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Eight quality management principle are listed in the ISO9000 family of standards [1–3] and have been identified to facilitate the achievement of quality objectives:
1Customer-focused organization: Organizations depend on their customers and therefore should understand current and future customer needs, meet customer requirements and strive to exceed customer expectation.
2Leadership: Leaders establish unity of purpose, direction and the internal environment of the organization. They create the environment in which people become fully involved in achieving the organization’s objectives.
3Involvement of people: People at all levels are the essence of an organization and their full involvement enables their abilities to be used for the organization’s benefit.
4Process approach: A desired result is achieved more efficiently when related resources and activities are managed as a process.
5System approach to management: Identifying, understanding and managing a system of interrelated processes for a given objective contributes to the effectiveness and efficiency of the organization.
6Continual improvement: Continual improvement is a permanent objective of the organization.
7Factual approach to decision making: Effective decisions are based on the logical and intuitive analysis of data and information.
8Mutually beneficial supplier relationships: Mutually beneficial relationships between the organization and suppliers enhance the ability of both the organization and to create value.
The ISO9000 family of standards provides a quality management process mode (Fig. 1) and specifies generic quality management system (QMS) requirements based on these quality management principles for organizations that aim at achieving customer satisfaction through continual improvement of the QMS.
The process model displayed in Fig. 1 reflects graphically the integration of the four major clause headings. For a vertical loop example, management sets requirements under management responsibility; necessary resources are identified and employed within resource management; processes are created and driven under process management; results are measured, analysed and improved through measurement, analysis and improvement. Management review closes the loop, as the cycle returns to management responsibility for initiation of improvement. As an example of a major horizontal loop, the model recognizes the fact that customers play a significant role during input and output processes. Subordinate vertical and horizontal process loops will be created as the organization’s major processes are exercised.
QMS applied to component production
Each blood transfusion service (BTS) must develop and maintain a QMS which must be well designed, structured and organized to assure the quality and safety of manufactured blood and blood components and provide a basis whereby improvement in quality may be demonstrated . The QMS must cover all activities that influence the quality of the blood and blood components that are produced and include a mechanism for continuous improvement. This requires the development of clear policies, objectives and responsibilities, and implementation by means of quality planning, quality control, quality assurance and quality improvement. In practice , an efficient QMS relating to component production comprises a series of interrelated elements  (Fig. 2).
1. Organizational management: Top management of BTS should ensure that an environment for awareness and fulfilment of customer requirement should be created; the quality policy and quality objectives should be established; management review should be performed; the necessary resources should be provided. The physical resources to undertake the work must meet the required standards; this includes equipment, consumables, work areas, utilities, etc. The sufficient numbers of appropriately qualified and experienced staff should be available in the production processes, including quality control and quality assurance. All staff must have clear, documented and up-to-date job descriptions who are authorized by defined procedures.
An independent function with responsibility for quality assurance must be established. This quality assurance function will be responsible for oversight of all quality processes but need not necessarily be responsible for carrying out the activities.
A quality assurance manager must be identified who will be responsible for the quality assurance function. Top management must review the QMS at regular intervals to ensure its continuing suitability, adequacy and effectiveness and introduce corrective measures if considered necessary.
2. Training: BTS should ensure that their staff should be educated and trained to qualify them for the activities performed. Therefore, training needs required for achieving conformity of blood components should be determined and sufficient training should be provided to meet these needs; the effectiveness of training on a continual basis should be evaluated.
All personnel must receive initial and continued training appropriate to their specific tasks. Training and competencies must be documented and training records must be maintained.
3. Documentation: There are several types of documents including the standard operating procedures (SOP) – instructions on how to perform the work; forms – recording information in a standardized way; datasheets – easy to see information needed to perform the work; labels – information that indicates the type of product, expiry date and lot/batch and status of the product. SOP of each process should be developed to ensure that the processes are operated under controlled conditions, for example, processing, labelling, packaging, quarantine, release, storage, transportation, etc. Quality information should be recorded to demonstrate conformance to users’ requirements.
Effective document provides clear instructions on what to do and prevents errors that may result from spoken communication. It ensures consistency of manufacture and service provision, provides objective evidence that tasks have been correctly performed, permits investigation if problems arise, and facilitates traceability from donor to patient and vice versa.
Effective document control must be practiced to ensure that documents being used are current and an archive of superseded documents should be established to provide an historical record. Effective documentation, whether in written or electronic format, must be accurate, authorized, controlled at issue, and reviewed on a regular basis to ensure that it remains relevant.
4. Quality standards: The component specifications should be developed to ensure components (intermediate and final components) are consistent with the organization’s quality policy, objective and users’ requirements. Each type of product needs its own specifications in which all parameters (such as volume, level of bioactive substances) should be covered. The component specifications must be appropriate to the clinical use of the product, achievable and comprehensive.
There should be specifications for starting material, additive solutions, primary package material (bags) and equipment that will influence the quality of the final blood component.
5. Processes: The processes of blood component production consist of a series of activities (to be detailed in the third part).
6. Assessment: The components and component manufacturing processes should be monitored and evaluated to demonstrate that the components conform to specified requirements.
Quality control of blood and blood components must be carried out according to a defined plan to identify whether final products meet specifications. Regular self-inspection and internal audits must be implemented to monitor overall compliance with the QMS. Self-inspection and audit must be conducted independently by trained and competent persons according to approved protocols.
All audit results must be documented and reported to the management. Appropriate corrective and preventative actions must be taken to ensure that existing component non-conformity or quality problems are corrected and that recurrence of the problem is prevented.
How to implement a QMS in component production
Blood components may be prepared during collection using apheresis technology. Plasma, leucocytes, platelets and red cell concentrates may be obtained thus. Alternatively, components may be made by the post donation processing of whole blood that may be collected in the traditional manner. Within the process of blood component production, the related resources and activities that are mainly involved are as follows.
