Quality management in analytical R&D in the pharmaceutical industry: Building quality from GLP

 The pharmaceutical industry is one of the most regulated activity sectors. The regulation includes specific quality systems such as good laboratory practice (GLP), good clinical practice (GCP) and good manufacture practice (GMP). The principles of GLP mainly cover the formal quality aspects of a procedure and do not evaluate the technical aspects in depth. On the other hand, EN 45001 accreditation covers technical performance and is not suitable for pharmaceutical research and development (R&D) as it is almost impossible to comply with the requirements of the European standard in the pharmaceutical environment. The challenge to the pharmaceutical industry is, therefore, to develop quality systems, compatible with GLP principles, that not only cover formal quality items but also ensure good scientific and technical performance. An implementation process focused on real quality improvement is the best way to achieve this objective, culminating in formal recognition of the quality system by third-party assessment. In the case of analytical R&D, the EURACHEM/CITAC Guide CG2 is a very good tool that can help in the definition, analysis and selection of the non GLP quality elements that will be useful. Received: 30 June 1999 / Accepted: 18 October 1999     

Quality assurance in analytical chemical laboratories: Towards harmonization and integration of current standards

This article presents the results of a comparative study of the main quality assurance (QA) and good laboratory practice (GLP) regulation systems and standards for analytical chemical laboratories currently being applied in Europe. A growing number of laboratories are being confronted with the need to cope with two or more of these systems, which involves separate audits and inspections for certification and accreditation. As these regulatory systems have essentially the same aims, there is an increasing interest in harmonization of QA and GLP guidelines. As a first step in exploring the possibilities of harmonization, similarities and differences of the current systems, compiled in the form of cross reference tables, have been analyzed (from a laboratory practice point of view) by a study group of EURACHEM, The Netherlands. The conclusions of this study have recently been endorsed by the Committee of EURACHEM Europe.     

Integrating accreditation, good laboratory practice and good manufacturing practice in an industrial analytical laboratory

 The Analytical Laboratory of BASF is a central service unit for chemical analysis which can be used by all departments within the company. It carries out routine as well as non-routine work and has a high amount of R&D orders. A quality system conforming with GMP rules was installed in the 1970s, followed by a GLP system about 6 years later. In 1995 an EN 45001 certificate was granted, which also stated the conformity with ISO 9002. A "types of test" orientated system was chosen for accreditation. This was better suited to the needs of a testing laboratory with a high amount of non-routine work than a purely test-procedure orientated accreditation. An integrated quality system has now been developed from these activities. It has partly common elements and partly differing elements taking into account specific regulations. For example, instrument calibration, staff training, validation of test procedures and the use of computerized systems are covered by uniform rules. Other elements such as handling of samples and report generation are arranged according to the individual requirements of the various standards. Rules and regulations are laid down in a system of documents which comprise the quality manual, general standard operating procedures (SOPs), laboratory-specific SOPs and test procedures. The quality system has been accepted by other accreditiation bodies on application of special accreditations (workplace safety, biodegradable polymers). But it has had no advantageous influence on getting GLP certification. An integrated system is very complex and requires appreciable resources. Management of processes and documentation can only be handled by extensive use of computers. Frequent training of staff and internal audits are necessary to keep the system at an acceptable level. In order to reduce the complexity of quality management regulations a harmonization of the different quality systems would be desirable. Received: 1 October 1998 · Accepted: 10 January 1999     

QASKI – the quality assurance system of the National Institute of Chemistry

 The quality assurance system (QASKI) developed and implemented in the National Institute of Chemistry is presented. It tries to eliminate the incompatibilies between the present methods of quality assurance used in research and development institutes such as good laboratory practice and accreditation. Since 1991, QASKI has been used for internal accreditation of laboratories located in the institute, regardless of the fact that some of them deal with routine analyses and others with research and development. Every laboratory that wishes to ensure the credibility of its research or routine work enters QASKI and at the same time chooses an external method of approval. All interested laboratories, study directors, principal investigators, internal auditing staff, heads of documentation, quality assurance unit staff, the Director of the institute and the Quality Management Board participate in the internal system.     

