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Quality Control
Rutendo Kuwana
Technical Officer, WHO, Geneva
Training workshop: Training workshop on regulatory requirements for registration of Artemisinin based combined medicines and assessment of data submitted to regulatory authorities, February 23-27, 2009, Kampala, Uganda.
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 2 |
Good Practices for Quality Control Laboratories
Supplementary Training Modules on Good Manufacturing Practice
WHO Technical Report Series, No. 902, 2002. Annex 3
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 3 |
Objectives
To discuss Good Practices for Quality Control laboratories including quality systems and infrastructure
To understand the role and importance of the Quality Control laboratory in:
– sampling and testing– materials, equipment and systems
To discuss approaches in inspecting a Quality Control laboratory
Part One.
Quality ControlQuality Control
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 4 |
Management and infrastructure:
Organization and management
Quality systems
Control of documentation and records
Data processing equipment
Personnel
Premises, equipment, instruments and other devicesPart One.
Quality ControlQuality Control
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 5 |
Organization and management:
Function in accordance with national legislation
Operate in accordance with the guideline–WHO Technical Report Series, No. 902, 2002, Annex 3
See also general texts on Good Manufacturing Practices and Good Practices in Quality control
–WHO Technical Report Series, No. 908, 2003, Annex 4
Part One 1.1– 1.2
Quality ControlQuality Control
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 6 |
Organization and management (2):
Personnel– Managerial and technical positions to ensure operation in
accordance with quality systems– No conflict of interest
Organizational chart and job descriptions
Supervision and training
Part One. 1.3
Quality ControlQuality Control
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 7 |
Organization and management (3):
Large laboratories may have subunits
A central registry responsible for:– receipt and distribution of samples– keeping records and documents of incoming samples– allocation of work and responsibilities– maintaining specifications "up to date" (specifications
"archive")
Quality ControlQuality Control
Part One. 1.4
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 8 |
Quality system:
Management to establish, implement and maintain quality system
– It should cover policies, systems, programmes, procedures and instructions
Communicated, available, understood and implemented
Documented in a quality manual– available to the laboratory personnel– maintained and updated by a responsible person
Quality ControlQuality Control
Part One. 2.1
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 9 |
The quality manual should contain at least:
Organizational chart; operational and functional activities
General and specific quality assurance procedures
Proficiency testing schemes
Use of reference materials
Feedback and corrective action (for testing discrepancies)
Quality ControlQuality Control
Part One. 2.1
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 10 |
The quality manual should contain at least (continued):
Procedure for dealing with complaints
A flow chart for samples – QA is responsible for reviewing and approving sampling procedures. Sampling may be conducted by other persons provided they have been appropriately trained
Details of audit and quality system review
Qualification of personnel
Training and maintaining competence of staff
A quality policy statement
Quality ControlQuality Control
Part One. 2.1
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 11 |
Control of documents
Documentation is essential
Procedures to control and review all documents
The laboratory must establish and maintain procedures for identification, collection, indexing, access, storage, maintenance and disposal of quality documentation and technical records
Quality ControlQuality Control
Part One. 3.1
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 12 |
Records
All original observations, calculations and derived data, calibration, validation and verification records, etc. and final results must be retained on record for an appropriate period of time, e.g.
– whole length of time the drug is on the market
Records to contain sufficient information to permit repetition of tests and include, e.g.:
– identity of the personnel involved in sampling, preparation and testing of the samples
– Instruments, equipment, etc.
Quality ControlQuality Control
Part One. 4.1 – 4.2
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 13 |
Records must be:
Legible and readily retrievable
Stored and retained in a manner that prevents modification, damage or deterioration and/or loss
Held secure and in confidence
Includes reports from internal audits and management reviews and records from possible corrective and preventive actions
Quality ControlQuality Control
Part One. 4.3
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 14 |
Use of NotebooksUse of Notebooks
Bound and pre-numbered
Loose sheets – pre-numbered, printing controlled and should be stored as control records
Electronic data collection system
Raw data should be recorded at the time of production
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 15 |
SOPs: written and authorized
For administrative and technical operations, such as:
Purchase and receipt of consignment of materials
– e.g. samples, reference material, reagents
Internal labelling, quarantine and storage of materials
Appropriate installation of each instrument and equipment
Sampling and inspection
Testing materials, describing the methods and equipment used
Quality ControlQuality Control
Part One. 4.4
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 16 |
Testing Methods and ResultsTesting Methods and Results
Analytical methods and test procedures should be cross referenced (e.g. pharmacopoeia) or detailed to be understood by the local analyst.
