ORAL DOSAGE FORM SOPs

1.0 PURPOSE

To provide a detailed procedure for “Good Chromatographic practice and Integration or’ chromatographic data.

2.0 SCOPE:

This procedure is applicable to “Good Chromatographic practices and Integration of chromatographic data” how to setup a chromatograph, how to prepare a sequence, how to prepare method/QNT, how to integrate/generate results in the quality Control Department

5.0 PROCEDURE:

5.1 Prerequisites

5.1.1 Analyst shall ensure that the instrument to be used for analysis is in state of calibration.

5.1.2 Instrument usage shall be documented in the instrument usage log book concurrently if electronic logbook is not available.

5.1.3 Respective operational/user management SOP shall be followed.

5.2 Prior to each HPLC analysis, the analyst shall ensure following at the minimum

5.2.1 There are sufficient quantities of diluent and mobile phase available to complete the analysis.

5.2.2 Injector rinse solution, seal wash solution and mobile phases are degassed.

5.2.3 Auto-sampler vials should be filled up to visually about 80% of capacity or up to the graduation mark provided on the vial. Vial should not be over filled.

5.2.4 Auto-sampler vial caps are not overtightened.

5.2.5 Mobile phase lines and rinse lines are free of air bubbles when visually examined.

5.2.6 Analyst shall flush all the solvent flow line with appropriate solvent before and after the usage.

5.3 Reverse phase chromatography:

5.3.1 In case of Reverse phase chromatography (i.e. Mobile phase is polar and stationary phase is non polar), all the solvent flow line shall be flushed with moderate hot Milli-Q |grade or equivalent water (about 60°C) to remove salts and solvents used in previous analysis, matter that HPLC shall be flushed with organic solvent like acetonitrile or methanol and then agar with Milli-Q grade or equivalent water. Convert normal phase HPLC (where non polar solvents like hexane, heptane is used in mobile phase) to reverse phase (where polar solvent is used like methanol/acetonitrile used in mobile phase) by sequential rinsing with isopropyl alcohol, 100% methanol and aqueous methanol (methanol: water (50:50)) through the system, then rinse with hot water.

5.3.2 Use water: acetonitrile (20:80) mixture as the rinse solution when switching the normal phase HPLC to reverse phase system, if not specified in the method.

5.3.3 Use water: Acetonitrile (80:20) mixtures as a seal wash for reverse phase systern unless otherwise specified in the test procedure.

5.4 Normal phase chromatography:    

5.4.1 ln case of Normal phase chromatography (i.e. Mobile phase is non-polar an stationary phase is polar) all the solvent flow line shall be flushed with non-polar solvent (i e. Hexane or heptane) prior to analysis or as per specific test procedure.

5.4.2 Convert reverse phase HPLC (if polar solvent is used like methanol or acetonitrile in mobile phase) to normal phase (if non polar solvent like hexane, heptane is used in mobile phase) by first rinsing with hot water through the system to remove salts/buffers, then rinse the system with aqueous methanol (Water: Methanol (50:50)), 100% Methanol and solvent iso propyl alcohol. then rinse with normal phase mobile phase like hexane/ ethyl acetate or other non-polar solvent as applicable.

5.4.3 HPLC to normal phase system.

5.4.4 Use mobile phase or other miscible organic solvent as a Seal wash for normal phase systems unless otherwise specified in test procedure

Note: When switching from reverse phase to normal phase, seal wash should be flush with reverse phase seal wash to remove any salts before moving to the normal phase seal wash

5.4.5 To convert any normal phase system in reverse phase procedure followed must be reverse as that given for conversion of system in normal phase.

5.4.6 Ensure that the solvent flow lines have been purged off air bubbles and cheek the systems for leaks before begin any run.

5.4.7 Ensure that the pressure is steady and is well below the maximum allowable pressure before beginning of any run.

5.4.8 After the completion of analysis, the solvent flow line and HPLC column shall be flushed with

5.4.9 Milli-Q grade or equivalent water followed by organic solvent. All four channels of the instruments shall be stored in Acetonitrile or methanol to avoid any fungal contamination or rust formation.

