All procedures and processes in the laboratory that affect the output of the laboratory must be carried out correctly to assure accuracy and reliability of testing. An error or departure from established protocols within any process can jeopardize the accuracy of laboratory results. Improvement in quality can be achieved by documentation, standard operating protocols (SOPs), proficiency testing, analysis of data, and internal audits designed to reveal weaknesses and ensure adherence to the SOPs. QA is concerned with the prevention of errors by addressing all inputs that are critical to a high functioning laboratory such as qualifications for reagents, maintenance of equipment, and management of human resources so that staff are highly trained and motivated.
Reviews and analysis of the output and performance of the staff are conducted to determine if the SOPs have been followed and to detect any issues that require attention and modification. Each stage of the workflow in the laboratory, therefore, requires careful attention as each is critical to assure quality in the laboratory.
There are 5 key objectives of a quality assurance programme. An overview and guidelines for each of the listed activities are discussed below:
- Develop standard operating procedures (SOPs)
- Monitor laboratory output and performance
- Provide and maintain a highly trained and knowledgeable staff
- Ensure quality of reagents, sufficient supplies, and maintenance of equipment
- Maintain appropriate records and establish a document control system
(1) Develop standard operating procedures (SOPs)
SOPs are documents that contain written step-by-step instructions that laboratory staff should follow when performing a procedure. SOPs should be prepared by experienced, technical staff in the laboratory, revised by their immediate supervisor and approved by the Director of the laboratory. A laboratory will have an SOP for each process (such as accessioning samples) and all laboratory tests that are conducted in the laboratory.
The goal is to write the SOP with sufficient attention to detail (dilution of reagents and precise timing instructions) so that each staff member will perform the test in exactly the same way, ensuring that the same result can be expected from all staff. Staff that does not normally perform the procedure should be able to do so by following the SOP.
All steps in the procedure should be analysed, identifying possible variations or potential “error points”, which could introduce error. If different laboratories develop their SOPs based on the same standardized procedures used throughout the network, direct comparisons of their results can be made. It should be emphasized that all laboratory staff must follow the SOPs exactly. It is important that SOPs are written in a manner that eliminates ambiguity. Flow diagrams may be useful for some activities and processes.
(2) Monitor laboratory output and performance
All laboratories should have regular and thorough processes for monitoring the accuracy and performance of their procedures and the persons performing them. Performance monitoring should be a continuous process in each laboratory. Important indicators of performance include the timeliness of reporting results and summary reports of laboratory data, and the concordance rates for confirmatory testing and annual proficiency tests. See section 12.3 and section 12.4, for more information on confirmatory testing and the annual proficiency tests, respectively.
The process of assessment is a tool for examining laboratory performance and comparing it to standards, benchmarks, or the performance of other laboratories. A combination of internal quality assurance (IQA), performed within the laboratory using its own staff, and external quality assessment (EQA) that is conducted by a group or agency outside the laboratory, is the recommended approach to ensuring quality. Laboratory quality standards are an important part of the assessment process, serving as benchmarks for the laboratory.
Internal assessments or on-site audits should be conducted to identify non-compliance with SOPs or deficiencies in the SOPs that need attention. Reviews of non-conforming events, corrective action taken, and the effectiveness of that corrective action to address the problem are important for ongoing quality improvement.
(3) Provide and maintain a highly trained and knowledgeable staff
A good quality laboratory depends on qualified, motivated staff. Each individual in the laboratory must have a full understanding of QA and the importance of teamwork in successfully implementing QA. An organizational chart should be prepared and distributed that clearly shows the appropriate lines of authority and the functions and responsibilities of each person. Most of the activities in the measles and rubella laboratory such as EIA testing, cell and virus culture, molecular techniques and interpretation of results require staff with a strong scientific and technical training, good technical skills and considerable experience.
Human resources staff and the laboratory manager should regularly review training needs and make arrangements to ensure that technical and scientific staff receive training according to those needs identified and proposed by the heads of department. The training offered to staff should directly contribute to the success of the objectives of the QA. A continuing education programme must be developed which includes on-site as well as external training. The staff training programme should be formalized into records that are maintained as part of the required documentation.
