topic guide 4.4: quality assurance in the laboratory

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Unit 4: Quality assurance and quality control

Ensuring the quality of analytical data in the laboratory is essential to ensure ongoing customer confidence in any laboratory’s work, and this is the purpose of quality assurance (QA). QA is typically ensured by having a quality management system (QMS). Many organisations have also attained one or more QA standards.

In Topic guide 4.1 you were introduced to QA and QMS. In this topic you will learn about a number of QA standards relevant to analytical laboratories.

On successful completion of this topic you will: • understand quality management systems (LO3) • understand the accreditation process (LO4).

To achieve a Pass in this unit you will need to show that you can: • compare quality management standards (3.2) • explain the operation of a quality management system (3.3) • analyse the differences between quality management systems in two

laboratories (3.4) • explain the benefits of accreditation (4.1) • discuss laboratory accreditation procedures (4.2) • analyse how accreditation may influence the quality management

system (4.3).

Quality assurance in the laboratory4.4

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4.4: Quality assurance in the laboratory

1 Introduction to quality assurance (QA) standards

There are a number of quality assurance (QA) standards designed to ensure quality. Some are specific to a particular industry, while others are more general in their scope. The International Organization for Standardization (ISO) is responsible for producing many standards. We will be considering the following standards:

• ISO 9001:2008 ‘Quality management systems – Requirements’ • ISO/IEC 17025:2005 ‘General requirements for the competence of testing and

calibration laboratories’ • ISO 15189:2007 ‘Medical laboratories – Particular requirements for quality and

competence’ • Good Laboratory Practice (GLP) • Good Manufacturing Practice (GMP).

ISO 9001 is a widely applied general standard that can be applied to any form of manufacturing or service industry. The other standards are specific to the analytical and pharmaceutical industries.

ISO 17025 is designed for laboratories that test and calibrate materials and equipment. ISO 15189 is specifically for clinical (medical) laboratories.

Good Laboratory Practice (GLP) applies to the safety testing that new chemicals and pharmaceuticals have to undergo before they are sold or used commercially. Good Manufacturing Practice (GMP) is the standard that regulates the manufacture of pharmaceuticals.

There are two different kinds of standards for quality systems: • where the level of competence is set by an authoritative organisation. For

example, ISO 17025 defines the minimum requirements for the QA system as applied to specific tests, plus the overall management structure of the laboratory. Independent assessors judge whether a lab has reached this standard

• where the level of competence or the quality is set by the customer. Here the role of the QA system is to ensure that the requirements of the customer are fully met. This is the case for ISO 9001.

Activity 4.4.1Consider who the clients are for the work carried out at your laboratory or workplace.

• Are they internal and/or external to your company or institution? • How do your lab’s clients make use of the results?

Activity 4.4.2 • Does your workplace have a written quality management system? • Identify any features or elements of the system that affect or relate to your work. • Do you have internal audits to ensure you are working to the requirements of your

organisation’s system? • Who is the most senior person in your organisation responsible for quality?

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ISO 9001:2008ISO 9001:2008 is primarily concerned with enabling an organisation to ensure the quality of a product or service. It is very general in its scope as it is intended to be applicable across both the service and manufacturing sectors, and it has been widely adopted in the chemical industry.

It is concerned with what the organisation should do to ensure that the customer’s requirements are understood and met and that any applicable regulatory requirements are achieved. It aims to enhance customer satisfaction by having an effective quality system that ensures that the organisation conforms to customer and regulatory requirements, and that the organisation’s performance is continually improved.

ISO 9001:2008 is the latest version of the standard – the 2008 refers to the year in which this version of the standard was adopted.

ISO 9001:2008 has eight sections. Like most ISO standards, the first three are brief paragraphs covering the scope of the standard, and the reference sources for terms and definitions used. The remaining five relate to:

• the quality management system • responsibilities of top management • human resources and infrastructure • generating and providing the product or service • monitoring the implementation of the QA system.

ISO 17025:2005The ISO standard most relevant and applicable to analytical laboratories is ISO/IEC 17025:2005 ‘General requirements for the competence of testing and calibration laboratories’. IEC is the abbreviation for the International Electrotechnical Commission. In Europe this standard is known as BS EN ISO/IEC 17025:2005, where EN is the abbreviation for Norme Européenne (i.e. European standard) and BS is the abbreviation for British Standard.

ISO 17025 is divided into five sections. Sections 1–3 are brief paragraphs covering the scope of the standard, and the reference sources for terms and definitions used. Section 4 covers management requirements and section 5 covers technical requirements. Section 4 and many of the more general statements and headings in section 5 relate directly to equivalent sections in ISO 9001, but ISO 17025 also covers requirements for technical competence that are not covered by ISO 9001.

