Good Laboratory Practices (GLP) – SOP & Guideline

Standard Operating Procedure SOP for Good Laboratory Practices (GLP) in line with the Schedule L1 requirement of the drug and cosmetic act.

Good Laboratory Practices (GLP) embodies a set of principles that provides a framework within which laboratory studies (activities) are planned, performed, monitored, recorded, reported, and archived.

Good Laboratory Practices (GLP)

1.0   Purpose:

    • The purpose of this SOP is to describe the Good Laboratory Practices (GLP) to be followed to obtain reliable and reproducible results meeting regulatory standards with effective usage of time, manpower, and resources.                          

2.0   Scope:

    • This SOP is applicable to all activities which to be performed in the Quality Control Laboratory.

3.0   References & Annexures : (Good Laboratory Practices – GLP)

    • Investigation of Out of Specification Analysis Result – SOP
    • Destruction of Excess Samples  after Analysis – SOP
    • Working Bench Practices – SOP
    • Disposal of waste generated in Quality Control – SOP
    • Maintenance of Laboratory Instruments – SOP
    • Event Reporting and Investigation – SOP
    • Handling of Out of Calibration – SOP
    • Sampling procedure of raw materials – SOP
    • Finished Product Sampling of Drug Products – SOP
    • General Practice of HPLC – SOP
    • Planned Modification System – SOP
    • Change Control Procedure – SOP
    • Training and Development – SOP
    • Contract Laboratory testing – SOP
    • Sampling and acceptance quality level of  packing material- SOP                                         
    • Internal Quality Audit – SOP
    • Laboratory Close Down Checklist  (Annexure -1)
    • Laboratory Cleaning Procedure / Checklist (Annexure -2)
    • Label for Purified Water (Annexure-3)

4.0   Responsibilities: (Good Laboratory Practices – GLP)

Good Laboratory Practices (GLP)

    • The Analyst shall be responsible :

    • To follow the good laboratory practice as described in SOP.
    • To train the Lab assistant/workmen to follow the procedure as described in SOP.
    • Section Head shall be responsible :
    • To follow the good laboratory practice (GLP) as described in the SOP.
    • To ensure and train the Analyst to follow the procedure as described in SOP.

    • QC Head or designee shall be responsible :

    • Check the compliance of the SOP for Good Laboratory Practices (GLP).
    • Follow the good laboratory practice (GLP) procedure as described in SOP.
    • Impart training to all concerned personnel before the implementation of SOP.
    • To review the report and related documentation in case of any discrepancy.
    • To ensure that the procedure is followed as per SOP.

    • Quality Assurance shall be responsible:

    • To ensure the implementation of practice is being followed as per SOP.

    • Quality Head shall be responsible:

    • Shall be accountable for the compliance of this SOP.

    • Regulatory Affairs and Plant Head:

    • To review and approve the SOP.

5.0   Abbreviations & Definition of terms :

    • DQ: Design Qualification.
    • IQ: Installation Qualification
    • GLP: Good Laboratory Practices
    • PQ: Performance Qualification
    • GMP: Good Manufacturing practices
    • LED: Light Emitting Diode
    • SISPQ: Safety, Identity,  Strength, Purity, and Quality

    • Good Laboratory Practice (GLP):

    • Good Laboratory Practice embodies a set of principles that provides a framework within which laboratory studies (activities) are planned, performed, monitored, recorded, reported, and archived.
    • GLP help to assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessment.
      • Notebooks or analysis sheet,
    • Thereof, that may be the results of general observations and other activities and such raw data shall include-
      • Software (electronic data),
      • Dictated observations or recorded data from automated equipment.
    • The raw data also includes the result of-
      • Environmental monitoring,
      • Records of instruments/equipment,
      • Integrator output from analytical equipment,
      • Worksheet used to read a note,
      • Information from Light Emitting Diode (LED) display of any equipment.

6.0 Procedure – Good Laboratory Practice (GLP):

    • The attainment of quality objectives, product quality, efficacy, and safety is the responsibility of senior management but requires the participation and commitment of staff which is vital.
    • There must be comprehensive and effectively implemented Quality Control systems that should be fully documented and its effectiveness monitored.
    • Ensure Quality Control System should be adequately resourced with competent personnel and proper premises, equipment, and facilities to ensure that Quality Control Functioning is effective in meeting the requirements.
    • Written job responsibilities of Quality Control personnel should be laid and followed strictly. (Under the good laboratory practices – GLP)
    • The structure of the organization which is fundamental to the satisfactory operation of QC should be appropriately defined including the hierarchies as per the functions.
    • The QC department should be independent of the Production department and warehouse.
    • The QC department should be under the authority of the QC Head who has appropriate qualifications and experience and reports directly to the top quality management.
    • Quality Control should not be confined only to Laboratory operations,
    • But should effectively involve in decisions, which may concern the Quality of the products.
    • Quality Personnel should have access to production and warehouse areas for Sampling and investigation as appropriate.

  • The QC should have a Quality Objective which includes: (Good Laboratory Practices – GLP)

    • To ensure that all the products manufactured in the company are analyzed as per their specifications,
    • Products leading to meet the desired quality standards of marketing authorization such that the delivered products will fit for their intended use and will help in maintain and improving patient’s health.
    • Products should not place patients at risk due to inadequate safety, quality, or efficacy.
    • The basic requirement under good laboratory practices (GLP) are-
      • Follow the concept of continuous improvement and make the best use of management resources in all quality matters.
      • Comply with all applicable laws and regulations.
      • Ensure all-round development of personnel through adequate training.
      • Create a suitable environment for everyone to participate in quality.
      • Ensure that all activities carried out are safe for personnel who come in contact with work.

