ORAL DOSAGE FORM SOPs

1.0 PURPOSE

This SOP is to provide a guideline to facilitate compliance with Data Reliability in GMP data across the data life cycle.

2.0 SCOPE: 

This SOP is applicable for following departments:

• Warehouse
• Manufacturing and packaging
• Engineering
• Quality Assurance
• Quality Control
• Human Resources
• Administration and security (for only GMP related activities)

This SOP is also applicable to outsourcing activity where contract givers and contract acceptors are involved through technical agreement including contract laboratory and service providers (example- calibration and maintenance services, qualification services).

5.0 PROCEDURE:

5.1 Embedding Data Reliability across data lifecycle:

5.1.1   Data governance and Data Reliability elements/ principles are important factors for embedding         reliability of data for information obtained in production and control of pharmaceutical products          across product/data lifecycle. Throughout the data lifecycle, all data shall be created/acquired,          processed, reported,  reviewed, analysed, reported, transferred, stored and retrieved, continuously monitored until retired/destructed in accordance with Data Reliability principles/ elements.

5.1.2   It is applicable to all types of data such as paper data, electronic data, hybrid of both paper and electronic data, static data and dynamic data.

5.1.3   Data reliability shall be embed through following elements but not limited to.

• Training, awareness and Building a culture of Quality
• Data Reliability Process design of Paper system
• Management system and governance (Management review)

5.2 Training, Awareness and Building a culture of Quality:

5.2.1 Majority of data reliability issues are resultant of accidental breaches because of lack of awareness and capabilities of individuals.

5.2.2 Data reliability awareness and capabilities shall be achieved by ensuring training to each level of the employees.

5.2.3 Personnel should agree to abide by Data Reliability principles/ elements and should be made aware of potential consequences in cases of non-compliance through training.

5.2.4 Quality assurance shall prepare various training modules as mentioned below but not limited to for trainings related to data integrity.

5.2.5 “Good documentation practices”

• ALCOA ++
• “Basics of Data integrity” and “Consequences of data integrity breaches”
• Do and Don’ts with paper and electronic data.
• Role based trainings.
• Measures to prevent and detect Data Integrity breaches for paper and electronic systems
• Annual refresher training should be provided to all the employees.

5.3 Data Reliability Process Design on paper system:

5.3.1 The goal is to achieve design excellence through a simplified procedure which supports recording of data with highest level of data reliability meeting current regulatory requirements.

5.3.2 Data recording format/ document shall be designed in such a way that it permits hassle free recording of data and meeting data reliability related requirements (GDP and ALCOA+ requirements).

5.3.3 Quality Processes in departments like manufacturing, packaging, Store, Facility and engineering, quality control, quality assurance operations, HR/administrations, EHS, security shall be evaluated for data reliability supporting document designs throughout the product life cycle

5.3.4 All such processes like recording of batch manufacturing activities, batch testing activities, batch packaging activities, operation of cGMP software, handling of QMS activities, document control, validations, and reviews should be assessed for its document design to evaluate that those designs are supporting data reliability requirements (GDP and ALCOA+ requirements).

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1.0 PURPOSE

To describe the procedure for Management Reporting System for Quality Issue.

2.0 SCOPE:

This SOP is applicable for Management Reporting System for Quality Issue.

5.0 PROCEDURE:

    5.1 The Quarterly report shall contain following information but not limited to.

• Organizational Changes.
• List of New Joinee in QA/QC.
• List of Resignations.
• Qualification/Validation/Periodic Calibration performed.
• Process Deviation.
• Change Controls
• Major Changes.
• Non-conformance Report.
• Batch failure & reprocessing.
• Stability Studies-new charging.
• Stability studies-Failure.
• Market Complaints.

5.2 Analysis –QC.

• Out of Testing.
• Out of Specification (OOS).
• Analyst Qualification.
• Incidence.

5.3 The Monthly report shall prepared by In-charge –QA.

5.4 Head Quality Control Department shall prepare report and send it to Officer/Executive QA.

5.5 The Officer/Executive QA shall prepare combined report and send to Head-   QA.

5.6 The head –QA shall review the report and send it to Management.

5.7 The Style and pattern of Report shall be as per attached Annexure No. :- JSA/QA/022/F-01/R0

5.8 Data collection for each quarter done up to the last date of the month and report shall be completed in first week of the next month.

