Quality assurance and AMR surveillance

Introduction

Microbiology laboratories need to produce test results that are timely, accurate, precise and reliable. Maintaining a high-quality standard in a laboratory is essential in order for doctors, veterinarians, and public health officials to have confidence in the test results the laboratory produces. In antimicrobial resistance (AMR) surveillance, there is the additional challenge of ensuring that data generated in different sectors can be compared or interpreted with reference to other sectors.

In this module, you will learn about the key principles underlying laboratory quality, and the processes a laboratory puts in place to ensure that it operates to a consistently high standard and generates good-quality and reliable data. You will probably be familiar with many of the terms used in the context of quality, and even if you aren’t, many of them may sound similar, for example, ‘quality control’, ‘quality assurance’, and ‘quality management system’.

After completing this module, you will be able to:

• explain the importance of data integrity and quality in laboratory practice in the AMR surveillance context
• outline quality assurance measures in the context of AMR surveillance
• describe the key components of laboratory practice that underpin the quality testing and analysis of antibiotic resistance data
• recognise that your role is an integral part of the AMR surveillance process and that you are responsible for managing quality standards in the workplace
• reflect on the different components of a quality management system and how they are applied in your workplace, and what improvements could be made to ensure that your workplace is obtaining, recording and reporting good quality data.

1 The importance of data integrity and data quality

It is essential that microbiology laboratories generate data that are fit for purpose (that is, are of high quality) and are trustworthy (have integrity). High-quality data are accurate, consistent, reliable and timely, while data have integrity if they are accurate, validated and complete. You will learn more about these terms in the Fundamentals of data for AMR module.

The principles and practices described in this module minimise the likelihood of an error occurring at each step of the testing process. Doctors and veterinarians must be confident about laboratory reports of test results to inform clinical decisions for a sick person or animal, such as deciding which treatment to give or what additional tests are needed.

For AMR surveillance, pathogen identification and an antibiotic susceptibility test (AST) must be robust and reliable. This is because the data are used to make important healthcare decisions, for example on the procurement of drugs and drug budgets, producing empirical treatment guidelines or developing vaccination programmes at local, national and international levels. Having high-quality, accurate data ensures that meaningful comparisons can be made between different sites, regions and countries, which inform the generation of policies to reduce infection rates and improve patient care. The AMR data collected over time are key to determining trends in resistance patterns and informing public health interventions.

High-quality data generated by microbiology laboratories are the foundation for good patient care and effective AMR surveillance. Incorrect data can negatively impact decision- making at all levels. It is vital that all those employed in a laboratory recognise the need to work to agreed standards of practice and follow measures to ensure that data are reliable.

2 Ensuring quality in the laboratory

What is ‘quality’?

There are many notions associated with the term ‘quality’. For an organisation, quality is associated not only with the products and services it produces to satisfy a demand, but also the processes in place to generate these products or services. In a biomedical laboratory, several factors can affect the final report – the competency of the technician, the laboratory procedure, the reagents used in the assay, the equipment and the facilities. In Figure 1, these and other factors are grouped into 12 quality systems essentials (QSEs) covering organisation and management, process control, and continuous improvement – a cornerstone of any quality management system (QMS) (WHO 2011a). You will learn about QMSs in Section 3.3.

Figure 1 The 12 quality systems essentials that are a critical requirement for a laboratory’s quality management system. Note that ‘process control’ covers all laboratory activities of the laboratory workflow.

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Twelve circles labelled ‘Organisation’, ‘Personnel’, ‘Equipment’, ‘Purchasing and inventory’, ‘Process control’, ‘Information management’, ‘Documents and records’, ‘Occurrence management’, ‘Assessment’, ‘Process improvement’, ‘Customer service’, and ‘Facilities and safety’.

Figure 1 The 12 quality systems essentials that are a critical requirement for a laboratory’s quality management system. Note that ...

The principles of ensuring high-quality data include:

• making sure that basic standards are met
• establishing procedures at all test stages to minimise errors and ensure results are reproducible and reliable
• measuring performance against international standards
• monitoring and improving practice.

