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Review by Heidi Hanes Review date 10-Feb-20

Botswana-Harvard HIV Reference Laboratory

(BHHRL)

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Quality Manual

Document No.: BHHRL/001PL01

Version : 1.0

Signed, Quality Manager : Date : Effective Date :01/03/2008 Page 1 of 21

Title: QUALITY MANUAL

Name, Title Signature, Date Prepared By:

Munyaradzi P. Mangwendeza, Quality Manager

Name, Title Signature, Date Approved By: Dr. Rosemary Musonda, Laboratory Director

Review Date Revision Date Signature, Date

Annual Review

Location: Copy Number: Location: Copy Number Master file 1

Director – Dr. Musonda

2

Director – Dr. Mine

3

Lab Managers – Mr. S. Moyo Mrs. K. Makhaola

4 5

Distributed To:

Lab Co-ordinator 6

Copy Number: _________


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Table of Contents Page 1. Introduction 3 2. References 3 3. Terms And Definitions 3 4. Management Requirements 4

4.1. Organization 4 4.2. Management System 6 4.3. Document Control 7 4.4. Review of Contracts, Orders and Research Project Proposals. 8 4.5. Referral of Laboratory Testing 8 4.6. Purchasing Services And Supplies 9 4.7. Service To The Client 9 4.8. Complaints 10 4.9. Control Of Nonconforming Work 10 4.10. Improvement 11 4.11. Corrective Action 11 4.12. Preventive Action 11 4.13. Control Of Records 12 4.14. Internal Audits 12 4.15. Management Reviews 13

5. Technical Requirements 13 5.1. General 13 5.2. Personnel 13 5.3. Accommodation And Environmental Conditions 14 5.4. Test Methods and Method Validation 15 5.5. Equipment 17 5.6. Measurement Traceability 18 5.7. Sampling 18 5.8. Handling and Transport of Samples 19 5.9. Assuring The Quality Of Test And Calibration Items 19 5.10. Reporting Of Results 20

6. Appendices 21


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1. Introduction 1.1. The Botswana Harvard HIV Reference Laboratory (BHHRL) is a medical

testing laboratory involved in both diagnostic and research testing. The management of BHHRL understands and recognizes the importance of the work carried out by the institution and has thus placed great value in quality management. In this regard, management has developed a Quality Management System based on the international standard ISO/IEC 17025:2005 (BOS ISO/IEC 17025:2005 as adopted by the Botswana Bureau of Standards).

1.2. The quality management system is defined and documented in this Quality Manual and other documents that make up the Quality Management System documents. Documentation of the Quality Management System used at BHHRL follows a 4-tier pyramid made up of Quality Manual, Policies and Procedures, Work Instructions and Forms/Records.

1.3. The Quality Manual itself defines the Quality Management System, states responsibilities of the personnel affected by the system and makes reference to the standard operating procedures for all the activities that make up the Quality Management System.

1.4. The Quality Manual will also be used to inform those who use our services of our Quality Management System and the various controls used to assure testing service quality.

1.5. The Quality Manual shall be reviewed annually and revised when and as necessary so as to be up to date and reflect the Quality Management System that will be currently in use. It shall be issued on controlled copy basis to all those affected by the Quality Management System and on an uncontrolled copy basis to suppliers and those who use our services.

1.6. For effectiveness, the Quality Manual should be used in conjunction with all the documents it makes reference to as well as others that make up the Quality Management System documents.

2. References

2.1. BOS ISO/IEC 17025 Standard – General Requirements for the Competence of Testing and Calibration Laboratories.

2.2. ISO 9000 - Quality Management Systems -- Fundamentals and Vocabulary 3. Terms and Definitions

3.1. Refer to document: BHHRL/001PR015 Quality Management System Terms and Definitions


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4. Management Requirements 4.1. Organization

4.1.1. The BHHRL is constituted by the Botswana Harvard AIDS Institute Partnership for HIV Research and Education. Botswana Harvard Partnership and the MoH diagnostic laboratory established to support the National anti retroviral programme (MASA). The BHHRL has been established as part of the collaborative research and training initiative between the Botswana Government and the Harvard AIDS Institute which was established in 1996.

4.1.2. BHHRL has legal responsibility over its activities and carries out its activities in a manner that meets the requirements of the BOS ISO/IEC 17025:2005 International Standard making sure clients’ needs are fulfilled as well as those of all regulatory authorities and organizations. This Quality Management System covers all work carried out at the BHHRL main facilities as well as all the clinics situated in the country that carry out activities for and under oversight by BHHRL.

4.1.3. The laboratory is not part of any other organization that carries out work other than medical testing and HIV research work and the responsibilities of all key personnel in the organization that have an involvement or influence on the testing activities of the laboratory, are clearly defined to prevent any potential conflict of interest.

4.1.4. The laboratory has technical and managerial personnel who have the authority and resources needed to carry out their duties which include implementing, maintaining and improving the Quality Management System as well as identifying the occurrence of departures from the Quality Management System or from the procedures for performing test and to initiate actions to prevent or minimize such departures.

4.1.5. The Terms and Conditions of Service of BHHRL have been developed to ensure that personnel do not have undue internal and external commercial, financial and other pressures and influences that may adversely affect the quality of their work. They have also been developed to ensure that BHHRL and its personnel are not involved in activities that would diminish confidence in BHHRL’s competence, impartiality, judgement or operational integrity.

4.1.6. It is the policy of BHHRL to protect the confidential information of those involved in our activities including protecting electronic storage and storage of results. To this end all employees are required to sign a confidentiality document on employment.

4.1.7. BHHRL has in place an organogram that defines the organization and management structure of the laboratory, relationships with other


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organizations as well as the relationship between Quality Management System, technical operations and support services.

4.1.8. BHHRL has in place an authority matrix which specifies the responsibility, authority and interrelationships of all personnel who manage perform or verify work affecting the quality of test.

