1.0 Purpose
2.0 Scope
3.0 Responsibility
4.0 Abbreviations and Definitions
5.0 Materials and Equipment
6.0 Precaution / Health and Safety Considerations
6.1 Provide adequate training to the users before implementing any procedure. So that no confusion arises during its routine use.
7.0 Procedure
7.1 Laboratory Set-up (for GMP Compliant Laboratory):
7.1.1 The design of the Laboratory facility should provide adequate degree of separation of the different activities to assure safe and proper conduction of laboratory work.
7.1.2 All laboratory activities must be described in written and approved procedures (SOPs) and appropriate records to be maintained (as applicable).
7.1.3 Personnel must be appropriately qualified, trained and supervised to carry out their duties safely and effectively.
7.1.4 Laboratory must be maintained in a clean & tidy and safe condition with appropriate control of waste materials.
7.1.5 Special attention should be given to :
7.1.5.1 Avoid cross contamination within the laboratory and between the laboratory and manufacturing areas.
7.1.5.2 Disposal of waste and effluents, including discharges from fume cupboards.
7.1.5.3 Space for storing reagents, equipment, retention samples and records.
7.1.5.4 Separate laboratory for micro-biological testing.
7.1.5.5 Effective cleaning procedure for laboratory glassware (both for general & microbial testing) & instruments.
7.2 Personnel and Training:
7.2.1 Each person working in Quality Control laboratory should have specific job description.
7.2.2 Personnel should be trained in all procedures they are required to perform in support of the conduct, supervision or direction of GMP. These should include training in technical procedures, equipment, SOPs, GMP and computer systems, as well as other areas.
7.2.3 Personnel training should be documented in each individual’s personnel records including the CV and and/or training records. Satisfactory completion of training should be signed-off by the individual’s supervisor or designated/authorized trainer.
7.2.4 Training should be performed by someone knowledgeable and proficient in the
procedure. This may be the associate’s supervisor or a designated/authorized trainer. The Head of Laboratory (i.e. Quality Control In-Charge) has overall responsibility for the
maintenance of a GMP standard laboratory. The head of Laboratory supervises the
technical conduct, data collection; review and reporting within their area of expertise and can authorize and document minor SOP deviations. The Head of Laboratory must be
aware of all SOP deviations and assess their overall impact. If needed, Head of QA may have to be involved.
7.3 Equipment And Validation:
7.3.1 Equipment used for testing must be qualified and calibrated at pre-determined intervals by appropriate methods. Adequate records of such tests must be maintained and retained for review (as applicable).
7.3.2 Records should be maintained for all activities including maintenance, repairs, testing, calibration and qualification/validation of equipment. Actions taken to correct any problems or malfunctions should be documented along with testing to verify proper functioning.
7.3.3 Significant relocations or changes to critical equipment should be followed at least by a documented Installation Qualification to assure the equipment has been properly set-up and assembled and that the movement had no adverse affect on equipment
performance. Example: An IQ summary may be written down in equipment log book for simple type equipment relocation or repair case.
7.3.4 Laboratory equipment should be re-validated or re-qualified after any significant changes to the system or its environment of the equipment. It is recommended that periodic evaluation of the system status, including a review of all changes made, be conducted approximately once in every two years.
7.3.5 An inventory list for all equipment should be present with their specific identity number and should be a part of the SOP relevant to qualification of equipment's.
7.3.6 The calibration should be frequent enough to assure data validity.
7.3.7 Suitable arrangements should be made for protecting sensitive apparatus against humidity, temperature and vibration.
7.4 Reference Standards & Laboratory Reagent:
7.4.1 Reference standards must be obtained from a suitable source. The evidence for the structure must be established either by comparison against an official or compendial standard or must be characterized by analytical methods, that allow the absolute determination of identity. Purity, content, assay or potency are determined either against an official or compendial standard or are established by absolute analytical methods.
7.4.2 The reference standards must be distributed, stored and handled under adequate conditions so as to preserve their properties and to avoid any contamination. In particular, they must be protected from humidity, light, heat as appropriate for each substance.
7.4.3 The reference standard containers must be adequately labeled, indicating at least the identity of the standard (name), the batch / lot number for multiple use containers, a number of each individual container to guarantee unambiguous traceability, and special storage requirements.
7.4.4 All reagents (purchased from external suppliers) and solutions (prepared internally) used must be appropriately labeled, stored and controlled to indicate identity, titer or concentration, storage requirements, and expiration date.
7.4.5 All reagents and solutions must be labeled with an expiration date. If the manufacturer’s label does not include an expiration date, it must be determined based on laboratory experience or other scientific references/rationale. Specific stability testing is not required.
7.4.6 On the basis of documented evaluation or analysis, shelf life of a reagent may be extended.
7.4.7 Interim or temporary containers such as those used within methods or assays for making dilutions should be labeled adequately to uniquely identify and trace the container according to its purpose within the method or assay. These containers need not contain all the labeling requirements for reagents and solutions. For example, they may just be identified with the composition of solvents and purpose. However, if such containers may be used for more than a 24-hour period, they should be labeled with an expiration date and storage conditions.
