Pharmacopoeial Harmonization - Microbiological Examination of Non-sterile Products
- Implementation deadlines are close
- Lab methodologies will need re-validating
- Media manufacturers need to revise product range
The deadlines for regional implementation are now imminent, however pharmacopoeial harmonisation, as a concept, is not new. From the informal discussions within the pharmaceutical industry over 20 years ago, came the formation, in 1989, of the Pharmacopoeial Discussion Group (PDG), consisting of representatives from the pharmacopoeial authorities of Japan, USA and Europe (Britain withdrew in 1992 having aligned with Europe).
The goal was to attempt to harmonize the differing standards and specifications contained within the regional compendia. It is to such specifications that the true test of harmonization is applied, i.e. for a given set of analytical procedures and acceptance criteria (APAC) the same accept/reject decision should be made regardless of geographical location. In terms of patient welfare this is a significant progression, as the extra work (and cost) involved in the current licensing of pharmaceuticals between jurisdictional boundaries inevitably results in delays to the availability of medicines.
At about the same time as the formation of the PDG and, recognizing the need for a joint regulatory-industry forum, the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) was formed in April 1990. Members of the ICH are as follows:
- European Medicines Agency (EMEA)
- European Federation of Pharmaceutical Industries and Associations (EFPIA)
- Ministry of Health, Labour and Welfare, Japan (MHLW)
- Japan Pharmaceutical Manufacturers Association (JPMA)
- US Food and Drug Administration (FDA)
- Pharmaceutical Research and Manufacturers of America (PhRMA)
Also present at ICH meetings are the organizations acting as observers and providing the link to non-ICH regions, these include:
- World Health Organization (WHO)
- International Federation of Pharmaceutical Manufacturers and Associations (IFPMA)
The PDG is not a member of the ICH, however as both organizations operate in a similar process driven way, they have evolved to meet in parallel and report freely. It is recognized that the PDG is the primary source of harmonized texts. The IHC, through its expert working groups (EWG) then facilitates the regulatory involvement and approval. The Q4B EWG was specifically set up to address the regulatory acceptability of pharmacopoeial proposals.
Microbiology - technical practicalities
In terms of microbiology, the harmonized chapters closest to implementation are those associated with the testing of non-sterile products. Formerly the Microbial Limits Tests, the harmonized chapters now refer to Microbial Enumeration Tests (USP <61>,
EP 2.6.12); Tests for Specified Micro-organisms (USP <62>, EP 2.6.13); and Microbiological Quality of Non-Sterile Pharmaceutical Products (USP <1111>, EP 5.1.4). Implementation dates have been pushed-out from 2007 to 2009 or 2010 depending
upon region but allowance is made for the early adoption of harmonized chapters in the development of new products.
The microbial enumeration tests are those designed to report a count for bacteria, yeasts and filamentous fungi. Methodology can be pour plate, surface spread plate or, new to the harmonized chapter, membrane filtration.
Incubation times and temperatures will change from some current regional chapters as well as detail in the preparation of samples (suitability test), removal of anti-microbial activity, preparation of inoculum and the growth promotion requirements
are better defined.
The tests for specified micro-organisms will result in changes to incubation times and temperatures; the choice of species to be used, media Q.C. requirements and the formulation growth media used. Some regions will have the option of re-testing removed
in the harmonized chapters.
All the potential changes will result in re-validation of methodologies and media used. This will be a huge challenge to laboratories with implementation deadlines less than a year away. The impact will also be felt by suppliers to the industry in
terms of re-formulation of media and changes to Q.C. procedures and also those contract laboratories providing services to the pharmaceutical industry.
As harmonization continues and implementation begins, the process of licensing of pharmaceuticals should become independent of geographical location, i.e. inter-changeability of licences within the ICH regions.
A more streamlined development process, linked to international co-operation in licensing should dramatically lower the cost of bringing medicines to the market. It should also reduce the time taken to bring new and current medicines to areas of the world where they are badly needed.
If pharmacopoeial harmonization delivers the above benefits then, through the efforts of the PDG and ICH, the achievement of what may have begun as an unrealistic goal will transform the reality of human healthcare in the 21st century.