As the number of available techniques to facilitate the study of human genomics has led to an exponential increase in investigation into genomic bio markersthe diagnosis of specific diseases. The AMA has decided that a guidance would be required to assist companies in implementing these technologies into clinical drug development.
These techniques are frequently used patient selection stratification or treatment strategies of patient groups, and the EMA is concerned the appropriate steps are not been taken hence the publication of this guidance.
excerpt from guidance
full text here
The availability of techniques that facilitate study of the human genome has led to an exponential increase in investigation into genomic biomarkers (GBMs) for diagnosis of specific diseases, as a marker of response to treatment or of prognosis. Theoretically genomic BMs should offer the advantage of improved specificity and reduction of heterogeneity that is an integral part of phenotypic population grouping. This is very attractive in drug development because of their potential ability to reduce drug attrition and to reduce overall developmental costs, that are achieved through improved understanding of the mechanism of drug action, predict adverse events to individual drugs or as a group effect (e.g. CYP poor metabolisers), and use of novel development strategies in pre-clinical and clinical phases.
In clinical drug development, GBMs may aid and influence a wide range of areas: patient selection, stratification of treatment strategies or patient groups, early evaluation of treatment effect including adverse reactions, and prognosis. There is opportunity for the GBMs to be used for pre-defined subgroup analysis or to enable novel trial designs that might not be possible otherwise due to heterogeneity of clinical characteristics.1,2 GBMs could also play a valuable role in the risk management strategies including risk minimisation by aiding a priori identification of patients susceptible to develop severe adverse effects (e.g. HLA B*- 5701 and use of Abacavir).
While a number of these aspects are discussed in many publications in the recent years, specific aspects relating to drug development and discussion on regulatory considerations have lagged behind. The intention of this paper is therefore to provide an evidence based consideration of GBM related issues from a regulatory viewpoint. Mention is also made of co-development of a GBM diagnostic test for use with a medicinal product.
The principles established in the reflection paper are based on the experiences gained from the evaluation of dossiers within the EU regulatory processes —including marketing authorisation applications reviewed by CHMP, the scientific advice documents and additionally, the voluntary genomic data submission meetings (briefing meetings) at the Pharmacogenomic Working party (PGWP) over the last several years. It is expected that these principles guide both industry and the assessors in the evaluation of such biomarkers in relation to the qualification process in the context of clinical development (BM qualification in EU) and the assessment of benefit: risk balance of medicinal products or selection of the relevant target population. The paper should also be read in conjunction with other relevant guidelines listed at the end of the documents under section “Other aspects”.
Development of GBMs and diagnostic tests may involve additional development of tests (companion diagnostics) or specific kits (platforms) to detect for the presence or absence of the GBM. Issues relating to these are outside the scope of this paper but a short discussion is included. The readers are referred to appropriate guidelines/ papers for details (see section on other aspects).