Formulae – with explanations and simplifications. This makes easy review by a second person
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 17 |
Out of Specification ResultsOut of Specification Results
Must be handled based on a written procedure, that includes:
Checklist of potential defects (e.g. calculations, methods, visual appearance, test procedure modified, experience of analyst during test, calibration of equipment …)
Similar checklist for potential deviations in production
Checking sampling and sampling devices
Guidance on when re-sampling and re-testing may be required and documented justification in each instance
Inclusion of known control sample in any testing
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 18 |
Approval and Rejection of ResultsApproval and Rejection of Results
Before approval or rejection – criteria to be used and results to be averaged should be specified in SOP(s)
Criteria to include - averaging and/or rounding results and comparing results against specifications
Control charts can be used to detect trends and atypical results (see www.ivthome.com)
Rounding results should be according to pharmacopoeial requirements (see also ICH Q3A)
NB: take care when averaging results from atypical values e.g. outliers, or single result out of specification limits
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 19 |
Other SOPs:
Qualification, analytical apparatus
Calibration, maintenance, cleaning, sanitation
Safety measures
Personnel matters including
– qualification, training, clothing, and hygiene
Environmental monitoring
Preparation and control of reference materials
Quality ControlQuality Control
Part One. 4.4
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 20 |
Data processing equipment
Includes computers, automated tests or calibration equipment;used for collection, processing, recording, reporting, storage or retrieval of test and/or calibration data
Where used, requires systematic verifications of calculations and data transfers
For computer software developed by the user:– this documented in detail– validated or verified as being adequate for use
Quality ControlQuality Control
Part One. 5.1
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 21 |
Data processing equipment
Located in suitable environmental supporting operating conditions
Maintenance of computers and automated equipmentProcedures established and implemented for protecting data
integrity– Include, e.g. integrity and confidentiality of data entry or
collection, data storage, transmission and processingProcedures in place to describe how:
– Changes are made, documented and controlled for information maintained
– To protect and keep back-up data at all times
– To prevent unauthorized access or amendments to the data
Quality ControlQuality Control
Part One. 5.1
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 22 |
Personnel
Sufficient number, with necessary education, training, technical knowledge and experience
No conflict of interest or other pressure
Competence ensured for activities, performing tests and/or calibrations, validations or verifications, evaluation of results and signing test reports and calibration certificates
Staff undergoing training – supervised, with formal assessment after training
Personnel must be qualified on the basis of appropriate education, training, experience and/or demonstrated skills
Quality ControlQuality Control
Part One. 6.1 – 6.3
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 23 |
Personnel (2)
Permanently employed, or under contract
Contracted personnel to be supervised and sufficiently competent, motivated – work complying good practice of the laboratory
Current job descriptions for managerial, technical and key support personnel
Records of competence, educational and professional qualifications, training, skills and experience
– Readily available, and include date of confirmation of competence, plus criteria for confirmation and name of the confirming authority
Quality ControlQuality Control
Part One. 6.4 – 6.5
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 24 |
Premises - Central store
Separate for secure storage of samples, retained samples, reagents, laboratory accessories, reference materials
Appropriate storage conditions, e.g. refrigeration where necessary
Restricted access to designated personnel
Organized to accommodate incoming and outgoing samples, reagents, equipment, instruments and other devices
Quality ControlQuality Control
Part One. 7.7.1.1 – 7.7.1.4
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 25 |
Equipment, instruments and other devices
Designed, constructed, adapted, located, calibrated, qualified, verified and maintained
Purchased from approved suppliers – can give technical support, maintenance
Documentation in the language employed in the laboratory Appropriate test equipment, instruments or other devices in the
laboratory Suitable for correct performance of tests and/or calibrations,
validations and verifications Meet laboratory's requirements, and comply with the relevant
standard specifications, as well as be verified and/or calibrated
Quality ControlQuality Control
Part One. 8.1 – 8.3
Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 26 |
Use of Primary and Secondary StandardsUse of Primary and Secondary Standards
SOP required on – use, records, acquisition, identification and storage
For Pharmacopoeial methods – reference standards should be acquired from that pharmacopoeia.
Secondary standards to be routinely tested against the primary standard
When a non-Pharmacopoeial standard is used as a reference for assay the mean and standard deviation of the assigned assay value should be known. Retest/expiration date should be assigned