|Year : 2021 | Volume
| Issue : 5 | Page : 353-357
Impact of Organization for Economic Co-Operation and Development (OECD) principles of Good Laboratory practices (GLP) in India
Ekta Kapoor1, Neeraj Sharma1, Rupa Joshi2, Bikash Medhi2
1 National GLP Compliance Monitoring Authority, Department of Science and Technology, New Delhi, India
2 Department of Pharmacology, PGIMER, Chandigarh, India
|Date of Submission||07-Aug-2021|
|Date of Decision||12-Nov-2021|
|Date of Acceptance||15-Nov-2021|
|Date of Web Publication||24-Nov-2021|
Prof. Bikash Medhi
Department of Pharmacology, PGIMER, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kapoor E, Sharma N, Joshi R, Medhi B. Impact of Organization for Economic Co-Operation and Development (OECD) principles of Good Laboratory practices (GLP) in India. Indian J Pharmacol 2021;53:353-7
|How to cite this URL:|
Kapoor E, Sharma N, Joshi R, Medhi B. Impact of Organization for Economic Co-Operation and Development (OECD) principles of Good Laboratory practices (GLP) in India. Indian J Pharmacol [serial online] 2021 [cited 2021 Dec 3];53:353-7. Available from: https://www.ijp-online.com/text.asp?2021/53/5/353/331084
| » Introduction|| |
Good laboratory practices (GLP) is defined as a quality system which ensures the reliability and reproducibility of scientific data related to safety testing of chemicals. Basically, this quality system focuses on planning, performing, monitoring, recording, reporting, and archiving of the data related to nonclinical health and environment safety studies.
| » History of Good Laboratory Practices: Need and Origin|| |
The need for GLP arose in the mid-1970s when several toxicology studies went un-noticed for the quality and integrity of the scientific data. At that time, the United States Food and Drug Administration (USFDA) decided to adopt some regulations to prescribe the minimal standards for conducting pre- or non-clinical laboratory studies, which played a critical role in drug development and in supporting research and marketing permits for USFDA-regulated products.
During 1960s and 1970s, the vehemence of hazardous effects of the chemicals was very common in the United States which further led to the formation of new federal laws and amendments for the use of chemicals and pharmaceuticals. The office of New Drugs and marketed drugs in 1969 planned to inspect the animal research laboratories. These investigations revealed lack of quality standards for testing on animals. Moreover, incompetence, lack of knowledge, and sometimes outright fraud reduced the value of the results presented and put the regulators in doubt.
At that time, it was recognized that the industrial sectors involving cosmetics, food additives, pesticides, pharmaceuticals, etc., posed major challenges to the government regulators. Any inefficiency in the regulations had a major impact on the environment and human health. Moreover, different regulatory approaches in every Organization for Economic Co-operation and Development (OECD) country were a burden in terms of the expenses incurred and also form barriers to trade. [2,3] Therefore, in 1981, after experiencing various regulatory and scientific practices from different international as well as national sources, the OECD council has adopted the OECD Principles of GLP. Moreover, during assessment of the chemicals, the council decision has also adopted these principles as Annexure on Mutual Acceptance of Data (MAD) [C(81) 30(Final)].
The aim of OECD Principles of GLP is to support the improvement of quality test data. The mutual acceptance of the data depends upon the comparison of the quality of the test data obtained from different countries. Reliability on the test data of other countries had facilitated the testing process by saving time and resources while avoiding the duplication of the testing. In addition, they will also evade the technical barriers to trade which further improves the quality of human health and the environment safety testing.
| » The Mutual Acceptance of Data System of the Organization for Economic Co-operation and Development|| |
The OECD principles of GLP assured the production of reliable and high-quality test data associated to the safety of industrial chemical substances and their preparations. These principles have been formed in milieu of harmonizing testing procedures for the MAD. MAD is a multilateral agreement where national approaches to regulation of nonclinical safety studies are harmonized such that nonclinical safety data generated in an OECD member country can be accepted in the other countries provided the test methods are in acquiescence with the OECD Principles of GLP and the OECD Test guidelines. The MAD system supports to avoid contradictory or duplicative national requirements, also avoids creating non-tariff barriers to trade and offers a common platform for co-operation amongst national authorities. OECD countries and countries that are full adherents to MAD have decided that a safety test which has been carried out as per the Test Guidelines and Principles of OECD-GLP must be mutually accepted among all the OECD countries. This is the perception of “tested once, accepted for assessment everywhere.” This is turn protects the chemical industries from the over expenditure of the duplicate testing of the internationally marketed products
A non-OECD member country too can compete in the MAD system. Initially, such a country is designated as “Provisional Adherent” to MAD in the OECD, during which it can work with OECD and MAD adherent countries to complete its GLP compliance monitoring program. Later, the National GLP Compliance Monitoring Program of the provisional adherent country is assessed by the OECD's Working Party on GLP by nominating an evaluation team (a group of two to three experts) through the conduct of an onsite evaluation. The OECD's Working Party on GLP then ensures whether the provisional adherent country has fully implemented the OECD Council Acts pertaining to MAD. If all the requirements are met, the OECD agrees for grant of full adherent status of MAD to the country. Once a country becomes “full adherent” to MAD, then it must accept the data generated from OECD and other full adherent countries provided the data are generated under MAD conditions. India is a full adherent to MAD since March 3, 2011. As a result, data generated from the nonclinical studies by the Indian GLP laboratories acceptable in 37 OECD member countries and 7 nonmember MAD adherent countries. The MAD system provides the saving of around €309 million every year to the industry and governments. In addition, the reduction of the duplicate testing decreases the usage of animals and also creates the framework for sharing the data. Thus, apart from the monetary benefits of the MAD system, it avoids the duplication of efforts across countries. Moreover, it also reduces technical barriers to trade which have a positive impact on the global economy.
