Biotherapeutic products

Biotechnology describes biological processes that have been engineered. The most common industrial application of biotechnology is preparation of biological products from genetically engineered bacteria, yeast, fungi, or cells.

Cytokines, growth factors, hormones, and other regulatory peptides and proteins can be the examples of the products. They were originally extracted from tissues and secretions, often of human origin. With the advent of recombinant DNA technology, the preparation of pure, highly concentrated materials became possible, fundamentally changing the manner in which biological materials like these were produced and standardized. These complex products bring up new quality concerns such as the potential consequences of using genetically modified organisms, but they also provide hope of curing life-threatening diseases that are now currently untreatable.

Biotherapeutic products derived from recombinant DNA technology such as interferons, interleukins, and growth factors have provided a major advance in the safety and effectiveness of therapeutic peptides and proteins, and they have a successful record in treating many life-threatening and chronic diseases. Since contamination with unwanted pathogens can be greatly reduced and production volumes are expanded by the developed biotechnology, many more patients have increased access to biotherapeutic products. Technical issues such as the potential immunogenicity of active substances produced under differing manufacturing conditions must also be considered.


Control of chronic diseases is a major challenge for public health systems in both developed and developing countries. Biotherapeutic products have been successful in treating many life-threatening chronic diseases. However, the cost of innovative biotherapeutics has often been prohibitive, thereby limiting their use, particularly in developing countries.

The expiration of the patents and/or data protection for the first major group of originator's biotherapeutic products such as insulin, human growth hormone and erythropoietin has ushered in an era of products that are designed to be 'similar' to a the original licensed products which might contribute to increased access to these products at an affordable price.

The clinical experience and established safety profile of the original products should contribute to the development of similar biotherapeutic products (SBPs). The amount of and extent of data required for the licensing of SBPs are likely to be less than are normally required for the originator products. However, at the level of quality, the comparability data can be considered as additional data, over and above what is normally required for the originator product developed as a new and independent product; this is the basis for reducing the requirements for nonclinical and clinical data.

In addition, it is important to note that a biotherapeutic product that is not shown to be similar to the original product, i.e. its reference biotherapeutic product as indicated in WHO guidelines should neither be described as "similar" nor called SBP.


Written Standards

Biotherapeutic products

Guidelines for pharmaceutical and biological products prepared by recombinant DNA technology were adopted in 1983 and updated in 1990. Guidelines for human interferons prepared from lymphoblastoid cells and human interferons made by recombinant DNA technique have also been established.

Similar biotherapeutic product

As an increasingly wide range of SBPs are under development or are already licensed in many countries, a need for guidelines for their evaluation and overall regulation was formally recognized by the WHO in 2007. Guidance for the development and evaluation of well-established and well-characterized biotherapeutics was developed and adopted by the Expert Committee on Standardization in 2009. The recombinant analogues of vaccines and plasma derived products are excluded from the scope of the document. The intention of this document is to provide globally acceptable principles for licensing biotherapeutic products that are claimed to be similar to biotherapeutic products of assured quality, safety, and efficacy that have been licensed based on a full licensing dossier. On the basis of proven similarity, the licensing of a SBP will rely, in part, on non-clinical and clinical data generated with an already licensed reference biotherapeutic product (RBP).

Reference materials

WHO reference materials for cytokines/growth factors and endocrinological substances are available to qualified applicants:


Biotherapeutic products

Similar biotherapeutic product

WHO/KFDA Joint Workshop on implementing WHO guidelines on evaluating similar biotherapeutic products, Seoul, Republic of Korea, 24-26 August 2010

The first workshop on Implementing "WHO Guidelines on Evaluating Similar Biotherapeutic Products (adopted in 2009)" into the regulatory and manufacturers practice at the global level was held on 24–26 August 2010 in Seoul, Republic of Korea. The workshop featured speakers from regulatory agencies from various countries, clinical and scientific experts, representatives from the biopharmaceutical industry and WHO. As the outcomes of the workshop, 26 peer reviewed manuscripts have been published as a special issue in Biologicals in September 2011. The online published articles in this issue are freely accessible to the public at the link below:


Last update:

8 October 2013 16:16 CEST