Information must also be recorded and reported accurately. If the laboratory generates a reliable, accurate result but the wrong information is entered into the report, all the hard work done to get the result is wasted.

2.1 Meeting basic standards: facilities and safety

It is important to ensure that as far as possible the laboratory provides a safe and practical working environment.

The size, construction and location of the laboratory facility should be fit for purpose, with separate areas for different activities to optimise working conditions. Staff should have sufficient space for their work, should not have to deal with multiple distractions whilst processing samples, and should have access to the necessary equipment and commodities. Equipment should be in good working order and maintained and serviced as required by the manufacturer. Staff are entitled to expect a clean, safe and secure environment in which to work.

Safety within the laboratory includes:

• general safety – protection from standard workplace hazards such as trips, falls, fires, etc.
• biosafety – the measures taken to protect personnel and the environment from unintentional exposure to potentially infectious agents or to toxins.

Biosafety measures include:

• staff training
• strict adherence to protocols
• wearing personal protective equipment (PPE) such as gloves, lab coat and mask.

Something that is often considered alongside biosafety is biosecurity, which refers to the measures that protect the general population (outside the laboratory personnel working in the immediate lab environment) from intentional and unintentional exposure to hazardous organisms or toxins. Examples of biosecurity include preventing unauthorised access to hazardous materials, or the misuse or intentional release of organisms (WHO, 2006).

To ensure staff and public safety, infection control, risk assessments, cleaning and waste disposal should be covered by specific policies. Staff training and the monitoring of best practice should also be carried out with appraisal and feedback. Laboratory manuals should be regularly updated to reflect current biosafety and biosecurity guidance and standards. For clinical laboratories, guidance is provided by the World Health Organization (WHO, 2004, 2006), and for veterinary laboratories, by the manual of diagnostic tests and vaccines for terrestrial animals (OIE, 2019).

Activity 3: Biosafety and biosecurity measures in place in a clinical microbiology laboratory

Timing: Allow about 15 minutes

Look at Figure 2 below.

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Figure 2 An example of a door sign on a microbiology laboratory.

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An example of a safety sign. It is headed ‘CAUTION’ and includes a sign showing no eating, drinking or smoking; details of the PPE requirement; an indication of the biosafety level (BSL2); a signpost for a restricted area; a biohazard sign; and lab contact and emergency phone numbers.

Figure 2 An example of a door sign on a microbiology laboratory.

Identify the elements in the figure that are related to:

• a safe work environment
• biosafety
• biosecurity.

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Answer

A safe work environment

• A clear warning sign of caution
• Lab contact phone numbers
• Emergency phone numbers
• A Lab Safety Committee is active in this institution

Biosafety

• A biohazard sign
• A sign instructing no eating, drinking or smoking
• An indication of the biosafety level (BSL2)
• PPE requirement

Biosecurity

• A biohazard sign
• A signpost for a restricted area

2.2 Organisational structure

The laboratory should have a clear organisational structure with the roles and managerial responsibilities of all staff members made explicit. The Laboratory Director has overall responsibility and leadership for the running of the laboratory. The Laboratory Manager is responsible for organising the work of laboratory technologists and for maintaining quality standards and safety aspects.

The Quality Manager takes responsibility of the QMS, and for approving all the relevant documentation and processes. Depending on the size of the laboratory, additional roles dealing with biosafety, equipment, supplies, training etc. may be delegated (Figure 3).

Figure 3 An example of an organisational chart.

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At the top of the organisational chart is a Laboratory Director; beneath them, a Quality Manager and Biosafety Officer, and beneath them, boxes labelled ‘Immunology Department’, ‘Microbiology Department’ and ‘Haematology Department’. A line from the Microbiology Department leads to a Microbiology Laboratory Manager, and then to Microbiology Laboratory Staff, such as laboratory technologists and laboratory assistants.

Figure 3 An example of an organisational chart.

