Biological products, including vaccines, are distinguished from chemical pharmaceuticals by being derived from living organisms with a molecular composition too complex to be defined by physical or chemical means. In addition, the inherent variability of living organisms, the potential for contamination of materials with agents coming from starting materials or the environment, require special quality control and quality assurance mechanisms.
While the manufacturer has the primary legal responsibility for the safety, quality, and efficacy of the products they sell, the National Regulatory Authorities (NRAs), in particular in the countries where vaccines are manufactured, play a critical role in assuring product quality. NRAs are responsible for the review of licensing applications, lot release, and monitoring the performance of the product in their country. The scientific competence and harmonized practices of NRAs have become essential components of the quality assurance of products moving in international trade.
As part of its program of biological standardization, WHO documents the current regulatory practices for both general and product-specific topics to support national regulatory authorities and manufacturers so that the quality of all vaccines is of assured quality.
Guidance on regulatory functions
WHO first adopted recommendations for the national control of vaccines and sera in 1981. This regulatory oversight of biological medicinal products was revised in 1992 to include regulatory procedures for both manufacturing and importing countries, the function of the national control laboratory, and post-licensing monitoring. This guidance was further updated in 1994 to include recommendations for newly developing regulatory authorities.
Biological products, regulation and licensing
- Guidelines for national authorities on quality assurance for biological products; Adopted at ECBS 1991, TRS No. 822, Annex 2
- Regulation and licensing of biological products in countries with newly developing Regulatory Authorities; Adopted at ECBS 1994; TRS No 858, Annex 1
Lot release of vaccines
Lot release is a post-licensure activity conducted by national authorities on batches (lots) of vaccines before they are authorized for sale or use. While lot release has traditionally been considered to be an essential regulatory function for vaccines, it is practiced worldwide to different degrees.
Independent lot release involves the confirmation that each lot meets the specifications in the approved marketing authorization for the product and includes, as a minimum, a review of summary protocols of the results on quality tests conducted by the manufacturer. In some situations, re-testing of some critical parameters by the National Control Laboratories of the regulatory authority may be appropriate. Challenges include the increased volume of vaccines now licensed and in use, the increasing complexity of new vaccines requiring more sophisticated (and expensive) test protocols, and the increasing globalization of the industry. These factors create an increasing burden for NRAs and for the industry, and they are a particular problem for developing countries with limited regulatory experience and resources.
Guidance for National Control Laboratories
The duties and responsibilities of National Control Laboratories were described in 1991, and updated guidelines on the independent lot release of vaccines by regulatory authorities adopted by ECBS in 2010.
- Guidelines for national authorities on quality assurance for biological products, TRS No. 822, Annex 2
- Guidelines for independent lot release of vaccines by regulatory authorities, Technical Report Series, 978, Annex 2
- WHO/Health Canada Consultation on Vaccine Lot Release, Ottawa, Canada, 28 February-1 March 2007
Molecular methods in the control of vaccines
With the advent of molecular biotechnology, there are increasing uses of molecular methods for the characterization and QC of vaccines. The World Health Organization Expert Committee on Biological Standardization (WHO ECBS) has put an emphasis on harmonization of methods used in quality control and manufacturing of biological, and of vaccines in particular.