Good Practices in QC

Prepared by: Sajan Maharjan M. Pharm (1st Year) Kathmandu University (Working in SR Drug Laboratories)

Quality control laboratories

Sampling Testing
Test Reports Excipients Packaging materials Pharmaceutical Products Stability Testing Preparation of specifications Preparation of SOPs

Documentation

API

Good Practices in QC

Management and Infrastructure

Materials, equipments, instruments and other devices

Working Procedures

Safety

Internal Audits

Organization and Management

Records

Control of document

Management and Infrastructure

Premises

Personnel

Organization and Management

A Laboratory should have Managerial and technical personnel with the authority and resources needed to carry out duties and to identify the occurrence of departures from the quality management and initiate actions to prevent or minimize such departures. Arrangements to ensure that its management and personnel are not subject to political, financial and other pressures or conflicts of interest that may adversely affect the quality of their work.

A policy and procedure to ensure confidentiality of transfer of results or reports to protect data in archives (paper and electronic) Specify the responsibility, authority and interrelationships of all personnel
Provide adequate supervision of staff, including trainees, by persons familiar with the test, calibration, validation and verification methods and procedures. Ensure adequate information flow between staff at all levels. Maintain an up-to-date collection of all specifications and related documents (paper or electronic) used in the laboratory.
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Control of document
Each document, whether a technical or a quality document, should have a unique identifier, version number and date of implementation. Appropriate, authorized SOPs should be available at the relevant locations, e.g. near instruments. All the documents should be kept up to date and reviewed as required. Any invalid document should be removed and replaced with the authorized, revised document with immediate effect. All relevant staff should be trained for the new and revised SOPs. It is more relevant to prepare the revised documents by the initiator, or a person who performs the same function, reviewed and approved at the same level as the original document and subsequently released by the quality manager.

Records If you have not documented it, you have not done it
The laboratory should establish and maintain procedures for the identification, collection, indexing, retrieval, storage, maintenance and disposal of technical/scientific records (including analytical test reports, certificates of analysis and analytical worksheets). All original observations, including calculations and derived data, calibration, validation and verification records and final results, should be retained on record for an appropriate period of time All quality and technical/scientific records should be legible, readily retrievable, stored and retained within facilities that provide a suitable environment that will prevent modification, damage or deterioration and/or loss. Quality management records should include reports from internal and external audits and management reviews, as well as records of all complaints and their investigations, including records of possible corrective and preventive actions.

Personnel
Head of laboratory

-Check certificates of analysis (COA) and analytical testing reports -Ensure all key members of the laboratory staff have the requisite competence for the required functions -Ensure adequacy of existing staffs -Ensure training procedures are reviewed periodically -Ensure the technical management is adequately supervised -Ensure procedures for performing calibration, verification and qualification of instruments -regular in-service training programs to update and extend the skills of both professionals and technicians -monitoring of environmental and storage conditions

Technical management

Analysts

graduates in pharmacy, analytical chemistry, microbiology or other relevant subjects

Technical staff

diplomas in their subjects awarded by technical or vocational schools

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Premises
Suitable size, construction and location Rest and refreshment rooms should be separate from laboratory areas. Changing areas and toilets should be easily accessible and appropriate for the number of users Equipped with adequate instruments and equipment, including work benches, work stations and fume hoods Adequate safety equipment located appropriately Microbiological testing, if performed, should be contained in an appropriately designed and constructed laboratory unit The environmental conditions, including lighting, energy sources, temperature, humidity and air pressure, are to be appropriate to the functions and operations to be performed. The storage facilities should be well organized

Premises

Data entry and documentation equipped with computers

For equipments
Sensitive (UV, IR, HPLC, Balance)

Reagents

Storage of documents

Reference standard

Heat generating (Furnance, Oven)

Others

Non Toxic

Toxic

-Easy Retrieval -Safe

Proper indexing for easy retrieval

Danger Precaution

-Separate refrigerator -Dessicator -Bottles with proper enclosure -Properly placed with indexing

All specified storage conditions should be controlled, monitored and records maintained (if necessary). Access should be restricted to designated personnel only. 10

Reagents

Reference Substances

Materials, Equipment, Instruments and other devices

Calibration, verification of performance and qualification of equipment, instruments and other devices

Traceability

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Reagents

Bulk Reagents
(Purchased from supplier)

Prepared Reagents
(Prepared in Lab)

-Should be of appropriate quality. -Should be purchased from reputed and approved suppliers
Check label for:
Content Manufacturer Date received and date of opening of the container Concentration (if applicable) Storage conditions Expiry date or retest date

-Responsibility should be specified -use procedures in accordance with published pharmacopoeia or other standards where available.

Reagent Solution
Name Date of preparation and initials of technician or analyst prepared by Expiry date or retest date Concentration (if applicable)

Volumetric Solution
Name Molarity (concentration) Date of preparation and initials of technician/analyst Date of standardization and initials of technician/analyst Standardization factor

Stock reagents should be maintained in a store under the appropriate storage conditions Availability of clean bottles, spoons, funnels and labels, as required, for dispensing reagents from larger to smaller containers. 12 A person in charge should look after the storage facilities and their inventory.