5.4.10 Note: ln case of HPLC analysis. if column under usage is not used for analysis for more than six months then column shall be saturated with mobile phase for at least four hours before starting injection sequence as per STP. Analyst and reviewer shall ensure last usage date of column before starting analysis.

5.4.11 Reagents chemicals and standards which are to be used during the analysis shall be in validity period.

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1.0 PURPOSE

To provide guidelines for Quality Control

2.0 SCOPE: 

This procedure is applicable to the practices adopted in Quality Control laboratory

5.0 PROCEDURE:

5.1       General health condition of personnel must be satisfactory who are working in chemical testing laboratory.

5.2       Personnel should have clean shave, trimmed hair and nails.

5.3       Person with open wounds, any skin aliment or any respiratory tract infection shall not be permitted to work in clean zones.

5.4       Personnel hygiene

5.4.1    All staff shall be neat and clean. Clean laboratory apron shall be worn.

5.4.2    Hair shall be kept clean and covered with a cap while working in the Laboratory.

5.4.3    All staff shall change their footwear or shoe covers just before entering the testing laboratory.

5.4.4    Nails of persons working in the Laboratory shall be regularly trimmed.

5.4.5    Jewelry and unnecessary cosmetics shall not be worn in testing area.

5.5       Activity of personnel: Chemical section

5.5.1    Persons working with toxic and hazardous chemicals should wear hand gloves, nose masks and goggles during working.

5.5.2    A separate place should be designated for toxic and hazardous chemicals and it should be in lock and key (key should be with Manager or Designee Q.C dept.).

5.5.3    Persons should use rubber bulbs or appropriate pipeting device for transfer of solutions during analysis.

5.5.4    Person should work under fuming chamber during handling of fume generating reagent and chemicals.

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1.0 PURPOSE

To lay down a procedure for housekeeping in Quality Control Department.

2.0 SCOPE: 

This procedure is applicable to housekeeping of Quality Control Laboratory.

5.0 PROCEDURE:

5.1 Floors shall be mopped twice daily with water containing disinfectants used as per respective SOP.

5.2  Glass panels shall be sprinkled first with 'Colin' solution and subsequently wiped with a dry clean cloth, at least once daily.

5.3  Dustbins kt at different places in Quality control Laboratory shall be cleaned at least once daily.

5.4  Ceilings shall be cleaned for cobwebs at least once a 3 days.

5.5  All light covers shall be cleaned at least once in a week.

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1.0 PURPOSE

To lay down a procedure for cleaning and sanitization in Quality Control Department.

2.0 SCOPE: 

This procedure is applicable to cleaning and sanitization in Quality Control Department in Instrument and chemical section.

5.0 PROCEDURE:

5.1  All working tables shall be mopped with tap water at the beginning and end of the day's work

5.2 Clean dust on work equipment regularly.

5.3 Wash all work equipment to be used at the end of the working day.

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1.0 PURPOSE

To provide an Instruction for handling of Analytical reagents, Indicators, Limit test solutions and mobile phase.

2.0 SCOPE: 

This procedure is applicable for preparation, usage and destruction of Analytical reagents, Indicators, Limit test solutions and mobile phase prepared in the quality control laboratory.

5.0 PROCEDURE:

5.1 General instructions:

5.1.1 Use Purified Water wherever ‘Water’ is mentioned to be used for preparing of any solutions, unless otherwise specified.

5.1.2 Ensure all the chemicals used for the preparation of Analytical reagents, Limit test solution, Indicators, mobile phase are well within the validity period.

5.1.3 Use chemicals of high purity grade like GR, AR for preparation of Analytical reagents, Limit test solutions, mobile phases, etc.

5.1.4 Ensure to prepare as per the procedure given in the Standard Test procedure or General procedure or as per Pharmacopeia.

5.1.5 Store Analytical reagents, Limit test solution, Indicators, mobile phase etc. as per recommended storage condition.

5.1.6 Do not pipette from mouth, use rubber bulb.

5.1.7 A djust the meniscus of burettes by adjusting the height to eye level.

5.1.8 Before using analytical solution, ensure the clarity is good. If any physical change is observed, discard the solution.

5.1.9 Do not use any analytical solution, beyond the validity period

5.1.10 Use always Certified Class ‘A’ glass wares for quantitative analysis.

5.1.11 Incase of ready-made Reagents/Indicators/Volumetric solutions directly release for use after checking the identity and the physical condition of the container.