4.1.9. BHHRL executive management has appointed a technical manager who is known as the Laboratory Manager who has overall responsibility for the technical operations and provision of the resources needed to ensure the required quality of laboratory operations. The Laboratory Manager ensures that section 5 of the Quality Manual is implemented and maintained.

4.1.10. BHHRL executive management has appointed a Quality Manager who has the defined responsibility and authority for ensuring the that the Quality Management System related to quality is understood, implemented and followed at all times by all personnel and has direct access to the highest level of management at which decisions are made on laboratory policies and resources. The Quality manager ensures that section 4 of the Quality Manual is implemented and maintained.

4.1.11. BHHRL management ensures that appropriate communication processes are established within the organization, that communication takes place regarding the effectiveness of the management system, that its personnel are aware of the relevance and importance of their activities and how they contribute to the achievement of the objectives of the quality management system and that staff are encouraged to communicate to their supervisors all matters that impact adversely on the quality management process.

4.1.12. Communication channels available to BHHRL staff are, but not limited to, meetings, memos, email, notices on boards, and confidential suggestion box.

4.1.13. To ensure that activities flow in an uninterrupted manner, BHHRL management has appointed deputies for key managerial personnel. Management also provides adequate supervision for testing staff including those on training, by personnel familiar with methods and procedures, purpose of the test and with assessment of the test.

4.1.14. Refer to: 4.1.14.1. BHHRL Terms and Conditions of Service 4.1.14.2. BHHRL/001PR05 BHHRL Organogram


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4.2. Management System 4.2.1. The Quality Manual is the principal document that defines the Quality

Management System of BHHRL. The Quality Management System policies, procedures, and instructions are documented to establish and maintain continuity of each activity or function affecting quality. Quality Management ensures that quality documentation is communicated to, understood by and readily available to appropriate personnel for reference and implementation.

4.2.2. The Quality Management System is meant to: 4.2.2.1.Identify the processes needed for the Quality Management System 4.2.2.2.Determine the sequence and interaction of the processes needed in the

Quality Management System 4.2.2.3.Determine criteria and methods required to ensure the effective

operation and management of these processes 4.2.2.4.Ensure the availability of resources and information necessary to

support the operation and monitoring of these processes 4.2.2.5.Monitor measure and analyze these processes and implementing

actions necessary to achieve planned results and continual improvement.

4.2.3. All the procedures for BHHRL are continually improved in accordance with the requirements of the standard and laboratory management communicates to the organization the importance of meeting customer requirements as well as statutory and regulatory requirements.

4.2.4. Refer to: 4.2.4.1.Appendix 1 – BHHRL Organogram 4.2.4.2.Appendix 2 – Table of Deputies


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Quality Policy Statement

BHHRL management is committed to the provision of medical laboratory testing services that are of high international standards in line with the principles of good professional laboratory practice. Management is also committed to the provision of accurate, reliable, credible, relevant and timely laboratory results obtained from tests that are always carried out in accordance with stated procedures and client requirements while complying with the requirements of the ISO/IEC 17025:2005 International Standard. Management undertakes to periodically review the performance of the Quality Management System and quality objectives to ensure their effectiveness, continuing relevance and suitability in ensuring production of high quality laboratory results. It is, however, the responsibility of all BHHRL personnel to familiarize themselves with the content and requirements of the Quality Management System documentation and implement the policies and procedures as laid down, in all their work processes.

4.2.5. The requirements of the Quality Management System will be met by

documenting specific quality practices and activities for all processes, including meeting contractual requirements, understanding and meeting customer needs, and with emphasis on problem prevention. Changes to the Quality Management System will be made as conditions or services change or mature. Written quality and audit plans will be prepared for these changes which will be consistent with all other requirements of the quality management system.

4.2.6. Refer to: 4.2.6.1. Appendix 3 – Quality Management System Objectives

4.3. Document Control

4.3.1. BHHRL recognizes the importance of regulating the information made available to its personnel for use in their day to day work. As a result, management has established and maintains a procedure to control all documents, internally generated and from external sources, that form part of the Quality Management System documentation. These include documents of external origin such as regulations, standards, other normative documents, test methods as well as drawings, specifications, instructions and manuals.

4.3.2. Refer to: Document No: 4.3.2.1.BHHRL/001PR01 Document Control and Management.


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4.4. Review of Contracts, Orders and Research Project Proposals. 4.4.1. BHHRL ensures that the contract, order and research project proposal

review is conducted in a practical and efficient manner, and the effect of financial, legal and time schedule aspects are taken into account. For internal clients the review is done in a simplified manner.

4.4.2. The review of capability verifies that the laboratory possesses the necessary physical, personnel, and information resources, and that the laboratory personnel have the skills and expertise necessary for the performance of the tests in question.

4.4.3. The review may encompass results of earlier participation in proficiency testing and/or running of trial test programs using samples of known values in order to determine uncertainties of measurement, limits of detection, confidence limits e.t.c.

4.4.4. The review also covers any work that is subcontracted by the laboratory and if the contract needs amendment after work has commenced, the same contract review process is repeated and any amendments communicated to all affected personnel.

4.4.5. Refer to: Document No: 4.4.5.1.BHHRL/001PR02 Review of Contracts, Orders and Research Project

Proposals.

4.5. Referral of Laboratory Testing 4.5.1. It is the policy of BHHRL that any work that is subcontracted is placed

with competent subcontractors that are on the Approved Supplier List and are in compliance with this Quality Management System and requirements of ISO/IEC 17025:2005 or ISO/IEC 15189 International Standards.

4.5.2. Subcontractors are evaluated, selected and monitored by management of BHHRL except in cases where the client or regulatory agency specifies which subcontractor is to be used.

4.5.3. Where any work has been subcontracted, BHHRL shall not under any circumstances report that the work has been carried out by itself.

