How to meet ISO15189:2012 pre-analytical requirements in clinical laboratories? A consensus document by the EFLM WG-PRE

Pre-analytical quality indicators

ISO15189:2012 requirements and EFLM WG-PRE recommendations concerning pre-analytical quality indicators (QIs) can be found in Table 1. ISO15189:2012 requires laboratories to establish a quality policy with objectives to meet the needs and requirements of all users. To this end, the laboratory shall establish measurable QIs to monitor and evaluate performance throughout critical laboratory aspects, thus including the pre-examination phase. QI monitoring requires definition of the objective, methodology, interpretation, limits, action plan, and time of measurement. QIs are invaluable to confirm that laboratory quality objectives have been met, as well as for measuring efficacy of corrective/preventive actions. In addition, when deterioration of quality of blood collection is noted according to QI analysis, the laboratory must communicate this evidence and provide additional education and training to its users.

ISO15189:2012 suggest some examples of pre-analytical QIs (e.g., unacceptable samples, errors at registration and/or accession, corrected reports), but does not state how they should be monitored and evaluated. As a minimum, we recommend that laboratories should monitor one of the following QIs on yearly basis (e.g., during the management review): number and proportion of misidentification errors, test transcription errors, incorrect sample types, insufficiently filled samples, unsuitable samples, contaminated samples, hemolyzed samples, or clotted samples. We have chosen these QIs because they are included in the priority one category of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Model of Pre-analytical Quality Indicators [8], and because we believe that they are the easiest to implement in most laboratory settings and current-day Laboratory Information Systems (LISs) without requiring significant programming efforts. As a best-in-class solution, we recommend laboratories to monitor pre-analytical QIs in accordance with the framework provided by the IFCC Model, which defines procedures for data collection and provides quality specifications for evaluating laboratory results based on External Quality Assessment (EQA) [8]. We encourage participation in the IFCC EQA scheme for quality indicators [8]. While we acknowledge that monitoring pre-analytical QIs in such a way requires time and resources (e.g., software adaptations, additional EQA registrations), we would like to emphasize that selection of QIs, frequency of evaluation, and their calculation can be adapted to a specific laboratory setting based on risk assessment to identify pre-analytical processes which require higher priority for monitoring (e.g., sample identification or sample collection) [14], [15]. In this context, it should also be emphasized that ISO15189:2012 requires regular re-evaluation of QI methodology to ensure continued appropriateness.

Sample collection

ISO15189:2012 requirements and EFLM WG-PRE recommendations concerning sample collection can be found in Table 2. ISO15189:2012 requires that sample collection needs to be performed by adequately trained personnel, and laboratories should provide and supervise training concerning blood collection for all appointed personnel. In addition, the laboratory should assess competence of each phlebotomist according to established criteria described in the QMS. Reassessment shall take place at regular intervals (see below) and retraining shall occur when necessary, especially when analytical methods and/or instrumentation change. The effectiveness of training programs shall be periodically reviewed, e.g., based on personnel and user feedback. In addition to requirements specified in ISO15189:2012, the authors of this article make a number of additional recommendations. We minimally recommend that the necessary education, training (including scope, duration, competency criteria, and reassessment intervals), skills, experience, and where applicable, certification and licensure for each job title related to venipuncture processes, must be defined in the QMS. Training programs and competence assessments of pre-analytical procedures should be organized and documented under laboratory supervision. Competence reassessment of all personnel shall take place at least every five years. Finally, the joint EFLM-COLABIOCLI recommendation for venous blood sampling is recommended as best-in-class solution for training and competency assessment [16]. This guideline provides practical guidance on education, practical training, (re-)certification, and auditing of venous blood sampling procedures [16].

The ISO15189:2012 standard requires that facilities where patient sample collection procedures are performed (e.g., phlebotomy) shall enable sample collection to be undertaken in a manner that does not invalidate the results or unfavorably impacts the quality of examinations. As a minimum, we recommend to define specific requirements for dedicated phlebotomy rooms in the QMS. Further guidance on best-in-class solutions concerning the required elements (e.g., chair/bed, hand washing areas, waiting areas, supplies) can be found in the joint EFLM-COLABIOCLI recommendation for venous blood sampling [16].

Although this is not stated in the ISO15189:2012 document, we recommend that the performance of consumables potentially affecting the quality of examinations should be verified before use. As a minimum, the performance of a new type of sample collection system should at least be verified in 20 samples for a subset of tests. The laboratory defines the subset based on risk assessment. We recommend to also perform clinical and technical validation in accordance with EFLM recommendations as a best-in-class solution [17]. This local technical validation should be intended to verify if manufacturer claims about structure, assembly, functionality and safety of blood collection tubes are fulfilled. Preferably, over 240 blood collections should be randomized to both control (n=120) and comparative (n=120) groups, and all relevant technical information should be recorded; e.g., physical defects, vacuum failures, clotting, hemolysis [18]. As alternative and more stringent comparison, collection of two paired tubes from the same patient with the two different systems may be advisable [17]. Whenever reference intervals are verified during implementation of a new sample collection system, this should be performed according to Clinical & Laboratory Standards Institute (CLSI) standard EP28-A3 [18]. For sample collection systems already in use, where useful data are already available, a data-driven approach can be used as an alternative [19].