NATA: 50 years experience with accreditation

 Laboratory accreditation is becoming increasingly accepted around the world as a means of identifying technically competent laboratories. It is also being used as a mechanism for the acceptance of test data both nationally and internationally. The concept and mechanisms of accreditation have been developed over the past 50 years. The first national laboratory accreditation system appeared in Australia in 1947. This organisation, known as the National Association of Testing Authorities (NATA), has since taken a leading role in developing accreditation practices that are now used world-wide in evaluating testing, measurement and calibration laboratories. This paper examines the development of the world's first and largest laboratory accreditation system, and looks at the difficulties and triumphs in gaining acceptance and recognition by government and industry of the benefits of laboratory accreditation. Received: 24 June 1996 Accepted: 25 June 1996     

Is good laboratory practice necessarily good analytical practice? Is GLP necessarily GAP?

According to the chemical legislation in force in most of the industrialized nations to protect man and the environment from the harmful effects of hazardous substances and preparations, a product must be subjected to a large number of mandatory tests before it may be marketed, to demonstrate that it shows no adverse effects on man or the environment when properly handled. To ensure that the results of tests are comparable and above all verifiable, the OECD has drawn up a set of guidelines for Good Laboratory Practice, GLP, on the request of the FDA and EPA authorities in the USA. The application of these guidelines is now mandatory for all the tests specified by the chemical legislation, also for analytical methods. These methods not only apply to the stipulated determination of physical and chemical parameters they also apply to toxicological and ecotoxicological tests. Comprehensive documentation of all stages of these tests from preparatory work to reporting is designed to make the results verifiable. Agreement with the principles of GLP means that the procedures used in a test have been documented in such a manner as to be verifiable. However, does compliance with GLP necessarily guarantee accurate analytical values and thus correct test results? Is GLP necessarily also Good Analytical Practice, GAP? In the following the authors try to provide the answer.     

The experience of accreditation of an analytical laboratory at the Argentine Atomic Energy Commission

The implementation of a quality system based on the ISO/IEC 17025:1999 standard is a growing necessity for analytical laboratories to demonstrate their technical competence. In 2001, the Nuclear Analytical Techniques Group of the Argentine Atomic Energy Commission obtained the recognition of the International Atomic Energy Agency in the application of neutron activation analysis and the accreditation by the national accreditation body. The importance of the participation of the group in the Agency's Regional Programme for Latin America, ARCAL XXVI on Quality Assurance in Analytical laboratories is discussed, as well as the activities performed to attain these objectives. Some improvements worth mentioning resulted from the implementation of the quality system and, following the premise of continuous improvement, changes were introduced aiming at the laboratory re-accreditation.     

The Japan Accreditation Board for Conformity Assessment – Introduction to the Japanese accreditation system

 The background to the establishment of the Japan Accreditation Board for Conformity Assessment (JAB) is reviewed in relation to the latest global developments in conformity assessment activities. JAB (known as the Japan Accreditation Board for Quality System Registration at the time of its establishment) was established in 1993 as the accreditation body for quality system registration, the focal point for conformity assessment in the private sector in Japan. The extension of the area of accreditation was made in June 1996, covering all conformity assessment activities including laboratory accreditation, which resulted in the amendment of the name of the body to the current one. Various elements of the laboratory accreditation program are introduced to give the overview of this new program. Received: 2 October 1996 Accepted: 5 December 1996     

Pathology laboratory accreditation: the Australian experience

 The National Associating of Testing Authorities, Australia (NATA) is a laboratory accreditation company that has been involved in the accreditation of pathology laboratories since 1982. This role is carried out in conjunction with the Royal College of Pathologists of Australasia (RCPA). The accreditation process is known as the NATA/RCPA scheme. The NATA/RCPA accreditation scheme originated from the desire to raise professionalstandards in pathology. The scheme aimed to achieve this through a peer review process in which education and voluntary participation were stressed. In 1986, the Australian Federal Government adopted the scheme as its measure of the competence of testing by pathology laboratories seeking payment from the Commonwealth Department of Human Services and Health reimbursement scheme, Medicare. This meant that NATA/RCPA accreditation became mandatory for such laboratories. The benefits of peer review as a means for establishing professional competence and the challenges a mandatory accreditation program poses to such a scheme will be discussed. Received: 6 May 1996 Accepted: 29 May 1996     

