Application of quality principles in transfusion microbiology

Abstract

Over the past few decades, numerous transfusion scandals e.g. transfusion mistakes, transfusion transmitted infections have been repeatedly appeared in the newspaper and television. As a result, public concern has driven the transfusion community to work harder and harder in order to achieve a “zero risk transfusion”. Therefore, apart from the fundamental philosophy to achieve self-sufficiency, quality and safety become the two most important aspects in blood service operation. But the donated blood being a biological product, no one could guarantee that it is 100 per cent germ free. It is because even those important infections are screened out, some patients may still develop other infectious complications. Worse still, non-infectious complications may also manifest as symptoms and signs similar to infection at the beginning that masks the investigation and management. To tackle these, blood service has established its stringent set of criteria to allow only eligible donors to donate blood. Then every unit blood collected has to pass through meticulous infectious diseases screening tests before they can be used for patients’ transfusion. Although a zero risk and zero incidence in daily operation is virtually non-existent nowadays, with the many technological improvements over the last two decades, the safety level in blood transfusion has nevertheless achieved the ever best milestones in most developed countries. But how to lay down the foundation of safe and quality practice in day to day operation? As infectious disease screening in blood donation is one of the most important parts in securing blood safety, numerous efforts and a lot of resources have already been made to ensure infectious diseases screening are good enough or even state of the art. But with changing and dynamic environment transfusion communities nowadays face not only emerging infectious diseases but some old infections re-emerge to affect human health. Therefore, in order to ensure a safe and quality blood supply, it is necessary to establish system, procedures and processes for ongoing monitoring of the performance and for continued improvement. In the former, a quality management system will fit the purpose as the blood service’s performance and outcome are monitored to achieve the predefined level. Whereas the latter should evolve as a risk management approach that staff at the blood service proactively analyse and implement preventive measures in reducing any problem from occurring. Since quality and safety are usually coming hand by hand therefore a properly running quality management system would ensure a satisfactory performance in blood service that not only meet the expectation of the operators, its stakeholders, the patients and the society. In the blood supply chain, despite that a donor has declared to be safest and passed the stringent donor selection, there may still be a very small chance that the donor is infectious. A common example in Asia would be that a donor may be a chronic hepatitis B carrier that does not have any health problem at all at the time of blood donation. Alternatively, a donor may be in a phase of asymptomatic viraemia that only evolves into laboratory and clinical manifestations days after donation. In the former, it would not normally be a problem in a modern transfusion microbiology laboratory in missing out its detection because the current level of sensitivity of hepatitis B detection is indeed very good. However, the latter may pose a window period problem for that particular infection. Even a good laboratory may not be able to screen out if infective agents in the donor blood are at a lower than detection limit level. Therefore, maintaining optimum screening sensitivity to minimize any risk of post-transfusion infection is definitely needed. Otherwise, reduced assay sensitivity can result in failure to detect low-level infectious carriers. Besides, since the transfusion microbiology tests used at blood service are usually of high throughput, sensitivity and specificity, a sound quality management system and assurance programme are essential for smooth daily operation. The system has to be maintained in their predefined levels so as to allow consistent and desired output. Unfortunately, these advanced technologies always throw into drawbacks that blood service needs to address properly. First, the blood service needs to establish sound quality assessment for its introduction and implementation. The initial evaluation should have a formal quality planning so that objective evidence can be obtained. After the installation, appropriate quality measures have to be in place to monitor its performance. The quality procedures also require stringent preventive and corrective maintenance, quality control by external standards and controls, and statistical control on the daily performance. Although new technology will certainly bring about a better safety margin, it also results in more false positivity in general. False positive results can have significant impact on the blood products and donors outcome. While some countries may consider a universal approach to discard all true and false positive blood, others may establish secondary tests to confirm or exclude. In this regard, the quality planning should take note of this issue and in the subsequent performance reviews, the operators have to propose on appropriate measures to address. Concerning the quality principles in transfusion microbiology, references can be made use of that derived from good manufacturing practice and good laboratory practices. In developed western countries [1], national health system, or regulatory or accreditation body may have defined their own set of guidelines and standards that their blood service can follow. However, in countries