Category: QA SOP

SOP Title: Management Review Meeting

 

1. Objective:

To review the Quality System periodically to ensure its continuing suitability and effectiveness in satisfying the requirements of GMP and all Regulatory compliance as well as Quality Policy and objectives.

2. Scope:

This procedure is applicable to all elements of Quality Management System.

3. Responsibility:

All Departments Heads and Authorized persons.

4. Accountability:

Director:  All chairs the Management Review Meeting (MRM), review the reports presented in MRM and approve the decisions.

MR/DMR: Organize MRM, prepare and issue MRM agenda, reports, minutes, follow-up action on the decisions taken in MRM.  (MR/DMR) shall chair the meeting in absence of  Director

MR/DMR: Shall maintain MRM records, record of minutes.

 

5. Procedure:

5.2.1	The Management Review Meeting shall be organized once in 3 months or earlier as per requirement.
5.2.2	Director (or a person authorized by him) shall head the meeting.  Meeting to be attended by all HODs.  Other staff members and outside experts (as necessary) can be invited to the management review meeting by MR/DMR.
5.2.3	After deciding a suitable date, time and venue for the Management Review Meeting, MR/DMR shall issue a schedule along with the agenda, in advance, to the members considering the criteria in scope.
5.2.4	Decisions for implementation of preventive and corrective actions shall be taken for points discussed, and the responsibility fixed along with target date.  MR / DMR shall make minutes of the meeting and distribute to all members present.
5.2.5	Persons responsible for implementation of preventive and corrective actions shall ensure their implementation.  MR/DMR shall monitor the implementation of decisions taken in the MRM.
5.2.6	Implementation status of various decisions taken in the previous Management Review Meeting shall be reviewed.
5.2.7	Agenda: Following basic aspects shall be discussed and reviewed during MRM:
5.2.7.1	·         Review of quality policy and objectives. ·         Assessment of Quality System effectiveness and suitability. ·         Review production and maintenance. ·         Deviations. ·         Change control. ·         Incident reports. ·         Rejections. ·         Non conforming products. ·         Calibration & validation status. ·         Customer complaints. ·         Resources review. ·         Potential area for improvements & GMP compliance. ·         Internal and external audit reports. ·         Corrective and preventive actions. ·         Follow up actions on the previous review. ·         Any other quality related subjects. ·         Training.

  

6. Abbreviation:

Abbreviation	Expansion
MRM	Management Review Meeting
GMP	Good Manufacturing Practice
MR	Management Representative
DMR	Deputy Management Representative
SOP	Standard Operating Procedure
No.	Number

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SOP Title: Internal Audit/Self Inspection

1. Objective:

The self inspection procedure defines to determine the effectiveness of the Quality System, adherence to GMP requirements and verify compliance with the adopted Quality System. To detect the non-compliance and to recommend the necessary Corrective Actions for the improvement in the implementation of GMP.

2. Scope:

This procedure is applicable to all operations, procedure, system, material, equipment, facility and utility at the site related to product manufacturing, testing and storage. Self Inspection shall be conducted in Production, QC, Warehouse, Engineering and QA Department to evaluate compliance of GMP norms.

3. Responsibility:

All Departments: To cooperate in self inspection and implement the corrective actions of non compliances observed during inspection.

QA Departments: To ensure that non compliance report is communicated to all respective departments, corrective actions are taken and self inspection records are maintained.

4. Accountability:

Head QA/Plant Head.

5. Procedure:

5.1  Definitions:

Self Inspection: The self-inspection is the inspection carried out by the facility itself to evaluate the manufacturer’s compliance with GMP in all aspects of Production and Quality Control. The self inspection programme is designed to detect any shortcomings in the implementation of GMP and to recommend the necessary corrective actions.

