quality control rutendo kuwana technical officer, who, geneva training workshop: training workshop...

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


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


Management and infrastructure:

Organization and management

Quality systems

Control of documentation and records

Data processing equipment

Personnel

Premises, equipment, instruments and other devicesPart One.



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



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



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")


Part One. 1.4


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


Part One. 2.1


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)


Part One. 2.1


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


Part One. 2.1


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


Part One. 3.1


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.


Part One. 4.1 – 4.2


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


Part One. 4.3


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


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


Part One. 4.4


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


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


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


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


Part One. 4.4



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


Part One. 5.1



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


Part One. 5.1


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


Part One. 6.1 – 6.3


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


Part One. 6.4 – 6.5


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


Part One. 7.7.1.1 – 7.7.1.4


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


Part One. 8.1 – 8.3


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

quality control rutendo kuwana technical officer, who, geneva training workshop: training workshop...

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