5.2 Preparation of Reagents/Indicator/Limit Test Solutions/Mobile Phase

5.2.1 Analytical reagents:

5.2.2 Analyst shall prepare reagents as per the instruction provided in Pharmacopoeial monograph or Standard Test procedures or as per Analytical Methods or General procedures.

5.2.3 Record the preparation details of reagents in Analytical reagent register.

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1.0 PURPOSE

To provide an Instruction for handling of Reference Standards, In-house reference standards / Manufacturer’s standard and calibration standards to provide an Instruction for Handling of Primary standards

2.0 SCOPE: 

This SOP is applicable to, handling, usage of official reference standards and preparation, usage and handling of in-house reference standards, in-house/manufacturer’s standard, primary standards and calibration standards

5.0 PROCEDURE:

5.1       General instructions to be followed by Analyst:

5.1.1    Ensure to practice precautions provided in MSDS / SDS for the material of interest.

5.1.2    Store the reference standard in their respective storage condition after receipt as early as possible.

5.1.3    Check for any specific handling instructions and adhere to the same.

5.1.4    Minimize the exposure time while handling hygroscopic and light sensitive materials.

5.1.5    If standards are removed from refrigerated condition allow standard vial/container to attain room temperature before use. Wherever applicable check the attainment of room temperature preferably through Infrared probe or any suitable device

5.1.6    Dry only required quantity of the standard on a glass Petri dish, wherever applicable.

5.1.7    Do not dry the standards in their original container.

5.1.8    Do not put back any excess quantity of the dispensed material into the stock bottles.

5.1.9    When required to determine the water content of Reference Standard, use minimum quantity of the standard.

5.1.10   Proportionately smaller quantities of reference standards / in-house reference standard can be used, provided the final concentration is same as per the analytical method

5.1.11   If Reference standards, Impurity standards received from the contract giver or from the manufacturer, review the COA and the characterization documents (if available). Enter the details in “Reference Standard, Working Standard and Impurity standard Entry Register (Received from manufacturer/Contract Giver)”and use as such.

5.1.12   In this SOP, wherever “Master” is specified, it indicates that Master to be created once.

5.2       Reference standard source master creation

5.2.1    Analyst/Designee QC shall update Reference standard source details.

5.3       Reference standard pharmacopeia master creation

5.3.1    Analyst/Designee QC shall create all Pharmacopeia references (For e.g., BP, Ph. Eur., USP, etc.)

5.4       Reference standard / primary standard master creation:

5.4.1    Analyst/Designee QC shall update available Reference standards stock.

5.5       Handling of Reference standard:

5.5.1    Analyst/Designee QC shall check availability of current lots of Reference Standards from authorized distributors or from Pharmacopeia agency, and procure the same.

5.5.2    Analyst/Designee QC shall procure the standards from the sources Authorized

5.5.3    Analyst/Designee QC shall verify the details of material with source data (Catalog, website or pharmacopeia) and the correctness of Invoice / delivery challenge against received reference standard at the time of receipt;

5.5.4     If any discrepancy is observed, supervisor shall inform manager for necessary action.

5.5.5     Analyst/Designee QC shall enter the details in Reference standard stock register

5.5.6     If purity is not available on container label / catalog / literature supplied along with the container, analyst shall consider it as 100 %.

5.5.7     Analyst shall place the reference standard unit along with a desiccant (small silica gel bag) in a stainless-steel container or as per the design of the chamber.

5.5.8     Analyst shall store the Reference Standards in their original containers protected from heat, light and   moisture and keep them in cold condition (2°C to 8°C) or as directed in label / MSDS / SDS.

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1.0 PURPOSE

To provide written procedure for handling of raw data sheet, Assignment of tests to qualified analysts, result entry, review and disposition of samples.

2.0 SCOPE: 

This SOP covers the procedure for handling of raw data sheet, assignment of tests to qualified analysts, result entry, review and disposition of samples in the quality control laboratory.

