Drug Regulators, EMA (EMEA), Publish Draft Guidance on the Requirements for Quality Documentation Concerning Biological Investigational Medicinal Products in Clinical Trials

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This guideline outlines the requirements for the data to be presented on the biological, chemical and pharmaceutical quality of Investigational Medicinal Products (IMP) containing biological / biotechnology derived substances. In the EU, applications to conduct clinical trials are required to be submitted to the competent authority for approval prior to beginning a clinical trial in separately in each member state in which the trial is proposed to take place. Approval of trials is the responsibility of each involved Member State. This guideline aims to ensure harmonised requirements for the documentation to be submitted throughout the European Community. Available guidelines on the quality of biological / biotechnological medicinal products mainly address quality requirements for marketing authorisation applications. This guidance may not be fully applicable in the context of a clinical trial application; however the principles outlined in these guidelines are applicable and should be taken into consideration during development. A guideline on virus safety (EMEA/CHMP/BWP/398498/05) giving advice on the requirements for viral safety of IMP is available. The guideline on Strategies to Identify and Mitigate Risks for First-In-Human Clinical Trials with Investigational Medicinal Products (EMEA/CHMP/SWP/28367/07, current version) is also relevant. Assuring the quality of biological medicinal products is challenging, as often they consist of a number of product variants and process related impurities and it is difficult to predict the safety and efficacy profile of these variants and process related impurities. Unlike chemical entities, toxic impurities are generally not an issue, and the safety issues are more often related to the mechanism of action of the biological product or to immunogenicity. In the context of an overall development strategy, normally several clinical trials, using products from different versions of the manufacturing process, will be initiated to generate data to support a Marketing Authorisation Application. The objective of this document is to address the quality requirements of an investigational medicinal product for a given clinical trial, not to provide guidance on a Company’s overall development strategy for a medicinal product. Nevertheless, for all clinical development phases, it is the responsibility of the applicant (sponsor) to ensure protection of the clinical trial subjects using a high quality IMP that is suitable for its intended purpose, and to appropriately address those quality attributes that may impair patient’s safety (e.g. microbiological aspects, contamination, dose). There are clear differences between the requirements for a dossier for a clinical trial and a marketing authorisation dossier. Whilst the latter has to ensure a consistent, state-of-the-art quality of a product for widespread use in patients, information to be provided for an IMP should mainly focus on those quality attributes related to safety aspects. The extent of the information required for an IMP Dossier (IMPD) should take into account the nature of the product, the state of development / clinical phase, patient population, nature and severity of the illness as well as type and duration of the clinical trial itself. When compiling the quality part of the IMPD for phase II and phase III clinical studies, the wider exposure of patients to the product and the progressive product knowledge have to be taken into account compared to phase I clinical studies. Based on the diversity of products to be used in the different phases of clinical trials, the requirements defined in this guideline can only be taken as illustrative and cannot be expected to present an exhaustive list. IMPs based on innovative and/or complex technologies may require a more detailed data package for assessment.