Laboratories that meet the requirement for ISO 17025 also meet the requirement for ISO 9001, so there is the same focus on meeting the needs of the customer.

The technical requirements for ISO 17025 include demonstrating the following: • having trained, competent and knowledgeable personnel • having suitable laboratory facilities • using validated methods

Activity 4.4.3Is your laboratory or workplace accredited to any QA standard(s), and if so, which? Do external assessors visit and inspect your workplace?

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• providing estimates of the measurement uncertainty • demonstrating traceability of measurement by using calibrated instruments

and equipment and certified reference materials • demonstrating sample traceability by logging, labelling, storing and tracking

samples appropriately • monitoring performance with QC standards, control charts, replicate samples

and proficiency testing.

ISO 17025 assesses the competence of the laboratory and its analysts, and is intended to assure customers of the accuracy of analytical tests.

ISO 15189:2007Doctors rely on accurate and rapid analyses of clinical samples for the correct diagnosis and treatment of patients. ISO 15189 is aimed at ensuring that results of tests in clinical laboratories are of an appropriate standard.

ISO 15189, like ISO 17025, is divided into five sections. Sections 1–3 are brief paragraphs covering the scope of the standard, and the reference sources for terms and definitions used. Section 4 covers management requirements and section 5 covers technical requirements. Section 4 and many of the more general statements and headings in section 5 relate directly to equivalent sections in ISO 9001, but ISO 15189 also covers specific aspects that are not in ISO 9001.

As clinical samples are taken from patients, correct sample collection, transport and storage are crucial given that samples may be a biological hazard and may deteriorate quickly. Traceability of the sample and its analytical results to the originating patient is also essential – the consequences of assigning the wrong result to a patient could be fatal.

The amount of information provided to the clinical analyst is important as this can affect interpretation of data. Also some analyses may be time-critical or require the clinical scientist to alert doctors to a critical situation. Clinical laboratories must participate in proficiency testing schemes to demonstrate their effectiveness.

Good Laboratory Practice (GLP)New chemicals that are brought onto the market must be tested to determine their hazards and risks to users, the general public and the environment. Good Laboratory Practice (GLP) is a QA scheme for ensuring that safety testing of chemicals (covering pharmaceuticals, agrochemicals, cosmetics, food and feed additives and contaminants, novel foods and biocides) is carried out correctly, and that the results can be relied upon, for example, when making risk or safety assessments.

GLP was set up to prevent the submission of fraudulent data, and to ensure that the data submitted to regulatory and drug licensing authorities are a true reflection of the results obtained in tests. It is an international scheme, and therefore also ensures that the data produced are accepted internationally.

GLP provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived. Laboratories are accredited to carry out tests but the tests themselves are not accredited. In the UK, GLP is operated by the GLP Monitoring Authority (GLPMA) from within the Department of Health.

Key termTraceability: Property of the result of a measurement or the value of a standard whereby it can be related to stated references, usually national or international standards, through an unbroken chain of comparisons all having stated uncertainties.

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To ensure that data can be authenticated, all data generated must be fully documented and recorded. Laboratory protocols and standard operating procedures (SOPs) have to be written down and followed and any deviations from them have to be clearly identified and justified. However, there are no specific requirements for tests to be validated.

All raw data must be archived at the end of the study and indexed to allow orderly storage and rapid retrieval, and access to the archive must be controlled. The aim is to enable a clear data audit trail in case of future queries about the safety or hazards of a chemical being tested.

Take it furtherFind out more about GLP by looking at the MHRA website (www.mhra.gov.uk) and use the ‘Browse by A–Z’ link to find the GLP pages.

Good Manufacturing Practice (GMP)Pharmaceutical manufacturers have to ensure that their products are very high quality, and the standard that is applied is GMP. GMP has been defined as ‘that part of QA which is aimed at ensuring that medicinal products are consistently produced and controlled to the quality standards appropriate to their intended use’. In the UK it is the job of the Medicines and Healthcare products Regulatory Agency (MHRA) to regulate pharmaceutical manufacture.

The principles of GMP and its use in the control of the manufacture and sale of pharmaceuticals for human use are given in an EU directive, 2003/94/EC, ‘Laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use’.

The regulations include requirements for having a quality control laboratory to test starting materials, intermediates and finished products, and also the packaging materials for the products.

Take it furtherFind out more about pharmaceutical regulation by looking at the MHRA website (www.mhra.gov.uk) and use the ‘Browse by A–Z’ link to find the GMP pages.

