegylation or changes in DNA sequences,  fundamentally changing the manner in which biological substances like these were produced and standardized. However, these complex products raised new quality concerns – such as the potential consequences of using genetically modified cells – but they also provided hope of successfully treating life-threatening diseases that were previously completely untreatable. 

Regulatory concepts were put into place at a very early stage in the development of these products and these have been instrumental in establishing the quality, safety and efficacy of biotherapeutics which now play a major part in today’s medical practice.

Biotherapeutic Product Standardization

Written Standards

WHO published ‘Quality control of biologicals produced by recombinant DNA techniques’ in 1983 (Bulletin of the World Health Organization, 61). The article reviewed the application of recombinant DNA technology to the production of medically useful biologicals and outlined the tests that would be appropriate for controlling the safety and efficacy of these products. In particular, it aimed to inform scientists and administrators in countries not involved in the production of such biologicals of the problems in their control and use.

It was recognized that rDNA technology was a rapidly evolving field and that it was important that a flexible approach to the control of these products be adopted so that requirements could be modified in the light of experience of production and use, and the further development of new technologies. The 1st guidelines for such products were developed in 1991 and superseded those published in 1983. 

The replacement of WHO TRS No. 814 was adopted by the WHO ECBS in its 64th meeting in 2013 and will be published soon. It is based on experience gained over three decades of the technically demanding field. It provides the principles not only for assuring the quality of such products but also for evaluating their safety and efficacy.

Reference materials

International  Reference Standards are available to qualified applicants:

International Reference Preparations Catalogue