Humpage Technology Ltd
Principles of GLP and Compliance Monitoring - Good Laboratory Practice1. Introduction On 1 April 1997, the United Kingdom’s voluntary Good Laboratory Practice Compliance programme was superseded by a Statutory Instrument (SI) entitled The Good Laboratory Practice Regulations 1997. The regulations were based on the 1981 version of the Organisation for Economic Co-operation and Development (OECD) principles of Good Laboratory Practice (GLP). In 1998 the OECD issued the revised Principles of GLP and Compliance Monitoring. These were adopted by the EC in October 1998 and issued as Directives 99/11/EEC and 99/12/EEC. Consequently, in 1999, the UK Regulations were updated by SI 3106, as amended by SI 994, 2004, and are accompanied by a guide that interprets them and explains how compliance will be verified. The primary objective of the OECD Principles of GLP is to ensure the generation of high quality and reliable test data related to the safety of industrial chemical substances and preparations. It harmonises testing procedures so that results and other data are acceptable between laboratories and organisations, a process referred to as Mutual Acceptance of Data (MAD). Do not think, however, that GLP applies to any one particular sector or type of laboratory. It is a fundamental framework for ensuring that, wherever laboratory studies are carried out, all data generated is reliable, and that the studies are planned, performed, monitored, recorded, reported and archived in such a way as to ensure this reliability. For some laboratories, adherence to GLP is a statutory requirement. Other laboratories may follow the guidelines on a voluntary basis in order to demonstrate the rigour in which their work is carried out. However, test facilities that do not carry out regulatory studies (defined below) are not compelled to work in accordance with the principles of GLP. Such facilities are not eligible for admission to the UK GLP compliance programme. The purpose of this article is to explain the roles that instrument calibrations and calibration management play in GLP. It is a small, but highly important aspect of what is a very broad subject, but it's importance cannot be overstated. 2. Who Needs to Comply ? Compliance with the principles of Good Laboratory Practice (GLP) is a legal requirement for test facilities that undertake health and environmental safety studies, and some other testing, that will be submitted to regulatory authorities for the purposes of risk assessment. To comply with the GLP regulations, a test facility which conducts, or intends to conduct, regulatory studies must be a member of the UK GLP Compliance Monitoring Programme. These regulations define a 'regulatory study' as a non-clinical experiment or set of experiments in which:
Work that does not constitute a regulatory study as defined above (or an integral part thereof) is not required to be conducted in compliance with the principles of GLP. Examples of these are:
There are other regulations that cover the control of the quality of a manufactured product or service, examples being ISO 9001 and, for calibration laboratories ISO 17025. 3. Who Governs and Monitors GLP ? The UK GLP Monitoring Authority (GLPMA) has responsibility for monitoring test facilities for compliance with the principles of GLP. The work of the GLPMA is carried out by a unit within the Inspection and Enforcement Division of the Medicines Control Agency (MCA), which is an executive Agency of the Department of Health (DH). The range of test facilities monitored by the GLPMA include those involved in the health and environmental safety testing of human and veterinary pharmaceuticals, agrochemicals, cosmetics, food and feed additives and industrial chemicals. All enquiries concerning GLP should be addressed to: GLP Monitoring Authority Market Towers 1 Nine Elms Lane London SW8 5NQ 4. What is the Purpose of Calibration Management Within GLP? Almost without exception, testing will involve the use of measuring equipment, scientific instruments and other hardware. It is inconceivable that anyone would have confidence in the measurements produced by these instruments if they did not have a continuous record of traceable calibration. Furthermore, the calibration records must be readily available to all concerned including laboratory staff, inspectors and auditors, etc. It is essential, therefore, that GLP compliant laboratories have in place an effective and accurate calibration management system which gives access to all relevant information including: * Date of last calibration and calibration due date * All relevant current calibration data * Details of previous calibrations (historical data) * Operating and calibration procedures * Device details such as type, supplier, purchase date, etc * The person with responsibility for the instrument * The person who calibrated the instrument It is perfectly acceptable for laboratories to devise their own systems but be warned: designing such systems from scratch can be a time-consuming process, particularly if a paperless (i.e. computerised) system is required. The majority of laboratories elect to use commercially available calibration management software such as Calibration Toolbox ADO, which was designed, from the outset, to be used by laboratories working to GLP, ISO 17025 and other internationally accepted standards. 4.1 A Validated Calibration Management System
The ultimate responsibility for the validation of your system lies with your own laboratory. However, vendors of proprietary software, such as Caliso Calibration Toolbox, can play their part by providing you with validation documentation for their software, and tools for testing the software in its intended location, i.e. in your laboratory. Caliso Calibration Toolbox, which is widely used throughout the healthcare, pharmaceutical and biotechnology industries, is designed to automate parts of your company's quality control system and, because of this, has been subjected to strict validation/verification procedures. It is classed as "off the shelf" software in which by definition you, the end-user, played no direct part in the specification, development and testing. One of the key purposes of this document to demonstrate to you and any auditor, that the software has been designed, developed and tested in accordance with the internationally accepted guidelines for software validation.
4.2 Use, Calibration, and Maintenance of Equipment
Equipment used to generate data should be appropriately located, safe, suitable for the purpose, of appropriate design, and of adequate capacity. It should be calibrated and serviced regularly by trained staff so that performance is optimal and the results can be trusted. A designated person should be responsible for ensuring the proper use and maintenance of equipment and, where appropriate, for training staff in its use. When this is not possible, the users themselves should take on the responsibility. Records should be kept of calibration, servicing, faults, breakdowns, and misuse of equipment. A standard operating procedure should be maintained for each piece of equipment; in some cases this might be the manufacturer’s instruction manual. There should be easily accessible instructions for the safe shutdown of equipment in case of emergency. 4.3 Standard operating procedures Standard operating procedures (SOPs) should be documented for all routine methods and for individual items of equipment to ensure that data are collected consistently and accurately. When there is more than one approved technique for any given procedure, all should be covered by SOPs. SOPs should be written in simple language, readily accessible, and ideally in a standardised format. They should be updated as necessary, and only the current version should be available. Standard written protocols should also be available covering the process of seeking informed consent from patients or volunteers, to ensure clarity and consistency. Written protocols are likewise essential for ensuring strict adherance to regulations/licences, for example in research involving animals. 4.4 Maintenance of Calibration Records
4.5 Measurement Uncertainties and Other Issues As we have said, the primary objective of GLP is to ensure the generation of high quality data. Essential to this is the ability to produce estimates for the measurement uncertainty associated with calibrations. Your calibration management system should enable you to perform all the necessary analysis in accordance with NIST/GUM guidelines, including Type A and Type B uncertainties, combined uncertainties, coverage factor and expanded uncertainties. Other key GLP/GMP records to be maintained by our calibration management system are: * Unique ID number to identify each instrument or device * Calibration data storage and calibration histories * Compliant calibration certificate design * Easy access to standard operating procedures * Secure Audit Trail Acknowledgements
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