(Figure 3 is an example with a focus on the microbiology department of a clinical laboratory. Your workplace may be considerably larger with more sections or considerably smaller with staff members having more than one role. Note that the Quality Manager and Biosafety Officer advise the Laboratory Manager, but do not necessarily directly line-manage staff if resources are scarce or the laboratory is small.)

2.3 Good microbiological technique

Good microbiological technique refers to the basic technical methods that safeguard human errors and the misuse of equipment responsible for inaccurate results, accidents and laboratory-acquired infections (WHO, 2004). These methods ensure that specimens are transported in an appropriate container and received in a designated area, that samples are opened only by trained staff and handled appropriately when testing, and that samples are stored adequately and disposed of safely. For more about good microbiological practice see the Isolating and identifying bacteria module.

All test samples and cultures should be handled as if they are pathogenic using aseptic technique. Working aseptically creates a clean micro-environment that prevents organisms in the test samples contaminating the laboratory (a biosafety hazard), and the test samples themselves becoming contaminated with organisms from the environment. Cross-contamination is an important quality issue as it can lead to the wrong pathogen being isolated, compromising the test results. Routine checks should therefore be incorporated at various stages of the testing process to look for evidence of contamination.

Other strategies to avoid cross-contamination of samples and the workplace include careful handling of cultures and keeping the laboratory clean and tidy. Having clearly designated areas for storage of sterile, clean, used/contaminated and used/decontaminated items is recommended.

3 Minimising errors

As noted in Section 1, AMR surveillance relies heavily on local microbiology laboratories producing data of high quality and integrity (Seale et al., 2017). Procedures should be in place to minimise errors, and to make sure that results are reproducible, i.e. the same result will be obtained from a sample even when processed by different operators on different days, or even in different laboratories.

The processes that minimise errors include:

• standard operating procedures (SOPs) for all activities
• implementing quality controls (QCs)
• ensuring all staff are trained on equipment and procedures.

3.1 Standard operating procedures (SOPs)

SOPs are unambiguous written instructions covering routine laboratory operations as well as the organisation and management of the laboratory. By stipulating how a task should be done, SOPs ensure consistency in the workplace; this in turn reduces testing error and bias and leads to more reliable and accurate results. SOPs should be available for all procedures, and may be developed locally or for a national surveillance system developed nationally with adaptations for the for the local situation if needed.

SOPs use clear language, are easy to follow and have a standard format where the header summarises important information regarding document approval and classification (see Table 2). It is essential that SOPs are reviewed regularly and kept up to date, with previous versions being archived. Staff should be kept informed of updates.

A well-written, comprehensive SOP should provide all the information needed for a new member of staff to be able to complete the procedure exactly (see Table 3).

The SOP should include the scope, purpose and a step-by-step description of how to perform the entire testing process, including how the results should be analysed and interpreted (CLSI).

See Public Health England’s comprehensive catalogue of SOPs for examples.

3.2 Identifying where errors occur

Errors can be introduced at any stage of the path of workflow (as shown in Table 4): before the test takes place (pre-analytical), during the test (analytical) and after the test (post-analytical). It is important to identify where errors can occur and put in place controls and measures to reduce these. Using standardised procedures helps keep errors to a minimum.

3.3 Quality procedures to identify and minimise errors

Several terms are used to describe different aspects of laboratory quality: quality indicators (QIs), quality controls (QCs), quality assurance (QA), and quality management system (QMS). These terms are explained in Figure 4.

Figure 4 The organisation of quality procedures in quality management systems.

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A Venn diagram of how quality procedures are organised in a quality management system:

• QMS: A set of activities to develop, document and implement continual improvement of the overall process through regular management reviews, and corrective and preventive actions.
• QA (located inside QMS): A set of activities to monitor the overall testing process (which includes handling, processing and analysing samples) and using QCs and QIs over time to provide confidence.
• QC (located inside QA): Monitoring of each individual test or process to ensure that all quality requirements are being met.
• QI (also located inside QA):Observations, statistics or data used to determine the performance of a process.

Figure 4 The organisation of quality procedures in quality management systems.