5.0 PROCEDURE:

5.1 Raw data sheet templates preparation in MS word:

5.1.1     Analyst shall generate the raw data sheet template in Microsoft Word for the sample types mentioned.

5.1.2     Write the other sample types as mentioned in table in any of above sample types.

5.1.3     Create a template by capturing all steps mentioned in Standard Test Procedure for testing.

5.1.4     Provide only the input information which is required for performing calculations in raw data sheets. In template do not provide any calculation formula or space for performing calculations.

5.1.5     Leave blank space wherever weights / dilutions are mentioned in the steps and also for recording    observations / instrument readings.

5.1.6     Put the Minimum information needed to be captured in template.

5.1.7     Put additional information if required based on test requirement.

5.1.8     Provide provision for following templates

• Analyst sign and date [against each test]
• Reviewer sign and date [At the end of last page]
• Compliance (Complies / Does not comply)
• Specification limits for tests not having calculations
• References
• Other details (if any)

5.2       Recording Data

5.2.1     Analyst shall write raw data sheets online during analysis.

5.2.2     Analyst shall record all data in black ink only.

5.2.3     In case of failures, supervisor shall handle.

5.2.4     In case of OOT results, supervisor shall handle the case.

5.2.5     Upon completion of analysis of each test, ensure that test performed is duly signed and dated.

5.2.6     In case of a soiled RDS, Analyst/Designee QC shall replace the same with a new RDS and rewrite all   the relevant data in the new worksheet. Attach the soiled RDS also along with the new RDS. Cross  refer the new RDS to the soiled RDS with an explanation for the issue of the new RDS.

5.2.7     In case of finished product, RDS printing and Test assignment not applicable, results will be taken from respective SFG sample after its review.

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1.0 PURPOSE

To provide a written procedure for Technique Evaluation of an Analyst (analyst qualification).

2.0 SCOPE: 

This standard operating procedure is applicable Quality Control Department

5.0 PROCEDURE:

5.1 On-job training and evaluation of new analyst:

5.1.1 Analyst/Designee QC shall ensure induction in different sections of QC for the fresh analyst or experienced new analyst

5.1.2 Head QC shall Identify training needs of new analyst (both fresh and experienced) as per Job Role, complete analyst evaluation in following cases:

In case an analyst has not performed a particular Analytical technique for a more than a year,  perform analyst evaluation before assigning the analysis.

In case an analyst is absent for more than 6 months, perform analyst evaluation before assigning  the analysis. Refer Job Role Matrix.

5.1.3 Analyst/Designee QC shall organize classroom training/self-study to new analyst on applicable work Instructions/SOP.

5.1.4  Document classroom training / self-study in the Analyst training records

5.1.5  Ensure that every fresh analyst works with senior analyst for at least 30 days

5.1.6 Ensure experienced new analyst works with senior analyst for at least 10 days

5.1.7  Ensure that tests part of Batch release or Routine tests are not assigned to the fresh analyst or  experienced new analyst prior to qualification.

5.1.8  Train on systems / procedures / documentation and good laboratory practices pertaining to area of responsibility.   

5.2  Parameters for evaluation of analyst:

5.2.1 Evaluation on the Basic Analytical Techniques for Qualification of Analyst

Note: The basic analytical techniques shall be done by self-study of SOP, evaluation shall be performed based on the assessment of analyst.

5.2.2     Advance Analytical Techniques For Qualification of Analyst

5.2.3 Supervisor shall evaluate the Advance instrument technique on the test parameters based on the present Role requirement by the supervisor.

1.0 PURPOSE

To provide an Instruction for testing and reporting of results of Stability samples.

2.0 SCOPE: 

This SOP is applicable to quality control

5.0 PROCEDURE:

5.1  Analyst/Designee QC shall receive samples for analysis as per sampling interval as per the relevant procedure.

5.2   Check the samples for integrity. Store the received samples in the (secured) designated staging area under the storage condition as per the respective product storage label.

5.3  Ensure sufficient quantities of samples in unopened containers are handed over to microbiology    laboratory for microbiological tests immediately after receiving the samples for analysis.

5.4 Manual routing

5.4.1  Analyst/Designee QC shall enter the details of stability samples in AR. No. Register and allot  AR. No.

5.4.2     Analyst/Designee QC shall pull the stability samples and store the samples at respective product storage conditions till the initiation of testing.

