Practical guides 11: Hospital pharmacy quality control services

Transcription

1 ]ournu2 of Clinical Pharmacy and Therapeutics (1995) 20, REVIEW ARTICLE Practical guides 11: Hospital pharmacy quality control services G. J. Sewell PhD Medicines Research Unit, Department of Pharmacy, Royal Devon and Exeter Hospital, Exeter, U.K. SUMMARY This article briefly reviews the evolution, scope and operation of hospital quality control (QC) services. Recent initiatives and developments are considered alongside the traditional 'core' QUquality assurance (QA) work. Important new areas of work which could benefit from QC involvement are also discussed. INTRODUCTION The origins of organized quality control (QC) services in hospital pharmacy can be traced to 1964 when the Hospital Pharmacists Consultative Committee recognized the need for analytical monitoring of medicines produced by hospital manufacturing units and also medicines purchased from external sources. Although the analytical component of hospital QC services has continued to develop, QC departments have become increasingly involved in quality assurance (QA) issues outside of the laboratory setting. The constraints placed on hospital manufacture by the loss of Crown Immunity and Health Service reorganization in the late 1980s could have created an uncertain future for QC services. In reality, however, threats to the viability of hospital QC departments have not materialized. In the case of hospitals which have retained manufacturing units, compliance with Medicines Control Agency (MU) 'special' licensing requirements has increased the QC workload. Many QC departments have adapted to the changing healthcare environment and have developed their services beyond their traditional role to bring their capabilities and expertise to new areas of hospital pharmacy practice. In some cases, QC departments have grasped opportunities to extend their services well beyond the boundaries of the Hospital Pharmacy Department. Correspondence: G. J. Sewell, PhD, Medicines Research Unit, Department of Pharmacy, Royal Devon and Exeter Hospital, Exeter EX2 5DW, U.K Blackwell Science Ltd EVOLUTION OF HOSPITAL QC SERVICES The foundations of the hospital QC service were laid in the 1960s through a combination of internal demand and external legislation. In 1964 the Hospital Pharmacists Consultative Committee made a recommendation to the Ministry of Health that a system of analytical control should be introduced to monitor the quality of medicines produced by hospital manufacturing units and to examine medicines purchased from external sources. Although at the time not directly applicable to hospital manufacture, the Medicines Act of 1968 (I) and subsequent licensing regulations (2) indicated the will of Parliament to control and regulate the production of pharmaceuticals within the United Kingdom. In 1972 the Clothier Committee were asked to investigate and report on an incident in which contaminated infusion fluids (purchased from a commercial source) were used in the Devenport Section of Plymouth General Hospital (3). This report resulted in the issue of HM (73) 18, Contamination of Medicinal Products by the Department of Health and Social Security which required both commercial and hospital manufacturers to introduce QC systems (4). The application of the Medicines Act to health authorities was finally established in HSC(IS)128 (5), which instructed regional health authorities to ensure that defined systems of QC were in place. This health circular also determined the role of Regional Quality Controllers, although management responsibilities and relationships associated with this post were clarified in a further publication (6). A basic structure was therefore established in which Regional Quality Controllers provided monitoring and advisory and specialized analytical services to 'local' QC pharmacists working at unit or trust level. The term 'quality control' is synonymous with the sampling and approval of raw materials and packaging materials for manufacturing processes and with 149

2 150 G. 1. Sewell the testing of finished products. However, analytical testing is only a part of the work carried out by a hospital QC department. Almost 70 years ago, the Therapeutic Substances Act (7) recognized that the safety and efficacy of certain medicines were dependent on a broader approach to quality than testing of the hished product alone. In recent years, the hospital QC service has combined the traditional laboratorybased concept of QC with quality assurance (QA), an all-embracing term inclusive of all factors which individually or collectively influence the quality of medicines. This wider role of the QC service includes taking responsibility for the compliance of hospital manufacturing activities with Good Manufacturing Practice for Medicinal Products (GMP.) The issue in 1984 of the health circular HC (84) 3 by the Department of Health (8) was intended to restrict hospital manufacturing activities through the implementation of rigorous