3. Key GxPs in Medicine

As early as a research project has led to a development candidate this compound will be carefully investigated in the non-clinical development phase. These activities are covered by GLP, which was devised to promote the development of quality test data, both to help protect human health and the environment and to allow reliable scientific data to be shared between countries.

The current definition of GLP (cGLP), incorporated in the EU legislation and also in that of numerous countries worldwide, is given by the Organisation of Economic Co-operation and Developmen (OECD) document ‘Principles of Good laboratory practice’: “Good Laboratory Practice (GLP) is a quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported”. It should be applied unless specifically exempted by national legislation.

GLP covers safety testing not only in medicines, but also in other areas like pesticides, cosmetics, or veterinary drugs. Of course, the scope here is restricted to medicines, i.e. to “ ... the non-clinical safety testing of test items contained in medicinal products ... required by regulations for the purpose of registering or licensing ...The purpose of testing these test items is to obtain data on their properties and/or their safety with respect to human health and/or the environment.” (OECD Principles of GLP). Medicines could be synthesized chemicals, naturally occurring substances, biologics or living organisms.

As far as medicines development is concerned, the GLP Principles, in their regulatory sense, apply only to studies which are:

• non-clinical, i.e. mostly studies on animals or in vitro, including their analytical aspects;
• designed to obtain data on the properties and/or the safety of items with respect to human health and/or the environment;
• intended to be submitted to a national regulatory authority with the purpose of registering or licensing the tested substance or any product derived from or containing it.

Depending on national legislation, the GLP requirements for non-clinical laboratory studies conducted to evaluate drug/medicine safety cover the following classes of studies:

• Single dose toxicity
• Repeated dose toxicity (sub-acute and chronic)
• Reproductive toxicity (fertility, embryo-foetal toxicity and teratogenicity, peri-/postnatal toxicity)
• Mutagenic potential
• Carcinogenic potential
• Toxicokinetics (pharmacokinetic studies providing systemic exposure data for the above studies)
• Pharmacodynamic studies designed to test the potential for adverse effects (Safety pharmacology)
• Local tolerance studies, including phototoxicity, irritation and sensitisation studies, or testing for suspected addictive and/or withdrawal effects.

GLP is intended to guarantee that all laboratory results are reliable before going to the next step, i.e. ‘First-in-Human’ trials.  As safety testing also takes place along clinical trials GLP is therefore relevant in clinical development for the respective functions.

The test facility must meet strict standards in terms of procedures, equipment, and personnel. And every study must be planned, performed, monitored, recorded, archived, and reported under the proper conditions.

A few points to remember:

GLP Principles are independent of the site where studies are performed. They apply to studies planned and conducted in a manufacturer’s laboratory, at a contract or subcontract facility, or in a university or public sector laboratory.

GLP is not directly concerned with the scientific design of studies. The scientific value is judged by the respective regulatory authority evaluating a MAA. However, adherence to GLP will add to the overall credibility of the data.

Through the application of approved Standard Operating Procedures (SOPs) many sources of systematic error and artefacts may be avoided.

The requirement to formulate a study plan with a defined scientific purpose for the study will diminish the incidence of incomplete or inconclusive data.

When implementing GLP in a test facility, it is important to clearly differentiate between the formal, regulatory use of the term Good Laboratory Practice and the general application of “good practices” in scientific investigations. Any laboratory may consider that it is following good practices in its daily work. This does not comprise GLP compliance with all the requirements of the OECD GLP Principles.

For more details, please look at the respective EMA website: https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-laboratory-practice-compliance

Legal basis:
Directive 2004/10/EC on the harmonisation 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. (incorporates: OECD Series on principles of Good laboratory practice and compliance monitoring, Number 1, OECD Principles on Good Laboratory Practice (as revised in 1997))

Directive 2004/9/EC on the inspection and verification of good laboratory practice (GLP)