2 Comparison of QA standards for laboratoriesGeneral QA standards such as ISO 9001 are concerned with procedures, and are not concerned with the underlying science and the technical skills of analysts. They focus on the ability of the laboratory to control the analytical process, for example, by ensuring that the tests carried out are the ones the customer requires.

The advantages of ISO 9001 are that it is international and well recognised. The disadvantages of ISO 9001 for analytical laboratories are that it does not directly address any specific activities that assure the scientific validity of the analytical

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methodology being used: it is not specific for laboratories, it is not peer-assessed, and it is weak in the assessment of technical competence.

ISO 17025 is primarily concerned with traceability of calibration and measurement, and the accuracy and validity of the individual analytical measurements. It also ensures that the laboratory has proper management controls (using the management and procedural aspects of ISO 9001), in particular, in addressing the requirements of the customer.

The advantages of ISO 17025 for analytical laboratories is that it is international and well recognised, it covers data validity and technical competence, and it uses peer assessment by external experts to assess the ability of a laboratory to perform specific tests. The disadvantages are that it requires regular reassessment and is expensive to maintain. There are similar advantages and disadvantages with ISO 15189.

GLP is most concerned with data integrity in safety studies for submission to regulatory authorities such as the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK, or the Food and Drug Administration (FDA) in the US. It ensures that data obtained in safety trials can be authenticated. There is a particular emphasis on having clear data audit trails.

GLP has a general requirement for tests to be able to produce valid data, and for using validated methods where possible, but individual tests are not specifically assessed. It is the laboratory, its procedures and its ability to authenticate the data produced in tests that are assessed.

The advantages of GLP for analytical laboratories are that it is international and well recognised, and it ensures proper data audit trails. The disadvantages are that it is not a peer-assessed system and it is weak in the assessment of technical competence.

Take it furtherLook at the following link to the National Measurement System for information on several quality standards:

http://www.nmschembio.org.uk/GenericListing.aspx?m=355

3 Laboratory accreditationAccreditation schemes seek to ensure that laboratories are capable of conducting calibrations and tests in a technically competent and impartial manner so that customers can be confident in the validity of reports and certificates issued by accredited laboratories.

Many sectors that use results of laboratory tests now require that laboratories are accredited to an appropriate standard. For example, forensic laboratories now have to be accredited to ISO 17025, and hospital laboratories should be accredited to ISO 15189.

Where a customer wishes to or is required to use an accredited laboratory (perhaps to satisfy its own accreditation requirements) then an unaccredited laboratory cannot take on the work, which will be lost business. There may be

Key termAccreditation: A third-party statement that a laboratory has demonstrated competence in specified tests or calibrations and has an appropriate quality management system.

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sufficient business for an unaccredited laboratory to survive, but as regulation increases in many sectors, the opportunities for accredited laboratories will increase at the expense of unaccredited laboratories.

A lack of accreditation does not necessarily mean that a laboratory does not produce good-quality work, but there is no independent assessment of the overall quality system of the laboratory to show this. (Of course the results of proficiency tests demonstrate performance in specific tests on specific types of samples.) Accreditation improves customer confidence in the results it receives.

The United Kingdom Accreditation Service (UKAS) is the only accreditation body recognised by the UK government for the assessment of laboratories that carry out testing and calibration against internationally recognised standards. To achieve accreditation, a laboratory needs to be fully conversant with, and comply with, ISO 17025. UKAS accredits laboratories for specific tests or calibrations. These are listed in a Schedule issued to the laboratory on accreditation. To have a procedure accredited by UKAS, the following need to be established:

• full and absolutely detailed documentation of the procedure • documentation relating to sample traceability • evidence of the traceability of all analytical data back to calibration • comprehensive data demonstrating the validation of the method, including

an estimate of the measurement uncertainty • evidence that the staff involved in the analysis are adequately qualified and

trained for the purpose and that overall staffing levels are adequate • evidence of an effective programme for the quality control of data.

There is a two-stage procedure for accreditation. Stage 1 starts with the preliminary application. The laboratory must prepare its quality manual and validate all the tests for which the laboratory wants to be accredited. The quality manual sets out the quality system. It includes management and technical responsibilities, the laboratory’s Standard Operating Procedures (SOPs), quality control measures, and a system of quality audit and quality review.

Stage 2 of the UKAS accreditation process is the formal Request for Assessment, which is followed by the pre-assessment visit, then the actual assessment.

During the pre-assessment visit, the assessors will identify areas of weakness (e.g. documentation or technical matters) that the laboratory must address in order to pass its assessment. This helps to ensure that the laboratory does not put itself forward for the actual assessment until it is really ready to do so.