costing policies. Further rationalization of hospital manufacturing resulted from the loss of Crown Immunity in 1990 and the requirement for manufacturing facilities to be licenced by the Medicines Control Agency (MCA). The cost of upgrading facilities to MCA requirements at a time when many hospitals were obtaining Trust status precluded the continued operation of production units with marginal viability. These developments created, at least temporarily, an uncertain future for hospital QC services. Although some hospitals have lost their manufacturing and QC capabilities, most have retained some elements of production, typically non-sterile manufacturing and assembly. Stringent regulatory and licensing requirements have ensured the continued presence of a QC function in these institutions, although in some cases the post of QC Pharmacist is shared with other hospital pharmacy functions. Hospital pharmacy departments that still operate a comprehensive manufacturing service have, in many cases, actually increased the resources made available to their QC departments. Given the income generation potential of pharmacy manufacturing activities and the corresponding importance of QC, this apparently paradoxical development should not be surprising. The continuing importance of the hospital QC services is also partly attributable to diversification from the traditional QUQA role associated with manufacturing activities. Centralized intravenous additive services (CIVAS) are now an essential part of the hospital pharmacy service in the U.K. (9). A major QC input is required to ensure the safety, efficacy and quality of products prepared by CIVAS units (10). Other examples of diversification include the monitoring of surgical dressings (II), evaluation of infusion devices (12) and the application of QA and audit to other hospital pharmacy services (13). The provision of expert advice and the development of occupational exposure monitoring services (14) has enabled QC departments to undertake a key role in the application of the COSHH Regulations (15) to hospital wards and departments. Activities of this type, which transcend the conventional boundaries of hospital pharmacy, provide an excellent opportunity for pharmacists to demonstrate their expertise and flexibility to both hospital managers and fellow healthcare professionals. BENEFITS OF HOSPITAL QC SERVICES The principal benefit of a QC service is usually perceived as meeting the requirements of regulatory authorities such as the U.K. MCA and ensuring compliance with relevant rules and guidance on pharmaceutical manufacture. However, to obtain maximum benefit, QC services should be fully integrated with all functions of the Pharmacy Department. The current interest in 'patient-focused care' is meaningless unless the efficacy and safety of medicines can be assured (16). Such assurance can be achieved with a QC involvement in all aspects of the pharmaceutical supply chain, with particular emphasis on dispensary, CIVAS, procurement and distribution functions. A comprehensive QC service validates and supports these functions through a programme of audit, process and equipment monitoring and the sampling and testing of raw materials, consumables and finished medicines. In addition, the implementation of a rigorous QC programme throughout the Pharmacy Department is seen as a welcome development by risk-management consultants charged with assessing the insurance liabilities of hospitals with Trust status. Hospital QC services also have an important role in the procurement of medicines, dressings and surgical sundries by ensuring that value for money is obtained. This is achieved through the testing of commercially available medicines (1 7, IS), comparative evaluation of generic and branded medicines (19) and the testing of dressings (11) and surgical appliances (20). The contribution of modern QC services now extends beyond the confines of the base department Blackwell Science Ltd, Journal of Clinical Pharmacy 0 Therapeutics, 20,

3 Hospital pharmacy qualify control services 15 1 The testing of piped medical gases in accordance with the relevant Hospital Technical Memorandum (21) is an established responsibility of the QC pharmacist who is designated as quality controller to undertake this responsibility. Nomination of the quality controller for a given hospital is the responsibility of the Regional Quality Control Pharmacist (22). A more recent role for the QC service has arisen from the implementation of Regulation 10 of the COSHH Regulations (15), which requires that occupational exposure monitoring is carried out in workplaces where potentially hazardous substances are used. Hospitals invariably contain many areas in which monitoring is considered to be essential and several QC departments have made a significant contribution to this work (14, 23). Although external contractors could be employed for COSHH monitoring these are often expensive and the availability of resident expertise in this area ensures that problems can be