Good Practices for Quality Control Laboratories

1. Supplementary Training Modules on Good Manufacturing Practice Good Practices for Quality Control Laboratories Part 2: Materials and set-up of equipment, instruments and other devices WHO Technical Report Series, No. 902, 2002. Annex 3

2. Quality Control Specifications archive • Current versions of all specifications – as described in pharmacopoeial compendia or in manufacturers' registration documents The specifications archive must contain: • List of all pharmacopoeias in the laboratory • all updates and corrections must be noted • adequate numbers of supplements and addenda • File of non-pharmacopoeial quality specifications • numbered and dated, latest version • information relevant to the status of the quality specifications • corrections or changes appropriately handled, including producing a revised document as soon as possible Part Two. 9.1 – 9.2

3. Quality Control Specifications archive (2) • Use of the master copy • photocopies accounted for and controlled for use • Confidentiality of specifications Responsibility defined for: • Updating all pharmacopoeias – including supplements, addenda, and corrective measures used in the laboratory • Maintaining a specifications file Part Two. 9.3 – 9.5

4. Quality Control Reagents • Reagents, chemicals, including solvents and materials used in tests and assays – of appropriate quality and supplied with COA • List of prequalified suppliers • Clear responsibility in job descriptions for the preparation of reagents in the laboratory • SOPs according to pharmacopoeia or other standards • Records for the preparation, and standardization of volumetric solutions Part Two. 10.1 – 10.3

5. Quality Control • Reagent labels must clearly specify: • the contents, the manufacturer, the date received, and as appropriate, the concentration, standardization factor, shelf-life and storage conditions (purchased) • date of preparation, name and initials of person (if prepared in the laboratory) • Volumetric solutions: • the name of the manufacturer of the original reagent (where diluted), the date of preparation, the date of standardization and factor, and identify the responsible technician • Reagents must not be moved unnecessarily from unit to unit • Whenever possible, transportation in original containers • Subdivided in scrupulously clean, fully labelled containers Part Two. 10.4-10.5

6. Quality Control Inspect reagent containers when delivered (e.g. seals intact) • Inspection recorded on the label giving the date, name and initials • If tampered with, rejected, unless identity and purity can be confirmed Distilled water and deionized water • Water should be considered as a reagent • Precautions to avoid contamination during: • supply, storage and distribution • To comply with pharmacopoeia and other official requirements for quality Part Two. 10.6 - 10.11

7. Quality Control Storage • Appropriate storage conditions • Storage area with clean bottles, vials, spoons, funnels, and labels required for dispensing reagents from larger to smaller containers Store keeper responsibilities: • Store and inventory, expiry dates • Areas for flammable substances, for fuming and concentrated acids, etc. • Self-igniting materials, such as metallic sodium, stored separately Part Two. 10.12 – 10.14

8. Quality Control Reference materials • Used for testing and/or calibration, validation or verification of a sample or equipment, instruments or other devices • Responsibility must be assigned to a specific person • Registration and labelling with an identification number assigned • a new identification number to each new batch • number marked on each vial • quoted on the analytical worksheet at every use Part Two. 11.1. – 11.5

9. Quality Control Central register for reference materials containing information: • identification number of the material • precise description of the material • source • date of receipt • batch designation or other identification code • intended use of the material (e.g. as an infrared reference material, as an impurity reference material for thin-layer chromatography, etc.) • location of storage in the laboratory, and any special storage conditions • further indications (e.g. results of inspections) Part Two. 11.7

10. Quality Control Information file for reference materials containing information: • In addition to the central register – a file containing information on the properties of each reference material • Working standards – include the results of all tests and verifications Inspection • Inspected at regular intervals, no deterioration, appropriate storage conditions • Inspections must be recorded in the central register and/or the information file • See also "The general guideline on the establishment, maintenance and distribution of reference materials" Part Two. 11.10 – 11.14

11. Quality Control Calibration, validation and verification of equipment, instruments and other devices • Regular calibration, validation and verificationof all equipment, instruments and other devices used to measure the physical properties of substances must be performed • Specific procedures for each type of equipment, instrument and other devices must be established, having regard to the extent of which they are used, verified and calibrated at regular intervals according to SOP Part Two. 12.1 - 12.2

12. Quality Control Examples: • pH meters are verified with a certified solution at least once a day • Infrared spectrophotometers require verification at least once a day and calibration at regular intervals • Discuss other examples . . .

13. Quality Control • Authorized personnel to operate equipment • Instructions on the use, maintenance, verification and calibration of equipment, instruments and devices (e.g. a copy placed beside each apparatus together with a schedule of the dates) • The results of verification must be recorded • Each item of equipment, instrument – uniquely identified • Records must be maintained Part Two. 12.3 – 12.5

14. Quality Control The records must include at least the following: • name of equipment, instrument and other devices • manufacturer's name, type identification, serial number or other unique identification • verification/calibration to comply with the specifications • current location, where appropriate • the manufacturer's instructions, if available, or reference to their location Part Two. 12.5

15. Quality Control The records must include at least the following (2): • dates, results and copies of reports, verifications and certificates of all calibrations, adjustments, acceptance criteria, and due date of next verification/calibration • maintenance carried out to date and the maintenance plan • history of any damage, malfunction, modification or repair. It is also recommended to keep records and additional observations of the time, the equipment, instruments or devices were used Part Two. 12.5

16. Quality Control • Prevent contamination or deterioration – perform systematic verifications • Maintenance procedures and records • Defective instruments – taken out of service, and clearly labelled or marked • Status of calibration and the date when recalibration is due, indicated • Instruments to be satisfactory before being returned to service Part Two. 12.6 – 12.10

17. Quality Control • Analytical equipment, instruments and other devices can be either • grouped together • dispersed between the various units • protected from extreme states of humidity or temperature in a specially designed area and • adequately protected to be resistant to corrosion and against mould and fungal growth • See also Procedures for verifying and calibrating instruments in The International Pharmacopoeia, andValidation of analytical procedures used in the examination of pharmaceutical materials gives chemical and physicochemical attributes Part Two. 12.11 – 12.12

18. Quality Control Traceability • Analytical specificities of each measurement procedure and reference material that is used to ascertain traceability, must be known • Traceability chain, including measurement procedures and reference materials at all levels, must be prepared • Laboratory investigations – applies to measurement procedures as well as to reference materials used Part Two. 13.1 – 13.3

19. Quality Control • There are quantitative and qualitative measurement procedures • “Semi-quantitative” measurement procedures • less accurate and less precise than quantitative measurement (“Limit tests”) • Qualitative measurement procedures are descriptive Part Two. 13.4, 13.6 -13.7

20. Quality Control Reference materials have assigned values of a quantity. Hierarchy for reference materials: • Primary chemical substance • has appropriate qualities within a specified context, and whose value is accepted without requiring comparison to another chemical substance • Secondary chemical reference substance • characteristics are assigned and/or calibrated by comparison with a primary chemical reference substance. The extent of characterization and testing of a secondary chemical reference substance may be less than for a primary chemical reference substance. This definition may apply inter alia to some substances termed “working standards Part Two. 13.8 (a-b)

21. Quality Control • International Biological Standards • a category of biological reference material having World Health Organization (WHO) status • A working standard(working calibrator) has an assigned value of a quantity • A manufacturer’s product calibrator is used for the calibration of a routine measurement procedure of an end user • A control material is used to test for the precision and accuracy of results. A control material should have a matrix similar to the samples to be measured. Assigned values with an uncertainty of measurement appropriate to the intended use should be given Part Two. 13.8 (c-f)