Experience with in-house PT-schemes in the chemical industry

There are many different means of demonstrating the quality of performance of an analytical laboratory. Proficiency testing (PT) is just one! As in other analytical fields, interlaboratory comparisons play an important role in the chemical industry. Collaborative trials or method performance studies do have a long tradition in this field. Sometimes they were designed as laboratory performance studies with the clear aim of making analytical results comparable, e.g. petrol, coal, gas, noble metals analyses – not to mention the biggest PT scheme run on a daily world-wide basis – trade itself. All this is an ongoing process, which started long before the idea of assessing and accrediting the performance of analytical laboratories was born. However, when striving for accreditation in 1996, the analytical production laboratories of the Chemicals Business Unit of the Bayer AG in Germany implemented another facet of PT schemes. In-house-PT schemes are performed regularly and turned out to be useful in evaluating, monitoring, and thus improving, the quality of routine analytical work. Received: 5 December 2000 Accepted: 15 January 2001     

The Slovak National Accreditation System

 After the split of the Czechoslovak Federation, the Slovak National Accreditation System was established in November 1993, being the only system in this country executing accreditation and certification. This system is strictly based on EN 45 000 and covers testing laboratories from both the mandatory and voluntary areas of metrological laboratories, products testing and certification, quality systems, and good laboratory practice. It seeks to reach the level of compatibility accepted and recognized by EU member countries. The development and basic features of the Slovak National Accreditation System, its basic principles, and the structure and competence of accreditation bodies are described in this article.     

Validating automated analytical instruments to meet regulatory and quality standard requirements

Analytical laboratories are more and more faced to meet official regulatory requirements as described in FDA and EPA good laboratory practice, good automated laboratory practice and good manufacturing practice regulations or to officially establish quality systems, such as specified in the ISO 9000 Series quality standards, in the ISO Guide 25 or in the EN 45001 guidelines. The impact on analytical instrumentation will be the requirement for stringent validation of analytical equipment and methods which increase the overall analysis costs. An overview is presented on the validation requirements using e.g. gas chromatography, high performance liquid chromatography, capillary electrophoresis and UV-visible spectroscopy and on the strategy to meet such needs at minimal extra costs with the help of an instrument vendor. It is recommended to use instrument hardware that has already built-in tools for self-verification and which is to be validated at the vendor's site. Performance testing in the user's laboratory is done using standard operating procedures as supplied with the instrument. If resources in the user's laboratory are limited, the performance verification is done by the vendor. Software and the entire computer system is validated prior to shipment at the vendor's site. Acceptance testing is done in the user's environment following the vendor recommendations. Analytical methods are validated automatically at the end of method development using a dedicated software. The software can be customized such that it can also be used for daily automated system suitability testing. Security and integrity of analytical data are ensured by saving the raw data together with instrument conditions and instrument log-books in check-sum protected binary register files for long-term archiving.     

Can single-operator laboratories comply with all of the requirements of ISO/IEC 17025:2005?

ISO/IEC 17025:2005 states that its requirements are “applicable to all laboratories regardless of the number of personnel” and would therefore include single-operator laboratories. However, there are reservations as to whether these laboratories can comply with all of the requirements without jeopardizing independence of judgement and impartiality. Similarly, there are some requirements of ISO/IEC 17025:2005 including staff supervision, internal communication processes and appointment of deputies that are considered unlikely to apply to a single-operator laboratory. The ISO/IEC 17025:2005 is widely used as the international standard of quality assurance by which accreditation bodies assess the competency of testing and calibration laboratories. There does, however, appear to exist, disagreement amongst accreditation experts when considering single-operator laboratories. Some accreditation bodies accredit single-operator laboratories, whilst others require additional human resources prior to granting accreditation. This discrepancy leads to unfair competition amongst laboratories as a single-operator laboratory by definition needs less resources (both human and financial) to achieve and maintain accreditation, compared with a laboratory where additional human resources need to be sought prior to and in order to maintain accreditation. The ISO/IEC 17025:2005 is in the process of being revised, and this is an opportune moment to address the issues aforementioned with the aim of removing ambiguity and enhancing clarity. In addition, the hope is to assist the accreditation bodies themselves to adopt a consensus approach when granting accreditation towards single-operator laboratories.     

