Industrial placements form part of many undergraduate chemistry courses and many of these students go on to work as analytical chemists in a wide range of areas. If students are to take advantage of the opportunities on offer, they will need to be aware of the basic regulatory requirements of 'good laboratory practice' Students who want to work as analytical chemists in industry need to be introduced to the basic regulatory requirements of 'good laboratory practice'
Undergraduates need to be aware of professional regulations related to the practice of analytical chemistry in industry
- 'Good lab practice' relates to monitoring, reporting and storing analytical data, and ensures confidence in the validity and integrity of data
A recent survey of job vacancies showed that ca 30 per cent of chemistry jobs on the New Scientist website and ca 40 per cent of similar positions on Monster were for analytical work in such areas as pharmaceuticals, forensics, bioanalytical work, environmental monitoring and many more. We spend a good deal of time teaching undergraduates the principles and techniques of analytical chemistry, but feedback from potential employers often suggests that applicants are let down by a lack of basic knowledge of regulatory requirements and how reproducibility in analytical work is ensured, all of which fall under the banner of 'good laboratory practice' (GLP).
Good laboratory practice
The principles of GLP were formulated by the Organisation for Economic Cooperation and Development (OECD) in 1981. Fundamentally, analytical data generated in accordance with GLP in one member country should be accepted in another member country. GLP thus serves to facilitate trade and cooperation between countries. The European Community later accepted the principles of GLP, ratified as EC Directives, which come under UK law as a UK Statutory Instrument. The Good Laboratory Practice Monitoring Authority (GLPMA) is a part of the Medicines and Healthcare products Regulatory Agency (MHRA) which is responsible for administering the UK GLP Compliance Monitoring Programme whereby laboratories and other facilities that do regulatory studies are subject to routine biennial inspection (see Box 1). For such organisations membership of the GLP compliance programme is mandatory, and all work must be done in accordance with the principles of GLP. These are not codes of practice or guidelines, they are regulatory requirements.
The GLP principles cover all parts of a study, from considering how to do the work, through monitoring, to reporting and storing the data. GLP relates to studies - in pharmaceuticals, agrochemicals, veterinary drugs, industrial chemicals, cosmetics, food and feed additives, and biocides - in which risks to users, consumers and third parties (including the environment) are assessed and compliance to GLP is required. Adherence to GLP allows a regulatory body assessing any such study to have confidence in the validity and integrity of data obtained when, for example, making risk or safety assessments. If individual countries can confidently rely on data developed in other countries, duplicate testing can be avoided, thereby saving time and resources. Note, however, that GLP is not concerned with the scientific validity of the studies, this is the responsibility of the assessors to whom the studies are submitted.
This may sound like a rather dry topic to put across to undergraduates - it would be all too easy to get bogged down in a long series of acronyms and regulations. However, it is clearly important to address GLP at some stage in the curriculum. At the same time there is always pressure on the timetable and it is undesirable to devote too much time to 'non-chemistry' topics.
Against this scenario we have worked with staff from the GLPMA of the MHRA to put together a teaching package that fits easily into the curriculum, is interesting to the students and hopefully provides students with the basic requirements of working in a regulated analytical environment, either as placement students or as full-time employees.
We believe there are two ways to make GLP both accessible and interesting to students. First, we need to consider the sort of jobs that our students may be doing in a few years time. So part of the taught material focuses on the expectations of individuals in ensuring compliance to GLP. We introduce students to the roles of a study director and a principal investigator - both jobs that they may well be doing a few years after graduation but probably roles that they have not considered (see Box 2). These are responsible positions and it is useful to emphasise to the students that such responsibilities could soon be theirs.
Since many graduates are likely to work as analysts at the start of their careers, we address the question - what is expected of an analyst who does part or all of a study? The key point, perhaps, is traceability of the work that the analyst has done and to emphasise that the analyst is responsible for recording raw data and for the quality of this data. Moreover, employers expect that they will be aware of GLP. Secondly, we ask the students to consider data which have been recorded as part of a study and, in particular, to look for potential flaws in the recording of these data.
The most interesting way to approach a topic like this is by encouraging student involvement. Following an introductory lecture, we ask students to work in teams on workshop problems. Two problems that we have found to be particularly interesting are:
to consider a list of tasks in a study and decide on who should be responsible for those tasks;
to consider a set of calibration data and decide on whether the data would be compatible with GLP.
