Throughout the product development cycle and across all the therapeutic areas, there are many common reporting components required by regulators, regardless of geography. In addition there are regulator specific document and data requirements that may need consideration if products are to be marketed in specific regions.
Effective Medical helps your business throughout all phases of drug development and lifecycle management and has expertise in the requirements of all main regulatory regions.
Our writers and consultants work with your teams to ensure the creation of optimal regulatory and pharmacovigilance documents to the formats and standards expected by regulators, minimising potential delays caused by errors and inaccuracies. Additionally we can advise on geographic-specific and general regulatory obligations.
Quality is essential, and therefore we ensure all of our outputs receive a full in-house quality control review before release to client, including checks for language, data accuracy and adherence to client requirements, in addition to a thorough review for scientific accuracy via a senior member of the writing team.
The following examples outline some of the regulatory documents on which Effective Medical often provides writing expertise. Click here for further details of pharmacovigilance documents and services.
Clinical Study Protocol (CSP)
Every clinical investigation begins with the development of a CSP, which contains key information on how a trial will be conducted and ensures the safety of the subjects and integrity of the data collected. As data in the clinical development programme evolves then so will CSPs by way of protocol amendments to ensure accuracy of trial conduct. Effective Medical develops the CSP working alongside in-house teams (including clinical, safety and statisticians) to deliver scientifically robust documents.
Informed Consent Form (ICF) and Participant Information Sheet development
Existing as an appendix to a Clinical Study Protocol (CSP), the ICF fulfils ethical requirements to ensure study participants are aware of the benefits and risks of trial participation. Key to delivery is the requirement to convey the main content of the CSP to participants in layperson language. Effective Medical are able to develop the ICF as part of the CSP development or as a standalone deliverable.
Clinical Trial Authorisations (including IND applications, IMPD production & EC/IRB approvals)
The documentation required for obtaining authorisation to conduct a clinical trial varies by region.
In the EU written approval is required prior to commencing a trial, which involves the submission of numerous documents to a competent authority. Documentation required for this process includes a covering letter / application form, the study protocol, Investigator’s Brochure, and an Investigational Medicinal Product Dossier (IMPD).
The IMPD is an evolving document which includes summaries of information related to the quality, manufacture and control of the Investigational Medicinal Product, data from non-clinical studies and from its clinical use, as well as a summary of the risk-benefit profile of the medicinal product under study.
Upon submitting a clinical trials authorisation request, proof of Ethics Committee (EC) approval is also required. The documents required for obtaining EC approval are similar to those for the overall clinical trials approval application with some notable additions (including details on the suitability of the principal investigator, details regarding insurance, indemnity and financial arrangements).
Further details on this approval process can be found here.
In the US written approval is not required prior to commencing a trial, however a study can only begin 30 days after the submission of an Investigational New Drug (IND) application to the FDA (unless otherwise notified). Documents required to obtain IND approval are a summary of pre-clinical data and any clinical data from previous studies in humans, provision of specific manufacturing information, and the supply of relevant study protocols/investigator information (including commitment to obtain review of all proposed studies by an Institutional Review Board [IRB]). As with trials in the EU, the documents required for obtaining IRB approval are similar to those needed for the IND application.
There is also a requirement to ensure all applicable studies are registered on the ClinicalTrials.gov website upon initiation, and subsequently maintain and update this information as the study progresses.
Unlike the US or EU, the Asia-Pacific region currently does not have a harmonised regulatory body and rules pertaining to clinical trial authorisations vary for each country in the region. Nevertheless, in specific counties in this region (e.g. China and Korea) marketing authorisation of new therapies will only be granted if local populations are included in clinical trials.
Working alongside in-house teams, Effective Medical will develop the individual documents required to obtain approval for the conduct of a clinical trial and can ensure all region-specific requirements are fulfilled to ensure regulatory compliance. Project management support can also be undertaken to ensure the coordination of all contributions and provide reassurance that all the necessary approvals and documents are in place prior to application to ensure a smooth and time-efficient procedure.
Conduct of Clinical Trials in the EU
Investigator Brochure (IB)
Containing all information about a drug to-date, the IB is a critical document maintained throughout the entire clinical programme and documents the emerging safety profile of an investigational product. Effective Medical will provide project management expertise where required, seamlessly integrating into in-house teams to deliver part, or all of, an IB as directed.
Clinical Study Reports (CSR)
The production of a CSR at the end of an interventional study is mandatory in most circumstances and requires significant cross-functional input in order to ensure accurate interpretation of the data collected. Effective Medical will provide project management expertise where required, seamlessly integrating into in-house teams to deliver part, or all of, a CSR as directed.
Common Technical Document (CTD)
In July 2003, the CTD became the mandatory format for new drug applications in the EU and Japan, and the strongly recommended format of choice for NDAs submitted to the FDA. Working with clinical and safety teams, pre-clinical and regulatory, Effective Medical commonly deliver Modules 2, 4 and 5 of the CTD, however we are able to deliver Module 2 and provide input into Module 1 through our network of consultants. We have experience of all routes to marketing authorisation (including fast track approval/designation, breakthrough therapy, etc) and our experienced team can provide guidance and support to aid the production of high-quality marketing authorisation documentation.
Individual Patient Narratives
Required for the Clinical Study Report (and the Common Technical Document in the absence of a CSR for specific studies), clinical narratives can be delivered either alongside these documents or as a standalone project. Effective Medical has expertise in writing narratives for a broad spectrum of therapeutic areas and will work with teams to project manage the narrative writing process (if required) and produce concise and complete narratives which fulfil all current regulatory guidance.
Paediatric Medicines Development (PIP and PUMA)
In January 2007 the Paediatric Regulation was brought into effect in the EU to address the development and authorisation of medicines for use in children (birth to 17 years), implementing a number of changes into the regulatory environment for paediatric medicines.
A Paediatric Investigation Plan (PIP) is now required in the EU for new medicines (those not licenced before January 2007 or currently authorised medicines seeking a new indication, pharmaceutical form or route of administration), which outlines the plan for the development of medicines for use in the paediatric population (or requests a waiver/deferral from this requirement). PIPs should be produced early in development in order to allow for timely consultation with the EMA’s Paediatric Committee (PDCO).
Additionally, the Paediatric Regulation introduced the paediatric-use marketing authorisation (PUMA), which provides incentives for the development of medicines exclusively for use in children but which are already authorised and no longer covered by intellectual property rights.