assessed as they arise and that an adequate frequency of monitoring is maintained. Many QC departments undertake formulation and stability studies on medicines manufactured as hospital specials. Although relatively few of these studies are published in the pharmaceutical literature, most QC departments make available their data to the national Stability Database (24). The provision of information on defective medicines to the Analytical Information Centre (AIC) database is a further example of the contribution made by hospital QC services to pharmaceutical projects of national significance. OPERATING A QC SERVICE Level of service The level of QC service required will be dependent upon a number of factors, including the nature and throughput of manufacturing and CIVAS activities, the requirement for additional services such as occupational exposure monitoring and the availability of support from regional or sub-regional QC laboratories. Local QC services are normally restricted to the routine analysis and testing of raw materials and finished products with further activities tailored to departmental and hospital needs. Sophisticated analytical testing, sterility testing, microbiological testing of non-sterile products, and stability studies are often centralized in regional or sub-regional laboratories. The regional QC laboratories (which may also provide a local QC function to their base hospital) normally undertake the majority of testing and evaluation work required to support the adjudication of medicines, dressings and surgical sundries under consideration for regional or supra-regional purchasing contracts. Staffing The QC manager is usually a registered pharmacist with a career background in a manufacturing or QC discipline. With the exception of regional posts, it is now common for the post of QC manager to be combined with other managerial or operational responsibilities within the Pharmacy Department. However, to avoid a conflict of interest, the QC manager must not have any direct involvement in manufacturing operations or any other function which could compromise the independence of the QC operation. Many hospital QC managers are also eligible for registration as Qualified Persons in accordance with Article 22 of the Directive 75/319/ EEC (25). Although there is no requirement for the QC manager to hold Qualified Person status in the conditions pertaining to U.K. specials manufacturing licences, the Code of Practice for Qualified Persons (26) is widely applicable to QC in the hospital service. Guidelines on the responsibilities of the QC manager and training requirements for key QC personnel are also set out in the Rules and Guidance for Pharmaceutical Manufactures (27). The larger regional QC laboratories normally have an additional pharmacist or senior scientist in post with responsibility for the day-to-day management of the laboratory. In smaller laboratories providing only local services, this responsibility is typically held by a senior pharmacy technician or a scientific officer with a degree or HND in a science subject containing a strong element of applied analytical chemistry. Technical work in the QC laboratory is normally undertaken by staff employed on the Medical Technical Officer grade with a BTec qualification in pharmacy or other similar qualifications in a science subject. Recent skill mix reviews have led to the introduction of staff with no formal academic qualifications to support technical staff. Such individuals are normally employed on the Assistant Technical Officer scale and will undertake routine duties such as preparation of reagents and environmental monitoring. Given the complex documentation and data management systems necessary in even a modest-sized QC Blackwell Science Ltd, Journal of Clinical Pharmacy & Therupelcfics, 20,

4 152 G. 1. Sewell department, the importance of competent secretarial support should not be overlooked. Facil if ies The basic requirements for QC laboratories are outlined in the Guide to Good Manufacfuring Pracfice for Medicinal Products (28). Laboratories should be segregated from production areas and should be of appropriate design and adequate size to prevent product mix-ups and cross-contamination. The testing of materials or products with particular hazards (e.g. biologicals and radiopharmaceuticals) should be separated from other QC procedures. The premises should also provide separate areas for the storage of samples and documents, office work and staff rest or refreshment facilities. Laboratories should be well ventilated, preferably using a mechanical air handling system, and should be supplied with mains electricity, gas and hot and cold water services. Since many qualitative tests are dependent on colour comparisons, natural light supplemented with good quality artificial lighting should be provided. A stainless steel sink and drying cabinet should be available within the laboratory for the washing and drying of glassware. A good quality fume cupboard, preferably with external ducting, is