4.5.4. Refer to: Documents No: 4.5.4.1.BHHRL/001PR04 Referral of Laboratory Testing 4.5.4.2.BHHRL/010PR01 Purchasing and Receipt of Services and Materials 4.5.4.3.BHHRL/001PR02 Review Of, Contracts, Orders and Research

Project Proposals. 4.5.4.4.BHHRL/010PR04 Approved Supplier List


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4.6. Purchasing Of Services And Supplies 4.6.1. BHHRL uses only such services and supplies that are of the quality

needed to sustain confidence in the results of tests carried out. To assure this, management has established policies and procedures for the selection and purchasing of services and supplies it uses that affect the quality of the tests. The procedures include purchasing, reception and storage of reagents and consumable materials relevant to test.

4.6.2. Purchased supplies and consumable materials that affect the quality are not used until they have been inspected or otherwise verified as complying with standard specifications or requirements defined in the methods for test concerned.

4.6.3. All suppliers of critical supplies/services that may affect the quality of testing are evaluated and records maintained. Supplier status is maintained in through the use of the Approves Supplier List.

4.6.4. Refer to: Documents No: 4.6.4.1.BHHRL/010PR01 Purchasing and Receipt of Services and Materials 4.6.4.2.BHHRL/010PR03 Approved Supplier List, 4.6.4.3.BHHRL/010PR02 Inventory Control

4.7. Service to the Client

4.7.1. BHHRL afford clients, or their representatives, cooperation to facilitate clarification of the client’s request and to monitor the performance of the laboratory in relation to the work performed, provided confidentiality is ensured to other clients. Such cooperation may include, but is not limited to, providing reasonable access to relevant areas of the laboratory for the witnessing of test performed and preparing, packaging and dispatching of tests samples needed by the client for verification purposes.

4.7.2. Client observation of testing is acceptable to the extent that it does not interfere with the testing process. Personnel should report to the Laboratory Manager when observations become intrusive.

4.7.3. The Laboratory Manager is the point of contact for the maintenance of contacts with client, providing advice and guidance in technical matters and opinions and interpretations based on results. The Laboratory Manager also informs the client of any delays or major deviations in the performance of test.

4.7.4. The Laboratory and Quality Manager encourage and obtain feedback, both negative and positive, from clients for the purposes of improving the Quality Management System.


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4.7.5. Refer to: Document No: 4.7.5.1.BHHRL/001PR06 Handling Complaints/Suggestions and

Monitoring Client and Staff Satisfaction

4.8. Complaints 4.8.1. BHHRL has established a policy and procedure for the resolution of

complaints received form clients or other parties. Records of all complaints are kept as well as those for the investigations and corrective actions instituted.

4.8.2. The Quality Manager monitors complaints and any other discrepancies that may raise doubt about compliance with policies and procedures. If it is determined that sufficient cause exists, an audit of those areas of activities involved will be performed according to the internal audit procedures.

4.8.3. Refer to : Document No: 4.8.3.1.BHHRL/001PR08 Corrective and Preventive Actions and Continual

Improvement 4.8.3.2.BHHRL/001PR06 Handling Complaints/Suggestions and

Monitoring Client and Staff Satisfaction, 4.8.3.3.BHHRL/001PR08 Corrective and Preventive Actions and Continual

Improvement BHHRL/001PR011 Internal Audits. 4.8.3.4.BHHRL/001PR06 Handling Complaints/Suggestions and

Monitoring Client and Staff Satisfaction

4.9. Control of Nonconforming Testing Work 4.9.1. Identification of nonconforming test work or problems with the Quality

Management System can occur at various points with in the Quality Management System and technical operations such as customer complaints, quality control, instrument calibration, checking of consumable materials, staff observations or supervision, test report, management review and internal and external audits.

4.9.2. BHHRL has thus established and maintains a Control of Nonconforming Work SOP that is implemented when any aspect of its testing or the results of its work, do not conform to its own procedures or the agreed requirements of the client.

4.9.3. Where the evaluation indicates that the nonconforming work could recur or that there is doubt about the compliance of the laboratory’s operations with its own procedure, the Corrective and Prevention Action SOP is


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promptly followed to identify the root causes of the problem and to eliminate them.

4.9.4. Refer to; Document No: 4.9.4.1.BHHRL/001PR07 Control of Nonconforming Work, 4.9.4.2.BHHRL/001PR08 Corrective and Preventive Actions and Continual

Improvement

4.10. Improvement 4.10.1. BHHRL continually improve the effectiveness of its Quality Management

System through the use of the quality policy, quality objectives, and audit results, analysis of data, corrective actions, preventive actions and management review.

4.10.2. Refer to: Document No: 4.10.2.1. BHHRL/001PR08 Corrective and Preventive Actions and

Continual Improvement

4.11. Corrective Action 4.11.1. BHHRL’s quality management system is set towards the prevention of

nonconformities. The Corrective and Preventive Action SOP is thus utilized for implementing corrective action when nonconforming work or departures from the policies and procedures in the Quality Management System or technical operations have been identified. The procedure designates appropriate authorities to implement corrective action.

4.11.2. If the identification of nonconformities or departures casts doubts on the laboratory’s compliance with its own policies and procedures, or its compliance with the ISO/IEC 17025:2005 International Standard, the appropriate areas of activity are promptly audited in accordance with the Internal Audit SOP.

4.11.3. Refer to: Document No: 4.11.3.1. BHHRL/001PR08 Corrective and Preventive Actions and

Continual Improvement BHHRL/001PR011 Internal Audits.

4.12. Preventive Action

4.12.1. Needed improvement and potential sources of non-conformances, either technical or with the Quality Management System are identified as per the SOP on Continual Improvement and/or the Corrective and Preventive Action. If preventive action is required, action plans are developed, implemented and monitored to reduce the likelihood of the occurrence of


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such nonconformities and take advantage of the opportunities for improvement.