  • Quality Policy – Good Laboratory Practices (GLP):

    • The philosophy of the company is to win and retain customer through excellent services and provide a consistent level of quality comfort
    • The company is committed to consistently manufacture and deliver Pharmaceutical Products of dependable quality that comply with national and International Quality Standard.
    • The assurance of high quality is by strictly adhering to current Good Manufacturing Practices and Good Laboratory Practices (GLP).
    • This compliance ensures consistent Quality, Safety, and Efficacy of products.
    • Consistently high-quality standards will be reached through a team effort and with the contribution of trained personnel through ongoing training that results in transparent and effective Quality Management.
    • The factors that contribute to a sound quality culture are
      • Participation of all personnel,
      • Adoption of contemporary technology, and design of the state of the art facility,
      • Installation of sophisticated equipment and building a sound scientific understanding.
    • Every individual has a definite role and responsibility under good laboratory practices (GLP).
    • This role definition ensures that each team member contributes significantly to all aspects of our integrated manufacturing operation.
    • Companies believe and emphasize continuous improvement in all areas of our functioning to achieve excellence.
    • Set achievable and well-defined goals and measure performance periodically against defined standards.
    • The company is committed to providing a safe and secure working environment.
    • The company is committed to better living, it seeks to manufacture and distribute products that result in a better quality of life for the people that world over.

    • Under the Good Laboratory Practices (GLP) followings should be available with QC (as required)

      • Pharmacopoeia & its supplement or addendum,
      • Other reference material and
    • Quality Control is responsible for fulfilling the regulatory requirements for product registration.
    • Organogram is to be prepared for the Quality Control department, define the job responsibilities of the individual hierarchy in the laboratory.

  • General Requirement of Good Laboratory Practices (GLP):-

    • Good Laboratory Practices (GLP)/GMP concerns all people who work in areas where it applies, whether they are managers, supervisors, or staff.
    • It also affects those ‘indirectly’ involved, in activities such as maintenance, cleaning, record keeping, and in ‘support’ areas such as the quality and personnel departments, etc.
    • Although staff working in a Good Laboratory Practices (GLP)/GMP environment is carrying out different tasks using different skills, there are some basic rules which can be generally applied.

    • Basic Rules of Good Laboratory Practices (GLP) to be followed includes:-

    • Make sure to have the correct written instructions before starting a task.
    • Do not carry out a task for which you have not been trained or in which you do not feel competent.
    • Always follow instructions precisely.
    • If in doubt, ask. def ine in advance what we are going to do Check that we have done and what we should have done

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    • Keep records of information, results, and actions are taken.
    • Make clear accurate records of what was done and the checks carried out.
    • Check that the instrument/equipment/material used is clean, calibrated, and correct ones as per the procedure.

    • Always be on guard for labeling errors, labels should always be held securely and not left lying around.

    • Always notify if labels are seen either detached or appear to be incorrect or are in the wrong place, report any labels that are damaged or dirty.

Related: Good Workbench Practices.

    • Never remove a label that has been incorrectly applied and never stick a new label over an old one of the same type.
    • If the label is incorrectly affixed, strike it off, sign and paste the new correct label adjacent to it.
    • The Quality Control Laboratory should be clean and the workbenches kept tidy in Accordance with written cleaning schedules.
    • The activity of cleaning should be recorded in the format. Refer annexure -2.

    • Cleaning of QC Lab under the Good Laboratory Practices (GLP):

    • Keep everything clean and tidy.
    • The cleaning of Raw Material, Packaging material, Finished Product, and Stability samples storage compartment is to be done by using a vacuum cleaner (if required) followed by a clean soft lint-free duster.
    • Carry out cleaning fortnightly or earlier as and when required.
    • Clean the drying oven, Refrigerator, Stability Chambers, Incubators, etc used in the Quality Control Laboratory as per the procedure and frequency specified in the respective operating procedure.
    • Clean the workbenches after completion of work or at the end of the day whichever is earlier and keep the respective specification, SOP’s etc. used, back at the designated place.
    • General and specific written down instructions for safety shall be circulated to each staff member and the instructions be revised periodically as appropriate (e.g., poster display, Audio-visual material, and by seminars/conferences).
    • While closing the Quality Control laboratory, ensure that all water taps, instruments (which are not running), equipment, computers are put ‘OFF’.
    • Put off the lights, AC’s and inform the engineering department to put off the AHU’s (wherever required) and close the department.
    • The laboratory main door keys should be submitted to the security department along with a filled laboratory close down the checklist. Refer Annexure-1.

  • Premises and utilities of QC under the Good Laboratory Practices (GLP): 

    • Quality Control Laboratories should be separated from production areas and warehouses.
    • Independence of Quality Control from Production is considered fundamental to the satisfactory operation of Quality Control.
    • Laboratory for in-process control can be located in production areas; provided the operations of the production process do not adversely affect the accuracy of the laboratory measurements, and the laboratory and its operations do not adversely affect the production process.
    • The layout and design must aim to minimize the risk of errors, hazards and permit effective cleaning, operation, and maintenance.
    • The workflow (material and personnel), utilization, and hazards of operation should be considered for defining area g. wet area, dry area, area to handle hazardous chemicals, heating operations, washing/cleaning operations, etc. should be adequately segregated for effective and safe functioning.
    • Separate instrument room with the adequate area may be provided for sensitive and sophisticated instruments, to protect from vibration, electrical interference, etc. and to control adequate temperature and humidity as required for analysis (Good Laboratory Practices – GLP).