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1.0 PURPOSE

The purpose of this SOP is to facilitate an effective Quality Risk Management process covering life cycle of a drug product and drug substance and to ensure that

• Risks are proactively identified across the organization
• Responsibilities for managing risks are clearly stated, understood and accepted.
• To provide a systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle.

2.0 SCOPE:

The scope of this SOP covers the Quality Risk Management process to be adopted through the product life cycle. It applies to the stages of drug product lifecycle including the following but not limited to design, development & manufacture, and key quality events e.g., Change Management, Deviation Management, Product Recall, Handling of Market Complaints, Handling of OOS of commercially Manufacturing product including the Validation batches, EMP etc.,

5.0 PROCEDURE:

5.1 Two primary principles of Quality Risk Management are :

• The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient; (Diagram -1-Quality Risk Evaluation Pyramid).
• The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk (Diagram -2 - Documentation Level).

5.2 Applicability of Quality Management Program :

Following are the possible areas of implementation of QRM initiatives. The appropriateness of QRM requirement shall be determined on case to case basis and during the assessment of respective element of drug product lifecycle. Applicability of Quality Risk Management includes, but not limited to, the areas listed in the table below and Supplier.

5.3 Risk assessment using ‘Risk Management tools’: In specific cases, where there is limited knowledge available with the organization for a particular process or product, a more detailed    assessment in addition to the above approach shall be performed using one of the Risk Management tools (e.g., FMEA).

5.4 Quality Risk Management for Facilities, Equipment and Utilities, design of facility/equipment:

The objective of deploying the QRM initiatives for Facilities, Equipment and Utilities, design of facility/ equipment is :

• To determine appropriate clean room zones while designing & operating buildings and facilities
• To determine appropriate product contact materials for equipment and containers
• To determine appropriate utilities
• To determine appropriate preventive maintenance & calibration requirement for associated equipment.
• To determine the impact of new equipment / utilities or their extension to an existing operating facility / processing line / utility distribution system. This includes relocation of equipment within or between the sites, where applicable.

5.5 Quality Risk Management for Regulatory Operations (Inspection and assessment activities) :

The objective of deploying the QRM initiatives for Regulatory Operations is :

• To evaluate impact of proposed variations or changes
• To identify risks that should be communicated between inspectors and assessors

5.6 Quality Risk Management for Integrated Quality Management (covering key QMS elements e.g., Change management, Deviation management, Complaints, Audits etc.).

5.7 Quality defects

• To provide the basis for identifying, evaluating, and communicating the potential quality impact of a suspected quality defect.
• To facilitate risk communications and determine appropriate action to address significant product defects.

5.8 Periodic review

• To provide recommendations for improvement based on trend results of data within the product quality review.

5.9 Change management / Change control

•   To evaluate the impact of changes to the product quality, facility, equipment, material, manufacturing process, or technical transfers & to determine appropriate actions preceding the implementation of a change, e.g., additional testing, (re)qualification, (re)validation, or communication with regulators.

5.10 Following are typical examples, but not limited to, of key Quality impacting changes that may require  Quality Risk assessment :

5.11 Continual improvement

To facilitate continual improvement in processes throughout the product lifecycle.

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1.0 PURPOSE

To describe a procedure to define the requirements for signature for all master batch formula for processing and packaging record, Batch processing and control records, validation protocols, Standard operating procedures, Finished & intermediate product specifications & Standard testing procedures and certificate of analysis etc.  

2.0 SCOPE: 

This SOP is applicable for manufacturing facilities.

5.0 PROCEDURE:

5.1 All system related documentations of Production, QA, QC, Warehouse, Engineering, EHS & Human Resources, RA, and Responsible Pharmacists shall be signed by that to be approved by QA Head.

5.2   “Authorized Person” means that any person signing the documents should have sufficient knowledge, training and expertise to adequately review and approve data, information conclusions and recommendations contained therein

5.3 Specimen signature list of authorized signatories in the prescribed form is to be maintained in QA as  per format No.: -JSA/QA/024/F-01.

5.4 Each person who signs documents in Production, QA, QC, Warehouse, Engineering, EHS & Human Resources RA, and Responsible Pharmacists must sign its full and initial signatures in the authorized  signatories list.