an essential requirement in even the smallest of laboratories. Valuable information on the selection and performance of fume cupboards is provided in Health Equipment Information leaflet Number 86 (29). If materials or products submitted for analysis or sterility testing are likely to include cytotoxic drugs, hormones or sensitizing antibiotics, the laboratory should be equipped with a microbiological safety cabinet to BS5726 Class 2 (30) or, better still, an isolator designed for handling cytotoxic drugs which can be operated under negative pressure. Due consideration should be given to the safe storage of materials and solvents used in the QC laboratory. Adequate space must be provided for apparatus, consumables and chemicals and, in particular, consideration needs to be given to the safe storage of flammable solvents in accordance with the relevant Department of Health Building Note (31). Analytical equipment should be of good quality and from reputable suppliers. Volumetric glassware should be of Class A tolerance. Instrumentation used in analytical development and routine analysis, including analytical balances, UV-visible spectrophotometers and high-performance liquid chromatography systems should be capable of producing hard-copy printouts of analytical data. Microcomputer-based instrumentation and data-handling systems should have adequate password protection to enable laboratory managers to restrict access to dderent levels of the programme. Laboratory refrigerators should be fitted with either a temperature record chart or a maximum-minimum thermometer to facilitate regular temperature monitoring. Equipment should be included in a routine monitoring programme to ensure that performance and accuracy meets with Pharmacopoeia1 standards (32). To ensure that analytical equipment is reliable and correctly maintained, it is recommended that a manufacturer s service contract is taken out on all key items of equipment. The QC Department should be provided with facilities for the storage and rapid retrieval of records and there should be access to a good quality photocopying service for the reproduction of master documents. A comprehensive library of official literature, reference books, data tables, chemical and apparatus catalogues, and manufacturers equipment manuals should be available within the QC Department. Examples of key information sources are provided at the end of this article. Method of operation The diversity and complexity of QC services necessitate the implementation of clearly defined systems of work. Systems should be in place for the receipt and storage of samples taken for testing, adequate segregation of products undergoing analysis and the correct completion of all documentation. All laboratoryprepared reagents and microbiological media should be clearly labelled with the reagent name, date of preparation, date of expiry (if appropriate) and the signature of the person responsible for their preparation. Wherever possible, pharmacopoeia1 reference materials should be obtained for use as analytical standards. In cases where this is not possible, reference materials used in quantitative analysis should be of certified purity or independently standardized. Similarly, reagents used in volumetric analysis should be of certified concentration (these are usually supplied as concentrates) or should be standardized and the concentration factor determined. Documentation is the key to good control laboratory practice and the effective operation of a QC Blackwell Science Ltd, ]ournal of Clinical Pharmacy & Therapeutics, 20,

5 Hospital pharmacy quality control services 153 service and standard operating procedures (SOPs) form the cornerstone of QC operations. SOPs are required for the operation and cleaning of laboratory apparatus, the quarantine, sampling and testing of raw materials and finished products, environmental monitoring of production areas, the approval or rejection of raw materials and packaging components, and the release of finished products. Each SOP must be clear and comprehensive and should be dated and approved by the QC manager. A separate SOP must be prepared for the safe operation of the QC laboratory. This document should incorporate the requirements of the COSHH Regulations (15) and should be in general accord with the hospital or trust health and safety policy. It is often helpful to summarize the procedures controlled by SOPs in the form of a flow chart which outlines the workflow and the point of input of each SOP. The control documentation for analytical testing is based on analytical worksheets and a master worksheet, signed and dated by the QC manager, is required for each raw material, packaging component and finished product that will be tested. Photocopies of the master worksheets are made as required and the test results, any calculations used, product or raw materials batch numbers, the date of testing and the signature of the analyst must be recorded directly on the worksheet. The testing schedule on analytical