    • Prevent the entry of insects and rodents besides cross-contamination.

    • The laboratories shall be designed, constructed, and maintained so as to Following should be considered while designing the laboratory.
      • Interior surface (walls, floor, and ceilings) shall be smooth and free from cracks, and permit easy cleaning and disinfection.
      • Adequate provision is made not only for space and equipment for carrying out the necessary tests but also for utilities like water, electrical power, and gas.
      • Air ventilation system shall ensure a dust-free environment.
      • Tabletops shall be constructed with acid, alkali, and solvent resistant material and shall be smooth and free from crevices as far as possible.
    • Quality Control Laboratories should be designed in such a way that sufficient space is given to avoid mix-ups and cross-contamination.
    • The design of the Laboratory should take into account the suitability of construction materials and ventilation.
    • The design of the Laboratory should take into account the suitability of construction materials and ventilation.

    • The workbench used for the preparation of the solution should be clean and clutter-free.

    • Adequate segregation should be provided between analysts working on the same bench adjacent to each other.
    • A separator/partition can be provided to segregate the work area of the analyst.
    • This is required to avoid contamination which could occur if segregation is not adequate.
    • There should be adequate and suitable storage space for samples, standards, laboratory reagents, apparatus, accessories, and records.

    • Adequate ventilation, air filtration, and exhaust systems should be provided, where appropriate.

    • These systems should be designed and constructed to minimize risks of contamination, cross-contamination, and hazard and should include equipment for control of air, pressure, dust, humidity, and temperature, as appropriate.
    • Appropriate measures should be established and implemented to prevent cross-contamination from personnel, materials etc. moving from one dedicated area to another.
    • The dedicated area should also be considered when the material of an infectious nature or high Pharmacological activity or toxicity is involved (e.g. cytotoxic anti-cancer agents etc.) unless validated deactivation and/or cleaning procedures are established and maintained.
    • Adequate lighting should be provided in all areas to facilitate cleaning, maintenance, and proper operations under the Good Laboratory Practices (GLP).
    • Laboratories should be provided with a regular supply of water of appropriate quality for cleaning and testing purposes.
    • For analytical preparations wherever water is to be used use ‘Purified water’. For chromatographic analysis like HPLC, UPLC, etc. Use ultrapure water.
    • Whenever the water purification system of the laboratory is under maintenance, alternatively purified water points are given in the QC department to be used,
    • Whereas for chromatographic preparations, commercially available HPLC grade water to be used.

    • For the collection of purified water from the QC department, follow the procedure specified below.

      • Every day, collect fresh water and store the same in suitable container in the laboratory.
      • During collection, drain the water from user point for sufficient time as per procedure.
      • Before collecting water into the container, rinse the container twice, and discard the washings.
      • Wipe the outer surface of the filled container and label it (Refer Annexure No.:3)
      • Alternatively a separate purified water line can be provided in the laboratory from the water purification system of the unit catering water to different manufacturing departments.
      • At the end of the day, drain the unused water completely and keep the container dry.
      • Suitable drains are to be provided for the laboratory; drains should be of adequate size and should be provided with an air break or a suitable device to prevent back-siphonage, where appropriate.
      • Temperature and humidity of the different areas of Laboratory like instrument room, titration room, Reserve sample room, sampling room should be maintained as per requirement and should be recorded twice a day; when wet / dry bulb thermometer is used.
      • Wherever the digital thermo hygrometer having the facility to record minimum and maximum temperature / Humidity is used, record the observed temperature and Humidity once a day along with the maximum and minimum value recorded.
      • Proper access control should be incorporated to guard the area where restricted entry is necessary.
      • The area should be labeled appropriately as per operation for better control under good laboratory practices (GLP).

    • Laboratory Safety under the Good Laboratory Practices (GLP) :

    • The laboratory should be provided with an eye washer, first aid kit, etc. for any emergency which may arise during operation.
    • Similarly, the required fire extinguisher should be available in the laboratory to extinguish any fire in case of an emergency.
    • An emergency exit should be available at an appropriate place for exit during an emergency.
    • Along with the stability samples, walk-in chambers/incubators can also be used for the storage of other samples like reserve samples of API, which are required to be stored at the same temperature/humidity conditions.
    • To avoid mixing of samples, dedicated racks/trays with proper labeling should be provided.
    • A list of all samples of individual type should be maintained along with the location chart for easy retrieval of the samples.
    • The individual sample is to be properly labeled as per the respective labeling procedure. 
    • All samples to be periodically reviewed and expired samples if any are to be disposed of as per respective specification and procedure specified in the current version of respective SOPs.

  • Personnel – Good Laboratory Practices (GLP) :

    • There should be an adequate number of personnel qualified by appropriate education, training, and/or experience to perform and supervise the tasks assigned.
    • A laboratory shall have a Head Quality Manager or Technical Manager for carrying out all technical activities and for implementation of a documented quality system.
    • The Head of the laboratory must be of high professional standing with experience in drug analysis and laboratory management
      • Ensuring the control and maintenance of documents including the quality system as per the requirements of regulatory authorities which involves all raw data, SOP s, documentation exhibits, protocols, training charts, etc;
      • Planning and organizing the audit of the quality system and initiation as well as follow up action of the corrective actions, if any;
      • Investigation of technical complaints;
      • Taking final responsibilities for recommending any regulatory action in the event of noncompliance of tested samples.
    • All personnel prior to employment should be medically examined and then after they should be periodically re-examined for medical fitness.