4.12.2. Preventive action is a pro-active process to identify opportunities for improvement rather than a reaction to the identification of problems or complaints and may involve analysis of data, including trend and risk analysis and proficiency testing results.

4.12.3. Refer to : Document No: 4.12.3.1. BHHRL/001PR08 Corrective and Preventive Actions and

Continual Improvement

4.13. Control Of Records 4.13.1. BHHRL has established and maintains a Control of Records SOP to

manage quality and technical records. Such records are maintained to provide evidence of conformance to requirements and of effective operation of the Quality Management System. The SOP ensures identification, collection, indexing, access, storage, maintenance and disposal of quality and technical records. Quality records also include reports from internal audits and management reviews as well as corrective and preventive action records.

4.13.2. All records are held secure and in confidence and procedures are implemented to protect and back-up records stored electronically and to prevent unauthorized access to or amendments of these records.

4.13.3. All records are retained for the defined time. 4.13.4. Refer to: Document No:

4.13.4.1. BHHRL/001PR012 Records Control and Management.

4.14. Internal Audits 4.14.1. BHHRL periodically and in accordance with a predetermined schedule

and procedure, conduct internal audits of activities to verify that operations continue to comply with requirements of the Quality Management System and ISO/IEC 17025:2005 standard. The internal audit program is designed to address all elements of the Quality Management System including the testing activities.

4.14.2. It is the responsibility of the Quality Manager to plan and organize audits as required by the schedule and requested by management and audits are carried out by trained and qualified personnel who are independent of the activity being audited.

4.14.3. Refer to: Document No: 4.14.3.1. BHHRL/001PR011 Internal Audits.


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4.15. Management Reviews 4.15.1. BHHRL management periodically, and in accordance with a

predetermined schedule and procedure, conducts a review of the laboratory’s Quality Management System and testing activities to ensure their continuing suitability and effectiveness and to introduce necessary changes and improvements. These reviews are held at a minimum of at least once annually.

4.15.2. The reviews take account of customer feedbacks, complaints, changes in type and volume of work, the results of comparisons and proficiency tests, assessments by external bodies, the outcome of recent internal audits, corrective and preventive actions, reports from managerial and supervisory personnel, the suitability of policies and procedures, recommendations for improvement and any other factors such as quality control activities, resources and staffing.

4.15.3. Records of management reviews are maintained and actions are carried out within an appropriate and agreed time period.

4.15.4. Refer to: Document No: 4.15.4.1. BHHRL/001PR013 Management Review.

5. Technical Requirements

5.1. General 5.1.1. BHHRL recognizes that many factors determine the correctness and

reliability of the tests performed by the laboratory. These include contributions from human factors, accommodation and environmental conditions, test and calibration methods and method validation, equipment, measurement traceability, sampling and handling of samples.

5.1.2. The extent to which the factors contribute to the total uncertainty of measurements differs considerably between types of tests. BHHRL takes into account these factors in developing test procedures, in training and qualification of personnel and in selection and calibration of the equipment it uses.

5.1.3. Refer to: Document No: 5.1.3.1.BHHRL/001PR016 Accommodation and Environmental Conditions

and Process Control.

5.2. Personnel 5.2.1. BHHRL management ensures the competency of all who operate specific

equipment, who perform tests, evaluate results and sign reports. Staff undergoing training is adequately and appropriately supervised. Personnel


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performing tasks are qualified on the basis of appropriate education, training, experience and /or demonstrated skills as required.

5.2.2. The Laboratory Manager formulates goals with respect to education and skills of the laboratory personnel. Training needs are identified and any necessary training is provided as per the Training SOP. Training programs are relevant to present and anticipated tasks of the laboratory and the effectiveness of the training is evaluated.

5.2.3. BHHRL uses personnel who are contracted to the laboratory. 5.2.4. The Laboratory Manager ensures that contractual, additional technical

employees and key support personnel are adequately supervised and work in accordance with the laboratory’s Quality Management System. The Laboratory Manager authorizes specific personnel to perform particular types of tests, to issue test reports, to give opinions and interpretation and to operate particular types of equipment.

5.2.5. The Quality Manager maintains current job descriptions for managerial, technical and key support personnel involved in testing. The Quality Manager maintains records of relevant competence, educational and professional qualification, training, skills, and experience of all technical personnel. This information is readily available and includes the date on which authorization and/or competence is confirmed and criteria on which the authorization is based and the conforming authority.

5.2.6. Refer to: Document No: 5.2.6.1.BHHRL/001PR014 Training and Competency Assessment 5.2.6.2. BHHRL/009PL01 Health and Safety Manual

5.3. Accommodation and Environmental Conditions

5.3.1. BHHRL management ensures that the environment in which testing is performed does not invalidate the results or adversely affect the required quality of any measurement.

5.3.2. Sampling and testing performed at sites other that the permanent facility are performed under the same specifications. The technical requirements for accommodation and environmental conditions that can affect the results of the tests are recorded in method SOPs.

5.3.3. Management ensures that there are effective separations between neighbouring areas in which there are in compatible activities and that measures are taken to prevent cross-contamination.

5.3.4. Refer to: Document No: 5.3.4.1.BHHRL/001PR016 Accommodation and Environmental Conditions

and Process Control.


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5.3.4.2.BHHRL/009PR02 Housekeeping 5.3.4.3.BHHRL/009PL01 Health and Safety Manual. 5.3.4.4.Appendix 5 – List of Technical SOPs

5.4. Test Methods and Method Validation

5.4.1. BHHRL uses appropriate methods and procedures for all tests within its scope including sampling, handling, transport, storage and preparation of items to be tested and where appropriate, an estimation of the measurement uncertainty as well as statistical techniques for analysis of test data.

5.4.2. BHHRL maintains instructions on the use and operation of all relevant equipment and on the handling and preparation of items for testing where the absence of such instructions could jeopardize the results of tests. All instructions, standards, manuals and reference data relevant to the work of the laboratory are maintained current and are made available to personnel. Deviation from test methods occur only if the deviation is documented, technically justified, authorized and accepted by the client.