without these, many of them may resolve to follow those issued by these developed countries. Therefore, WHO has also outlined the principles of quality management in transfusion microbiology for use in developing countries [1]. Basically, these quality standards and guidelines provide reference to blood service on the implementation, maintenance and monitoring of their own quality assurance system. The blood service itself should base on their local environment to develop their own set of quality management system, quality procedures, work instructions or standard operating procedures, forms and all relevant documents. In general, one can apply the quality principles in the following areas: (1) quality planning and definition of quality objectives; (2) quality assurance and quality control; and (3) management and performance review. For the quality assurance programme, it should contain at least a few key elements i.e. internal quality control; external quality assessment; standard operating procedures; laboratory record documentation and maintenance; laboratory worksheet; and quality monitoring and quality audits. The blood service has to designate sufficient staff to be trained in leading the establishment and implementation of the quality management system, definition of the quality objectives, development of the quality manuals, procedures, standard operating procedures and forms, training of all the staff to understand and familiarize the quality system. The staff competency should be regularly assessed and refresher training should be provided to all staff involved. Lastly, within the quality management system, there should be systemic and periodic review on their compliance to the predefined operational procedures and guidelines, operational performance and outcome analysis, frequencies and severity of system failures, performance at both internal and external quality assurance programmes and audits. While implementation of more commonly known quality principles in transfusion microbiology can present no problem to most blood services, a few additional points have to be born in mind. First, it is frequently observed that the application of statistical techniques on the transfusion microbiology tests results is inadequate. Secondly, there is in general a limited availability of suitable external quality assurance programmes in transfusion microbiology. Since blood donation screening has a different requirement in comparison with hospital diagnostic tests and the residual risk in transfusion transmitted infection is getting much lower, accurate detection of very low level of virus or bacteria is critically needed. At present, the availability of this type of external quality assurance programme is very limited. On the extreme case, blood service may only rely on the control samples from the assay manufacturer alone for the internal quality control. Although international reference laboratory may provide suitable reference materials, they are usually of high cost. An alternative is to store and use in house low level positive materials from sero-converted donors for periodic quality assurance. Fortunately there is growing international co-operation to establish reference standards e.g. in bacteria [2]. Overall, it remains a long road to solve the issue on how to obtain suitable and sufficient reference materials for regular performance. Another area the author would like to draw the attention is on the quality aspects of microbiology reagents and assay kits because it is not uncommonly to hear product recalls from the manufacturer. Since the choice of blood donation screening microbiology tests platform, assays and kits is rather limited and the high and stringent requirement on blood availability and safety in clinical blood transfusion therefore blood service normally does not have room to switch for alternate microbiology testing platform within a short period of time. As such, good quality control of all the incoming reagents and tests kits is crucial. It is therefore essential not to ignore proper quality control measures on this area. Recently, Nightingale et al. reported on the UK approach in systematic monitoring of transfusion microbiology test kit performance [3]. Then Kitchen and Newham further summarized their experience on lot release testing for serological infectious disease assays [4]. These findings prompted the operators of blood service in applying quality principles to monitor not only the ongoing performance of the assays and run-to-run variation using external controls and standards, but also any lot to lot variations that may affect the infectious disease testing performance. Solely relying on the manufacturer’s provided information may not be sufficient. Last but not the least, blood service should also derive mechanism in periodic scanning of the regulatory, quality, safety and technological development in blood transfusion so as to introduce changes timely. A simple approach that is practised nowadays is to have experience sharing among transfusion communities in form of working group and networking. In summary, although quality principles have been well applied in transfusion microbiology, there is still room for further improvement. There is an obvious need to have continual staff development so as to develop their interest and awareness in the quality management and render them committed towards a safe and quality outcome aiming at the ultimate benefit of the patients requiring blood transfusion. Without this driving force, no matter how good quality system has been implemented, it will not be sustainable. Journey in quality and safety is of no end in particular when judging from the stakeholders’ perspective and appropriate resources, time and efforts should be put in by a cost effective and efficient manner. No potential conflict of interest to declare.