| » Scope of Organization for Economic Co-operation and Development Principles of Good Laboratory Practices|| |
The OECD Principles of GLP apply to the nonclinical safety testing of test items contained in medicinal/pharmaceutical products, medical devices, cosmetic products, veterinary drugs, pesticide products, industrial chemicals, and food additives along with feed additives. Generally, the test items are synthetic in nature; however, sometimes, they are of natural or biological origin or can be living organism. The rationale behind testing them is to acquire data of their safety related to human use or environment. The safety studies conducted under these principles consist of the work performed in the laboratories and green houses and may be in fields.
GLP Certification is granted to conduct studies in various areas. The detail of the areas of expertise is given in [Figure 1].
|Figure 1: Various areas of expertise required to conduct studies under good laboratory practices certification|
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| » Components of Good Laboratory Practices|| |
The main components covered by OECD Principles of GLP include the ten primary elements of the quality system [Figure 2].
|Figure 2: Ten components of the Organization for Economic Co-operation and Development principles of good laboratory practice|
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In addition, the GLP system covers all the ethical aspects of the animal experiments such as study design, ethical guidelines, ethical approval, sample size (number of animals), treatment schedules, doses, routes of administration, experimental methodology, data acquisition and analysis, and reporting and recording of all the steps followed in experiments. The documentation of the experiments is the key component for GLP Certification. The adherence to the OECD principles of GLP ensures high standards of toxicity studies with global relevance. The results of these studies hold greater weight in making decisions regarding their safety profile with worldwide acceptance. When different organizations conduct research in compliance with the GLP principles, all the procedures and protocols followed during the experiments are made diligently and carefully in accordance with the OECD Principles of GLP and the Standard Operating Procedures of the test facility (TF), which are followed invariantly by all the personnel involved in the experimental procedures.
| » National Good Laboratory Practices Program and Status of Organization for Economic Co-operation and Development-Good Laboratory Practices in India|| |
Indian GLP Program is based on the principles of OECD GLP principles. The National GLP Compliance Monitoring Authority (NGCMA) came into force on April 24, 2002, underneath the administrative control of the Department of Science and Technology (DST), Government of India, through a decision of the Union Cabinet. The functioning of National GLP Program occurs through an Apex Body, comprised Secretaries of concerned Ministries/Departments under the chairmanship Secretary, DST. This Apex Body oversees smooth functioning of the National GLP Program as per the OECD Principles of GLP and OECD Council norms. The Apex Body is maintained with the support of Technical Committee on GLP, which is an advisory body of NGCMA on cases of GLP Certification and various technical matters concerning GLP. The main responsibilities of NGCMA Secretariat (in DST) are to make policies and procedures for GLP compliance monitoring in the country as per the norms of OECD. The secretariat also conducts various capacity building activities on GLP, to ensure creation of a GLP ecosystem in the country.
At present, in the country, the ever-increasing demand of the GLP compliance monitoring has been served with the 17 well-trained GLP inspectors from various government laboratories, universities, and institutions (public funded) m and they assess the applicant capability for the technical competence as per the OECD principles of GLP and test guidelines. It is most important to know that GLP Certification is voluntary in nature. For the GLP Certification, the TFs required to submit the prescribed application form by NGCMA along with the required application fee. The TFs have to submit the prescribed application fee and apply in the prescribed application form of NGCMA. After receiving the application form, the NGCMA conduct the preinspection of the TF followed by final inspection. The technical committee on GLP checked the final inspection report and give recommendations that were further verified by the GLP Chairman and final decision on grant/nongrant of the GLP Certification would be taken. Although the GLP Certification of any TF is valid for 3 years, the surveillance inspections can be performed by GLP secretariat after 18 months of the GLP Certification, and during the last year, i.e., 3rd year, the re-certification inspection has also be performed to sustain the certification of the TF.