5.4.3. Methods for test including methods for sampling, are selected and used to meet the needs of the client and are appropriate for the test undertaken. Methods published as international, regional or other national standards are used whenever possible. The latest valid edition of a standard is used unless it is not appropriate or possible to do so. When necessary, the standards are supplemented with additional details to ensure consistent application.

5.4.4. If the method to be used in not specified by the client, the laboratory selects appropriate methods published either in international, regional, or national standards or by reputable technical organizations or in relevant scientific texts or journals or as specified by the manufacturer. Laboratory developed methods or methods adopted by the laboratory may also be used if they are appropriate for the intended use and if they are validated. The client is informed as to the method chosen. The laboratory confirms that it can properly operate standard methods before introducing the tests. If the standard method changes, the confirmation is repeated.

5.4.5. The laboratory immediately notifies the client when the method proposed by the client is considered to be inappropriate or out of date.

5.4.6. Introduction of laboratory-developed methods is a planned activity assigned to qualified personnel equipped with adequate resources. Plans are updated as development proceeds and effective communication amongst all personnel involved is ensured.

5.4.7. When it is necessary to employ non-standardized methods, these are subject to agreement with the client’s requirement and the purpose of the


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test. The methods developed are validated appropriately before use and are available for examination by the client and other authorized recipients. New test methods are not used until written procedures have been developed.

5.4.8. All standard and non-standard test methods and procedures, including those developed by the laboratory are validated to ensure that such methods and procedures are fit for the intended use and are relevant to the requirements of ISO/IEC 17025:2005 as well as the client. Validation is as extensive as is necessary to meet the needs of the given application or field of application. If changes are made to validated non-standard methods, the influence of such changes is documented and if appropriate a new validation is carried out. The results of such validation are recorded together with the procedure utilized and any other relevant information. The record states whether the method or procedure is fit for the intended use.

5.4.9. Validation is always a balance between costs, risks, and technical possibilities and the range and accuracy of the values obtainable from validated methods, as assessed for the intended use, is relevant to the client’s needs.

5.4.10. Any calibrations performed in-house are subject to the SOP on Estimation of Uncertainty of Measurement.

5.4.11. The SOP on Estimation of Uncertainty Measurement is applied for testing uncertainness of measurement, except when the test methods prohibit such rigorous calculations. In certain cases it is not possible to undertake metrologically and statistically valid estimations of uncertainty of measurement. In these cases the laboratory attempts to identify all components of uncertainty and make the best possible estimation and ensure that the form of reporting does not give an exaggerated impression of accuracy. Reasonable estimation is based on knowledge of the performance of the method and on the measurement scope and makes use of previous experience and data. When estimating the uncertainty of measurement, all uncertainty components which are of importance in the given situation shall be taken into account using appropriate methods of analysis.

5.4.12. In cases where a well organized test method specifies limits to the values of the major source of uncertainty of measurement and specifies the form of presentation of calculated results, the laboratory is considered to have satisfied the estimation of uncertainty of measurement by following the test method and reporting instructions.

5.4.13. Calculations and data transfers are subject to appropriate checks in a systematic manner. The accuracy of the calculations is verified, data transfers are checked for typographical errors, omissions and mistakes.


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When computers or automated equipment are used for the acquisition, processing, recording, storage, or retrieval of test data, BHHRL ensures that:

5.4.14. Computer software developed by BHHRL is documented in sufficient detail and suitably validated or otherwise checked as being adequate for use.

5.4.15. Procedures are established and implemented for protecting the integrity of data; such procedures include but are not limited to, integrity and confidentiality of data entry or collection, data storage, data transmission and data processing.

5.4.16. Computers and automated equipment are maintained to ensure proper functioning and are provided with the environmental and operating conditions necessary to maintain the integrity of test and calibration data.

5.4.17. N.B. commercial software in general use within its designed application range is considered to be sufficiently validated.

Refer to: Document No: 5.4.17.1. BHHRL/001PR018 Method and Equipment

Validation/Verification, 5.4.17.2. BHHRL/001PR017 Estimation of Uncertainty of Measurement, 5.4.17.3. BHHRL/001PR019 Control of Monitoring and Measuring

Devices, 5.4.17.4. BHHRL/001PR012 Records Control and Management. 5.4.17.5. Appendix 5 : List of Technical SOPs

5.5. Equipment

5.5.1. BHHRL is furnished with all the items of sampling, measurement and test equipment required for the correct performance of the tests. In those cases where BHHRL needs to use equipment outside its permanent control, it ensures that the requirements of ISO/IEC 17025:2005 as well as those of other regulatory authorities are met.

5.5.2. Equipment is operated by authorized personnel only. Up-to-date instructions on the use and maintenance of equipment are readily available for use by the appropriate laboratory personnel.

5.5.2.1.Refer to: Document No: 5.5.2.2.BHHRL/001PR020 Equipment and Instrument Management 5.5.2.3.BHHRL/001PR022 Measurement Traceability and Control of

Measuring Instruments. 5.5.2.4.BHHRL/001PR07 Control of Nonconforming work


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5.6. Measurement Traceability 5.6.1. All equipment used for tests including equipment for subsidiary

measurements (e.g. for temperature monitoring) having a significant effect on the accuracy or validity of the results of the tests, is calibrated before being put into service. BHHRL maintains an SOP on Equipment and Instrument Management and Control of Monitoring and Measuring Devices to control maintain and calibrate its equipment.

5.6.2. The program of calibration of equipment is designed and operated so as to ensure that calibrations and measurements made by the laboratory are traceable to the international system of units by means of an unbroken chain of calibrations or comparisons linking them to relevant primary standards of the SI unit of measurement

5.6.3. Refer to: Document No: 5.6.3.1.BHHRL/001PR022 Measurement Traceability and Control of

Measuring Instruments.