Finally, ISO requires that the laboratory shall have documented procedures for appropriate collection and handling of primary samples. As a minimum, we recommend that procedures for sample collection should be available in the QMS and, ideally, these should be in line with current EFLM-COLABIOCLI recommendation for venous blood sampling [16]. When the laboratory changes an examination procedure, ISO requires the laboratory to review the associated reference intervals and clinical decision values, when applicable. As a minimum, we recommend that blood collection conditions and test catalog information should be reviewed whenever instruments, methods or sample collection systems change (e.g., with introduction of a new type of blood tube, see above). For a best-in-class solution, we recommend that blood collection conditions and test catalog information are reviewed at least every year and whenever sample collection procedures are adapted.

Sample transport

ISO15189:2012 requirements and EFLM WG-PRE recommendations concerning sample transport can be found in Table 3. ISO15189:2012 requires laboratories to have a documented procedure for selecting external services and suppliers, to ensure that the quality of the service is guaranteed at all times. In addition, the performance of external suppliers must be monitored and evaluated to ensure that purchased services or items consistently meet required and pre-defined criteria defined in the QMS. These requirements also concern suppliers involved in transportation (on behalf of the laboratory) of patient samples from external venipuncture sites (e.g., general practitioner surgeries) or other laboratories or hospitals. Nevertheless, the ISO15189:2012 document does not state how frequently suppliers should be evaluated and fails to provide specific guidance concerning evaluation criteria. As a minimum recommendation, we propose that criteria pertaining to transport time, transport temperature, or other relevant transport conditions (e.g., acceleration forces for samples conveyed by pneumatic transports systems), as well as traceability and training of personnel and resolution of complaints should be clearly defined in the service level agreement. In addition, evaluation of supplier performance should be performed on yearly basis by evaluation of transport time (e.g., time between shipping and reception) and temperature (e.g., min-max temperature data). The accuracy of declared time, temperature, and other relevant transport conditions must be reviewed regularly for each transportation mode based on risk assessment and, when necessary, corrective actions must be undertaken. For best-in-class solution, higher frequency of evaluation (at least yearly) with additional criteria besides transport time and temperature (e.g., sample identification, rejection criteria, and hemolysis) should be performed. Additional possibilities for monitoring include continuous temperature monitoring during transportation, electronic track and trace of samples within their transport container (including collection, pick-up, travel, and arrival), continuous g-force monitoring in pneumatic tube system (PTS) transport and more detailed transport times based on electronic registration of exact sampling time. We believe that current-day (laboratory) information systems are capable in monitoring these elements. For elements that cannot be monitored by the laboratory itself, data must be monitored by the external supplier and communicated to the laboratory.

Sample reception

ISO15189:2012 requirements and EFLM WG-PRE recommendations concerning sample reception can be found in Table 3. ISO15189:2012 requires that the laboratory QMS defines personnel qualifications including education, training, experience and skills needed for each person involved in the TTP, including sample collection. To ensure that samples received in the laboratory meet acceptance criteria relevant for the requested examination(s), sample reception should only be performed by authorized personnel. As best-in-class solution, we recommend that the appointed staff members should be subject to regular reassessment.

Sample acceptance

The ISO15189:2012 requirements and EFLM WG-PRE recommendations concerning sample acceptance can be found in Table 3. The ISO15189:2012 document requires that rejection criteria for problems with identification, sample suitability, sample integrity, transport time, and temperature are defined in the QMS. If a sample does not meet the acceptance criteria, it should be rejected unless it is clinically critical or irreplaceable. In this case, ISO15189:2012 requires that the final report indicates the nature of the problem and, where relevant, that caution is required when interpreting test result.

As a minimum concerning correct patient identification, we recommend that correct identification of the patient should at least be verified by a minimum of two, preferably three, unique patient identifiers, one of which is the full name of the patient [20]. Each sample should be unequivocally identified and traceable to a unique laboratory request. As best-in-class solution, we recommend that electronic identification of patient and his/her samples occurs at time of blood collection and no further manual data entry steps are needed during sample reception (to avoid any errors). In addition, the laboratory should define in the QMS how it will monitor, improve, and maintain quality of patient identification, preferably by correct use and interpretation of pre-analytical QIs and education of its users (see section on “Pre-analytical quality indicators”).

ISO15189:2012 requires that transport temperature and time are monitored during transport. As a minimum, we recommend that when no continuous temperature monitoring is available during sample transportation, evaluation of sample integrity upon arrival in the laboratory shall be based on the worst-case scenario (e.g., only min and max temperature available). Criteria concerning transport temperature and time should minimally be based on manufacturers’ recommendations or scientific literature. The laboratory QMS must also include time and temperature limits for requesting additional examinations on the same primary sample, and thereby the overall length of storage (e.g., days) that samples will be stored in the laboratory before being discarded. As best-in-class, assessment of sample acceptance with respect to temperature and time should be performed automatically through the LIS, and the laboratory should produce its own stability data concerning storage temperature and time through experimental validation studies.

Concerning sample integrity, we minimally recommend checking for Hemolysis-Icterus-Lipemia (HIL) whenever a requested analysis is known to be affected by these parameters. Afterwards, management of samples checked for HIL should be handled according to EFLM recommendations [21], [22]. The HIL measurement shall be preferably performed using automated systems rather than by visual inspection. For best-in-class solution, the laboratory should implement an automated system integrated with the LIS for detecting, reporting, and interpreting HIL data, which automatically provides information within the final report about the impact of sample problem (negative or positive interference) on a test-by-test basis.