Assessment covers three key elements: • the impartiality of the laboratory • the technical competence of the staff, the suitability of the equipment and

environment, and the validity of individual test methodologies • the effectiveness of the organisation’s management system.

Any non-conformances must be addressed by the laboratory. Very often these are to do with documentation, and can be dealt with by post, without the need for a further assessment visit.

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Laboratories undergo a yearly surveillance visit (the first visit will be 6 months after initial accreditation), with a full reassessment every fourth year. Once a laboratory has been accredited, it can add further tests to the scope of its accreditation at any time, although it is usually much cheaper to do this as part of the annual surveillance visit.

Accreditation can influence the quality management system of a laboratory through the emphasis on having written procedures for its activities and ensuring that staff adhere to them, and also by requiring the lab to be able to show that staff have been trained to carry out the procedures through keeping up-to-date training records and identifying training needs. Accreditation also requires the top management in the organisation to review the lab’s management systems and technical activities, and this can assist in enabling improvements to be implemented quicker than if the lab has to push these on its own, especially if additional finance is required.

Accreditation has many benefits. For the customer it gives confidence that the lab carrying out the analysis has been assessed by experts in the field and has been shown to produce reliable results, and is committed to providing a high-quality service. When government sets standards, for example, for drinking water quality, the use of accredited labs can give the public confidence that the government standards are being monitored to a uniform standard across the country.

Benefits for the company include the potential for increased business since some customers may be required to use an accredited lab by their own customers or regulatory authorities. When a lab is accredited to ISO 17025 its analytical results are accepted internationally, and therefore the lab will be in a stronger position to gain business from customers working in overseas markets – the customer will be able to avoid the possibility or requirement for repeat testing of samples in a foreign country by another lab. Accreditation can also give the company legal protection by demonstrating that it adheres to strict protocols, and it is therefore showing due diligence.

Case study: Accreditation of an independent pharmaceutical testing company to ISO 17025Senior laboratory staff had an initial meeting with UKAS (this first session was free), and they visited a lab that had already been accredited to get an idea of the work and costs that would be involved in obtaining accreditation. They paid external consultants to advise on the preparation of the quality manual and other documentation, as they felt that this was the part of the process where they would have least expertise.

A quality policy stating the overall quality philosophy of the lab was written and signed by the technical director. The quality manual was written using the headings of ISO 17025 as a guide, and including issues relating to the organisation, accommodation and staff. It also included a flow diagram showing the analytical process from sample receipt, storage and analysis to reporting and archiving, and covering procedures for corrective action. Equipment was calibrated and suitable reference materials obtained. Analytical methods were validated, and the measurement uncertainties and acceptance criteria (what constitutes an acceptable result) determined.

A pre-assessment visit from UKAS resulted in some fine-tuning before the formal assessment visit. The assessors reviewed the lab’s procedures including procedures for document control, dealing with customer complaints and internal audits. Then they checked training records, observed analysts in action, performed vertical audits (following a sample) and horizontal audits (checking calibration records) and asked staff about their understanding and awareness of the lab’s QMS.

At the end of the visit a number of minor recommendations were made, and when the lab had completed these, they were awarded their accreditation, and the much-prized certificate and schedule detailing the test for which they had been accredited.

The assessors revisited the lab 6 months later and are due to revisit a year after that as part of the regular surveillance process.

Activity 4.4.4If your workplace is accredited, make some notes on the accreditation and/or surveillance process as you observe it or encounter it.

Activity 4.4.5Look at the UKAS website, www.ukas.com, to find out more about UKAS and the accreditation work that it undertakes. What other standards does it accredit organisations to?

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Take it furtherLook at the following page of the National Measurement System website, which describes an accreditation case study:

http://www.nmschembio.org.uk/GenericListing.aspx?m=358.

4 Applying quality assurance in the laboratoryQuality management systems and QA standards are only of use if they are actually implemented and adhered to in the lab. To illustrate how QMS is implemented in real-life situations, two case studies are given below – the first one describes QMS in a hospital cell pathology laboratory, the second one describes QMS in a forensic laboratory.

Case study: QMS in cell pathology laboratoriesQuality in a hospital cell pathology laboratory in the UK is covered by Clinical Pathology Accreditation (CPA) guidelines which are based on ISO 15189. Documentation such as risk assessments, COSHH and SOPs are held online as controlled documents and staff have to sign to confirm they have read all relevant documents.

QC procedures include checks on the quality of cell staining, and on sample traceability – checking patient data against sample labels to ensure that results are assigned to the correct patient.

Internal QA includes regular audits, both vertical (tracking one sample from receipt through analysis to the final report given to clinical staff) and horizontal (for example, checking all samples from one particular type of test or checking the level of reported cell abnormalities).