5.7. Sampling 5.7.1. BHHRL maintains and utilizes a Laboratory Service Manual and an SOP

for Sample Collection for sampling when it carries out sampling of blood and other samples for subsequent testing.

5.7.2. Both the Laboratory Services Manual and the SOP on Sample Collection are available at all locations where sampling is undertaken. The sampling process takes into consideration the factors to be controlled to ensure the validity of the test results.

5.7.3. The sampling process, wherever reasonable, is based on appropriate statistical techniques.

5.7.4. Where the client requires deviations, additions, or exclusions from the documented sampling procedure, these are recorded in detail with the appropriate sampling data and included in all documents containing test results and communicated to the appropriate personnel.

5.7.5. BHHRL utilizes procedures for recording relevant data and operations relating to sampling that forms part of the testing that is undertaken. These records include the sampling procedure used, the identification of the sampler, environmental conditions (if relevant) and equivalent means to identify the sampling location as necessary and if appropriate the statistics the sampling procedure is based upon.

5.7.6. Refer to: Document No: 5.7.6.1 BHHRL/002PR01 Laboratory Services Handbook


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5.7.6.2 BHHRL/002PR02 Specimen Management: Collection, Transportation and Storage.

5.8. Handling and Transport of Samples 5.8.1. BHHRL maintains an SOP on Sample Management for the transport,

receipt, handling, protection, retention and disposal of samples, including all provisions necessary to protect the integrity of the test samples and to protect the interest of the laboratory and the client.

5.8.2. BHHRL also maintains the SOP for test sample identification. The identification is retained through out the life of the item in the laboratory. The system is designed and operated so as to ensure that samples cannot be confused physically or when referred to in records or other documents. The system, when appropriate, accommodates for the sub-division of groups of samples and the transfer of the samples within and from the laboratory.

5.8.3. Upon receipt of the test samples, any abnormalities or departures from normal or specified conditions as described in relevant test sample method are recorded. When there is doubt as to the suitability of a sample, when an item does not conform to the description provided, or when the test required is not specified in sufficient details, the laboratory consults the client for further instruction before proceeding and records the discussion.

5.8.4. BHHRL maintains procedures for and appropriate facilities for avoiding deterioration, loss or damage to the test samples during storage, handling and preparation; instructions provided with the samples are followed. When samples have to be stored under specified environmental conditions, these conditions are maintained, monitored and recorded. Where a sample or portion of a sample is to be held secure (e.g. for reasons of record, safety, or value, or to enable complementary tests to be performed later), the laboratory makes arrangements for storage and security that protect the condition and integrity of the secured samples or portions concerned.

5.8.5. Refer to: Document No: 5.8.5.1.BHHRL/002PR03 Specimen Management : Collection,

Transportation and Storage 5.8.5.2.BHHRL/002PR01 Laboratory Services Handbook

5.9. Assuring the Quality of Test Results

5.9.1. BHHRL maintains quality control procedures for monitoring the validity of tests undertaken. This monitoring is planned and reviewed and may include but not limited to the following:


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5.9.1.1.1. Regular use of certified reference materials and internal quality control using secondary reference materials.

5.9.1.1.2. Participation in inter laboratory comparison of proficiency testing programs

5.9.1.1.3. Replicate tests using same different methods. 5.9.1.1.4. Re-testing of retained where applicable 5.9.1.1.5. Correlation of results for different characteristics of items. 5.9.1.1.6. Internal quality control schemes using statistical techniques.

5.9.2. Resulting data is recorded in such a way to detect trends and where practicable, statistical techniques are applied to the reviewing of the results.

5.9.3. Refer to: Document No: 5.9.3.1.BHHRL/001PL02 Quality Assurance Program,

5.10. Reporting of Test Results

5.10.1. The results of each test or series of tests carried out by the laboratory are reported accurately, clearly, unambiguously and objectively and in accordance with any specific instructions in the test methods. The results are normally reported in a test report and include all the information requested by the client and necessary for the interpretation of the test results and all information required by the method used.

5.10.2. In case the test is performed for internal clients, or in the case of a written agreement with the client, the results may be reported in a simplified way and may not require the formalized test report but all data is readily available and kept permanently on file.

5.10.3. When opinions and interpretations are included in the test report, the basis upon which the opinions and interpretations have been made is documented. Opinions and interpretations are clearly marked as such in the test report. If such opinions/interpretations are verbally communicated to the client, the appropriate dialogue is recorded in writing. Opinions and interpretations included in a test report may comprise, but not be limited to the following:

5.10.4. Opinion on the statement of compliance/non-compliance of the results with requirements

5.10.4.1.1. Fulfilment of contractual requirements 5.10.4.1.2. Recommendations on how to use the results 5.10.4.1.3. Guidance on how to use the results.

5.10.5. When the test report contains reports of tests performed by subcontractors, these results are clearly identified.

5.10.6. The format is designed to accommodate each type of test carried out and to minimize the possibility of misunderstanding or misuse. Attention is


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given to the layout of the test report especially with regard to the presentation of the test data and ease of assimilation by the reader.

5.10.7. Material amendments to a test report after issue are made only in the form of a further document or data transfer, which includes the statement “Supplement to Test Report…………” or an equivalent form of wording. Such amendments meet all the requirements of ISO/IEC 17025:2005. When it is necessary to issue a complete new report, it is uniquely identified and contains a reference to the original that it replaces.

5.10.8. Refer to: Document No: 5.10.8.1. BHHRL/001PR025 Reporting of Laboratory Results, 5.10.8.2. BHHRL/001PR026 Handling of Laboratory Data.

