Present Status of Good Laboratory Practices

Present status of Good Laboratory Practices

Dr. Subhash C. Mandal

Chairman, Regulatory Affairs Division (RAD)

Indian Pharmaceutical Association

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Preamble:

Good Laboratory Practice (Schedule-L1) is now a mandatory requirement in the Pharmaceutical industry. It has already been implemented mostly in the developed countries and even in some developing countries. GLP has been made mandatory in India from 1st November 2010 through inclusion of Schedule L1 in the Drugs and Cosmetics Rules.

Good laboratory practice(GLP) generally refers to a system of management controls for laboratories and research organizations to ensure the consistency and reliability of results as outlined in the Organization for Economic Co-operation and Development (OECD) principles of GLP and national regulations. It applies to non-clinical studies conducted for the assessment of the safety of chemicals to man, animals and the environment, but it does not include clinical research. The internationally accepted definition of GLP is as follows:

“Good Laboratory Practice (GLP) embodies a set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived. These studies are undertaken to generate data by which the hazards and risks to users, consumers and third parties, including the environment, can be assessed for pharmaceuticals, agrochemicals, veterinary medicines, industrial chemicals, cosmetics, food and feed additives and biocides. GLP helps assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessments”.

Status:

GLP in OECD member countries:

OECD has about 34 full members round the globe, from North and South America to Europe and Asia-Pacific. They include many of the world’s most advanced countries but also emerging countries like Mexico, Chile and Turkey, where GLP is compulsory. OECD also work closely with emerging economies like the People's Republic of China, India and Brazil and developing economies in Africa, Asia, Latin America and the Caribbean.

Mutual Acceptance of Data (MAD):

The testing of chemicals is labour intensive and expensive. Often the same chemicals are being tested and assessed in several countries. The OECD council therefore adopted a council decision in the year of 1981- on Mutual Acceptance of Data (MAD)- stating that test data generated in any member country in accordance with OECD Test Guidelines and Principles of Good Laboratory Practice (GLP) shall be accepted in other member countries for assessment purposes and other uses relating to the protection of human health and the environment.

In line with the internationalization of research, the scheme is expanding beyond OECD countries. Today, India has become the third key emerging economy to sign up to MAD, after Singapore and South Africa, while Argentina, Brazil, Malaysia and Thailand are provisional adherents to the system.

GLP in the OECD non-member countries:

An inspection in non-member economies by OECD inspectors will not guarantee that, if they are found to be in compliance, their data will be accepted in other member countries than the one to which they are submitting data and which has thus sent inspectors to verify the accuracy of their compliance statement.

GLP in European Union:

The European Council had adopted two basic directives and a decision relating to the application of the GLP principles since 1987 which are-

Directive one: " Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 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."

This directive prescribes the obligation of the Member countries to designate the authorities responsible for GLP inspections in their territory. It also comprises reporting the internal market and regulatory requirements regarding mutual acceptance of data.

Directive two: “Directive 2004/9/EC of the European Parliament and of the Council of 11 February 2004 on the inspection and verification of good laboratory practice (GLP)".

The Directive requires that the OECD revised guidelines for compliance monitoring procedures for GLP and the OECD guidance for the conduct of test facility Inspections and study audits must be followed during laboratory inspections and study audits.

European Economic Community (EEC) Council had taken a decision on 28.07.1989 on the acceptance by the EEC of an OECD decision / recommendation on compliance with principles of good laboratory practice. Apart from these directives there are also 'Product Oriented Directives' referring to GLP obligations in EU.

GLP in USA:

USA has its own rules applicable for preclinical trials in US on animals prior to Clinical research in humans is 21 CFR 58. Anybody interested to submit data in support of a New Drug Application in the USA required to follow 21 CFR 58 if research is conducted in USA or required to follow OECD guidelines or 21 CFR 58 if research conducted outside USA.

GLP in India:

National Good Laboratory Practice (GLP) Compliance Monitoring Authority (NGCMA) under the Dept. of Science & Technology, Govt. of India is working to approve the Industries/test facilities/laboratories engaged in manufacturing of industrial chemicals, pharmaceuticals, veterinary drugs, pesticides, cosmetic products, food products, feed additives, etc., since 2002. Though this approval is voluntary some laboratories have already obtained GLP Certificate from this authority. Data generated by these GLP certified laboratories are accepted by the OECD countries.

GLP (Schedule-L 1) under Drugs and Cosmetics Rules:

Govt. of India has notified GLP as mandatory vide G.S.R.780 (E) dated 10th November 2008 under schedule “L-1” with effect from the 1st November, 2010. This includes requirements in details about General requirements, Premises, Personnel, Equipments, Chemicals and reagents, Good house keeping and safety, Maintenance, calibration, and validation of equipments, Reference materials, Quality system, Internal quality system audits, Management review, Standard Operating Procedures, Protocols and specifications archive, Raw data, Storage and archival,

Most of the GMP complied companies have already improved their laboratories during compliance of Schedule M. A major part of the GLP requirements have been covered by the revised schedule M especially under section 5 & 6 of the same.

2007 edition of the Indian Pharmacopoeia (IP) has prescribed some stringent requirements which need the service of some sophisticated and costly instruments. Except big and medium scale companies most of them are yet to provide costly instruments like- AAS, HSGC, IR etc. and are outsourcing it to approved laboratories. Some of them are trying to procure the same.

Conclusion:

Manufacturers exporting their products in the OECD member countries have already complied with OECD requirements of GLP in addition to the country specific requirements. Some manufacturers have complied 21 CFR 58 requirements who are exporting in USA in addition to OECD requirements. There are some manufacturers who have already complied with the requirements of GLP voluntarily.

India is full-member for Mutual Acceptance of Data (MAD) in the OECD's Working Group on GLP w.e.f March 3, 2011. As a consequence, the data generated by Indian GLP laboratories is acceptable in all the OECD member countries. This facilitates export of chemicals, drugs, pesticides etc. to these countries. Manufacturers of Drugs and Pharmaceuticals may procure GLP Certificate from National Good Laboratory Practice (GLP) Compliance Monitoring Authority under the Department of Science & Technology, Government of India which may give them edge over their competitors (http://www.indiaglp.gov.in/) as the data generated by the GLP certified laboratories is accepted by the OECD countries.

Good Laboratory Practice has been made mandatory through inclusion of Schedule L1 to the Drugs and Cosmetics Rules effective from 1st November, 2010. This requirement is mandatory for manufacturing Drugs in India and is different from OECD requirements.