worksheets, including the type of test, method of testing, limits to be applied, and the number of samples of the batch to be tested (e.g. for sterility testing), are derived, where possible, from The British Phamacopoeia (32). In cases where there is no appropriate pharmacopoeia1 monograph for a material or product, the testing schedule and acceptance limits must be based on the product specification and the intended clinical use. Test methodology should be clearly presented on the worksheet; where detaiied methodology is required, a cross-reference to the appropriate SOP should be given. Similar worksheets are required for environmental monitoring of production areas and the testing of piped medical gases, the testing schedule for the latter being derived from HTM 2022 (21). Any variations from the approved methodology should be recorded on the worksheet, and further calibration, validation, or investigational work written up in laboratory books should be cross-referenced. Completed worksheets normally accompany raw material purchase documents or finished product batch documents for assessment by the quality controller. The third category of documentation is concerned with the maintenance of records. Records may be maintained as a hard copy or on a computer database. In the case of the latter, it is essential that data are backed up daily onto a tape to avoid loss of data through disc or program failure. The receipt of all materials and products for testing should be recorded together with details of samples sent to external contractors for testing, so that the progress and completion date of testing can be monitored. Records summarizing the analytical, microbiological, sterility and pyrogen test results (if appropriate) should be maintained for every batch of each product or materials tested. Such records are invaluable for comparative purposes when reviewing current test results, since the detection of trends in test results may highlight production difficulties or non-compliance with production procedures. Other records to be maintained include records of analysis carried out by external contractors, certificates of conformity for raw materials, containers and closures, results of environmental and equipment monitoring and performance and maintenance records for QC laboratory equipment. Environmental monitoring and equipment performance records should be reviewed regularly by the QC manager and the date of each inspection of these records should be recorded. Although not essential, it is advisable to record workload statistics since these can be used to support bids for increased resources which may be required by the QC department. The additional effort of maintaining a QC departmental diary will help to ensure that routine environmental monitoring, equipment performance tests and equipment maintenance are carried out according to schedule and are completed on time. It is recommended by legal experts that a QC department in a hospital with Trust status should maintain all QC documentation in a retrievable form for a period of 11 years (Bevan Ashford, solicitors, Bristol, personal communication). In the absence of nationally organized training schemes, it is usual for new members of staff or staff seconded on a temporary basis to receive in-house training. Such training schemes should be designed to meet individual needs and records of training and level of competency should be maintained by the QC manager. The overall performance of the QC laboratory (including the competency of staff and the operation of equipment) can be assessed by external audit. Laboratory testing schemes organized at both regional Blackwell Science Ltd, Journal of Clinical Pharmacy 6 Therapeutics, 20,

6 154 G.]. Sewell and national levels have been developed in the U.K.. Participating laboratories are supplied with blinded samples and a schedule of testing. The type of product or material supplied and the tests to be undertaken vary on a rotational basis. The results of each interlaboratory test are collated centrally and fed back to participating laboratories together with the mean and the standard deviation of results obtained by the full cohort of laboratories for comparative purposes. The QC manager should regularly review the operation of the QC service to ensure compliance with current regulations and guidelines relating to the manufacture and QA of medicines. Systems of work, the skill mix of staff and the assignment of priorities to the workload must also be re-assessed at regular intervals if the needs of the Pharmacy Department, clinical staff and, ultimately, the patient are to be met on a consistent basis. INTERACTION WITH OTHER PHARMACY SECTIONS Manufacturing and assembly The principal QC services provided to production sections are likely to be concerned with the approval of raw materials and packaging components and the release of finished products. However, the QA function has assumed greater significance in recent years and the approval of production batch documents and