External QA checks occur via proficiency testing schemes through NEQAS and assessment against CPA guidelines.

All staff must be trained for the work they do, and they have to demonstrate their competence. Each individual has a training log with details of their individual training programme appropriate to their grade and career structure.

Case study: QMS in forensic science laboratoriesQuality in a forensic laboratory is guided by the accreditation requirements for ISO 17025. For each type of forensic case there will be a procedure describing how the case should be processed. This covers how evidence is to be recovered from submitted items and prepared for analysis, what type of analysis to do and how to interpret and report the results. There will be procedures for sample traceability (chain-of-custody as it is known in forensic science) and the validation of analytical methods, and there will be SOPs detailing the specific steps in each activity.

Regular QC checks include use of control charts. Ongoing QA includes regular calibration of equipment, control of reagents, participation in proficiency testing schemes and internal audits. The lab would also be subject to visits from UKAS assessors as part of the process required to achieve and maintain accreditation to ISO 17025.

Staff have to be trained to carry out their work correctly and training records have to be kept in accordance with ISO 17025. There is a lengthy training process to become a reporting officer (a person who puts together a case file, writes court reports and presents evidence in court).

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Although forensic science and hospital cell pathology labs are very different in the types of sample and analysis they deal with, several common themes emerge from the two case studies. Both types of lab place an emphasis on adherence to written procedures and use of appropriate QC controls. Both types of lab demonstrate the quality of their work by internal audits, external proficiency testing and accreditation or adherence to external guidelines. In both types of lab staff must be properly trained for their roles, and this must be demonstrated by training records. Sample traceability is vital in both forensic analysis and cell pathology – the labs must be able to demonstrate that each result relates to the correct original sample. The interpretation and reporting of results is an integral part of the process and requires appropriate training.

It can be seen that, however different the types of sample are that a lab analyses, the fundamental issues and aspects of QA are largely the same.

Activity 4.4.6Look at the UK NEQAS website, www.ukneqas.org.uk, to see the range of tests carried out in clinical laboratories.

• Why is it important that clinical laboratories produce accurate results? • What could be the consequences of a hospital laboratory producing incorrect results?

Now consider forensic science laboratories. • Why is it important that these laboratories produce accurate results? • What could be the consequences of a forensic laboratory producing incorrect results? • Are you aware of any recent criminal cases where there have been issues with the forensic

analysis?

Portfolio activity (2.3, 3.1, 3.3, 4.2, 4.3)Write a report on quality assurance in your laboratory.

• Note whether your lab or workplace has a formal quality management system, and who has overall responsibility for QA in your organisation.

• Note whether your lab is subject to internal audit as part of the QMS, and if so what is reviewed. • Comment on the training you have received to carry out your work, and whether this is

recorded in a training log. • Comment on whether your lab has written SOPs, and – crucially – whether staff adhere

to them. • Note whether your lab is accredited to a specific QA standard, and if so what the accreditation

process is. State whether your own or other people’s work is reviewed by the assessors. • Comment on how the accreditation and the accreditation process affect your work, your lab

and your organisation. • Note and comment on any other aspect of quality assurance in your lab and organisation.

ChecklistAt the end of this topic guide you should:

be familiar with and be able to compare a number of relevant quality assurance standards

be aware of the UKAS accreditation process

be able to compare how quality is assured in different types of laboratories.

Further readingQuality Assurance in Analytical Chemistry (E. Prichard and V. Barwick, 2007), Wiley

Biomedical Science Practice: Experimental and Professional Skills (H. Glencross, N. Ahmed and Q. Wang, 2010), OUP

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AcknowledgementsThe publisher would like to thank the following for their kind permission to reproduce their photographs:

Shutterstock.com: Olivier

All other images © Pearson Education

Every effort has been made to trace the copyright holders and we apologise in advance for any unintentional omissions. We would be pleased to insert the appropriate acknowledgement in any subsequent edition of this publication.

About the authorCatherine Duke obtained a BSc in Chemistry and a DPhil studying heterogeneous inorganic reagents, both from the University of York before spending time at Brock University in Ontario, Canada using FTIR, fast atom bombardment mass spectrometry and solid state NMR to study solid materials and surfaces. Returning to the UK, she spent two years working as a Teaching Company Associate with Contract Chemicals in Knowsley (a manufacturer of fine chemicals), where she was first introduced to the area of quality assurance. She has spent the last 20 years as a lecturer at the University of Wolverhampton, teaching analytical chemistry and laboratory quality assurance.

topic guide 4.4: quality assurance in the laboratory

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