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Hosted jointly by the European Agency for the Evaluation of Medicinal Products (EMEA), and EFPIA, the ICH Steering Committee and its Expert Working Groups met in London 6-7 November 1996, and made further significant progress towards the initial targets for the harmonisation of technical requirements for medicinal products in the European Union, Japan and the USA.
With less than a year before the Fourth International Conference on Harmonisation, 16 - 18 July 1997, Brussels, a major item on the Steering Committee's agenda was the programme for the Conference. ICH 4 will be a major event marking the completion of the initial targets for harmonisation of requirements for the technical and scientific data which is needed to demonstrate the safety, quality and efficacy of new medicinal products in order to meet the registration requirements in the European Union, Japan and the USA. Participants in the Conference will include senior politicians, government officials and chief executive officers of companies and over a thousand participants are expected.
Following the established working methods which are an essential feature of the success of the ICH Process, joint regulatory/industry Expert Working Groups met, at the time of the ICH Steering Committee to progress the technical harmonisation topics under discussion. Five finalised tripartite harmonised ICH Guidelines were adopted by the Steering Committee and recommended for implementation in the European Union, Japan and the USA. These include guidance on clinical safety reporting and extensions to recommendations on quality evaluation through stability and impurity studies. Five draft texts on which scientific consensus has been reached were also released for formal regulatory consultation (Step 2 of the ICH Process). These include the design of clinical studies, safety studies on biotechnological products, the non-clinical testing required before undertaking studies in humans, and controls on solvent impurities in drug substances.
The Steering Committee also confirmed a decision made by correspondence in early October 1996, to release for consultation, a guideline on specific aspects of genotoxicity testing. This brings the total number of finalised ICH guidelines to 24 with an additional 9 under regulatory consultation and means that the process is well on target to achieve the harmonisation objectives set for ICH 4.
As a follow-up to the Survey on Utilisation of the ICH Guidelines which was conducted prior to the Third International Conference on Harmonisation (ICH 3), Japan, a second industry survey will be conducted to allow the Steering Committee to make a further assessment of the use and impact of the harmonised guidelines. An analysis of the results and comparison with the results from the 1995 survey will be made as part of the preparations for ICH 4.
The Steering Committee also received a report on the "diagnostic phase" of a Special Project to examine the feasibility and impact of harmonising the format and content of registration applications suitable for submission in all three regions. A timetable for action was approved by the Steering Committee in which industry experts in the three regions will take the lead in preparing a more detailed analysis of the similarities and differences in the way in which data are presented in the EU, Japan and the USA, with a view to developing a Common Technical Document.
7 November 1996, London
Clinical Safety Data Management
The tripartite harmonised ICH
guideline on Periodic Safety Update Reports (Code E2C) gives
guidance on the format and content of safety updates, which need to be provided
to regulatory authorities, at intervals, after products have been marketed. The
guideline is intended to ensure that the world-wide safety experience of a
medicinal product is provided to authorities at defined times after marketing
with maximum efficiency and avoiding duplication of effort.
Quality of Medicines
A tripartite harmonised ICH guideline on
Photostability Testing (Code Q1B) was adopted and will
form an annex to the main stability guideline. This gives guidance on the basic
testing protocol required to evaluate the light sensitivity and stability of new
drugs and products.
A further extension to the ICH Stability Guideline on Stability Testing for New Formulations (Code Q1C) defines the circumstances under which reduced stability data can be accepted, at the time of filing an application, in the case of new formulations of already approved medicines.
A major ICH guideline on Impurity Testing for New Drug Substances was adopted in March 1995 and has now been complemented by a guideline on Impurities in Dosage Forms (Code Q3B) which makes recommendations on the content and qualification of impurities that may arise in the drug products due to degradation of the active ingredient or interaction with other components.
Requirements for validation of the test procedures used to demonstrate the quality of medicinal products are required throughout the development and manufacturing process. An earlier guideline which harmonised the definitions and terminology has now been supplemented by an ICH Guideline on Validation of Analytical Methods: Methodology (Code Q3B) which extends the previous text to include the actual experimental data required, along with the statistical interpretation, for the validation of analytical procedures
Clinical Testing for Efficacy
An important draft guideline on
the design of clinical trials reached the stage where there is scientific
consensus among the experts from the six ICH parties and these will now be
released for wider regulatory consultation, under Step 2 of the ICH
Process. This is on General Considerations for Clinical Trials
(Code E8) and sets out the general scientific principles for the conduct,
performance and control of clinical trials. The guideline addresses a wide
range of subjects in the design and execution of clinical trials and in the
evaluation of the scientific validity of protocols
Safety Studies
Consensus was reached on a draft guideline on
Safety Studies for Biotechnological Products (Code S6). This
highlights the differences between the toxicity testing which is appropriate for
new chemical substances and products of biotechnology and covers the use of
animal models of disease, determination of when genotoxicity assays and
carcinogenicity studies should be performed, and the impact of antibody
formation on duration of toxicology studies.
A draft Addendum to the existing ICH Guideline on Dose Selection for Carcinogenicity Studies (Code S1C rev) has been released for consultation and includes additional recommendations on the criteria for selecting the upper dose limits for carcinogenicity studies.
The Steering Committee also noted the release consultation, in October 1996, of the ICH Draft Guideline on Genotoxicity: Standard Battery Tests (Code S2B) which was agreed under the procedure for clearance by correspondence which has been adopted by the Steering Committee. The Guideline addresses two fundamental areas of genotoxicity testing: the identification of a standard set of assays to be conducted for registration, and the extent of confirmatory experimentation in any particular genotoxicity assay in the standard battery.
Non-clinical Testing and Clinical Studies
Consensus has been
reached on a draft guideline on Non-Clinical Safety Studies for the
Conduct of Human Clinical Trials for Pharmaceuticals which addresses
principles for the development of non-clinical strategies on the timing of
toxicity studies in relation to the conduct of clinical trials. The draft text
represents an important step forward on requirements for the different phases of
clinical development but it is recognised that there remain some further
important issues to be resolved, within this topic.
Quality of Medicinal Products
A consensus draft was released for
consultation on Impurities: Residual Solvents (Code Q3B)
which recommends the use of less toxic solvents in the manufacture of drug
substances and dosage forms, and sets pharmaceutically acceptable limits for
residual solvents (organic volatile impurities) in drug products. The draft
guideline has been released for consultation under Step 2 of the ICH
Process
See ICH Topics for a full listing of ICH Guidelines and their Status.
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