6. Appendices 6.1. BHHRL Organogram 6.2. Table of Deputies 6.3. Quality Management Objectives 6.4. List of Technical SOP’s

Revision History: Revision Level:

Revision Date:

Revised By: Brief description of revision:

*2

*2

APPENDIX 1 - BHHRL/001PR05 BHHRL Organogram

Lab Director Dr Rosemary Musonda

PBMC Lab*1

Lemme Kebaabetswe Lebogang Mhango Motswedi Anderson

Specimen Management Ms Busisiwe Mlotshwa

Lab Manager Mr Sikhulile Moyo

Research Lab coordinator

Keikantse Matlhagela

Quality Assurance Manager Munyaradzi Phibeon

Mangwendeza

Specimen Reception Kedibonye Rammidi

Kgakgamatso Keothepile

Angela Nkhutelang Sethunya Ledikwe

Specimen Inventory Susan Kobe

Motswana Motshepe Nthebogang Phiri

Supplies/Lab Admin Kutlwano Aupiti Taboka Moloi

Chemistry Lab Baitshepi Jorowe Dineo Mongwato

Serology Lab Victoria Maiswe

Hematology Lab Matshediso Zachariah

CD4 Lab Talkmore Maruta Gaone Retshabile

DNA PCR Lab Dorcus Moses

Viral Load Lab Phillimon Sebogodi

Terrence M.

Quality Assurance Unit Early Manyiwa – Deputy QAM

Tuelo Baitseng Zachariah Matshediso

Philimon Sebogodi (Safety Officer)

Research Lab Team Ulrik Fried (Post Doc/Research Fellow) Thabo Diphoko (Forgarty Fellow) Ching Na Rim (Forgarty Fellow) Raabya Rossenkan (PhD Student)

BHP Protocol Specific Allocations

Dikotlana (BHP011) Victoria Maiswe

Tshedimoso (BHP012) Lemme Kebaabetswe

Tshepo (BHP007) Models of Care Baitshepi Jorowe

MmaBana (BHP016) Phillimon Sebogodi

Dorcus Moses

Mashi_Plus (BHP019)

Mashi (BHP004)

Botsogo (BHP010) Models of Care Kgalalelo Johane

CTU (ACTG/IMPAACT) BHP017/BHP023 Lebogang Mhango Motswedi Anderson Gaone Retshabile

Basadi (BHP018) Host Genetics (BHP022)

Chabeni Zimba Kebaneilwe Lebani

Bana-Baylor Talkmore Maruta

Shipping Tuelo Baitseng

Philimon Sebogodi Thato Iketleng

Project Director Dr Joseph Makhema

*1 Assigned scheduled event *2 Policy, regulatory and Global Issues (routine activities reported to the Lab Manager)

Approved by: Dr. Rosemary Musonda Title: Laboratory Director Sign:……………………………………………………………. Date:…………………………………….

APPENDIX 2 – QUALITY MANUAL BHHRL Table of Deputies The policy of BHHRL is such that a top management member will ‘ACT’ in place of the absent manager/director. The name of the acting manager/director is circulated to staff if and when the need arises. Post Incumbent Deputizing Project Director Dr. Joe Makhema On acting capacity Lab Director Dr. Rosemary

Musonda On acting capacity

Lab Manager Mr. Sikhulile Moyo On acting capacity Quality Manager Mr. Phibeon

Mangwendeza Ms. Early Manyiwa

Research Lab Coordinator Dr. Keikantse Matlhagela

*appointed when needed

Specimen Management Supervisor

Ms Busisiwe Mlotshwa

*appointed when needed

Approved by: Dr. Rosemary Musonda, Laboratory Director Signed:………………………….. Date: …………………………..

APPENDIX 3 – QUALITY MANUAL BHHRL Quality Management Objectives 1. Achieve laboratory accreditation by December 2009 2. Achieve certification of relevant and critical laboratory sections 3. Meet customer expectations for on-time delivery of results. 4. Avoid waste and excessive cost of running tests without jeopardizing quality of

results obtained. 5. Provide a safe and healthy working environment for all employees. 6. Obtain fewer customer quality concerns 7. Pass internal and external audits 8. Maintain EQA performance above 80% Approved By: Dr. Rosemary Musonda, Laboratory Director Sign: ………………………………….. Date: …………………………………

APPENDIX 4 – Quality Manual

Document number Document title

002/WIN-01 Daily Specimen Reception and Processing 002/WIN-02 Specimen Rejection Creteria 002/EQI-01 Beckman Allegra 21 Centrifuge Operating Instruction 007/TME-02 Amplicor HIV-1 DNA test 007/TME-01 QIAmp DNA Blood kit 001/PRC-03 Transporting of Specimens Within the Laboratory 001/PRC-05 Sample Storage 003/EQI-01 Becton Dickinson FACS Calibur Flow Cytometer Operating Instructions 003/WIN-03 Running TRUCOUNT Controls 003/WIN-04 Ensuring FACSCount Pipetting Precision and Accuracy 003/WIN-06 Validating CD4 results using LDMS 005/TME-01 Whole Blood Analysis (Full Blood Count) Using XE-2100 Haematology Analyser- 003/WIN-05 Work Listing Samples For CD4 Testing Using Laboratory Management

Information Systems (LMIS) 003/TME-02 Enumeration of absolute counts of CD4, CD8 and CD3 T lymphocytes in unlysed

whole blood using BD FACSCount System 003/WIN-07 FACSCOMP 003/EQI-02 Operating Instructions for Becton Dickinson's FACSCount System 003/TME-03 Automated Staining for flow cytometry lyse/no-wash applications using BD

Sample Processor (SP-1) 001/PRC-04 Validation of Equipment, Testing Methods, Materials and Processing -Standard

Operating Procedures 004/EQI-02 COBAS AMPLICOR Analyzer 004/EQI- 01 Equipment Operating Instructions for COBAS Ampliprep Analyser 004/TME- 02 COBAS Ampliprep AMPLICOR HIV-1 Monitor Test, version 1.5 004/TME-01 COBAS Ampliprep/COBAS Monitor Test, version 1.5 008/TME-06 Urine Microscopy 008/TME-05 Urinalysis - COMBUR 10 Test 003/TME-01 Enumeration of Leucocyte Subsets Using FACS Calibur Flow Cytometer 008/TME-03 Quantitaive Determination Of Clinical Chemistry Analytes In Plasma And Serum