5.2  Procedure:

5.2.1	Composition of Self Inspection Team
5.2.1.1	Self inspection team shall comprise of personnel having adequate qualifications, experience, training and familiar with GMP in the areas of Production, Warehouse, QC, QA and Engineering.
5.2.1.2	Self inspection team shall be selected by management or QA Head who shall specifically conduct self inspection in the relevant areas at the site.
5.2.2	Conduct of Self Inspection
5.2.2.1	Self inspection shall be conducted as per the schedule by the self inspection team in all departments or area of interest viz. Production, QC, Warehouse, Engineering, QA etc in normal operation condition of the facility.
5.2.2.2	Self inspection team shall prepare inspection schedule and send to QA Head which shall be then communicated to all departments.
5.2.2.3	If any change in the schedule is needed, it shall be discussed with the Department Heads/Plant Head and then sent to the self inspection team.
5.2.2.4	Self inspection team shall inspect the facility considering all aspects given in 5.2.4 inspection program.
5.2.2.5	A checklist (Annexure) having specific contents i.e. points to be inspected, observation, corrective action to be taken, responsibility, target date, and compliance shall be followed for self inspection.
5.2.2.6	Observations shall be filled in checklist online or concurrently during inspection for respective check points.
5.2.2.7	Corrective actions for non compliances shall be discussed and recommended in the checklist with responsibility and set target date of implementation.
5.2.2.8	If required, corrective actions shall be accomplished through separate CAPA process within set target date.
5.2.3	Reporting
5.2.3.1	All the observations made during the audit shall be recorded, reviewed as specified in Annexure and then sent to the QA Head and Management.
5.2.3.2	The observation report and corrective action shall be discussed with the Concerned Department and compliance report shall be submitted to the self inspection team within 15 days.
5.2.3.3	If required, self inspection team shall re-inspect the non compliance/ discrepancy to ensure compliance as per recommended corrective actions.
5.2.3.4	Final self inspection report shall be prepared, reviewed and sent to the QA Head and Management.
5.2.3.5	The outcome of the self inspection shall be taken up and discussed in the Management Review Meeting.
5.2.4	Inspection Programme
Written instructions for the self inspection shall have to include below mentioned aspects on the GMP requirements:
5.2.4.1	QMS.
5.2.4.2	Personnel.
5.2.4.3	Maintenance of buildings & equipment.
5.2.4.4	Equipment.
5.2.4.5	Premises including personnel facilities.
5.2.4.6	Storage of Starting Materials & Finished Product.
5.2.4.7	Production & In process Controls.
5.2.4.8	Quality Control System.
5.2.4.9	Documentation.
5.2.4.10	Sanitization & Hygiène.
5.2.4.11	Validation & Revalidation Programmes.
5.2.4.12	Calibration of Instruments or measurement systems.
5.2.4.13	Recall procedures.
5.2.4.14	Complaint management.
5.2.4.15	Labels Control.
5.2.4.16	Results of previous self inspection and any corrective steps taken.
5.2.5	Quality Management System (QMS)
5.2.5.1	Suitability and effectiveness of Quality Systems and its control, responsibility and awareness of the Quality System.  The company Quality Policy, objective and its practical use, quality audits and record for any desired improvement.
5.2.6	Personnel
5.2.6.1	Organization chart including key personnel.
5.2.6.2	Adequate number of personnel in each department.
5.2.6.3	Required qualification and experience to perform their work satisfactorily.
5.2.6.4	Job responsibilities of key personnel and authorized person for finished product release.
5.2.6.5	Medical Examination for safe working.
5.2.6.6	Training of all personnel in the practices of clothing & personal hygiene and written instruction related to personal hygiene.
5.2.6.7	Instructions to prohibit cosmetic items, eating, drinking, chewing, smoking or storage of foods in Production areas.
5.2.7	Building and Premises
5.2.7.1	Design, location, and construction for suitability of carried out operation and to minimize the risk of errors and effective cleaning and maintenance in order to avoid cross contamination.