    • The Quality Control Head should ensure that the personnel is medically fit to carry out the job.

    • Personnel suffering from an infectious disease or having open lesions on the exposed surface of the body should not engage in activities that could result in compromising the quality of the analysis.
    • Under the Good Laboratory Practices (GLP), Any person shown at any time (either by medical examination or supervisory observation) to have an apparent illness or open lesions should be excluded from activities where the health condition could adversely affect the job function until the condition is corrected or qualified medical personnel to determine that the person inclusion would not jeopardize the safety or quality of function.
    • All employees shall be instructed to report about their illness or abnormal health condition to their immediate supervisor so that appropriate action can be taken.

    • Hierarchy according to the job responsibilities and functions should be clearly defined.

    • The job responsibility should be assigned according to the competency of the person and it should be timely revised for addition or deletion of responsibilities assigned previously.
    • The job responsibilities of the personnel engaged should be specified in writing and followed strictly.
    • Personnel should practice good sanitation and health habits.
    • Smoking, eating, drinking, chewing, or keeping plants, food, drinks, and personal medicines should not be permitted in Laboratory areas, where they might adversely influence the product quality.
    • Personnel should wear clean clothing (As per company policy) suitable for the activity with which they are involved and this clothing should be changed when appropriate.

    • Personnel should strictly follow entry/exit and gowning procedures.

    • While sampling and handling of cytotoxic materials, steroids, hormones, radioactive material, poisonous, carcinogenic materials, etc.,
    • While handling hazardous chemicals and while performing sterility, microbiological analysis, endotoxin testing procedure of change of clothing, and use of personal protective equipment and safety appliances should be strictly followed.
    • Personnel should avoid direct contact with material/product.
    • Never handle any chemicals, raw materials, intermediate or finished, unpacked products with bare hands. Always use the appropriate hand gloves while handling the same.
    • All personnel should follow the time schedule with respect to shift and should be punctual in attendance.

  • Training Management under the Good Laboratory Practices (GLP):

    • Training should be regularly conducted by qualified individuals and should cover, at a minimum, the particular operations that the employee performs and GMP as it relates to the employee’s functions.
    • Good Laboratory Practices (GLP) ultimately depends on people.
    • The individual skills and understanding of people about their work can be developed by training.
    • Training should be given on both the theory and practice of the work being undertaken in a particular area, as well as relevant ‘on-job’ (i.e. task-based) training.
    • Records of training must be maintained.
    • Training should be periodically accessed.
    • All staff, including new staff and existing staff, should be given basic training on Good Laboratory Practices (GLP) during induction and at regular intervals subsequently.
    • These training programs should be periodically updated.
    • In addition during training, emphasis should be laid on regulatory requirements, health, safety, and hygiene.

  • Instruments / Equipments / Accessories – Good Laboratory Practices (GLP):

    • The laboratory shall be furnished with all types of instruments/equipment as may be necessary for carrying out the different activities within the laboratory.
    • The analytical instruments shall be housed in a dust-free environment and whenever required, conditions of temperature and humidity shall be maintained and periodic checks on temperature and humidity to be made and recorded.
    • The instruments, instrument bench, and surrounding areas shall be kept clean, tidy, and free from vibration at all times.
    • Instruments requiring calibration shall be calibrated at regular intervals and records of such calibration or maintenance be maintained.

    • There shall be written instructions in the form of Standard Operating Procedures for the operation.

    • Other equipment/accessories such as burette, pipettes, volumetric flasks, weight boxes, thermometers, etc shall be thoroughly checked for accuracy of calibration before acceptance for use.
    • All Instruments / Equipment, accessories like HPLC / GC columns, thermometers, etc, should be identified with a unique code number.
    • Standard Operating procedures of Instrument/Equipment should be displayed near each instrument/equipment and should be followed whenever used.
    • All the equipment/accessories used in the laboratory having proper markings/scale on it, like the thermometer, vernier caliper, measuring scale, etc. are to be checked for the legibility of the markings, before every usage.
    • Also in the case of digital equipment/accessories e.g. digital flow meter, digital burettes, etc., legibility of the digits display to be ensured before usage.
    • If any of the same is found with the poor legibility, rectify the defect / discontinue the same from usage.
    • All such equipment/accessories should be verified for the readability by an in-house/ outside testing agency during every calibration.

Related: SOP for Internal & External (Outside) Calibration

    • The observation should be recorded and documented in the calibration certificate.
    • Users on receipt of the certificate should verify the check performed.
    • Usage Log should be maintained for usage records of major instruments/equipment.
    • Usages record should be recorded in the respective format.

    • Individual column usage log for HPLC, UPLC & GC columns should be maintained.

    • The temperature and humidity of stability chamber /walk-in chambers/incubators, refrigerators, etc., should be maintained as per requirement and data should be recorded.
    • Whenever instruments/equipment are in use overnight it must be indicated with the proper status label.
    • All the desiccators used in the laboratory should contain a sufficient quantity of suitable desiccant.
    • The desiccant should be replaced weekly or when desiccant losses its effectiveness (From blue to white or pink) whichever is earlier.
    • If any instrument/equipment/component/accessory is not qualified/ calibrated as not to be used or does not meet calibration or under maintenance, should be made inaccessible or inactive or labeled as ‘Under Maintenance’ such that its misuse can be avoided.
    • Instrument/equipment should be maintained in the appropriate surrounding to support proper functioning.
    • e.g. Chromatographic instruments having oven/thermostat should be maintained with surrounding constant temperature less than an ambient condition to avoid drift in retention time during analysis, walk-in-chambers / incubators should be placed in the area having temperature control otherwise may impact on the thermal controlling system of the machine.
    • Water from instrument/equipment (e.g. Water bath, Sonicators, etc.) should be changed regularly.
    • When instrument/equipment is not in use for a longer period (e.g. breakdown) water should be removed and the instrument/equipment kept dry.
    • Work involving the evolution of harmful and obnoxious vapors shall be carried out in a fume cupboard.
    • The exhaust system of the fume cupboard shall be checked frequently to ensure that it is in order.
    • At the end of the day’s operation or after use, instrument/equipment should be cleaned and switched off and kept covered wherever possible.

