Good manufacturing practices

Transcription

1 ORIGINAL PAPER 1AR-10 ISBT Science Series (2009) 4, 6 10 Journal compilation 2009 International Society of Blood Transfusion Good manufacturing practices Blackwell Publishing Ltd A. Ahmed Quality Manager, National Blood Transfusion Services, Egypt GMP introduces the application of Quality assurance principles in all steps involved in the collection, preparation, testing and distribution activities. GMP resulting in an increase of the availability of blood products. Key words: Manufacturing, products, quality assurance. Definition Good manufacturing practice (GMP) is the part of quality assurance (QA) that : ensures that products are consistently produced and controlled: (i) quality standards; (ii) marketing authorization ensures consistent production and control of products cover both production and quality control assure the quality of medicinal products assure the safety, well-being and protection of the patient. Aim The aim of GMP is diminishing risks that cannot be controlled by testing of product: (i) contamination and cross-contamination and (ii) mix-ups (confusion). Basic requirements for GMP Basic requirements for GMP are listed as follows: clear, written instructions and procedures trained operators records of actions, deviations and investigations records for manufacture and distribution proper storage and distribution systems for complaints and recalls. Elements of GMP Elements of GMP include: (i) quality management; (ii) personnel; (iii) contracts; (iv) purchasing; (v) premises and Correspondence: Afaf Ahmed, Quality Manager, National Blood Transfusion Services, Egypt afaf_ahmed_nbtc@yahoo.com Conflicts of interest: The author declares no conflicts of interest. equipment; (v) documentation; (vi) production; (vii) quality control; (viii) complaints and recall; and (ix) self-inspection. What is quality? What do we mean by quality? We mean (i) a product/ service that does its intended job; (ii) it meets the customer s requirements; (iii) it is fit for purpose; (iv) it conforms to requirements. We do not mean: (i) expensive items and (ii) Name products. What is quality management? What is quality management? It is the aspect of management function that determines and implements the quality policy, and the overall intention and direction regarding quality, as formally expressed and authorized by top management. The basic elements are: (i) an appropriate infrastructure or quality system encompassing the organization structure, procedures, processes and resources and (ii) the systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for quality. What is termed quality assurance? The totality of actions is termed quality assurance : quality assurance is a management tool; quality assurance covers everything that can effect the quality of the products or services; quality assurance system should be used to build quality into the products; it aims to make sure that the products are safe, effective, fit for purpose; managerial responsibilities are defined; 6

2 Good Manufacturing Practices 7 Key personnel Authorized person Head of Production Head of Quality Control May delegate functions not responsibility Heads of Production and Quality Control should be independent of each other should possess appropriate qualifications should possess appropriate experience Fig. 1 Quality assurance. in job descriptions, the manufacture, supply and use of correct starting and packaging materials; it includes system known as GMPand QC; and QA, GMP and QC are interrelated aspects of quality management (Fig. 1). Personnel Personnel requirements: adequate number of persons with necessary qualifications with practical experience an individual s responsibilities should not be so extensive as to present a risk to quality must work to defined procedures (standard operating procedure, SOP) must report any errors or mistakes the organization provide the resources to allow the staff to do their work all responsible staff should have specific duties recorded in individual written job descriptions have adequate authority to carry out responsibilities may delegate to designated deputies with qualifications no gaps or unexplained overlaps organization chart all personnel should be aware of GMP must receive training in GMP: initial training continuing training including hygiene standards records of training must be kept motivated to support the establishment and maintain high-quality standards prevent unauthorized access to production areas storage areas QC stop personnel who do not work in these areas using them as passageway. Contracts Contracts must be correctly defined. Written contract (i) must ensure satisfactory quality; (ii) stipulate quantities and (iii) stipulate quality requirements. Purchasing Purchasing include: specification, quantities and delivery times. Verify the quality of the incoming goods. Premises Premises should be designed so that work flows through each area in a logical fashion. There should be adequate space for working, and for storage. Work and storage areas must be kept clean, and cleaning should be recorded. Work and storage areas must be maintained within adequate temperature limits. Equipment Equipment must be located, designed, constructed, adapted and maintained to suit the operations to be carried out. Measuring equipment should be calibrated at defined intervals, and calibration records must be kept. Critical equipment must have planned maintenance schedules. All incoming materials and finished products Materials Materials should be quarantined after receipt or processing until released for use or distribution and should be stored under appropriate conditions: (i) orderly fashion (batch segregation); (ii) materials management; (iii) stock rotation (FEFO). Starting materials are labelled, as follows: name and internal code supplier s batch number(s) and manufacturer s on receipt status (e.g. quarantine, on test)