Using COBAS Integra 400 Plus 008/EQI-01 COBAS Integra 400 Plus 008/TME-04 Reporting Critical Chemistry and Haematology Results 006/TME-01 Manual HIV ORTHO Antibody-Capture Test 006/TME-02 Manual Method for MUREX HIV -1.2.0 006/TME-03 Enzyme Immunoassay for the Detection of Hepatitis B Surface Antigen in Human

Serum or Plasma- Murex HBsAg Version 3. 006/TME-04 An Enzyme immunoassay for the detection of antibodies to Hepatitis C virus

(HCV) in human serum or plasma. Murex anti-HCV (Version 4.0) 006/TME-06 Qualitative Determination Of Human Chorionic Gonadotrophin (hCG) In Urine For

Early Detection Of Pregnancy- ABBOTT TestPack Plus hCG COMBO with OBC 006/WI-05 Vironostika Less Sensitive EIA



006/WI-04 An enzyme immunoassay for the detection of antibodies to hepatitis C virus (HCV) in human serum or plasma. Murex anti-HCV (Version 4.0)

006/WI-03 Enzyme Immunoassay for the Detection of Hepatitis B Surface Antigen in Human Serum or Plasma- Murex HBsAg Version 3.0

006/WI-01 HIV ORTHO ANTIBODY- CAPTURE TEST 006/WI-02 MANUAL ELISA METHOD FOR MUREX HIV 1.2.0- WORK INSTRUCTION 004/WI-01 Manual RNA Extraction (COBAS AMPLICOR HIV-1 Monitor Test, Version 1.5

Standard) HIM 004/WI-02 Preparing Working Master Mix (COBAS AMPLICOR HIV-1 Monitor Test, Version

1.5 Standard) HIM & PHM 004/WI-03 Loading A- Rings (COBAS AMPLICOR HIV-1 Monitor Test, Version 1.5 Standard)

HIM & PHM 002/EQI-02 Multifuge 3L Heraeus Centrifuge Operating Instructions 002/WIN-04 Standard Operating Procedure for Specimen Collection, Transport and Results

handling for the Botswana Vaccine Trail Units in Gaborone and Jwaneng for HIV Vaccine Trial Network Protocol 903

002/WIN-03 Specimen Collection, Transport and Results handling for the Botswana Vaccine Trail Units for HIV Vaccine Trial Network Protocol 048

009/EQI-01 GUAVA PCA CELL COUNTER 009/TME-01 Isolation of Peripheral Blood Mononuclear Cells (PBMCs) 007/TME- 03 HLA TYPING 001/PRC-22 Bi-Distiller Operating instructions 008/EQI-02 Roche Integra Cassette Mixer Operating Instructions 008/WI-01 Urinalysis COMBUR 10 Test 006/EQI-01 Welcome Shaker 006/TME-05 Syphilis Rapid Plasma Reagin (RPR) Test- Qualitative 006/TME-07 Haemagglutination kit for the detection of antibodies to Treponema pallidum in

human serum- Wellcosyph HA* 001/PRC-16 Autoclave Operating Instructions 002/WIN-05 HVTN 048 Specimen Reception 002/WIN-07 Laboratory Data Management System (LDMS) 002/WIN-08 Shipping Diagnostic Specimen 002/WIN-09 Capturing the Tracking Form Information Using Laboratory Management

Information Systems (LMIS) 002/WIN-11 Receiving Specimens into Laboratory Management Information Systems (LMIS) 002/WI-07 HVTN Sample Reception 002/WI-08 Creating LDMS labels using Zebra Printer 002/WI-09 HVTN 048 LDMS Logging and labeling guide 009/WI-01 PBMC Specimen Processing 009/EQI-02 Biofuge Primo Centrifuge /Operation Instruction 009/EQI-03 Water Bath Operating Instructions 009/EQI-04 Multifuge 3 s-r Centrifuge Operation Instruction



006/WI-08 BEHRING ELISA PROCESSOR (BEP2000) OPERATING INSTRUCTIONS 006/WI-06 Bio-Tek ELX50 Automated Strip Washer Operation Instructions 006/WI-07 Bio-Tek ELX800 Universal Plate Reader Operation Instructions 007/EQI-03 Operation of the GILSON Pipetman 007/WI-01 DNA EXTRACTION-QIAGEN KIT 007/WI-02 DNA EXTRACTION- SPECIMEN PREPARATION 007/WI-03 DNA EXTRACTION- REAGENT PREPARATION 007/WI-04 Operation of the GRANT QBT2 Block Incubator 007/WI-05 Maxi-Mix Vortex Mixer Operation Instructions 007/WI-06 DNA Detection 007/WI-07 IEC Micromax Microfuge 007/WI-08 DNA Amplification 007/WI-09 Ultra Violet (Hood)- Captair bio by erlab Operation Instruction 007/WI-10 ABI PRISM 3100 Genetic Analyzer Operation Manual 007/WI-11 GeneAmp PCR System 9700 004/WI-04 Loading Specimens and controls for Ampliprep 009/WI-02 Starting the GUAVA PCA Cell counter 003/TME-04 Double- Platform (Dual) Enumeration CD4+ T-Cells By Flow Cytometry 002/WIN-06 HVTN Specimen Rejection Criteria 001/PRC-21 Transporting Of Specimens From Site To Laboratory 002/WIN-12 HVTN 903 Specimen Reception Standard Operating Procedures 002/WI-10 HVTN 903 LDMS Logging and labeling guide 002/WIN-13 Reporting Syphilis Titer Results 002/WIN-14 Reporting Results From the Clinic to BHHRL