  • Computerized systems – Good Laboratory Practices (GLP):

    • Computer systems are used in the Laboratory for various purposes like controlling instruments, preparation of documents, preparation of labels, etc.
    • Computerized systems with application software for instrument/ equipment should be validated.
    • The depth and scope of validation depending on the diversity, complexity, and criticality of the application.
    • Appropriate installation qualification and operational qualification should demonstrate the suitability of computer hardware and software to perform assigned tasks.
    • The computerized systems should have sufficient controls to prevent unauthorized access or changes to data.
    • The software should not be left open and unattended to avoid misuse.
    • After use, save the data and close all operating systems properly and then switch off the computer system.
    • In case the software or system does not have control features, manual controls to be employed including access restrictions, limited operating body, training to all concerns, and detailed instructions in operating procedure.
    • The deletion of any data generated is forbidden.
    • In the case of corrections, authorization from the concerned head is necessary.
    • All the data i.e. initial raw data and revised/corrected data to be retained.
    • Justification of revision to be documented on initial data.
    • Data that are to be considered for further evaluation needs to be identified, hence incorrect or previous data to be stamped with necessary instructions.

    • The written procedures should be available for each operation.

    • To operate the computer system with instruments, refer concerned instrument operating procedure.
    • For documentation purposes, use a suitable operating system like MS word, excel, etc.
    • The major documents prepared like specifications, SOP, STP, etc. using the MS word, excel should have password protection. 
    • While preparing/updating any document, save the entered data periodically, assign the suitable file, and the pathname to the document prepared to have easy retrieval of the same in the future.
    • For every computer system, ensure that the anti-virus kit is installed to avoid loss due to any virus threat.
    • Along with the review of hard copy, the reviewer should verify the electronic copy randomly to ensure the correctness of data.
    • The hard copy and electronic copy should be the same in all.
    • Where critical data are being entered manually, there should be an additional check on the accuracy of the entry which can be done by the second operator or by the system itself.
    • Incidents related to a computerized system that could affect the quality application should be recorded and investigated.
    • Changes to the computerized system should be made according to a change procedure and should be authorized, documented, and tested.

  • Qualification of Lab Instruments under Good Laboratory Practices (GLP):

    • All new major instruments/equipment should be qualified before use and relevant Operating procedures should be prepared.
    • Qualification is usually carried out by conducting the following activities, individually or combined.
    • User Requirement Specification:
    • Design Qualification (DQ):
    • Documented verification that the proposed design is suitable for the intended purpose.
    • Installation Qualification (IQ):
    • Documented verification that the instrument/equipment as installed/modified, complies with the approved design, the manufacturer’s recommendations, and/or user requirements.
    • Operational Qualification (OQ):
    • Documented verification that the instrument/equipment as installed or modified performs as intended throughout the anticipated operating ranges.

    • Performance Qualification (PQ):

    • Documented verification that the instrument/equipment and ancillary systems, as connected, can reform effectively and reproducibly based on the approved method and specification.

    • Re-qualification is necessary for the following circumstances.

      • When the instrument/ equipment is shifted from one laboratory (Change in premises) to another laboratory, re-qualification (IQ, OQ, and PQ) is required.
      • Modification / up-gradation of instrument / equipment.
      • When the instrument/ equipment is shifted within the laboratory premises (one room to another room), re-qualification is not required, in-house calibration is required.
      • When the instrument/ equipment is upgraded or after having a major repairing, qualification (OQ/PQ) is required.
      • Replacement of major component of instrument/equipment.

  • Calibration and Maintenance under Good Laboratory Practices (GLP):

    • Each instrument/equipment should have a calibration status tag; indicating the date of calibration, the due date for the next calibration with the sign, and date.
    • Calibration status should be ensured for validity prior to use.
    • All instruments/equipment should be calibrated as per the defined schedule and as per the procedure.
    • The standard operating procedure for the calibration should be available.
    • The records of calibration should be maintained.
    • The standards used for calibration should have traceability with national and international standards (wherever applicable).
    • Emphasis should be given on planned preventive maintenance to minimize the potential for breakdown and the same should be recorded in the instrument/equipment history log.

  • Validation / Verification of Analytical Methods (Good Laboratory Practices – GLP):

    • The policy, intentions, and approach to validation, including analytical method, and persons responsible for design, review, approval, and documentation of each validation phase, should be documented.
    • Non-compendial analytical methods should be validated whereas compendial (Pharmacopoeial) methods need verification to check the suitability of testing methods under actual conditions of use.
    • Validation/verification provides assurance of result reliability and reproducibility.
    • Appropriate qualification of analytical instruments should be considered before starting the validation of analytical methods.
    • A written protocol should be established that specifies how validation/verification will be conducted.
    • The protocol should be reviewed, approved, and authorized by the designated authorities.
    • A validation/verification report should be prepared, summarizing the results obtained and drawing the appropriate conclusions, including the recommendation for changes if any, based on the study.
    • Any deviations or variations from the protocol if done should be documented with appropriate justification.
  • Method Transfer – Good Laboratory Practices (GLP):
    • The analytical method should be transferred to the laboratory staff successfully.
    • The process of method transfer provides confidence to users and certifies them to perform analysis correctly and independently.