5.5 QA department has to maintain the specimen signatories of all departments’ personnel and records as  per format No.: - JSA/QA/024/F-01.

• Quality Assurance department has to be maintained an authorized signatories list for all the below listed master documents but not limited to
• Master manufacturing documentation.
•  Batch Processing and Control Record.
• Standard Operating Procedures.
• Site Master File.
• Validation Master Plan.
• Validation Protocols.
• Finished & intermediate product specifications.
• Certificate of analysis.

5.6 Review the list of authorized signatories regularly as new employees are hired and responsibilities changes.

5.7 Frequency:

• At the time of new joining
• After 02 Year ± 30 days of Joining

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1.0 PURPOSE

To describe the procedure for the preparation of Compliance report as part of corrective action for the recommendations made during external audits.

2.0 SCOPE:

This SOP is applicable for preparation of Compliance Report for any recommendations or observations made during Certification/GMP audits by Regulatory bodies or authorities.   

5.0 PROCEDURE:

5.1  Any minor, major or critical non-conformance (NC) recommended during the audits shall be corrected    within a subsequent period with the co-operation of related departments.

5.2 Prepare non-conformance (NC) report department wise and handover it to the respective departmental       heads.

5.3 Compliance report prepared shall be provided with all information about the recommended points.

5.4 Observations/recommendations made during inspection shall be mentioned clearly.

5.5 Corrective action plans taken against the non-conformance (NC) and its present status must be provided with the report as part of the remarks.

5.6  A copy of report shall be forwarded by QA Department or QA-Head to the concerned auditors as soon as the completion of all related activities on the non-conformance.

5.7 Evidences of corrective actions taken may be attached as annexure as a part of the Compliance report.

5.8 Compliance Report format is given in the format No.: JSA/QA/025/F-01/R0.

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1.0 PURPOSE

To provide a procedure for conducting Periodic Quality Review to:

• Evaluate the performance of products manufactured and compare against the established quality standards.
• Determine the need for changes in the product specifications or manufacturing procedures/controls, if required.
• Determine if validation or re-validation is needed and confirm change control systems.
• Identify product improvement/ cost reduction/ cycle time reduction opportunities.
• Identify significant trends in product quality and to apprise management of these trends.

2.0 SCOPE:

This procedure is applicable to products manufactured during the review period at manufacturing site and commercialized. Batches manufactured only for regulatory fillings/ submissions and not commercialized are not included in this scope.

5.0 PROCEDURE:

5.1 Data required to compile PQRs shall be collected routinely (electronically/ by any suitable means) to facilitate preparation of PQR on time.

5.2 An annual planner with target dates shall be prepared (refer annexure III) by end  of December of every year and circulated to concerned department, by QA, for getting the relevant information on time and   the product review shall be completed as per the timelines.

5.3 Numbering of PQR: the numbering of the product quality review report shall be as follows:

• PQR/XX-XXXX/YYYY where:
• “PQR” denotes product quality review
• ‘XX-XXXX’ denotes the Product code of the product under review.
• ‘YYYY’ denotes the year of review.
• Example: PQR/FG-A001/2023 – indicates the PQR for the product bearing FG-A001 code for the year 2023.

5.4 Selections of products/ batches for review:

• PQR shall be prepared for all batches of all commercialized pharmaceutical products manufactured in the previous year, irrespective of the number of batches produced during the year. This includes, but is not limited to, batches with history of performance failures (internal {‘e.g yield variations, out-of-specification, etc’}, external{‘e.g customer complaints, etc ‘ or combination as applicable).
• Products not produced during the current review period but produced in the previous review period shall also be covered in the planner.
• Representative products from nutritional (at least one product each from tablets and capsules) shall be considered for review.
• If the product formula/code/process/specifications are same for various markets/packs, collate all relevant information in a single PQR format highlighting only the applicable differences.
• Note: For products that have single SFG and FG code respectively, the data shall cover the applicable details.
• If a product has single SFG and multiple FG codes, the data review shall cover all elements of multiple FG code details.
• If two or more API vendors are covered in a single item code, include the details explicitly.
• Clubbing of various strength of a particular product into a single PQR for a specific customer/market is also acceptable. e.g Amoxicillin tablets 500 mg and 1000 mg, with two separate FG codes can be clubbed into one PQR.

