Medicines and Devices regulatory support, guidance and compliance issues
Drug development is long and complex. Medicines regulation requires approvals at a number of stages throughout the development process, and throughout the life of the product on the market. Activities carried out by regulatory agencies include approval of clinical trials and inspections of manufacturers, clinical trials, laboratories to ensure standards of GMP, GCP, GDP, GLP.
In the European Union, Member States (MS) have one or more Competent Authorities which have these responsibilities. In addition, the European Medicines Agency (EMA) has responsibility for some products and also coordinates activities across MS. The individual MS authorities and the EMA work together in a regulatory network.
In the UK, the Competent Authority is the Medicines and Healthcare products Regulatory Agency.
Within Europe much of the legislative basis for regulation is at a European level with European Directives transposed into national law, European regulations directly applicable in each EU MS, and in addition national legislation, such as The Medicines Act 1968, in the UK. The European network has produced extensive guidance.
Regulatory standards and science continues to evolve, and of recent note includes major amendments to the requirements for medical devices (including in vitro diagnostics), and the yet to be implemented new clinical trial regulation:
» UK government: Introductory Guide to new medical device regulations launched (external webpage)
» European Medicines Agency: Clinical Trial Regulation (external webpage)
Good Clinical Practice (GCP)
Good Clinical Practice (GCP) is a set of internationally recognised ethical and scientific quality standards concerning the designing, conducting, recording and reporting of clinical trials that involve human subjects. Compliance with GCP principles provides an assurance that the rights, safety and welfare of trial subjects are protected and from a regulatory perspective, that the results of the clinical trials are trustworthy and credible.
The principles of GCP are outlined in the GCP Directive 2005/28/EC, the Clinical Trials Directive 2001/20/EC and the International Conference on Harmonisation Guideline on GCP ICH Topic E 6. ICH E 6 covers important definitions, ethical committee review, the role of the investigator and sponsor, the expect contents of the clinical trial protocol and investigators brochure. The Topic provides a unified standard, facilitating the mutual acceptance of clinical data by regulatory authorities.
» GCP Directive 2005/28/EC (PDF)
» European Commission: Clinical trials – Directive 2001/20/EC (external webpage)
» ICH: Efficacy Guidelines (external webpage)
Good Laboratory Practice (GLP)
GLP embodies a set of principles that provides a framework of standards within which laboratory studies are planned, performed, monitored, recorded, reported and archived. The principles of GLP help promote the collection of high quality data and reduce the need for duplicate testing.
Scientific and Regulatory Advice
The aim of scientific advice is to facilitate the development and availability of high-quality, effective and safe medicines. Scientific advice and protocol assistance can be sought from Regulatory Authorities regarding key areas of development of a medicinal product. Companies and academics may request scientific advice either during the initial development of a medicinal product, before the submission of a marketing authorisation application (MAA) or in the post-authorisation setting. Seeking scientific advice is particularly important if a development plan deviates from the recommendations found in published regulatory scientific guidelines / pharmacopeia monographs or if these documents are considered by the sponsor not to have sufficient detail. Specific scientific issues that may be addressed include quality, non-clinical and clinical aspects of a development programme, pharmacovigilance plans and regulatory guidance.
Sponsors may seek scientific advice from the competent authorities of individual member states or from the European Medicines Agency (EMA) if pan-European advice is sought. Advice from the EMA is given by the Committee for Medicinal Products for Human Use (CHMP) on the recommendation of the Scientific Advice Working Party (SAWP). A fee, depending on the scope of the advice is usually payable. Fee reductions are available for designated orphan medicinal products, for the development of medicinal products for paediatric use and advanced therapy medicinal products and for registered small and medium-sized enterprises. Qualification procedures are also available, for example biomarker validation:
» European Medicines Agency: Qualification of novel methodologies for medicine development (external webpage)
The EMA also provides scientific advice in parallel with the United States Food and Drug Administration (FDA). It should be noted that scientific advice received from the EMA is not legally binding for either party with regards to any future application for a marketing authorisation and the advice may be adopted or rejected at the sponsor’s discretion. However, seeking and adhering to scientific advice may reduce the likelihood of major objections being raised during a MAA, increasing the probability of a successful outcome.
Seeking UK advice
Regulatory Information Service:
020 3080 7400
» RIS.NA@mhra.gov.uk (email)
Clinical trials helpline:
020 3080 6456
» firstname.lastname@example.org (email)
» MHRA: Clinical trials guidance (external webpage)
Scientific advice service that can be requested at any stage of the development of a medicinal product, in face to face meetings (fees payable, regulatory meetings are free):
» Medicines: get scientific advice from MHRA (external webpage)
Broader scope meeting where general ‘pipeline’ approaches can be discussed:
Joint meetings with NICE, plus optional advisory input from CPRD
Innovation Office to help organisations of all backgrounds and sizes navigate the regulatory framework and one stop shop for those working in regenerative medicines – free of charge service
» MHRA Innovation Office (external webpage)
PIM designation meeting for entry into the Early Access to Medicines Scheme
» MHRA: Apply for the early access to medicines scheme (EAMS) (external webpage)
In Europe, the CHMP in consultation with working parties and the competent authorities of EU member states prepares scientific guidelines. The goal of these guidelines is to assist in the preparation of marketing authorisation applications for medicinal products and to provide a basis for harmonisation in the interpretation and application of Community Directives. The guidelines cover the detailed requirements for the demonstration of the quality, safety and efficacy of medicinal products and are considered as complementary to other official documents such as the European Pharmacopeia monographs.
CHMP clinical efficacy and safety guidelines cover many different topics (some covered by ICH Topics):
» European Medicines Agency: Scientific guidelines (external webpage)
Guidelines on pharmacogenomics (PG):
» European Medicines Agency: Multidisciplinary: pharmacogenomics (external webpage)
Incentives are available for medicines that meet a number of criteria in the treatment, prevention or diagnosis of a rare disease that is life-threatening or chronically debilitating:
» European Medicines Agency: Orphan designation (external webpage)