QIs are observations, statistics or data that prove the organisation is meeting its intentions, for example, that its blood culture contamination rate is below 3%. QCs monitor whether the test performs as expected – for example, using a control organism to ensure that reagents or media give the expected result or growth. QA looks at the overall process to confirm that the requirement for quality is fulfilled. This involves tracking QCs and QIs and analysing trends. In the analytical phase, for example, QA ensures that all the relevant SOPs are in place, staff have been trained, the necessary QC checks are being done, and the results are recorded and reported correctly for that process.

Finally, a laboratory QMS is a systematic integrated set of activities to establish and control all processes in the workflow path. The founding principle of a QMS is continual improvement. It manages resources, conducts evaluations and makes continual improvements to ensure consistent quality results. A good QMS ensures that when errors are detected, both preventive and corrective measures are implemented to improve a process (WHO, 2011a; Carey et al., 2018).

3.4 Using controls

A control is included in laboratory tests to check the effectiveness of a test and ensure that reagents and equipment are functioning as expected: for example, a test may not work as expected due to changes in environmental conditions or experimental error. Including a full range of controls is particularly important for qualitative or semi-quantitative tests which are common in microbiology laboratories.

Microbiology laboratories need to maintain a stock of control organisms, with known characteristics, to provide QC for different tests. For example, when checking the reagents used for an oxidase test, laboratories should use a known oxidase positive organism (usually Pseudomonas aeruginosa) and an oxidase negative organism (such as E. coli). Control strains should be obtained from a reliable source, for example the American Type Culture Collection or the UK National Collection of Type Cultures, and stored and cultured according to the provider’s instruction. Control strains are also used to ensure that selective or indicator media have been prepared correctly.

3.5 Instruments and equipment

As well as looking at processes, a good quality management system (QMS) will make sure that instruments and equipment are functioning correctly. Instruments must be installed and used according to the manufacturer’s instructions. Any new equipment should be validated before being used routinely and kept maintained in full working order, and all staff should be trained on its use.

Equipment and instruments may also need to be calibrated: calibration is a set of operations that establishes, under specified conditions, the relationship between an instrument response and the corresponding values of a standard. For example, to calibrate a balance, appropriate known weights are selected and the balance reading is set to the value of these standards before measuring any unknown weights. Similarly, calibrated instruments such as temperature probes or thermometers are used to check whether facilities such as air-conditioned animal facilities or cold rooms are at the correct temperature. For equipment the frequency of calibration, the method used and the record of the calibration status should all be according to the manufacturer’s instructions.

3.6 Information management

4 Continual improvement

As well as performing all the necessary product and process quality checks, laboratories should be recording, monitoring and measuring their performance to ensure that standards are maintained over time. Laboratories should also strive to identify and promote good practice and look for ways of improving their performance.

4.1 The PDCA model

The PDCA wheel (Plan–Do–Check–Act) developed by Edwards Deming is a widely used model for improvement processes in clinical settings (Figure 6).

Figure 6 The PDCA continual improvement cycle. In this process, QA (symbolised by a wedge) ensures that quality requirements are met while QCs are parts of the ‘Do’ phase.

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The wheel has four sections, labelled ‘Plan’, ‘Do’, ‘Check’, ‘Act’, accompanied by arrows to denote a continuing process. The ‘Do’ phase is related to a QC; the ‘Check’ phase is related to a QA. Quality improvement increases over time.

Figure 6 The PDCA continual improvement cycle. In this process, QA (symbolised by a wedge) ensures that quality requirements are met ...

The model has four phases:

• Plan identifies opportunities for improvement and defines an action plan.
• Do corresponds to the pre-analytical, analytical and post-analytical phases of the workflow in a biomedical laboratory. (This may also be called the implementation phase.)
• Check analyses the efficacy of any new measures that have been implemented to see if the process is being improved.
• Act analyses the information from the ‘Do’ and the ‘Check’ phases, validates the approach and sets up corrective and preventive actions, thus improving the overall quality of the QMS.