(4) Ensure quality of reagents, sufficient supplies, and maintenance of equipment
All reagents should be inspected to ensure that the seals are intact upon receipt in the stockroom or when distributed to the laboratory. These inspections should be recorded with the initials of the person responsible for the inspection and the date on the label. Expiration dates should be recorded and monitored. Reagents that are mixed or diluted in the laboratory should be prepared in conformity with written SOPs.
At least a six months’ reserve stock of reagents should be held in the laboratory at all times. Given the long delivery times and difficulty of transporting supplies to some countries, reagents should be ordered 6 to 12 months ahead of predicted needs. Predicting the utilization of reagents can be challenging due to the epidemiology of measles and rubella disease. An outbreak requiring the immediate testing of hundreds of samples can rapidly consume current stocks of test kits and require rapid revision of forecasted needs.
Managing stocks of reagents requires regular checks of inventory at scheduled intervals to record stock used and stock remaining. This is especially important when supplies are provided by a third party which may have a timetable for ordering at certain times of the year and the synchronization with their timeline is critical. Some WHO regional offices have the capacity to hold reserve stocks of reagents including test kits should a large outbreak occur. However, the need for regular communication of reagent stock levels to the regional coordinators is vital.
Reference materials and internal controls may be produced by the laboratory for its own use or be provided by reference laboratories in the network or from other organizations. If the laboratory choses to produce its own reagents, then producing large volumes minimizes the frequency and efforts required to validate these materials. If a third party provides materials, then consideration of transportation conditions becomes important to ensure reagent potency is maintained.
It is recommended that an inventory system is maintained for supplies. A central inventory or logbook of reagents should be kept containing the following:
- Name of the item, supplier and trademark name (origin)
- Lot number, date of receipt, and expiration date (if applicable)
- Location and conditions of storage
- Quantity of material, with dynamic and trigger points for replenishing
The inventory should contain all the information relating to the properties of the items. All staff should be aware of the need to complete an update of the inventory as and when they use or replenish supplies, however, overall responsibility for managing the inventory should be in the hands of the laboratory manager or a designated staff member.
Many kinds of equipment are used in the laboratory, and each piece of equipment must be functioning properly. Choosing the right equipment, installing it correctly, ensuring that new equipment works properly, and having a system for maintenance are all necessary for quality assurance.
Equipment such as pipettes, incubators, refrigerators, freezers, thermometers, thermocyclers, and sequencers are essential components for generating accurate assay results. Failure or non-compliance of the equipment can be the cause of assay problems and it is essential that regular calibration and preventative maintenance be undertaken. Often the equipment manufacturer will provide a user manual that includes instructions and suggested schedule for equipment maintenance and/or calibration. Following the manufacturer’s recommendations will reduce the chances of failure or non-compliance.
All equipment should have clear and accessible documentation of the processes required for calibration, maintenance and performance recording. Critical equipment such as refrigerators, freezers and incubators should be monitored continually either through once or twice daily manual recording or a continuous electronic monitoring system with out-of-range alarms established. SOPs should be written for each instrument that cover basic operation and maintenance procedures. Detailed logbooks should be maintained with documentation of preventive maintenance, non-routine maintenance and repairs.
(5) Maintain appropriate records and establish a document control system
The product of the laboratory is information, primarily in the form of test reporting. Information (data) needs to be carefully managed to ensure accuracy and confidentiality, as well as accessibility to the laboratory staff and to the health care providers. Records must be meticulously entered and maintained so as to be accurate and accessible. It is important to address both the use and maintenance of documents and records. Information may be managed and conveyed with either paper systems or with computers; both are discussed, along with the use of worksheets, in Chapter 11. Data management and reporting of laboratory results.
Documents, by definition, require updating. A system must be established for managing them so that current versions are always available. Documents such as SOPs will be easier to manage and update by use of standardized formats and a document numbering system. Even without a QMS in place, a document management system can be developed using the suggestions included in section 16.5 of the WHO Handbook, Laboratory QMS [1].
Each SOP should be signed and dated to ensure that the procedures being used are up-to-date. Modifications should not be made without going through appropriate channels in the laboratory. Protocols should be reviewed on a regular basis. Refer to WHO recommendations as appropriate for assays and protocols that have been adopted for routine testing for measles and rubella. Consistency in the quality control measures incorporated into SOPs allows the surveillance programme to analyse aggregate data and directly compare results from all of the laboratories in the measles and rubella laboratory network.