The introduction of NGCMA in the country in 2002 transformed the culture of the generation of nonclinical data and enabled the Indian TFs to meet the requirements of global nonclinical data as per the OECD Principles of GLP. Before 2004, India was largely dependent on foreign laboratories for generating the nonclinical data causing major foreign exchange burden. More importantly, non-GLP data from Indian TFs were an important technical barrier for international acceptance.
The journey of Indian GLP Certification started in 2004 with four GLP-certified TFs. This boosted the credibility of nonclinical safety data from Indian TFs. The demand for GLP data increased, resulting in more number of TFs applying for GLP certification. Before India became a full adherent to MAD in the OECD, the Indian TFs had to approach GLP monitoring authorities of countries such as The Netherlands, Switzerland, Germany, and Belgium for GLP Certification, which was cumbersome and expensive. Further, this had limitations of acceptability of data in respective countries and few other countries which recognize that particular country's authority. This limited the global acceptability of the Indian data. A historical milestone was the full adherence of India to MAD in the OECD on March 3, 2011. Corollary, the data created by Indian GLP TFs are found to be acceptable among every OECD member countries and nonmember full adherent to MAD countries. This revolutionized the nonclinical testing ecosystem in India. As a result, GLP-certified TFs steadily increased, and over the years, their number has reached 50 as of April, 2020, which is located in 15 states of the country. These TFs are capable of conducting nonclinical studies on all major categories of test items – pharmaceuticals, pesticides, industrial chemicals, veterinary drugs, feed additives, food additives, cosmetics, and medical devices. The robustness of GLP monitoring compliance system in India through NGCMA, cost advantage, shorter turnaround time, availability of competent inspectors, and faster approval process of GLP certification are the factors to create a conducive environment to attract more international business. It is advisable that the potential of Indian TFs should be highlighted strategically in major international forums.
To remain contemporary to the needs of the country, NGCMA interacts continuously with Indian and international regulatory authorities. This has resulted in identification of new scopes such as testing of medical devices and conducting joint inspections/study audits at the request of the regulators of OECD member countries and MAD adherent countries. To achieve the speed and scale to expand the National GLP Program, NGCMA, entered into a MoU with Quality Council of India (QCI) on December 31, 2013. The principal objective of this MoU was to establish a mechanism wherein QCI shall support NGCMA for effective implementation of the GLP Certification Program through a structured approach by managing the operationalization of the same.
For capacity building, NGCMA has regularly organized several residential intensive training programs for GLP inspectors (both basic and refresher trainings). Such training programs have been organized in Jaipur, Noida, Delhi, Hyderabad, Bengaluru, etc. Further, NGCMA has a mechanism of continuous feedback from TFs, members of technical committee on GLP, and lead inspectors of NGCMA to update and harmonize inspectors' understanding on emerging issues. Under the collaborative MoU with QCI, NGCMA has conducted more than 100 capacity building programs for academic institutions, national scientific laboratories, and GLP TFs in the country. This has created a strong GLP ecosystem of credible data generation in India.
NGCMA hosted the 12th OECD training course for GLP inspectors in October 2015 in Hyderabad. In this training course, faculty from OECD and national experts were resource persons. A total of 79 inspectors were trained and the training course was highly appreciated by the OECD, since it was one of its kind to include facility tour to the toxicology and other laboratories of a Contract Research Organization (CRO), so as to provide real-time hands-on training to the participants for the conduct of GLP studies.
| » Good Laboratory Practices in Academic Institutes|| |
The GLP Certification is playing an important role in economic development of the country. The number of GLP-certified TFs including CROs has been increasing steadily after India attained the status of a full adherent to MAD. However, only three GLP-certified TFs are from government sector, especially from academia. In India, the academic institutions such as National Institute of Nutrition (NIN), Hyderabad, and National Institute of Pharmaceutical Education and Research (NIPER), Guwahati and Hyderabad, are contemplating their animal house/toxicology facilities for GLP Certification. For capacity building of scientists and researchers as well as for handholding of these government institutes, NGCMA organized sensitization workshops in NIPER – Hyderabad and Guwahati.