4.2 External quality assessment

An external quality assessment (EQA) compares the performances of different laboratories. A proficiency testing scheme (PTS) is the most cost-effective and useful EQA method. PTS involves regular dispatch of test isolates to laboratories, to be processed using the normal testing methods by staff who routinely handle such samples. Results are analysed by a reference laboratory which provides feedback and allows comparison with results from other participating laboratories.

If participation in a formal PTS is not possible, assessment of quality may be achieved through a combination of within-country retesting/rechecking by a reference laboratory and internal QA with periodic external observation of practices and procedures by qualified personnel (WHO 2011a). In situations where a PTS for a specific test is not available, interlaboratory comparison to compare results and interpretation can be developed.

4.3 Accreditation

A certificate of accreditation is an official recognition of the quality and competence of a laboratory’s operations in line with international standards. It is an acknowledgement that the tests carried out by the laboratory are reliable and accurate. To achieve accreditation, laboratories are assessed by certified external experts, who review all aspects of the laboratory QMS according to recognised standards. Laboratories may be accredited for different types of work: for example, a reference laboratory may be accredited for providing clinical testing, and also separately accredited for providing a PTS.

One of the most widely recognised accreditation schemes is the International Standards Organisation (ISO) scheme. Ideally, public health laboratories should comply with the ISO 15189 quality standard, which covers both management and technical operations and is specific to clinical laboratories. Veterinary laboratories should comply with the ISO quality standard ISO/IEC 17025, which is used as a measure of the laboratory’s competence in testing and calibration activities. Compliance with country-specific standards may also be necessary for formal accreditation. In recognition of the fact that many laboratories in low- and middle-income countries will need substantial support to achieve ISO accreditation, the World Health Organization’s Regional Office for Africa (WHO AFRO, 2017) has established a framework for improving the quality of public health laboratories in developing countries, the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) programme. This framework provides a step-by-step, realistic programme for laboratories to follow to help them achieve accreditation. It incorporates its own star rating system to indicate how laboratories are performing against the simplified standard.

4.4 Staff training and development

At the most basic level, individuals monitor the quality of their own work. Staff are responsible for making sure that they have been trained on each procedure that they undertake and have read the SOPs and any other relevant documents. Staff are also responsible for making sure that they perform the correct QC checks.

All staff should receive training in health and safety, biosafety and biosecurity, and quality management. Additionally, each member of staff should be trained for the tests that they undertake and in the equipment they use. SOPs should be in place for all staff-related operations, including the recruitment and induction of new personnel, training and assessment.

As well as initial training, ongoing education and training (known as continuing professional development (CPD)) is essential to ensure that staff keep their knowledge and skills up to date and are encouraged to learn additional skills and competencies relevant to their jobs. For example, training will be needed on any new tests, procedures or items of equipment introduced into the laboratory, and only staff who have been trained should undertake a new process.

All training undertaken should be recorded and the competence of staff assessed regularly with outcomes documented. Each staff member should maintain a training log to document their training progress and help identify any gaps that need to be addressed.

5 Examples of quality assurance for core processes

Quality assurance should cover every aspect of the test process, from taking the sample to reporting the result. In this section you will consider the QA needed for some core laboratory processes.

5.1 Specimen handling and storage

The accuracy, reliability and timely reporting of test results depend on having good quality samples as a starting point. Laboratories should therefore take proactive steps to ensure that samples received for testing meet their requirements and reject those samples that do not (Figure 7).

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Figure 7 An example of a sample rejection form (WHO, 2015).

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An example of a sample rejection form. At the top is a space to fill in details of the patient and the sample. Below that is a checklist of reasons why the sample does not meet the criteria of a good specimen for the test(s) requested, along with a space to fill in further details, if required. Reasons include:

• Sample was collected in improper container
• Sample not properly sealed/was leaking
• Sample was improperly labeled/Patient ID & date of collection was not clear
• Sample material was inappropriate for the test(s) requested
• Sample volume was inappropriate for the test(s) requested
• Sample was not accompanied by a request form/sample could not be related to a request form
• Patient name/date of collection on request form did not match the same details on the sample label
• Other

Figure 7 An example of a sample rejection form (WHO, 2015).