  • Sampling Procedure under Good Laboratory Practices (GLP) :

    • Sampling is the process of abstraction of a portion of material or a group of units from a larger quantity of material or collection of units.
    • In order to test a  small portion and obtain information that can be used as a basis for action on the large quantity or collection of units or for monitoring the production process. 
    • Since the logic of sampling is that of generalizing with the information obtained from a portion about the whole batch/consignment, a sample must accurately represent the batch /Consignment that is being tested.
    • Sampling should be done in accordance with approved written procedures.
      • The procedure should describe.
      • The quantity of sample to be withdrawn
      • Instruction / precautions to avoid sample contamination/deterioration
      • Type and condition of the sample container to be used
      • Identification of container sampled
      • Any special precautions to be taken
      • Instructions for cleaning and storage of sampling equipment.
    • The procedure for the sampling of all input materials and products is as described in the current version of
      • Finish Product sampling SOP.
    • Sampling staff should be trained for sampling activity and should have knowledge of the nature of the samples to be handled and should refer respective specifications for the same.
    • Sampled containers should be adequately labeled and should have information for traceability.

  • Testing, Reporting, and Certification of Analysis (Good Laboratory Practices – GLP):

    • Testing should be conducted under the direct supervision of competent technical staff.
    • There should be written procedures for testing materials and products at different stages of manufacture, describing the methods and instruments/equipment to be used.
    • The samples of raw materials, packaging materials, intermediate products (If required), bulk products, and finished products should be tested before use.
    • All samples for analysis should be registered in and numbered for easy retrieval of samples and records related to them.
    • The Specification should be available for every product/item
    • Testing should be done as per approved specifications.
    • The results obtained should be Checked for compliance against the specification.
    • All calculations should be checked.
    • The records of testing should be maintained.
    • While performing tests, instructions for use, and storage of Laboratory reagents, volumetric solutions, reference standards, culture media, etc. should be followed.
    • The instruments/equipment should be used within the permitted range and as per the written operating procedures.

    • In case of analysis of temperature-sensitive material stored at 2 – 8 0 C or in the freezer (between -25 0 C to -10 0 C), follow the procedure as below.

      • Collect the sample from the respective storage areas and allow the same to attain the ambient temperature before using i.e. weighing, pipetting, etc.
      • Do not expose the sample to ambient temperature for longer duration i.e. for greater than 60 minutes.
      • During analysis close the sample container immediately after use and do not leave it open.
      • Preserve the sample container away from heat.
      • Replace samples back to the storage area immediately after sample preparation.
    • The test record should include the-
      • Name of material/product,
      • Reference to the relevant specification and testing procedure,
      • Test results, including observations and calculations,
      • Initials of persons performing testing,
      • Initials of persons verifying the testing and calculations,
      • A clear statement of release or rejection (or other status decision) and dated signatures of the designated responsible persons.
    • In the case of the chromatographic analysis like HPLC, the Mobile phase prepared should be properly labeled.
    • The label should indicate ‘Mobile phase for’, ‘Validity ’,’Date and sign’.
    • No batch of material/product should be released for sale or supply prior to certification by a qualified person that is in accordance with the requirement of relevant authorities.
    • After completion of the analysis and review of data, glassware should be cleared from the Discard the contents from glassware and keep for washing.
    • The disposal of waste material and balance analytical samples should be done carefully.
    • The disposal of broken glassware should be done as per the procedure.
    • A certificate of analysis should be prepared for the required consignment.
    • The certificate should list each test performed in accordance with specifications, including the acceptance limits and results obtained.

  • Retention of Samples (Reserve Samples / Control sample) :

    • Samples from each batch of critical raw material, the finished product should be retained. 
    • Finished products should be kept in their final packaging (market pack) and should be stored under the recommended conditions.
    • The packaging and holding of reserve sample is for the purpose of potential failure evaluation of the quality of the batches and not for future stability testing purposes.

  • Stability Studies under Good Laboratory Practices (GLP):

    • Stability studies should be carried out to obtain evidence on how the quality of a drug substance varies with time under the influence of factors such as temperature, humidity, and light and enables the establishment of recommended storage conditions, retest periods, or shelf-life for drug substances or drug products.
    • The test procedures used in-stability testing should be stability indicative.

Related: SOP for Stability Study of Drug Product

    • A documented on-going testing program should be designed to monitor the stability of each product and the results should be used to confirm appropriate storage conditions and retest/expiry dates.

    • The protocol for the on-going program should include, but not limited to

      • Relevant physical, chemical, microbiological test methods
      • Reference to test methods
      • Description of container closure system(s)
      • Testing intervals (time points)
      • Description of storage conditions
      • Other applicable specific parameters to the product
    • Stability samples should be stored in containers that simulate the market container e.g. if the API is marketed in bags within the fiber drums, stability samples can be packaged in bags of the same material and in smaller-scale fiber drums.
    • Product failures should be promptly reported to Unit Head, regulatory affairs, R & D, Quality Assurance, and customer (if applicable) for necessary action.
    • The possible impact on the batches distributed in the market should be considered.
    • A summary of the data generated should be written and maintained.
    • This summary should be subjected to periodic review.