5.2.7.2	Electrical supply, lighting, Temperature, Humidity and Ventilation that can adversely affect the pharmaceutical products during manufacturing and storage or the accurate functioning of equipment.
5.2.7.3	Provisions made to prevent entry of insects and rodents.
5.2.7.4	Provisions made to restrict entry of unauthorized personnel in Production, Quality Control and Storage areas.
5.2.8	Ancillary Areas
5.2.8.1	Suitability of rest & refreshment sufficient number for workers, separation from other areas, maintained at clean and sanitary condition with washing facilities.
5.2.8.2	The maintenance workshop separated from Production and QC area.
5.2.9	Storage Areas
5.2.9.1	Capacity to allow orderly storage of the various categories of materials.
5.2.9.2	Suitability, separation of sampling area, weighing area, Quarantine area, Raw, Packing, Intermediate Bulk and Finished Materials, storage of Rejected, Recalled or Returned materials or products.
5.2.9.3	Walls and ceilings cracks, crevices and repair.
5.2.9.4	Special storage conditions of Temperature and Relative Humidity.
5.2.9.5	Secure and separate storage area for sensitizing materials.
5.2.9.6	Criteria of controlled drugs to meet with regulations of storage room.
5.2.9.7	Receiving bays and physical (or by other means) separation of different categories of rooms.
5.2.10	Weighing Areas
5.2.10.1	Sufficient space for weighing of Starting Materials for the provision of dust control in the weighing area.
5.2.11	Production Areas
5.2.11.1	Dedicated and self contained facilities provided for producing sensitizing materials.
5.2.11.2	Separate area for non-medicinal products.
5.2.11.3	Production carried out in logical order, uniflow system and required cleanliness levels.
5.2.11.4	Adequate space for working, in-process and storage and logical positioning of equipment and materials.
5.2.11.5	Smoothness of wall, floors and ceiling and free from cracks and open joints.
5.2.11.6	Accessibility to pipe work, light fittings, HVAC and other services from outside the manufacturing areas.
5.2.11.7	Drains for trapped gullies or \shallow design to facilitate cleaning and disinfection.
5.2.11.8	Dispensing area and its operation.
5.2.11.9	Segregation of packaging lines and well lit area.
5.2.11.10	Change room space and changing facilities.
5.2.11.11	Sealing of doors for no loss of air, controlled and maintained Temperature Relative Humidity, number of air changes of circulating air in the section, microbial count of the section, disinfection and its effectiveness in the section requisite level of cleanliness.
5.2.12	Quality Control Area
5.2.12.1	Design of laboratories to suit the operations carried out, suitability of construction materials, and prevention of fumes.
5.2.12.2	Ventilation, working of air handling units, storage space for samples, reference standards & working standards.
5.2.12.3	Separate room for sensitive instruments with Temperature and Humidity control.
5.2.12.4	Separate laboratory for microbiological tests.
5.2.12.5	Air quality of the section, microbial count of the microbiological section, disinfection and its effectiveness in the section.
5.2.12.6	Requisite level of cleanliness, space of working, orderly and logical positioning of equipments and material.
5.2.12.7	Walls, floors and ceilings for cracks and repairs.
5.2.13	Equipment
5.2.13.1	Equipment location, design and construction to suit the operation carried out.
5.2.13.2	The layout and design of the equipments for the purpose of effective cleaning & maintenance.
5.2.13.3	Labeling of pipe lines of equipments to indicate the contents and directions of flow.
5.2.13.4	Equipments shall be checked for serving its intended use, calibration & validation on scheduled basis.
5.2.13.5	Procedure for handling defective equipments in the area.
5.2.13.6	Washing and cleaning equipments system of equipment to ensure no risk of contamination.
5.2.13.7	Sanitization and microbial contamination control of purified water generation and distribution system.
5.2.14	Production and inprocess control
5.2.14.1	All incoming materials and Finished Products for proper “Quarantine” immediately after receipt or processing till the release.
5.2.14.2	All materials and Finished Products for proper storage and in orderly fashion to permit batch segregation and stock rotation by a FIFO rule.
5.2.14.3	Starting materials supplies for Suppliers Name/Manufacturer Name which comply approved vendors list.