5.5 Completion of PQR:                                  Responsibility: Quality Assurance

5.5.1 Following criteria shall be considered for the completion of PQRs, as applicable:

5.5.2 As agreed in technical terms of supply with customer or specific requirements, if any.

OR

5.5.3 Within the first 03 months of every new calendar year for the products manufactured in the previous review period.

5.6 Preparation of PQR : Responsibility:  QA Department                                       5.6.1 Product information: A detailed description of the product under review including composition/strength, shelf life, customer/market details to whom, the product was manufactured/ supplied.

5.6.2 Review of previous PQR recommendations, and remarks, if any.

• The PQR report shall include all the actions that have been taken on the recommendations/ CAPA and remarks of the previous PQR.
• A review of adequacy of any other previous corrective actions on product processes or equipment
• A summary or conclusion of the results obtained from the implementation of the measures/CAPA  undertaken during the year shall also be recorded in the PQR.
• Comparison of Previous Year Trend shall be done.

5.7  Summary review: A summary statement for the number of batches, manufacturing date, batch size,  batch release status and period covered for the review. Include all markets/packs/specification/customer within a single scope if formula/ process and specifications are same. This section is also used to note any key observations and any unexpected results.

5.8 Starting & packing material details: APIs and primary packaging components from new / old approved sources and in particular the review of supply chain traceability of active substances review of key quality attributes as per current specification of APIs and primary packaging components (e.g trend analysis data of key API attributes like impurities- known and unknown, assay, LOD etc’ , details of received batches, rejections, deviations005, actions taken ,etc) used for manufacturing of the batches under review. Key quality attributes of excipients, wherever any change in source has been executed, shall also be reviewed.

5.9 Manufacturing and quality summary:

• Minimum, Maximum and average values shall be calculated (wherever required). Average, Minimum and Maximum values shall be calculated using Excel or suitable software (e.g., Minitab). Graphical presentation (I Chart / Line Plot) shall be made with UCL and LCL marked on the graph. Process Capability Analysis of selected CQA (Assay) shall be carried out. The data can refer from continual process verification.
• In case if LCL and UCL are beyond the specification limit, specification limit shall be considered as UCL and LCL.
• I chart shall be prepared for all CPP and CQA which have two sided specification limit.

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1.0 PURPOSE

To provide a procedure for conducting simple and technical training and evaluation of effectiveness for   the employees

2.0 SCOPE:

This procedure is applicable to all employees directly or indirectly involved in manufacturing, processing, packing, holding of materials/products and all supporting functions.

5.0 PROCEDURE:

Preparation of Master Training Requirement Index & Execution of Refresher training:​

5.1 Preparation of Master Training Requirement Index (Role-Task-Curriculum Document

5.1.1 Department Training coordinator/Designee shall prepare the Master Training Requirement index (TRI) for the department (Refer Annexure-2). Assign a version number starting with 00.

5.1.2 The TRI shall be prepared for every task level i.e. execution, supervision, management. E.g. QA- Execution- IPQA where

Execution = Task Level

IPQA = Role​

5.1.3 Include the applicable tasks for identified roles, relevant content i.e. SOPs/WI/modules.

5.1.4 Define the training method and the type of assessment by tick mark in respective columns. Mode of  training can be self-study, classroom training or on the job training. (This is required for referenc purpose only and this document shall be considered as a guideline in terms of training required for SOP change, new employees training and annual refresher training. In case of new employee training mode of training and method of assessment may vary.

5.1.5 Send the Master TRI to HOD for approved.

5.1.6 After approval of the Master TRI, Department Training Coordinator/Designee file the original Copy in the employee training record file

5.1.7 The Master TRI must be reviewed annually by HOD for ensuring adequacy. The TRI can be revised in case of any of the following:

5.1.8 Introduction of a new product / equipment / customer to the facility which may lead to change in facility procedures.

• Introduction of a new product / equipment / customer to the facility which may lead to change in facility procedures.
• Arising out of regulatory inspections and changing regulatory needs.
• Audit observation.
• Introduction of a new SOP / WI.
• Mandatory revision period- once in two years.