  • Chemicals, Reagents, Glassware, and Analytical Standards (Good Laboratory Practices – GLP):

    • Special attention should be given to the quality of laboratory reagents, volumetric glassware, and solutions, standards.
    • Reagents and standards should be prepared and labeled as per written procedures.
    • For Chromatographic analysis like HPLC & GC, always use chromatographic grade solvents and reagents where ever applicable.
    • All reagents and solutions in the laboratory shall be properly identified with a label.
    • Validity should be provided as appropriate for analytical reagents or standard solutions prepared and should be indicated on the label.
    • Adequate space with proper storage conditions in the laboratory shall be provided for keeping reference and working standards and be maintained by the Quality Control department.
    • The standards and solutions should be labeled with the date of preparation, date of standardization, validity, and initials of the person preparing the same.
    • Soiled and disfigured labels of reagents and volumetric solutions should be replaced. Chemicals/reagents commercially purchased having soiled/disfigured labels should not be accepted or used.

    • Labels of empty reagent/chemical bottles should be defaced before disposal.

    • Empty bottles of hazardous chemicals/acids should be rinsed with water before sending for disposal.
    • The glassware used for analysis should be of appropriate quality and capacity.
    • Only Class A graduated glassware should be used unless validated.
    • A certificate of calibration should be maintained.
    • Graduated glassware should not be dried at high temperatures (generally more than 70O C) which could alter volumetric graduation.
    • The glassware should be examined before use for cleanliness and damage; do not use cracked, chipped or any other defective glassware.

  • Documentation under Good Laboratory Practices (GLP):

    • Good documentation constitutes an essential part of the system.
    • Clearly written documentation prevents errors from spoken communications.
    • Specifications, instructions, procedures, and records must be free from errors and available in writing.
    • Standard operating procedures should be available for sampling, inspection, and testing of raw materials, APIs, intermediates, bulk finished products, packaging materials.
    • Documents should be approved, signed, and dated by appropriate and authorized persons.
    • Strict adherence to documented procedures and specifications should be ensured.
    • Reproduced documents (such as Controlled copy or uncontrolled copy) should be clear and legible.
    • The reproduction of any documents from master documents must not allow any error to be introduced through the reproduction process.
    • The controlled copy should be issued for regular use.
    • Documents should be regularly reviewed and kept up-to-date.
    • When a document is revised, systems should be operated to prevent inadvertent use of superseded documents.

    • A master list of all documents should be maintained.

    • Any correction to a record should be scored with a single line and new entry should be made alongside the original entry, should be signed and dated; the correction should permit the reading of the original information. Where appropriate, the reason for the correction should be recorded.
    • There should be no overwriting and correction fluid/eraser should not be used.
    • Records should be made or completed at the time each action is taken and in such a way that all significant activities are traceable.
    • Documents should be preserved appropriately (product/material-wise or A.R.No. wise) for easy retrieval and for the appropriate time.

  • Change Control Procedure under Good Laboratory Practices (GLP):

    • A change control system should be established to evaluate all changes that may affect product quality.
    • The written procedure should provide for identification, documentation, appropriate review, and approval of changes.
    • The potential impact of the proposed changes should be evaluated.
    • When implementing approved changes, measures should be taken to ensure that all documents affected by the change are revised.
    • Permanent changes, which may impact directly or indirectly to Safety, Identity, Strength, Purity, and Quality of the product which is applicable to but not limited to,
      • Standard Operating Procedure (SOP)
      • Batch Manufacturing Record (BMR)/ Batch Packing Record(BPR)
      • Specification / Analytical Test Procedure / Analytical Templates.
      • Stability Protocol / Stability Templates.
      • Validation Master plan, Cleaning Validation Master Plan, Process Validation Master Plan,
      • Analytical Method Validation Master Plan, Equipment Qualification Master Plan.
      • Other miscellaneous documents in which the Change Control number is assigned.
      • Product Shelf life extension/reduction.
    • The temporary change is applicable to that momentary change/alteration which may impact directly or indirectly to Safety, Identity, Strength, Purity, and Quality of the product.

    • The Temporary change is applicable to the following but not limited to,

    • Manufacturing process.
    • Master formula / Composition.
    • Manufacturing equipment/machine or operating instrument.
    • This procedure is not applicable to,
      • Modification and/or breakdown related to building, facility, area (room), utility service, equipment, machinery.
      • Introduction of new equipment, utility, or instrument.
    • Every change should be identified, documented, reviewed, and approved for changes.
    • Depending on the types of change, the concerned body should be addressed and approval should be taken.
    • Separate logs should be maintained by Quality Assurance for change control depending upon the type of change.

  • Lab Event / Incident – Good Laboratory Practices (GLP):

    • Applicable to all events which can affect the safety, identity, strength, purity, and / or quality of the product which can be,
      • Utility/ Service related.
      • Production related or occurred during processing.
      • Raw / Packaging material sampling, testing, or release related as per recommendation.
      • In-process and finished product sampling testing related.
      • Confirmed failures out of repeat analysis and out of specification investigations.

Related: SOP for Lab Event / Incident

      • Unplanned deviations from approved procedures e.g. Standard operating procedure, protocol, BMR, etc., without prior authorization and documentation.
      • Any accident having an impact on SISPQ of the product.
  • Note:- Events related to equipment or machine breakdown shall be handled through a breakdown maintenance system. Due to a breakdown if the product can be impacted then the event shall be raised.
    • This procedure is not applicable for the manufacturing and analysis of trial batches, method development, and method transfer activities.
    • The deviation is a departure from an approved instruction or established standard all planned and unplanned deviations related to receipt, handling, storage, testing, and release should be recorded and investigated.
    • The deviation is a departure from an approved instruction or established standard all planned and unplanned deviations related to receipt, handling, storage, testing, and release should be recorded and investigated documented.