In collaboration with Translational Health Science and Technology Institute) and QCI, NGCMA has planned to organize a series of nine national sensitization workshops “National Series of Sensitization Workshops on Good Laboratory Practice (GLP) for Faculty and Scientists of National Laboratories and Public Funded Institutions.” Four workshops in different places have already been conducted and the rest are being planned in 2020–2021. A webinar on GLP was conducted at NIPER Kolkata for the scientists, researchers, and students of NIPER Kolkata and NIPER Hajipur. [4,7]
| » Impact Analysis of India Attaining Full Adherence Status to Mutual Acceptance of Data|| |
NGCMA, commissioned an “Impact Analysis Study of National GLP Program” in 2019–2020 to assess the impact of India attaining a full-adherent status to MAD in the OECD after about a decade of this achievement. The primary objective of the study was assessment of the current GLP TFs and their functioning to ascertain whether the TFs are meeting the expectations of the different stakeholders in terms of quality and scope of activities. In addition, the study was also meant to suggest ways for further strengthening of the GLP ecosystem so that India not only becomes self-reliant (Atma-Nirbhar) but also a global leader in GLP quality system. The study was designed and developed in a manner to seek inputs from the important stakeholders, namely, sponsors, regulators, GLP inspectors, and members of the NGCMA's Technical Committee on GLP. The responses were collected, collated, and analyzed and recommendations were submitted as the way forward toward strengthening the program.
The salient points that emerged from the impact analyses study are as follows: [4,6]
- Of the 50 GLP-certified TFs (till April 2020), 24 TFs (48%) are CROs, thus offering competition in time and cost of conducting GLP studies; 12 (24%) TFs perform only in-house nonclinical safety studies to support their parent manufacturing companies; 14 (28%) TFs perform both CRO and in-house services
- Currently, GLP-certified TFs in India collectively have the competence to conduct nonclinical health and environmental safety studies on eight types of test items and nine areas of expertise in 28 test systems, including both in vitro and in vivo studies
- Till 2019–2020, Indian TFs have conducted more than 60,000 nonclinical safety studies. These are valued at INR 7800 crores (USD 1.3 billion). This is a major step toward self-reliance in the development of New Chemical Entities. This program has a significant economic impact, in the absence of which the cumulative of these studies would have otherwise gone to GLP TFs outside India for safety assessment of molecules
- In the financial year 2018–2019, the Indian TFs conducted 12,808 GLP studies. The majority of the studies were conducted in the following two sectors – Pharmaceutical (~70%) and Pesticides (~15%) together contributing to 85%. The other sectors such as food, feed, cosmetics, and industrial chemicals collectively accounted for 15% of the GLP studies
- The market valuation of 12,808 GLP studies in financial year 2018–2019 was INR 1465 crores. Of this, the CROs accounted for 92% while in-house TFs accounted for 8%. The test item-wise analysis showed that pesticide testing in compliance with GLP accounted for a major part (66%) while pharmaceuticals accounted for 22%. All other test items contributed to less than 12%. It is evident that the other sectors of test items need to be encouraged to test their products in compliance with OECD principles of GLP, which will not only ensure human safety and boost consumer confidence but also optimize any idling GLP capacity in India
- Today, due to MAD status to NGCMA, Indian GLP TFs are attracting business from 48 countries. More and more studies are now being conducted in compliance with GLP and lesser as non-GLP studies. The total number of GLP studies increased three times between 2011 and 2018 with a Compound Annual Growth Rate (CAGR) of 14.7% while the non-GLP studies registered a negative CAGR of 4.1%
- Enhanced capacity of Indian GLP-certified TFs for conduct of nonclinical studies resulted in an excellent CAGR of 25.5% in the last decade. This was significantly higher than the comparative CAGR of non-GLP studies (1.5%) during the same period.
| » Future Perspectives of Good Laboratory Practices in India|| |
India has been designated the “Vice-Chair” of OECD's Working Party on GLP for 2021 and 2022, thus recognizing the contribution of the Indian GLP Program in the OECD. India's leadership in GLP brings a greater recognition of the country's certification of quality for global businesses. This is also a link in the chain to Atma-Nirbharta, which is to have structures and processes that are adhered to global standards.
To sum up, Indian GLP services offer competitive economical advantage. However, there is much scope for increasing the capacity of Indian GLP-certified TFs in pharmaceutical and all possible areas. It is estimated that approximately 100 such TFs should be created or upgraded to GLP status to meet the increasing demand of Indian stakeholders and also remain viable and competitive in the global scenario.
| » References|| |
Baldeshwiler AM. History of FDA good laboratory practices. Qual Assur J 2003;7:157-61.
Vijayaraghavan R, Ashok S, Swaminathan J, Kumar RG. GLP (Good laboratory practice) guidelines in academic and clinical research: Ensuring protection and safety. J Pharm Res Clin Pract 2014;4:89-104. [Full text]
Stanley VA. The journey of Indian GLP programme – Looking back and forward. Qual Assur J 2009;12:8-15.
Becker RA, Janus ER, White RD, Kruszewski FH, Brackett RE. Good laboratory practices and safety assessments. Environ Health Perspect 2009;117:A482-3.
Jena GB, Chavan S. Implementation of Good Laboratory Practices (GLP) in basic scientific research: Translating the concept beyond regulatory compliance. Regul Toxicol Pharmacol 2017;89:20-5.
[Figure 1], [Figure 2]