5.2 Mapping of Employees against TRI

5.2.1 Based on the job description/Role of employees, department Training Coordinator/designee shall map the employees against the identified Role task document. [Refer Annexure-2]. Write the name of the employees against applicable roles. Identify a subject matter expert for execution of training. Assign a revision number to the mapping document starting with 00

5.2.2 HOD shall approve the Employee Mapping Document

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1.0 PURPOSE

To lay down a procedure for operation, cleaning & calibration of Friability test Apparatus.

2.0 SCOPE:

This procedure is applicable for operation, cleaning & calibration of Friability test apparatus in the Quality control and production department.

5.0 OPERATION

5.1.1     Ensure that instrument is clean and free from dust

5.1.2     Connect mains cable to nearby electric point, then press mains ON on the rear view of the instrument. Display shows series of messages

5.1.3     Press on Mode -1 to select tablet weight entry mode. The display appear as

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1.0 PURPOSE

To lay down a procedure for the operation, cleaning and calibration of Leak Test Apparatus

2.0 SCOPE:

This procedure will be applicable for the operation, cleaning & calibration of Leak Test Apparatus in the quality control and production department.

5.0 PROCEDURE:

5.1 Place the unit on the level surface

5.2 Open the polycarbonate jar and fill the desiccators with sufficient amount of colored water solution,        so that strip or bottles which can be kept in sleeping and can accommodate approximately 4 bottles, or     any other sample which is sealed, can rest under water on resting plate

5.3 Place the tablet Strip/Blister/Bottle pack to be tested into the desiccators and close the jar tightly.

5.4 Switch ON the instrument.

5.5 Ensure that the vent plug is tightly closed and set the timer with INCREAMENT or DECREMENT to    desired timing. One can set the timer from 1 to 99 minutes. For example, Set it up to 5 minutes.

5.6 Apply gentle force from the top so that the vacuum starts developing within 30-45 seconds, which        will be indicated on the vacuum gauge fixed at the top of the unit.

5.7  After getting desired reading on the gauge, close the isolation valve. After the set time on the timer has elapsed, the vacuum pump will be switched OFF automatically.

5.8 The vacuum is maintained inside the jar till manually it has been released.

5.9 The set time and temperature are elapse will be indicated by beep. Remove the vent plug to release the vacuum.

5.10 Open the jar only after confirming that the vacuum gauge shows zero. Remove the tablet strip/Blister pack or bottles.

5.11 Now look for any water seepage in the strip or blister pack, tablet capsule or bottles. It will be wet if there is any leakage.

5.12 If bottles (filled with liquid sample) are to be tested, do not fill any solution into desiccators, test it in a dry condition, if bottles are leaked it will be wet at the cap

5.13 Remove the water from the desiccators

5.14 Cleaning procedure:

5.14.1 Clean the leak test apparatus by using purified water and clean outer and inner surface with the help of the lint free cloth,

5.14.2  Place the apparatus for dryness and change the desiccators water twice in a week or as required.

5.15 Calibration Procedure:

5.15.1 Take a calibrated stop watch and start timer of leak test apparatus and stop watch simultaneously, Note the reading at intervals of 60 seconds, 180 seconds, 300 seconds respectively Acceptance criteria: 10 seconds for each interval

5.15.2 Vacuum gauge calibration done by the external party, Frequency of calibration monthly for timer and  early for  timer, vacuum gauge and vacuum holding capacity.

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1.0 PURPOSE

To lay down a procedure for Operation of Vernier

2.0 SCOPE:

This procedure is applicable to Measure dimension of material used in IPQA

5.0 PROCEDURE:

5.1 Operation

• Ensure that instrument is clean and free from dust.
• Switch on the instrument display screen with help of green button and press yellow button for zero reading.
• Set the sample in the upper side or lower side jaws of the Vernier calipers depending on the   parameter, which is to be measured.
• Set the unit in millimeter / inch with help of grey button.
• Note down the reading display on screen, clean the Vernier caliper through lint free cloth.
• Ensure that Service engineer of equipment manufacturer attend the equipment as per Annual Maintenance contract of the equipment.

5.2 Inform to the equipment manufacturer’s service cell if the service engineer fails to attend the equipment as per contract or if any break down is predicted on equipment due to malfunctioning or erratic behavior of the equipment.

5.3 Vernier Caliper to be calibrated by authorized or trained eng. Personnel or by external party. Get the Service report after each visit of service engineer and check the performance of the equipment  before signing the conformance on service report

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