  • Out-of-specification / Out of Trend:

    • Any out of specification (OOS) / Out of Trend (OOT) test results observed in the Laboratory should be investigated and documented according to a procedure and should be reported to the relevant competent authorities.

Related: SOP for Handling of Out of Trend Results

    • The procedure should require analysis of the data, assessment of whether a significant problem exists, allocation of the tasks for corrective actions, and conclusions.
    • Any re-sampling and/or retesting after OOS results should be performed according to a documented procedure. Refer SOP for OOS and SOP for Out of Trend.

  • Contract Laboratory Analysis :

    • Analysis of certain materials for specific tests that cannot be carried out at the site can be done at approved contract laboratories.
    • The contract laboratories provided with the information and specification necessary to carry out the tests.
    • The use of contract laboratories should be in conformity with the principles of current Good Manufacturing Practices.
    • Contract Laboratories should be evaluated/audited by the contract giver.

  • Self Inspection (Internal Audits) – Good Laboratory Practices (GLP):

    • In order to verify compliance with the Quality Control system, regular internal audits should be conducted in accordance with an approved schedule.
    • The audit should be done by designated competent persons appointed by the top-management other than the in-charge of the laboratory.
    • Audit findings and corrective actions should be documented and brought to the attention of the responsible management of the firm.
    • All complaints and other information concerning potentially defective products must be reviewed carefully according to written procedures.
    • Records of complaints should be retained in order to evaluate trends, frequencies, and Severity to take additional and appropriate corrective action wherever applicable.

Laboratory Close Down Checklist  (Annexure -1)

Date:——————          

Sr.No Area Responsibility Yes No NA
1 Microbiology section Microbiology section —- —- —-
1 Autoclave switched off Checked By

Sign/Date:

Time:
2 Incubators /Refrigerator are kept on
3 All instruments switched off
4 Computer switched off
5 Media reagents/Solvents/Solutions Bottle kept back at the proper place
6 Sink cleared
7 All dustbins are cleaned.
9 All exhaust,blowers,lights switched off
10 Main light switch off

2

 Stability section Stability section —- —-

—-
1 All stability chamber/Cooling cabinet kept switched on Checked By

Sign/Date:

Time:
2 All computer kept switched on
3 AHU kept on(When required)
4 Check chambers water level/alarm facility is ok
5 All dustbins are cleaned.
Date:——————                                                             
Sr.No Area Responsibility Yes No NA
3 Washing Area Non routine  section —- —- —-
1 Sink cleaned Checked By

Sign/Date:

Time:
2 Lights switched Off `
3 All dustbins are cleaned.
4 Water purification system kept continuously on
5 Water taps off
6 Exhaust switched off
7 Fuming hood off
8 Acids placed on send bath
4 Hot Zone Area Checked By: —- —- —-
1 Electrical/Gas burners put off Checked By

Sign/Date:

Time:
2 Sonicator Switched off
3 Acid placed on send bath
4 Oven & Hot plate switched off
5 All exhaust, blowers, lights, and vacuum pump switched off
6 All dustbins are cleared.
7 The water bath switched off
8 All instrument/Equipment main switch off
Date:——————      
5 Wet chemistry/Titration Area Raw material section —- —- —-
1 Reagents/Solvents/Solutions Bottle kept back at the proper place Checked By

Sign/Date:

Time:
2 Sink cleared
3 All instruments/equipment main switched off
4 Computer switched off
5 All dustbins are cleaned.
6 Refrigerator/Cooling cabinet kept on
7 Exhaust switched off
8 All section main lights switch off
6 Documentation section Document section —- —- —-
1 All SOP/ATP  kept back at the proper place Checked By

Sign/Date:

Time:
2 All QC drawers are cleaned
3 QC dustbins are cleaned..
4 General cleanness of Laboratory is ok
5 QC document storage area is closed
6 Computer switched off

 

7 Instrument Room I and II Finish Product section —- —- —-
1 All Instrument main switched off  (where ever applicable) Checked By

Sign/Date:

Time:
2 Computer switched off (where ever applicable)                                                                                    
3 Lights main switch off
4 Gas cylinders valve closed
5 All Gas generator off
6 AHU kept on
7 Refrigerator/Cooling cabinet kept on
8 Column compartment closed
9 Instrument room door closed (where ever applicable) & Main QC door closed.
Note: Laboratory close down checklist to be filled at the end of shift when sectional activity are going to close.

Laboratory Cleaning Procedure / Checklist (Annexure -2)

Area Procedure Frequency
Dust Bins Remove the contents with the polythene bags and transfer to the house-keeping bin. Daily
Work benches Clean with the dusters/Lint-free cloth Daily
Floor Clean the floor with a vacuum cleaner or dry mopper with a disinfectant solution Daily
Grills of AHUs Spray with the soap solution and wipe with a dry cloth. Fortnightly
Windows frames & glass shields Spray with the soap solution and wipe with a dry cloth Weekly or as and when required
Instrument Top Clean with duster/Lints free cloths Daily
Tube light frames/shields Clean with duster/Lint-free cloth Daily

Label for Purified Water (Annexure-3)

Label for Purified Water
Item Purified Water

Date:

Signatures:

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