Reference Substances

Registration and labelling

An identification number should be assigned to all reference substances, except for pharmacopoeial reference substances A new identification number should be assigned to each new batch The identification number should be quoted on the analytical worksheet every time the reference substance is used The register for all reference substances should be maintained and contain the following information: identification code the location of storage in the laboratory expiry date or retest date certificate of a pharmacopoeial reference substance For reference substances prepared in the lab, the file should include the results of all tests

Retesting (monitoring)
All reference substances should be retested at regular intervals to ensure that deterioration has not occurred The interval for retesting depends on a number of factors, including stability of the substance, storage conditions employed, type of container and extent of use (how often the container is opened and closed) The results of these tests should be recorded and signed by the responsible analyst

1. 2. 3. 4.
5.

A person should be nominated to be responsible for reference substances

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Calibration, verification of performance and qualification of equipment, instruments and other devices All equipment, instruments and other devices requiring calibration should be labelled or coded to indicate the status of calibration and the date when recalibration is due. As applicable, the performance of equipment should be verified at appropriate intervals according to a plan established by the laboratory. Measuring equipment should be regularly calibrated according to a plan established by the laboratory. Specific procedures should be established for each type of measuring equipment. For eg: pH meters are verified with standard certified buffer solutions before use balances are to be checked daily using suitable test weights, and requalification should be performed annually using certified reference weights. Up-to-date SOPs on the use, maintenance, verification, qualification and calibration of equipment, instruments and devices should be readily available. Records should be kept of each of equipment, instrument or other device used to perform testing (separate log books), verification and/or calibration. Equipment, instruments and other devices shown to be defective or outside specified limits, should be taken out of service and clearly labelled or marked. When the equipment, instruments and other devices have undergone major repair, the laboratory should re-qualify the equipment to ensure its suitability for use.
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Traceability
The result of an analysis should be traceable, when appropriate, ultimately to a primary reference substance. All calibrations or qualification of instruments should be traceable to certified reference materials and to SI units (metrological traceability).

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Working Procedures
Incoming Samples Analytical worksheet Validation of analytical procedures - Done as per validation protocol - Revalidation will be required in case of a major change to the analytical procedure, or in the composition of the product tested.

Testing

In accordance with the work plan of the laboratory Follow the specifications
Should meet specification used Whenever doubtful (atypical) results are obtained they should be investigated

Evaluation of test results

Certificate of analysis
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Incoming Samples -Sampling plan and an internal procedure for sampling -Samples should be representative of the batches -avoid contamination and other adverse effects on quality, or mix-up -proper labelling must be done on the sampled container -data related to sampling should be recorded -assign a registration number for each received sample -Separate registration numbers should be assigned to raw materials, different dosage forms, or different batches of the same medicine The sample received should be visually inspected by laboratory staff to ensure that the labelling conforms with the information contained in the test request ( intimation) The sample prior to testing and the retained samples (control samples) should be stored safely. -Sample sent for testing is determined by the person responsible. -The examination of a sample should not be started until all relevant documents has been received. -A request for analysis may be accepted verbally only in emergencies.
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Sampling

Registration

Visual inspection

Storage

Forward to testing

Analytical worksheet The analytical worksheet is an internal document to be used by the analyst for recording information about the sample, the test procedure, calculations and the results of testing. A separate analytical worksheet should usually be used for each sample. The analytical worksheet should provide the following information: a) the date on which the analysis was started and completed b) description of the sample received c) description of test methods by which the sample was tested, including the limits d) the identification number of any reference substance used e) the identification of reagents and solvents employed f) the results obtained g) the interpretation of the results and the final conclusions (whether or not the sample was found to comply with the specifications) h) any further comments i) the name and signature of the analyst All values obtained from each test should immediately be entered on the analytical worksheet and all data obtained from recording instruments should be attached or be traceable to an electronic record file or document where the data are available. When a mistake is made in an analytical worksheet, information should be deleted by putting a single line through it and the new information added alongside. All such alterations should be signed by the person making the correction. The analytical worksheet should be kept safely together with any attachments, including calculations and recordings of instrumental analysis. 18

Safety
General Rules smoking, eating and drinking in the laboratory should be Prohibited staff should be familiar with the use of fire-fighting equipment staff should wear laboratory coats or other protective clothing, including eye protection highly toxic and/or genotoxic samples should be handled in a specially designed facility to avoid the risk of contamination all containers of chemicals should be fully labelled and include prominent warnings (e.g. poison, flammable, radioactive) adequate insulation and spark-proofing should be provided for electrical wiring and equipment, including refrigerators staff should be aware of the need to avoid working alone in the laboratory first-aid materials should be provided and staff instructed in first-aid techniques, emergency care and the use of antidotes.

Staff training For correct performance of techniques Appropriate use of personal protection items How to proceed in an emergency Ensure there is safety manual in each area of lab containing risk agents with handling precautions and emergency procedures.
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Internal Audits To carry out systemic and independent examination, to determine whether the activities and their results comply with the established documentation. Internal Audits are generally performed by staff who do not have direct responsibility for the area audited or by the QA department. Steps Review of documents Drawing up an audit plan Opening meeting between auditor and the area to be audited Performance of the audit: interviews, check list, observation Closing meeting Audit Report Follow-up audit
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Thank You
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