Certification of reference materials and accreditation of reference material producers: Questionable terminology leads to confusion

In the view of the Deutscher Kalibrierdienst (DKD) , a certifying body for reference materials can be considered to be a calibration laboratory. Therefore, accreditation of calibration laboratories in accordance with ISO/IEC 17025 is the most appropriate way to establish confidence in certificates for reference materials. If necessary, the criteria of ISO/IEC 17025 can be tailored to specific cases. There is no need to provide any new kind of reference-material specific accreditation. However, in view of the variety of reference materials and the practice existing in other countries, accreditation of testing laboratories and product certification bodies may optionally be acceptable as long as the same stringent principles with respect to traceability and measurement uncertainty are applied. Such accreditations but not accreditations of reference material producers (ISO Guide 34) are also covered by existing international mutual recognition arrangements (MRA).     

Accreditation in analytical laboratories: a critical assessment of its impact on human beings and techniques

Summary The relationships between Quality, Quality Assurance and Third Party Approval by accreditation based on formal application of EN 29002, EN 45001 and ISO Guide 25 are briefly outlined for analytical chemical laboratories working in the non-regulated area. The roles of human beings in laboratories and accreditation bodies are discussed and recommendations are made on how to minimize friction during accreditation processes. The structures of the European Accreditation Systems are reviewed and the efforts towards mutual recognition of the national accreditation bodies are described and critically assessed. The lack of competition based on free market conditions in the framework of company law is deplored. The assessment of laboratory systems, rather than assessing the activity of laboratories against technical standards, is recommended (unless it is otherwise requested). The beneficial effects of the process of accreditation on competence and quality of the activity of the laboratory are emphasized.     

The handbook of analytical methods for trace elements as adopted by the national reference laboratories for residues

The instrumental approaches, quality assurance schemes and management of chemical laboratories should in general be harmonized at the highest possible level. This is all the more so for the national reference laboratories (NRLs) for residues in live animals and their products which have to implement quality assurance systems inspired to the principles of good laboratory practice as well as to the general norms for the operation of testing laboratories (EN 45000 criteria). Directive 23/96/EC of 29 April 1996 prescribes that NRLs are assisted in this process by the four community reference laboratories (CRLs) for residues. To this end, the Rome CRL systematically collects in a handbook all the analytical methods in use at NRLs for the determination of As, Cd, Cu, Hg and Pb, as well as other chemical elements, in animal matrices. One major goal of this action is to foster the harmonization of analytical approaches by the NRLs and their ability to provide comparable results of similar quality. The Rome CRL is committed to revise this handbook twice a year. The role of the handbook is also to encourage the exchange of information among the NRLs as regards the possibility of improving existing methods.     

实验室认可基础、评审方法与发展趋势

从什么是实验室认可和中国实验室国家认可委员会、实验室评审认可依据和基本要求、实验室认可过程、现场评审技巧和国内外发展趋势五个方面对实验室认可作了介绍,可为我国实验室逐步实现与国际接轨的规范化管理提供借鉴。     

Integration of parallel-operating quality systems

Since the 1980s, quality systems have become an essential element in successful companies and institutions. Today those systems are indispensable to fulfill the needs of the customers and last but not least the requirements of the society. Depending on the company's activities and fields of services, it is necessary to establish various quality systems. The Institut Fresenius (IF) Group runs a number of analytical laboratories and sampling groups. The whole group was accredited according to DIN EN 45001 in 1994. Good Laboratory Practice (GLP) was introduced in 1992 and was certified by the national authority. For certain customers, IF Group is also obliged to work according DIN EN ISO 9001 or GMP. A comparison of these systems with respect to their different priorities shows the possibility of integrating their rules into one comprehensive quality system. The IF Group has therefore installed a quality system operating in parallel. Multilocation accreditations and/or certifications are taking these efforts into account. The benefits are: high transparency of the system for the customers, auditors and personnel, a reduction of maintenance costs, and great flexibility to react to new standards. Could these activities lead to a new Integrated Management System?