7.4.8 Expired reagents and solutions must not be used and should be discarded or removed from the laboratory. If they cannot be immediately discarded or removed, they should be clearly marked as “expired” and placed in a separate area of the laboratory designated and marked for expired materials. It may also be possible to extend expiration dates provided that sufficient data supporting the extension is obtained.
7.4.9 Water or marketed household cleaners (e.g., JET Powder) that are just used for cleaning or rinsing does not need to be labeled with all the requirements for reagents and solutions. Only its identity needs to be specified. Other cleaning or disinfecting materials should be fully labeled with all the requirements for reagents and solutions since effective use of these materials may be essential to the proper conduct of a GLP study.
7.4.10 The reagent or solution should only be stored as directed by the label.
7.4.11 Records of reagent or solution lot numbers should be mentioned in the appropriate log book in order to be able to track the lot number of reagent or solution used to the manufacturer or other quality records.
7.4.12 All waste reagents should be disposed according to their classification, which would be followed through relevant guideline of waste disposal.
7.4.13 Safety Precautions:
7.4.13.1 Always wear splash proof goggles, gloves and a laboratory coat when handling chemicals / waste chemicals.
7.4.13.2 For chemicals / waste chemicals that evolves fumes and vapor, the transferring of chemicals / waste chemicals should be done inside a fume cupboard.
7.4.13.3 To prevent escape of fumes and vapors, close the container tightly each time after the transfer of chemicals / waste chemicals is completed.
7.4.13.4 If chemicals / waste chemicals is handled outside a fume cupboard, the waste handler may need to take proper protection.
7.5 Records & Documentation:
7.5.1 All raw data entries should be entered directly, promptly (no later than within the same day) and legibly in ink (blue ink is preferred). They should also be signed (or initialed) and dated by the person responsible for the entry. Raw data should never be recorded in pencil.
7.5.2 Person responsible for entering the data must be identified and sign or initial the data. If more than one person is making entries, then each person needs to be identified and sign or initial the data.
7.5.3 All electronic data also to be signed by the responsible person.
7.5.4 All data should be checked by senior analyst and approved by Head of Quality Control. Photocopy of any data can be accepted after verifying it by Head of Quality Control.
7.5.5 During data record the unit must be stated in the same way as it is specified in
the specification (i.g. if specification is in ppm, the data should be recorded in ppm not in %).
7.5.6 Data must be recorded up to as many digits as it is mentioned in the specification (i.g. if specification is 100.0 – 100.2%, and result is found 101%, the result should be recorded as 101.0%, if it is found 100.55%, the result to be recorded as 100.6% etc.).
7.5.7 Any deviation from approved procedure and OOS/OOE results must be evaluated and investigated as appropriate, before the release decision is made and this should be incorporated with the original documents.
7.5.8 Retention of samples, specimens, raw data, laboratory records and reports must be securely stored and/or archived for specific time periods under appropriate conditions to ensure their integrity, and in such a manner that allows for easy retrieval and review.
7.5.9 All superseded documents should be archived for a fixed period of time.
7.6 Sampling For Routine Testing:
7.6.1 Samples should be representative of the material from which they are taken and should be taken in accordance with written instructions (relevant SOP for sampling).
7.6.2 Sampling instructions should include the method of sampling and equipment to be used and also amount of sample to be taken.
7.6.3 Sampling equipment / Utensils must be cleaned appropriately after each use which should be followed through a written procedure.
7.7 Testing:
7.7.1 Samples should be tested in accordance with the valid analytical methods detailed or referred to, in the relevant specification. The validity of the results thus obtained should be checked before the material is released or rejected by any authorized person. All relevant data, including calculations, must securely recorded, and checked (independently, as appropriate) in a manner that allows for trend analysis and traceability to personnel, equipment and procedure used.
7.8 Cleaning:
7.8.1 Cleaning of General glassware & Utensils:
7.8.1.1 After completion of work, pour off the content and rinse the glassware and Utensils with sufficient tap water in the basin. Remove the label / glass marking with a suitable organic solvent (e.g. methanol or acetonitrile). Keep the container filled with water until complete washing as discussed below. Put the stoppers in a separate container containing the cleaning solution as stated below (b) for about 30 – 60 minutes.
7.8.1.2 Prepare cleaning solution with liquid soap. Locally available brand TRIX or any other similar liquid soap of 0.5% (0.5ml /100 ml) in water can be used. Validity of the prepared solution is 7 days.
7.8.1.3 Brush up with a suitable brush taking it soaked in the soap solution and/or rinse the glassware or Utensils with sufficient tap water until complete removal of any visible residual matters, including cleaning agents. If apparent sticking observed sonicate it in ultrasonic bath for removal of these materials. If it cannot be removed, apply appropriate dilute acid or organic solvent, as applicable as stated below.