production SOPs together with environmental monitoring activities are now important areas of work for the QC manager and laboratory staff. Although the QC manager must remain independent of production operations, it is essential that QC and production staff develop a productive working relationship. Regular meetings between senior production and QC managers are essential to provide muha1 feedback on manufacturing issues, the setting of action levels for monitoring results, and the development of new products. The QC manager should have a key input into training and accreditation programmes for production staff and may assist in the design and monitoring of competency testing schemes. The local QC manager will normally have the responsibility for internal audit of manufacturing and assembly operations, whereas regional QC pharmacists will usually accompany the Medicines Inspector and production manager during site inspections by the MCA. Dispensa y QC departments have a long-established role in the testing and approval of ingredients used in extemporaneous dispensing. The occasional need for clinicians to use medicines or materials imported from outside of the U.K., often without a U.K. Product Licence, presents a considerable challenge to hospital riskmanagement policies. Detailed analysis and review of certificates of analysis (where available) by the QC department can provide further re-assurance on quality, efficacy and safety issues and help to facilitate a treatment which would otherwise not be available. The QC department can undertake formulation and stability studies on medicines prepared extemporaneously by the dispensary and can also advise on the interpretation of information from the literature and national stability data bases. The expertise of QC staff in the application of statistical methodology and in audit procedures can find utility in dispensary performance audits. These skills are in demand from all sections of the Pharmacy Department with an interest in audit or practice research. CIVAS and radiopharmacy The QC requirements of CIVA and radiopharmacy services will differ from those of manufacturing and assembly activities in that end-product testing is not usually possible. As a result, a much greater emphasis is placed on QA and process validation. The QA work will involve the approval of SOPs, the approval of infusion formulations, the development of monitoring, st& training and competency testing programmes, and the random testing of infusions returned unused from wards and clinics. Valuable guidelines on microbiological monitoring and acceptable limits for microbial contamination of aseptic preparation facilities have been published by the Parenteral Society (33). In the absence of end-product testing, the importance of process validation cannot be overstated. Recommendations published by the Department of Health on CIVA dispensing services (34) place considerable emphasis on validation. This function should become a routine element of the QC service and should include the validation of computer systems used by CIVA and radiopharmacy units and the validation of assigned product shelf-lives. Audit of CIVA and radiopharmacy units for compliance with local Blackwell Science Ltd, Journal of Clinical Pharmacy 6 Therapeutics, 20,

7 Hospital pharmacy quality control services 155 operating procedures and with national guidelines (34,35) is also normally undertaken by the QC pharmacist. In the case of cytotoxic drugs, where health and safety issues complicate drug handling and the preparation of infusions, audit tools have been published to help with this process (36). Drug information Ideally there should be a two-way exchange of information between the QC and drug information departments. The most obvious interaction will centre around the use of the drug information department by QC staff needing to supplement their own, more limited, literature and reference resources. New work or research projects to be undertaken by the QC department will often originate from a drug information enquiry. This may arise from a requirement for new products, new formulations of existing products, or the need for additional stability information to support a new method of drug administration. The QC department will be expected to support the drug information service through the provision of advice on the interpretation of literature relating to scientific and technical issues and to provide an opinion on issues arising from clinical practice such as Y-site and giving set compatibilities of drug infusions. Occasionally, the QC department may be asked to provide analytical support to assist in the identification of medicines or materials which may have been implicated in a clinical incident. This review of interactions between the QC department and other sections of the hospital pharmacy is not intended to be exhaustive. However, it should be apparent that integration of the QC department with other sections of the pharmacy service is essential to enhance the level