3 8 A. Ahmed Fig. 2 Document hierarchy. expiry date or retest date role of validated computer systems sampled containers identified. Documentation The main document types are: SOP, work instruction (must be followed at all times), forms (must be completed at the time a job is done), policies, specification, data and information sheet, external source document, letters, and records (Fig. 2). Control of documents Documents need to be controlled, approved and updated. Production Product are produced by calibrated equipment. Processes are described in SOPs. Trained staff. Consumables items are in date. Stock rotated when new items are delivered. Changes are controlled (to make sure that the new system work, not reduce the quality of the product, not have an adverse affect on any other systems). Validation performed Validation is the action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system actually leads to the expected results. Qualification is the action of proving that any premises, systems and items of equipment work correctly and actually lead to the expected results. (Validation usually incorporates the concept of qualification). Principle Manufacturer to identify what qualification and validation work is required. Essential part of GMP. Prove that critical aspects of work are controlled. Key elements of qualification and validation defined and documented. Scope The scope are qualification and validation applicable to any aspect of operation that may affect the quality of the product directly or indirectly: (i) premises, facilities (utilities), equipment and processes and (ii) significant changes. Principle Qualification and validation should be done in accordance with an ongoing programme: initial qualification and validation and and nnual review Qualification and validation maintain continued validation status. Policies are described in relevant documentation, for example, quality manual, or Validation Master Plan (VMP).

4 Good Manufacturing Practices 9 Types of documentation VMP Validation protocols Validation reports SOPs Documentation Documentation clearly defines responsibility of performing validation and is conducted in accordance with predefined, approved validation protocols. Recorded results and conclusions presented in written validation reports prepared and stored. Processes and procedures should be established on the basis of these results. Fig. 4 Precision is the degree of agreement among individual results. Importance Premises, utilities, equipment and processes. Critical importance and particular attention paid to validation of analytical test methods, automated systems and cleaning procedures. Some of characteristics that should be considered during validation of analytical methods: specificity, accuracy and precision (Figs 3 and 4). Quality control Quality control is concerned with sampling, specification and testing and final product testing and release. It is performed by both Quality Monitoring an Testing departments. Sample of the products needs to make sure that: (i) system is working; (ii) products meet specification; (iii) products will be effective for their intended use; and (iv) Products are safe. Sampling Samples must (i) be taken in accordance with written procedures; (ii) be tested in accordance with written procedures; and (iii) be assessed against documented specifications. What are Quality Indicators? Quality indicators are used as a measure of performance. They include incidents, contacts\complains, deviations and concessions. System for reporting Quality should be reported to QA departments. Indicators are reviewed periodically. Corrective actions are required where necessary. The reporting system for indicators include the requirement for them to be closed when action is complete. Corrective and preventive action Fig. 3 Accuracy is the degree of agreement of test results with the true value. Corrective action is the immediate action that is taken to correct a problem. Preventive action is a more long-term action that is put in place to prevent future recurrence.

5 10 A. Ahmed Complains and recall Recall of the product may be needed when there is a manufacturing fault or patient risk. Records of all recalls are kept, ensuring a full audit trial for each donation or product implicated. Self-inspection Purpose of Audit: audit is a way of inspecting systems to ensure that they are being carried out correctly and audits are carried out against standards. Internal audit Internal audit, or self-inspection, is used by staff to their own systems. Auditors should be independent of the departments they are auditing. External audit The purpose of an external audit is for customers and third prates to asset and organizations capabilities to meet specified requirement. Impact of GMP in blood establishments In blood establishments, GMP introduces the application of QA principles in all steps involved in the collection, preparation, testing and distribution activities: GMP supports systematic application of donor selection criteria for each donation; GMP ensures appropriate testing methods and testing kits, and use of suitable reagents; GMP requires the use of suitable facilities, equipment and materials; GMP reduces errors and technical problems in collection, preparation, testing and distribution; GMP ensures the existence of validated and robust processes, for example, disinfection of puncture site before collection, separation process, testing methods, freezing of plasma, andtransport (cold chain); GMP guarantees the release of products that comply with the safety and quality requirements; GMP ensures adequate documentation and full traceability for each collection and product, from donor to recipient; GMP strengthens the competence of the personnel; and GMP enables continuous improvement in collection, preparation and testing of starting material.