7.8.1.4 Dilute acid: e.g. 7.3% w/v HCl (2N HCl)
7.8.1.5 Organic solvents: e.g. Methanol, Acetonitrile etc.
7.8.1.6 Repeat 7.8.1.3 if required for appropriate cleaning and finally rinse with de-ionized water.
7.8.1.7 Observe carefully the appearance of any remaining object after cleaning. Wash it again if felt necessary.
7.8.1.8 Now, rinse them first with methanol and then with acetonitrile kept in wash bottle kept near the wash basin.
7.8.1.9 Dry the cleaned glassware & Utensils in the dryer (at about 60°C) for 12 – 24 hrs.
7.8.1.10 Keep the stoppers/closures in a bucket containing 0.5% TRIX solution; keep them for at least 30 in – 2 hrs.
7.8.1.11 Wash first with tap water and then with de-ionized water and put them in metallic net bucket for drying them for 12 - 24 hrs at about 60°C.
7.8.2 Cleaning of Glassware and Utensils for microbial use:
7.8.2.1 Follow the procedure described at 7.8.1.1 to 7.8.1.9 sequentially.
7.8.2.2 Wrap with aluminium foil and send them to microbiology lab. and sterilize them by autoclaving.
7.8.3 Cleaning of Vials for HPLC analysis:
Vials used for HPLC analysis should be cleaned with special care as follows:
7.8.3.1 Remove screw cap closure & septa and pour off the contents of the vial.
7.8.3.2 Soak them all (vial, closure & vial) in a container containing water until complete cleaning.
7.8.3.3 Wash with tap water with ultrasonication for 2/3 minutes & then 2/3 minutes with de-ionized water.
7.8.3.4 Make the vials empty and then rinse with water: Acetonitrile (1:1) and finally
with 100% methanol.
7.8.3.5 Ensure visual absence of any colour of any material in the vial.
7.8.3.6 Put these all in the metallic basket and dry them at about 60°C in the dryer for 12 – 24 hrs.
7.8.3.7 Store these all in designated clean place for use.
7.8.4 Cleaning of laboratory instruments:
7.8.4.1 After completion of every analysis, clean/wash the integrated parts/devices (e.g. Pump, injector, detector of HPLC; Cell of UV spectrophotometer; titration vessel of Karl-fisher titrator; electrode of pH meter etc.) of the equipment by washing with suitable solvents (e.g. water, water: acetonitrile, water: methanol, acetonitrile, methanol etc.) as appropriate for the parts/devices.
7.8.5 Cleaning of the laboratory and hygiene practice:
7.8.5.1 Laboratory must be maintained in a clean & tidy and safe condition with appropriate control and management of waste materials. Cleaner is responsible for cleaning as per requirements (except Laboratory equipment, for which dedicated QC personnel should perform the necessary cleaning). Laboratory supervisor has to check that all cleaning activities are performed satisfactorily.
7.8.6 Cleaning program and process for laboratory:
7.8.6.1 Laboratory floor & furniture: a) Floor, b) Wall, c) Roof /air handling system (defogger in & out) d) Every corner of laboratory spaces, e) Working benches, f) Documentation benches, g) Cupboard / cabinet, h) Drawer of each cupboard, i) Fume cupboard, j) Fire extinguisher, k) First aid box, l) Electric appliance including AC & m)Store room. Laboratory cleaner should hope the floor with the disinfectant solution at the beginning of every day and ensure clean status of the above with wiping of surface (as applicable).
7.8.6.2 Laboratory equipment: Responsible laboratory people should clean the sophisticated QC equipment and record the cleaning activity in the corresponding equipment activity log book as per requirement.
7.8.6.3 Laboratory in-charge (or a nominated person) is to supervise the cleaning activities.
7.9 Personnel safety & hygiene:
7.9.1 Laboratory staffs should use laboratory coat and eye protective glass during work. Personnel having spectacles do not need to wear lab goggles separately.
7.9.2 Flammable solvent should be handled under fume cupboard.
7.9.3 Face mask or gloves should be used as per the materials safety instruction.
7.9.4 Eating, drinking, chewing or smoking, or the storage of food, drink or combustible materials are prohibited in the laboratory.
7.9.5 Personnel must wash hands after each analysis or handling reagents or chemicals.
7.9.6 House Keeping: All the laboratory accessories, laboratory glassware, reagents, reference standards, test and retention samples, remaining samples (after completion of analysis), document files, sample containers, papers etc must be stored in the laboratory in designated areas considering its easy handling. The areas, cabinets or racks & drawers must be labeled properly for its contents. Each and every file exist in QC laboratory must be labeled properly for its identification of contents. Any cabinet, rack or drawer if remains empty, must be mentioned as empty.
7.9.7 Waste disposal: Laboratory should have a written down guidelines for disposal of laboratory wastes in a safely manner.
7.9.8 Archive: All protocols, raw data, samples of test and reference items, final reports and specimens should be transferred to the archives at the end of the study (signing of the final report).
8.0 Reference Document
8.1 WHO Guidelines, volume 2, second edition.
9.0 Annexure
9.1 Not Appreciable
10.0 Revision History
|
Revision No. |
Brief
reason for the revision |
Effective Date |
Remarks |
|
01 |
New |
|
|
11.0 Training
11.1 Head of Quality Control or his/her nominee shall give the SOP training before effective date.