of pharmaceutical services provided. THE FUTURE After a period of uncertainty resulting from the closure of non-viable hospital manufacturing units, the future for the hospital pharmacy QC service is now more secure. The QUQA workload associated with obtaining and maintaining *specials manufacturing and assembly licences and wholesaler dealer licences will ensure a continuing role for the hospital QC service. Furthermore, the rationalization of specials production and the possibilities for income generation have provided an impetus for remaining hospital production units to develop their product range so promoting parallel developments in QC services. A promising future is predicted for pharmacy aseptic services (9) and continuing growth in this area will place increasing demands on QC services, particularly the QA aspects associated with process validation, monitoring of facilities and audit. Recent guidance published by the Department of Health (34) recognized that in some hospitals standards of aseptic preparation camed out under Section 10, exemption of the Medicines Act, have not been concordant with nationally accepted standards. This document re-inforced the requirement to set up a comprehensive quality assurance programme for all aseptic preparation activities, whether or not they are licensed. It is likely that innovative QC departments will develop a much wider role and that the scope of their activities will extend further beyond the normal QUQA functions and beyond the boundaries of the pharmacy department. This will be mediated by a greater involvement in practice research, audit and collaborative work with other scientific departments (e.g. medical physics, clinical biochemistry). Opportunities to collaborate with the pharmaceutical and medical device industries on projects of mutual interest will increase. An informed and authoritative input into the development and purchase of commercially available products promises clinical benefits for the patient, operational benefits for healthcare staff and value for money for purchasing hospitals. Occupational exposure monitoring has been a growth area for many QC departments since the introduction of the COSHH Regulations (15). Many departments have now developed an established role in the exposure monitoring of antiseptics, dusts, anaesthetic agents and a variety of other substances used or produced within the hospital. In many cases, the involvement in monitoring will expand into an advisory role on COSHH issues which will encompass control methods and working practices. Interaction with senior managers and other healthcare professionals will further highlight the scientific and practical expertise available in the majority of QC departments. Such recognition is imperative if the QC function is to be viewed as a valued resource by the modem healthcare provider Blackwell Science Ltd, Jo~rnal of Clinical Pharmacy 6 Therapeutics, 20,

8 156 G. 1. Sewell CONCLUSIONS The hospital pharmacy QC service has made an outstanding contribution to the safety, quality and efficacy of medicines used in our hospitals and to the developments of clinical and pharmaceutical services. In future years, QC services should be able to consolidate, and in some cases enhance their QUQA responsibilities for production and preparation activities. It is important that QC pharmacists fully exploit new opportunities and actively contribute to practice research, audit and general quality initiatives which are applied to various aspects of the pharmacy service. These developments will require a much closer integration of the QC department with the work of other pharmacy sections. Opportunities for QC departments to expand their role have never been better and wider recognition of the blend of scientific and technical expertise coupled with strong practical skills offered by QC departments, will reflect well on the hospital pharmacy service as a whole. REFERENCES 1. Medicines Act (1968). 2. Department of Health and Social Security. The Medicines (Standard Provision for Licences and Certificates) Regulations (1971) SI1971 No Department of Health and Social Security. (1972) Report of fhe Committee Appointed to Inquire into the Circumstances, including the Production, which Lead to the Use of Contaminated Infusion Fluids in the Deuonport Section of Plymouth General Hospital, Chaired by C.M. Clothier. 4. Department of Health and Social Security. (1973) Contamination of Medicinal Products, HM(73)18. HMSO, 5. Department of Health and Social Security. (1975) Application of Medicines Act to Health Authorities, HSCIIS) Department of Health and Social Security. (1977) Health Services Management. Application of the Medicines Act to Health Authorities: Qualify Control, HN/77) Therapeutic Substances Act (1926). 8. Department of Health. (1984) Health Services Management: Manufacture of Products in the NHS, HC(84)3. 