These problems can also be used to teach transferable skills. Team working is important and we ask one member from each team to give a short presentation on their findings. This also serves to get students to question the way in which they address data. For example in one workshop problem, a Standard Operating Procedure (SOP) for calibrating a pipette requires the pipette to pass at 1 per cent accuracy. The analyst has done this by weighing 0.0050, 0.0250, 0.2000 and 1.0000 cm3 volumes of water but has used a four-figure balance for the work. Since you cannot measure 0.0050 cm3 with a 1 per cent accuracy on a four-figure balance, this test must fail. But is this a serious failure? The answer will depend on what the pipette is being used for in the studies. If it is crucial to measure 0.0050 cm3 volumes to this degree of accuracy then failure must be important, but if only larger volumes are being measured then the failure is not significant, but it does suggest that the SOP has been written without careful consideration and should have been revised. A useful exercise for the students is to take these ideas away and to consider, for example, the practical work that they are doing in other parts of their course. While they are not expected to work to GLP during undergraduate practicals, they should consider whether or not their work demonstrates good practice. They may like to write SOPs for apparatus that they use or devise a means to calibrate a spectrometer before recording a spectrum of an unknown sample.
Students would also benefit from considering the following simple questions as they undertake practical work: 'Am I making this measurement to a sensible degree of accuracy?'; 'How should I best save and store the data that I have recorded?'; 'Will the balance still work if it is on a surface which clearly is not level?'. A basic knowledge of
GLP helps them to consider such concepts and enhances their overall learning experience.
Student feedback on this work is generally good. Comments have included: 'It was much more interesting than I thought it would be'; 'I have come across GLP at placement interviews so this was useful'. However, one student did say: 'People should be able to record their own data properly; there is no need for an authority like this'. Clearly an idealist, but as we do not live in such an ideal world GLP will remain an important part in the lives of analytical chemists.
Dr Matthew Almond is a senior lecturer in the school of chemistry at the University of Reading, Whiteknights, Reading RG6 6AD and Dr Samantha Atkinson is a GLP inspector at the Medicines and Healthcare products Regulatory Agency (MHRA), 10-2 Market Towers, 1 Nine Elms Lane, London SW8 5NQ.
Good laboratory practice pocket book, MHRA. London: OECD, 1992.
Good laboratory practice, guidance on archiving, MHRA. London: OECD, 2006.
Good laboratory practice, OECD principles and guidance for compliance monitoring. London: OECD, 2006.
The good laboratory practice (codification, amendments etc) regulations. London: The Stationery Office, 2004.
W. Y. Garner, M. S. Barge and J. P. Ussary (eds), Good laboratory practice, standards and applications for field and laboratory studies. Oxford: OUP, 1992.
Box 1 - Good laboratory practice
GLP is only one of several areas of good practice monitored by the Medicines and Healthcare products Regulatory Agency.
Good clinical practice (GCP). A set of internationally recognised quality requirements which must be observed in clinical trials that involve human subjects.
Good manufacturing practice (GMP). The part of quality assurance that ensures that medicinal products are produced and controlled to the required standards.
Good distribution practice (GDP). The part of quality assurance that ensures that products are stored, transported and handled under suitable conditions.
Good pharmacovigilance practice (GPvP). The science of collecting information on adverse effects of medicines to identify information on potential new hazards and to prevent harm to patients.
Box 2 - Glossary
Study director - has the responsibility for the overall conduct of a regulatory study and for its final report.
Principal investigator - an individual who, in a multi-site regulatory study, acts on behalf of the study director and has defined responsibilities for one or more phases of the study.
QA programme - a defined system, including personnel, which is independent of how the study is done but is designed to assure test facility management of compliance to the principles of GLP.
Raw data - all original test records and documentation, or verified copies, which are the result of the original observations and activities in a regulatory study.
Reference item - any article used to provide a comparison with a test item.
Test item - an article that is the subject of a regulatory study.
Test system - any biological, chemical or physical system or combination used in a regulatory study.
Test facility - a facility which conducts or intends to conduct a regulatory study.
Test site - a location at which a phase of a regulatory study is conducted.
Master schedule - compilation of information to assist in the assessment of workload and tracking studies.