Drug research, medical devices and laboratory practice

A series of important rules are in place for the production of pharmaceuticals. First, we should mention OECD's Principles for Good Laboratory Practice (GLP). These have been approved by the EU. These principles apply primarily to pre-clinical and toxicological documentation. WHO also have issued Good Clinical Laboratory Practice (GCLP) which will allow clinical laboratories to ensure that safety and efficacy data is repeatable, reliable, auditable and easily reconstructed in a research setting. In 2004, the European Union issued Directive 2004/9/EC on the inspection and verification of good laboratory practice and Directive 2004/10/ECC on the harmonization of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances. To be approved, medicine must also meet the various Medical Products Agencies' regulations regarding Good Manufacturing Practice for medicine (GMP) that rest on a EU directive (Commission Directive 2003/94/EC of 8 October 2003). For more GMP-guidelines, see this collection

European Union

Naturally, the European Union's directives and ordinances regarding pharmaceutical production are essential. Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use has driven the latest years' development. A Commission Directive 2005/28/EC laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use has been added, as well as the requirements for authorisation of the manufacturing or importation of such products. EMEA has recently started work on implementing ethical standards for clinical trials done in third world countries, and presented a strategy paper: Acceptance of clinical trials conducted in third countries.

GCP & EMEA

In Europe, review in connection with clinical trials of medicine and inspection of medical devices is performed by the Medical Products Agencies. Clinical trials must be performed in agreement with the latest version of Good Clinical Practice (GCP). GCP addresses virtually all aspects of experimental work, and is especially focussed on the procedure of application to ethics committees. The publisher of GCP, the International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use(ICH), has also issued a series of supplementary guidelines concerning aspects of pharmaceutical quality control, security and the performing of clinical medicine studies. In Europe, the main responsibility lies with the European Medicines Agency (EMEA). A collection of guidelines from EMEA can be found here.

All medicine and medical devices must be approved for use by a Medical Products Agency or through EMEA in London. The safety and effect of a medicine is always to be based on clinical trials performed by the responsible medicine company. The exceptions to this rule are naturopathic and homeopathic preparations that can refer to reliable experience. Certain medicines can also be approved by licence, that is, for a limited time and for specified groups; for example, amphetamine for the treatment of children diagnosed with DAMP. When genetically modified organisms are part of a clinical trial, one should apply Directive 2001/18/EG.

First human trials & the International Clinical Trials Registry

In 2006, a clinical trial in London of a drug, TGN1412, designed to stimulate the immune system instead led to multiple organ failure in the human volunteers, creating quite a stir. The severe negative effects observed in the six human volunteers have led EMEA to issue a guideline on strategies to identify and mitigate risks for first-inhuman clinical trials with investigational medicinal products.

Recently, the World Health Organization (WHO) has urged research institutions and companies to register all medical studies that test treatments on human beings, including the earliest studies, whether they involve patients or healthy volunteers. As part of the International Clinical Trials Registry Platform, a major initiative aimed at standardizing the way information on medical studies is made available to the public through a process called registration, WHO is also recommending that 20 key details be disclosed at the time studies are begun. See also the Ottawa statement: Principles for international registration of protocol information and results from human trials of health related interventions. The Helsinki Declaration nowadays also demand that clinical trials be registred before recruitment of study subjects. Also the medical journals have established a requirement that all clinical trials be entered in a public registry before the onset of patient enrollment, as a condition of consideration for publication, for example at the webpage ClinicalTrials.gov.

In the US, the foremost bodies of regulations are the US Department of Health and Human Services' publication Regulations for the Protection of Human Subjects and the US Food and Drug Administrations' regulatory guidances.

Pharmacogenetics

A particular issue is pharmacogenetics, the study of how genetics relate to individual drug response. This subject falls under rules for research on human subjects and genetic research (including regulations concerning the use of biobanks), but there are also distinctive guidelines. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - ICH started the work by issuing Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories, and EMEA followed with a Note for guidance on definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories. EMEA, the principal European authority, has also provided a Reflection paper on the use of pharmacogenetics in the pharmacokinetic evaluation of medicinal products and a Reflection Paper on Pharmacogenomic Samples, Testing and Data Handling, as well as a Guideline on Pharmacogenetics Briefing Meeting and patient information in Understanding the terminology used in pharmacogenetics.

To the many organizations that have presented their own statements you find first and foremost the Council for International Organizations of Medical Sciences (Pharmacogenetics. Towards improving treatment with medicines) but also Human Genome Organisation (HUGO Statement on Pharmacogenomics (PGx): Solidarity, Equity and Governance) and European Federation of Pharmaceutical Industries and Associations - EFPIA (Pharmacogenetics in Medicinal Product Research and Development, Positon Paper). See also Elements of informed consent for pharmacogenetic research; perspective of the pharmacogenetics working group. PWG is a voluntary association of pharmaceutical companies involved in clinical drug trials and genotyping whose goal is to advance the understanding and development of pharmacogenetics by addressing non-competitive ethical, regulatory, and legal issues.

Last updated: 2010-01-04