5.4.3     Allot the sample to analyst.

            Note:

1. Issue only the required quantity of samples for particular test as specified in standard test procedure and enter the details in raw data sheet.
2. If the sample routing is manual and work sheet or template is not having provision for recording the issuance, use annexure as mentioned.

5.4.4 Analyst/Designee QC shall issue the worksheet to the analyst.

5.4.5  Analyst shall perform analysis and record the results in worksheet. 

5.4.6  In case of light sensitive products, perform the analysis by using low actinic (amber color) glass wares with minimum exposure to light. After withdrawing portion of the sample for the testing from the original container swiftly close the container and keep the sample back in original pack (carton/black polythene bag).

5.4.7 If the product is hygroscopic, perform the analysis including the opening/closing of standard/sample swiftly to avoid the moisture ingress.

5.4.8 In case products are sensitive to any other parameters (oxygen) ensure to follow standard test procedure while performing the analysis

5.4.9  In case of non-availability of testing facility, send sample to contract testing laboratory.

5.4.10   Upon completion of each test /analysis /receipt of report from In-house and public testing laboratory, analyst and supervisor respectively shall update results in worksheet

Store the remaining unused sample if required for any other tests as per the labeled storage condition except 30°C/65%RH, 30°C/75%RH and 40°C/75%RH which is to be stored at controlled room temperature.

5.4.11   Upon completion of complete analysis discard the remaining unused sample as per Waste management procedure, after getting the reports reviewed from supervisor.

5.4.12   Analyst shall check for OOT and OOS results if nay. Inform supervisor in case of OOT/OOS observed

5.4.13   Analyst/Designee QC shall review the data and log OOT/OOS in case if any.

5.4.14   Analyst/Designee QC shall conclude the OOT/OOS and provide disposition action in consultation with QA.

5.4.15   The analytical report shall be approved by QA.

Note: Decision of the disposition shall be taken by Quality assurance. Quality assurance will sign as "Reviewed by" at the end of the analytical report (Both chemical & Microbiology limit test reports)

5.4.16   Analyst shall compile and review the data after the approval of analytical report with change in version number at each interval. Print the compile data when necessary.

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1.0 PURPOSE

To provide written procedure for Handling of API and Primary Packaging materials.

2.0 SCOPE: 

This SOP covers Handling of APIs and Primary Packaging materials. This includes sampling, testing and Release/rejection decision on such materials.

5.0 PROCEDURE:

5.1 Receive the goods receipt note along with the filled location specific ware house check list for receipt of raw material / packaging materials from Stores / Ware house Department.

5.2 Ensure the availability of all the necessary information in the checklist.

5.3 Each batch of raw material / packaging material received at site shall be accompanied with a sufficient quantity of miniature sample as described in the respective specification of the material.

5.4 Ensure the miniature sample receipt information is available in the checklist or GRN such as quantity received, number of packs received, etc.

5.5 Refer the current list of approved vendors to ensure that the respective material is supplied from an approved vendor.

5.6 In case of any discrepancy, inform to Head-QC for further necessary action after discussion with Quality Assurance department.

5.7 Ensure the availability of certificate of analysis along with the consignment.

5.8 Enter the details of GRN in to the Raw materials / Packaging Inward Register.

5.9 The SR. No. in GRN shall be considered as A.R No. for a batch / lot of material received. For e.g. If the SR. No. is 1120000001, then the AR. No. allotted to a material is 112000001where 1120 is specific to Product Division, followed by a running serial number starting with 000001). This is the traceable   number for all future transactions for that particular material.

5.10 Enter into respective Ware house as per location specific Ware house Entry and Exit procedure.

5.11 The following activities shall be performed sequentially,

5.12 In case, if any of the pack is found to be damaged / unlabelled, indicate the same in the respective checklist (Refer Annexure - 1) and escalate to Head–QC for applicable actions.

5.13 The extent of damage shall be written in the checklist (Refer Annexure -1).

5.14 Refer location specific Ware house SOP for any decision on damaged containers.

5.15 Provide a copy of checklist to SCM for the necessary corrective action.

5.16 If sufficient quantity of miniature / representative sample is received along with the consignment, the material shall be tested as per valid specification and released / rejected as per location specific procedure.

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