In a clinical trial, it is the responsibility of the investigator to ensure that all laboratory procedures or tests are undertaken at laboratories that are compliant with applicable regulations, and operate at a satisfactory level of competence. To safeguard data credibility and reliability, the following must be ensured:
- Use only of standardized and validated test methods and systems
- All equipment (and reference materials, wherever applicable) are appropriately calibrated and traceable to international standards, to ensure their accuracy and precision
- All data, including raw (original) laboratory records are available for independent review and compliant with ‘Good Documentation Practice’
It is recommended that tests/procedures (clinical biochemistry, microbiology, haematology, clinical pathology, immunology, serology etc.), are conducted at a laboratory which is accredited to ISO 15189 standards [ISO 15189 is an international standard related to medical laboratories that specifies the quality management system requirements (including technical requirements)]. Similarly, it is advisable to ensure that the equipment are calibrated by an ISO 17025 accredited laboratory [ISO 17025 or ISO/IEC 17025:2017 is for general requirements for the competence of testing and calibration laboratories]. Both ISO 15189 and ISO 17025 are accredited by NABL (National Accreditation Board for Testing and Calibration Laboratories). NABL is a constituent board of Quality Council of India (QCI) and conducts third-party assessment of the technical competence of laboratories.
Good Laboratory Practice (GLP) is described in detail under Schedule L-1 of the Drugs and Cosmetics Act and Rules there under. In 2005, GLP was made mandatory by the Indian drug regulators, CDSCO for all toxicity studies. GLP mainly relates to pre-clinical studies (animal toxicology) and is a quality system concerned with the organisational process and conditions, under which such studies are planned, performed, monitored, recorded, archived and Fulfilling GLP requirements provide vital inputs necessary for initiating a clinical (human) study and are a pre-requisite for regulatory approvals in many countries, including India.
Good Clinical Laboratory Practice (GCLP) is a set of standards that provide guidance on implementing Good Laboratory Practice (GLP) and Good Clinical Practice (GCP) principles to the analysis of samples from a clinical trial. In brief, GCLP applies the principles established under GLP for generation of data used in regulatory submissions involving the analysis of samples from a clinical trial. At the same time, GCLP ensures that the GCP principles are adhered to. This ensures the reliability and integrity of data generated by analytical laboratories. It is advisable to adopt GCLP in a clinical trial in order to ensure that the quality of the trial matches to the best global practices. GCLP guidelines by ICMR (2008), WHO (2009) and DAIDS (2013) can be referred to and studied in detail.
Depending on the type of clinical trial being conducted, laboratory specific essential documents may be required, and need to be included in the master files. Some of these are:
- Laboratory certification or accreditation or established quality control or external quality assessment or other validation (for example, accreditation from NABL).
- IQC (Internal Quality Control), EQUAS (External Quality Assurance), PT (Proficiency Testing) data, wherever applicable
- Normal reference ranges
- Calibration certificates (for equipment to be used in the laboratory) from ISO 17025 accredited laboratory
- Instructions or manual (Quality manual, Primary sample collection manual, wherever applicable) for the laboratory
- An agreement or contract with the laboratory
- Curriculum Vitae of the Head / In-charge of the laboratory and all personnel, job description of all personnel
- A record of retained samples (to be maintained throughout the course of the trial)
- All SOPs (Standard Operating Procedures) related to the laboratory and the clinical trial
- Record of all relevant correspondence between the laboratory and CRO / Sponsor and Investigator(s).
The above list is not exhaustive, and should be customised as per the requirements of the trial being conducted. In addition to these, additional SOPs for laboratory procedures, should be maintained. Examples of SOPs include:
- SOP for quality control
- SOP for equipment calibration
- SOP for specimen collection
- SOP for accepting or rejecting a specimen
- SOP for specimen storage, recording, analysis, re-testing, disposal
It is important to note that all personnel involved in such activities must be trained in in “good practice” quality guidelines and regulations (GxPs) before they embark upon their duties.
References and Further Reading
- The Drugs and Cosmetic Acts and Rules, 1945, as amended up to the 30th of June 2005, Ministry of Health and Family Welfare, Government of India, available online (last accessed on 26.02.2019).
- Good Clinical Practices for Clinical Research in India, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, 2001, available online (last accessed on 26.02.2019).
- ICH Harmonised Guideline, Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2), current step 4 version, dated 9th November 2016, available online (last accessed on 26.02.2019).
- Becker, R. A., et al, Good Laboratory Practices and safety assessments, Environmental Health Perspectives, 2009, version 117, number 11, pages A482-83, available online (last accessed on 26.02.2019).
- S. Food & Drug Administration, Good Laboratory Practices for Conducting Nonclinical Laboratory Studies, 2005, 21CFR58, available online (last accessed on 26.02.2019).
- Organization for Economic Co-operation and Development (OECD), OECD Principles of Good Laboratory Practice (as revised in 1997), 1998, available online (last accessed on 26.02.2019).
- Good Clinical Laboratory Practices (GCLP), Indian Council of Medical Research, 2008, available online (last accessed on 06.03.2019).
- UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, 2009, Good Clinical Laboratory Practice (GCLP), World Health Organization, available online (last accessed on 06.03.2019).
- Division of AIDS (DAIDS) Guidelines for Good Clinical Laboratory Practice Standards, National Institute of Allergy and Infectious Diseases, final version 3.0, dated 9th July 2013, available online (last accessed on 06.03.2019).