5.2 Antibiotic susceptibility testing

One of the most important microbiological tests once a bacterial pathogen has been identified is the antibiotic susceptibility test (AST) to detect antibiotic resistance. AST data of high quality and integrity are needed to inform patient treatment with antibiotics and for use in AMR surveillance.

In order to achieve accurate and reproducible AST data and comparability of test results between laboratories, using a standardised methodology and test parameters is essential. Adherence to international quality standards such as those set by ISO is a basic requirement. Further standards have been set by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) both offer standardised AST methodologies and corresponding guidance to interpret the test results.

Laboratories should also ensure that they are using appropriate reference QC strains, and that there is an effective QMS covering all stages of the testing process.

More information on AST can be found in the Antimicrobial susceptibility testing module.

6 Quality assurance in your workplace

You should now have a better understanding of how QA is implemented in microbiology laboratories, and how essential it is to maintaining quality standards. Before you finish this module there are a couple of final activities to complete, which will help you to think about how this knowledge applies to your workplace.

7 End-of-module quiz

Well done – you have reached the end of this module and can now do the quiz to test your learning.

This quiz is an opportunity for you to reflect on what you have learned rather than a test, and you can revisit it as many times as you like. 

• End-of-module quiz

Open the quiz in a new tab or window by holding down ‘Ctrl’ (or ‘Cmd’ on a Mac) when you click on the link.

8 Summary

In this module you have learned how a quality management system underpins the operational efficiency of a laboratory, and the internal and external checks that guarantee AMR data quality and integrity. You have also been introduced to the idea of accreditation for laboratories as a way of ensuring that quality standards are maintained.

You should now be able to:

• explain the importance of data integrity and quality in laboratory practice and in the AMR surveillance context
• outline quality assurance measures in the context of AMR surveillance
• describe the key components of laboratory practice that underpin the quality testing and analysis of antibiotic resistance data
• recognise that your role is an integral part of the AMR surveillance process and that you are responsible for managing quality standards in the workplace
• reflect on the different components of a quality management system and how they are applied in your workplace, and what improvements could be made to ensure that your workplace is obtaining, recording and reporting good quality data.

Now that you have completed this module, consider the following questions:

• What is the single most important lesson that you have taken away from this module?
• How relevant is it to your work?
• Can you suggest ways in which this new knowledge can benefit your practice?

When you have reflected on these, go to your reflective blog  and note down your thoughts.

9 Your experience of this module

Now that you have completed this module, take a few moments to reflect on your experience of working through it. Please complete a survey to tell us about your reflections. Your responses will allow us to gauge how useful you have found this module and how effectively you have engaged with the content. We will also use your feedback on this pathway to better inform the design of future online experiences for our learners.

Many thanks for your help.

Now go to the survey.

References

Acknowledgements

This free course was collaboratively written by Cyril Buhler and Sarah Palmer, and reviewed by Priya Khanna, Claire Gordon, Natalie Moyen and Hilary MacQueen.

Except for third party materials and otherwise stated (see terms and conditions), this content is made available under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 Licence.

The material acknowledged below is Proprietary and used under licence (not subject to Creative Commons Licence). Grateful acknowledgement is made to the following sources for permission to reproduce material in this free course:

Module image: melpomen/123RF.

Figure 1 and Table 2: reproduced from Laboratory Quality Management System: Handbook, World Health Organization, copyright 2011, https://www.who.int/ ihr/ publications/ lqms_en.pdf (accessed 30 June 2021).

Figure 2: Clinical Microbiology Review, May 2018, 31 (3) e00062-17; DOI: 10.1128/CMR.00062-17.

Figures 3–5: developed by Cyril Buhler.

Figure 6: developed by Cyril Buhler, based on the PDCA cycle by Deming, W. Edwards.

Figure 7: reproduced from template sample rejection form, World Health Organization, copyright 2015, https://extranet.who.int/ lqsi/ content/ template-sample-rejection-form (accessed 26 January 2021).

Every effort has been made to contact copyright owners. If any have been inadvertently overlooked, the publishers will be pleased to make the necessary arrangements at the first opportunity.