9. Allwood MC. (1994) Practical guides I: Central intravenous additive services. Journal of Clinical Pharmacy and Therapeutics 19, Lee MG, Munton T, Haines-Nutt F, Thorn E, Jones K, Fenton-May V. (1992) The quality assurance of aseptic preparation in hospital services. The Pharmaceutical Journal, 248 (Hospital Supplement), HS Thomas S. (1983) The development of a surgical dressings monitoring facility. Proceedings of the Guild of Hospital Pharmacists (Autumn), No. 17, Hardy E, Sewell GJ. (1993) An evaluation of ambulatory infusion devices for use in home chemotherapy. Proceedings of the Third International Symposium on Oncology Pharmacy Practice, Toronto, Canada. Abstract No. 26, Shaw R. (1993) Quality assurance of hospital pharmacy services. The Pharmaceutical Journal (Hospital Supplement), Hs Sewell GJ. (1989) An evaluation of three systems for the extraction of methymethacrylate vapour in orthopaedic operating theatres. British Journal of Theatre Nursing, 26, HeaIth and Safety Commission. (1988) Control of Substances Hazardous to Health Regulations. 16. Anon. (1994) Caring about stability and compatibility (Editorial). American Journal of Hospital Pharmacy, 51, Lee MG, Ireland DS. (1988) Quality control (Letter). The Pharmaceutical Journal, 240, Bain R, Freeston L, Butler S. (1988) Quality control (Letter). The Pharrnaceufica/ Iotlrnal, 240, Lee MG, Ireland DS, Dwyer PJ, Weir PJ. (1993) Comparison of salbutamol inhalers available in the United Kingdom. The International Journal of Pharmacy Practice, 2, Cottenden AM, Ledger DJ. (1991) The IS0 Pod Leakage Project An update. NDA lournal of Nonwovens Research, 3, NHS Estates. (1993) Good Practice Guide: Medical Gas Pipeline Systems. Health Technical Memorandum 2022, 22. Fenton-May V, Ranshaw C. (1991) Medical gas testing and the hospital pharmacist. The Pharmaceutical Journal (Hospital Supplement), HS Brown AF, Musgrove N, O Sullivan J. (1984) Hazards of testing piped medical gases. The Phamaceutical Journal, 232, Grassby PF. (1994) UK Stability Database. Welsh Pharmaceutical Services, Pharmaceutical Unit, St Mary s Hospital, Penarth, W. Glamorgan. 25. Anon. (1975) Products for human use. Directive 75/319/EEC. Office for Official Publications of the European Communities, Luxembourg. 26. Medicines Control Agency. (1993) Code of Practice for Qualijied Persons: Rules and Guidance for Phamaceutical Manufacturers. 27. Medicines Control Agency. (1993) Guide to Good Manufacturing Practice for Medicinal Products: Personnel Blackwe11 Science Ltd, Journal of Clinical Phmacy 0 Therapeutics, 20,

9 Hospital pharmacy quality control services 15 7 Rules and Guidance for Pharmaceutical Manufacturers. 28. Medicines Control Agency. (1993) Guide to Good Manufacturing Practice for Medicinal Products: Premises and Equipment. Rules and Guidance for Pharmaceutical Manufacturers. 29. Department of Health. (1980) Laboratory Fume Cupboards: Recommendations Concerning Choice Installation, Performance, Routine Maintenance and Use. Health Equipment Information No. 86, 30. Department of Health. (1989) The Control of Substances Hazardous to Health: Guidance for the Initial Assessment in Hospitals Department of Health. (1988) Accommodation for Pharmaceutical Services. Health Building Note 29. HMSO, 32. Anon. (1993) The British Pharmacopoeia. HMSO, 33. The Parenteral Society. (1989) Environmental Contamination Control Practice. Technical Monograph No. 2, The Parenteral Society, Swindon. 34. Department of Health. (1995) Aseptic Dispensing for NHS Patients. 35. Quality Control Sub-committee. (1993) The Quality Assurance of Aseptic Preparation Services. Edition 1, Regional Pharmaceutical Officers Committee, 36. Allwood MC, Cass Y, Goss IJ, Lee MG, Shaw RJS. (1993) Health and safety aspects of cytotoxic services. In: The Cytotoxics Handbook. eds Allwood MC, Wright P, Radcliffe Medical Press, Oxford. APPENDIX: KEY SOURCES OF INFORMATION Official literature relating to QCIQA Rules and Guidance for Pharmaceutical Manufacturers. (1993) Health Technical Memorandum Good Practice Guide: Medical Gas Pipeline Systems. (1993) HMSO, The British Pharmacopoeia. (1993) The Pharmaceutical Codex. (1994) 12th edn, The Pharmaceutical Press, London (1994). Aseptic Dispensing for NHS Patients. Department of Health, London (1995) QAlQC reference matm'al Lee MG, Munton T, Haines-Nutt F, Thorn E, Jones K, Fenton-May V. (1992) The quality assurance of aseptic preparation in hospital services. The Pharmaceutical Journal, 248 (Hospital Supplement), HS Grassby PF. (updated 6-monthly) UK Stability Database. Welsh Pharmaceutical Services, Pharmaceutical Unit, St Mary's Hospital, Penarth, S. Glamorgan. Allwood M, Wright P, eds. (1993) The Cytotoxics Handbook. Radcliffe Medical Press, Oxford. Moffat AC. (1986) Clarke's Insolation and Ident$cation of Drugs. The Pharmaceutical Press, Health and Safety and COSHH Control of Substances Hazardous to Health Regulations (1988). (1993) The Control of Substances Hazardous to Health: Guidance for the Initial Assessment in Hospitals. (1989) HMSO, COSHH in Laboratories. (1989) The Royal Society of Chemistry, Blackwell Science Ltd, Journal of Clinical Pharmacy 6 Therapeutics, 20,