1. Facilities and equipments: The premises used for the processing of blood components should comply with good manufacturing practice. The workflow in an area should be arranged in a logical sequence to minimize the risk of errors.
All equipments must be designed and validated to suit its intended purpose and must not present any unacceptable risks to operators. Regular maintenance and calibration must be carried out and documented according to established procedures to ensure that the equipment can be operated reliably and consistently. All critical equipments must have a regular, planned maintenance to detect or prevent avoidable errors and keep the equipment in its optimum functional state. The maintenance intervals and actions must be determined for each item of the equipment. The maintenance status of each item of the equipment must be available. New and repaired equipments must meet qualification requirements when installed and authorized before use.
2. Selection of methodology: Procedures involved in components preparation should be specified. Methods used for the preparation of blood components (e.g. centrifugation, filtration, irradiation and freezing) must be validated.
To maintain a closed system throughout the separation procedure, a multiple bag configuration, either readymade or steriledocked, should be used. The design and arrangement of the pack system should be such as to permit the required sterile preparation of the desired component.
Sterile connecting devices should be used in accordance with a validated procedure. If validated and used properly, connection done using sterile connecting devices can be regarded as closed system processing. Time limits should be defined for the processing of blood components.
3. Labelling: The labelling of blood components should comply with the relevant national legislation and international agreements. Labels must be clear, concise and adhere to all processing and storage conditions. The label on the component ready for distribution should contain eye-readable information necessary for safe transfusion:
(a) The unique identity number, allowing full traceability to the donor and the collection, testing, processing, storage, release, distribution and transfusion of the blood component.
(b) The proper name, whole blood or blood component, including an indication of any qualification or modification.
(c) ABO group and Rh type, if applicable.
(d) The method by which the blood component was prepared, either by whole blood or apheresis collection.
(e) The standard contents or volume is assumed unless otherwise indicated on the label or in circular supplements.
(f) The number of units in pooled blood components and any sedimenting agent used during cytapheresis, if applicable.
(g) The temperature range in which the blood component is to be stored.
(h) The expiration date (and time if applicable), which varies with the method of preparation (open or closed system) and the preservatives and anticoagulant used.
(i) The preservatives and anticoagulant used in the preparation of the blood or blood components, when appropriate.
(j) The name, address, registration number and license number (if applicable) of the collection and processing location.
(k) For autologous blood products, the label should contain also the name and unique identification of the patient as well as the statement ‘Autologous Donation’.
When component production requires the use of subsidiary packs which are not an integral part of the pack assembly, for example, filtration, pooling and freezing, a secure system must be in place to ensure that the correct eye-readable and barcoded donation number is placed on each additional pack used.
When components are pooled there should be a system to ensure that the pool carries a unique identity number. When a component is divided a secure system must be in place to ensure that all sub-batches can be traced. Pre-printed labels to be attached to blood donations, documentation and components should be stored under secure conditions.
4. Quarantine and release: Effective system must be developed to prevent the release of untested or unsuitable blood products which must be segregated from blood products that are suitable for use.
There should be a system of administrative and physical quarantine for blood and blood components to ensure that they cannot be released until all mandatory requirements have been satisfied.
There must be a defined procedure for the release of non-standard blood and blood components under a planned non-conformance system. The decision for such a release must be clearly documented and authorized by a designated person and traceability must be ensured.
In the event that a final component fails release due to potential impact on patient safety then all other implicated components must be identified and appropriate action must be taken. A check must be made to ensure that other components from the same donation(s) and components prepared from previous donations given by the donor(s) are identified.
Where release is subject to computer-derived information, the following requirements must be met.
• The computer system must be validated to be fully secure against the possibility of blood and blood components which do not fulfil all test or donor selecting criteria, being released.
• The manual entry of critical data, such as laboratory test results, must require independent verification by a second authorized person.
• The computer system must block the release of all blood or blood components considered not acceptable for release. There must also be a means to block the release of any future donation from the donor.
In the absence of a computerized system for component status control, or in the event of computer system failure, the following requirements must be met:
• The label of a blood component must identify the component status and must clearly distinguish released from non-released (quarantined) component; records must demonstrate that before a component is released, all current donor declaration forms, relevant medical records and test results have been verified by an authorized person.
• Before final component release, if blood or blood component(s) have been prepared from a donor who has donated on previous occasions, a comparison with previous records must be made to ensure that current records accurately reflect the donor history.
5. Storage and transportation: Blood and blood products must be stored and transported under the correct conditions. Storage areas must provide effective segregation of quarantined and released materials or components. There must be a separate area for storage of rejected components and materials. Intermediate storage and transport must be carried out under defined conditions to ensure that defined requirements are met.
Storage and transportation conditions must be controlled, monitored and checked. Appropriate alarms must be present and regularly checked. Appropriate actions on alarms must be defined. Due to the potential deterioration of activity and function of labile blood components, conditions of storage and time prior to processing are vital to the preparation of components. Delays in preparation or unsuitable conditions of storage may adversely affect quality of the final components.
Blood components should be transported by a system which has been validated to maintain the recommended storage temperature of the component over the proposed maximum time and extremes of ambient temperature of transport.
6. Quality monitoring: QMS requires a monitoring system to monitor the quality of component preparation either during or at completion of a process. Monitoring focuses on appropriate parameters that need to be matched to the product and its intended use. Monitoring is an integral part of any production process which is a tool to generate data to feed back into the process – whether positive or negative.
All quality control procedures must be validated before use. The results of quality control testing must be continuously evaluated. Quality is the responsibility of all persons involved in the BTS processes. Management is responsible for a systematic approach towards quality and the implementation and maintenance of a QMS.