In the EU
For clinical trial approval, a Clinical Trial Application (CTA) must be submitted to regulatory bodies called Competent Authorities. A Research Ethics Committee (REC) also reviews the protocol and provides a positive or negative opinion. This is to ascertain that the proposed research respects the dignity, rights, safety and well-being of the participants. Pre-submission meetings are possible for companies who wish to obtain agency advice prior to submission. Companies must wait for approval by both the Competent Authority and the REC prior to initiating any clinical trials. Further information can be found in the guidance document released in 2010 by the European Commission detailing the request to the competent authorities for CTAs.
In terms of dossier content, the EudraCT form, the protocol, the investigator brochure (IB) and the Investigational Medicinal Product Dossier (IMPD) are the main components of the CTA.
EudraCT is a database of all clinical trials which commenced in the community from 1st May 2004, and also includes clinical trials linked to European paediatric drug development. Before any functionality of EudraCT* can be used for a given clinical trial, a EudraCT number must be created to provide a unique reference for that trial. Once this number is obtained, the sponsor can complete the EudraCT application form (creation of XML/PDF files of clinical trial applications).
The protocol is defined as per the international guideline ICH E6 as a document that describes the objective(s), design, methodology, statistical considerations and organization of a trial. The protocol also usually gives the background and rationale for the trial, but this could be provided in other protocol referenced documents.
The Investigator’s Brochure (IB) is defined as per ICH E6 as a compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of the investigational product(s) in human subjects.
The Investigational Medicinal Product Dossier (IMPD) is a document divided into four sections. It provides information on (1) the quality, manufacture and control of the IMP, (2) the non-clinical studies conducted with the IMP, (3) the clinical use of the IMP and (4) the overall risk / benefit assessment of the IMP in the proposed trial.
BlueReg has extensive experience of preparing and submitting CTAs in accordance with the current directive and additionally through the new pilot schemes in support of the upcoming Clinical Trial Regulation. BlueReg has the expertise to support agency pre-submission meetings, the preparation, review and submission of your application to the Competent Authorities, as well as address and minimize the risks of any validation queries or grounds for non-acceptance that may arise from the review of your application. Following submission, BlueReg will be pleased to support with amendments, agency responses, end of trial notifications or submit your results in the EudraCT database as per European policy 0070. BlueReg has the capability to provide full project management support for single and multi-market CTA submissions.
In the USA
The Investigational New Drug (IND) application must contain information in three broad areas:
– Preclinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans. Also included are details of any previous experience with the drug in humans (often foreign use).
– Manufacturing Information – Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product. This information is assessed to ensure that the company can adequately produce and supply consistent batches of the drug.
– Clinical Protocols and Investigator Information – Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks.
Once the IND application is submitted, the sponsor must wait 30 calendar days before initiating any clinical trials. During this time, the FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk. 21 CFR 312.82 allows meetings with FDA reviewing officials at the pre-IND stage and again at the End-of-Phase l (EoP1), at the sponsor’s request. The purpose of the pre-IND meeting is to review and agree on animal study designs needed to initiate human testing, to discuss Phase 1 trial scope (or further development trials) and design and confirm the IND content and format.
The purpose of the EoP1 meeting is to finalize the design of controlled Phase 2 trials and to ensure the data will be sufficient to support marketing approval.
BlueReg has extensive experience of preparing and submitting IND applications. BlueReg has the expertise to support the preparation, review and submission of your IND application to the US FDA, as well as providing support to prepare and conduct pre-IND and EoP1 meetings.