The International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use was established in 1990 as a joint regulatory/industry project to improve, through harmonization, the efficiency of the process for developing and registering new medicinal products in Europe, Japan and the United States, in order to make these products available to patients with a minimum of delay. ICH is a joint initiative involving both regulators and industry as equal partners in the scientific and technical discussions of the testing procedures which are required to ensure and assess the safety, quality and efficacy of medicines.
The focus of ICH has been on the technical requirements for medicinal products containing new drugs. The vast majority of those new drugs and medicines are developed in Western Europe, Japan and the United States of America and therefore, when ICH was established, it was agreed that its scope would be confined to registration in those three regions. WHO has the status of observer at the ICH meetings representing the interests of non-ICH countries.
To date, ICH has produced more than 45 guidelines; most of them focus on detailed technical requirements to evaluate the quality, safety and efficacy of products before they are authorized for the market in the three regions.
In addition to the initial objectives, the fifth ICH meeting held in Tokyo in May 2001 identified post-marketing surveillance as one of the future objectives for the forum.
Three topics were identified as being possible for harmonization in ICH guidelines: Periodic Safety Update Report (PSUR), Case Management Practices, and Roll out of New Drug Products
These and problems related to these issues were discussed in depth during an informal meeting of the ICH in Brussels, on 4-5 February 2002.
1) Periodic Safety Update Report (PSUR)
The ICH guideline, ‘Periodic Safety Update Reports for Marketed Drugs’ (Topic E2C) was developed based on the final report of CIOMS (Council for International Organizations of Medical Sciences) Working Group and finalized in the year 1996 to harmonize the frequency of submission and content of safety updates, to avoid duplication of effort and to ensure that important safety data are submitted with consistency to regulatory authorities. Although this guideline describes the format and content of PSUR, there are regional differences in the implementation and utilization of PSUR which poses regulatory difficulties. It is important to harmonize the understanding and development of the PSUR guidance so that, as far as possible, all regions adopt similar reporting procedures, in terms of frequency of reporting, quality of contents etc. This in turn would allow more harmonized regulatory control of drug products.
2) Case Reporting
The Extension of ICH guideline on ‘Clinical Safety Data Management: Definitions and Standards for Expedited Reporting’ (Topic E2A) to post-marketing should include the proposals contained in the CIOMS V report that addresses the current challenges in pharmacovigilance with some pragmatic solutions. Emphasis should be laid on quality and not the quantity of reports generated and a harmonized core data sheet should be employed to distinguish between the expected and the unexpected adverse reactions with a product.
3) Safe Rollout of New Drug Products
Safety concerns during the early phase of global marketing of new drug products should be addressed to improve product and public safety. Guidance on study design (criteria for post-marketing commitments) including post-marketing studies, based on pre-marketing data, should be explored. Safety studies on the suspected safety issues at the time of authorization (for example, drug interaction information, pediatric information) should be dealt with in a careful rollout phase that would include risk communications/interactions with health professionals.
A report of this discussion was received by the Steering Committee of the ICH. It agreed to launch two new topics: the development of a further guidance on Periodic Safety Update Reports (PSURs), which will be an addendum to the existing E2C guideline, and a guidance on Good Case Management Practices which will be a follow-up of the E2A guideline. Both are expected to be reviewed in draft form at the next meeting in Washington DC in September 2002. Further discussions are also planned on a third item: Early Phase Post-Marketing Vigilance.
Partnership with WHO
The WHO with its collaborating centre, the Uppsala Monitoring Centre, is the only official body with a truly independent and global perspective on drug safety. ICH’s continuing collaboration with WHO, in a complementary fashion, is essential particularly as ICH moves into the area of pharmacovigilance. WHO will continue as an observer at the ICH meetings on any issue related to pharmacovigilance and all ICH countries should be encouraged to participate more actively in the WHO Programme for International Drug Monitoring. A briefing paper on the activities of the WHO Programme for International Drug Monitoring and a discussion paper on WHO’S activities in the area of pharmacovigilance are available from QSM/EDM, WHO.