5.2.14.4	Vendor evaluation and approval procedure and records.
5.2.14.5	Containers of starting materials for integrity of packaging and seal.
5.2.14.6	Procedure for handling of defective or damage container receipt.
5.2.14.7	The designated Name of the product and the Reference Code.
5.2.14.8	The Batch No. given by the supplier or manufacturer.
5.2.14.9	The appropriate, status of the contents (e.g. Under Quarantine, Under Test, Released or Rejected).
5.2.14.10	The appropriate Expiry Date or a date beyond which re-testing is necessary.
5.2.14.11	Testing and release procedure of starting materials.
5.2.14.12	Dispensing procedure and area.
5.2.14.13	Intermediate & Bulk Products for appropriate storage conditions, in-process critical parameters controlled procedure. Identification of inprocess materials. Any deviations from the procedure and deviation Records.
5.2.15	Quality Control
5.2.15.1	Approved specifications & standard testing procedures, sampling procedures for Raw, Packing & in-process materials, procedure of releasing finished materials.
5.2.15.2	Stability data of the products manufactured (accelerated as well as routine programmed analysis), standard procedure of investigating product related complaints and the procedure for the procuring of reference standards and their records of analysis for the purpose as reference standard are checked.
5.2.15.3	Validity of prepared laboratory reagents and cultures.
5.2.16	Documentation
5.2.16.1	Master Formula Records for each products and batch size manufactured.
5.2.16.2	Batch production records for each product and data recording.
5.2.16.3	Production details, including reference to the main equipment used and batch yield, reference number (or Analytical Report No.) of starting materials used in production, the record of in-process controls being followed and results obtained.
5.2.16.	Details of any recoverable materials, initials of operators and the date of signature on Packaging Records, all Analytical Records related to batch processed the decision on the release or rejection of the batch, with date and signature of the person responsible for the decision.
5.2.16.	SOPs provided to all equipment for operation, cleaning, calibration and maintenance requirements.
5.2.16.	Documents compliance with marketing authorization.
5.2.16.	Control on document and data control and change-over procedures.
5.2.16.	Data entries shall be clear, legible and alteration made to the entry has been signed and dated.
5.2.16.	Data access restriction system for electronic data.
5.2.16.	Specifications for starting material Intermediate/Bulk Product, Finished Products, procedures for receipt and storage, sampling, testing, complaints and recall method.
5.2.17	Sanitation & Hygiene
5.2.17.1	Availability of written procedure for cleaning of the manufacturing area, checked for written sanitation programme.
5.2.17.2	Written instruction for hygiene, when manufacturing and handling the goods and instruction related to health, hygiene practices and clothing or personnel, disposal procedure of waste materials.
5.2.18	Validation Programme
5.2.18.1	Availability of Validation Master Plan, written procedure of validation of equipments (protocol), instruments, cleaning, disinfecting agents and disinfection related to the production process.
5.2.18.2	Reports and records generated related to validation (including URS, DQ, IQ, OQ and PQ) shall be checked.
5.2.19	Calibration Programme
5.2.19.1	Written procedure and record of calibration of balances, laboratory equipments, Pressure Gauges, Temperature recording devices, measuring equipments and hygrometers with status label.
5.2.20	Recalled Products
5.15.1	Recalled Products, including Quantity, Batch No., Type of Complaint, analysis of product and decision; secured area to keep recalled product till the decision. Reconciliation of delivered and recovered quantities.
5.15.2	Record of returned products, analysis of product, decision of release or re-labeling or reprocessing or destroying.
5.2.21	Complaints
5.2.21.1	Written procedure for handling of complaints and responsible person to evaluate the complaint status.
5.2.21.2	Action taken on complaints and recalls made.
5.2.21.3	Complaint trend analysis and efforts to minimize complaints with maximum probability.
5.2.21.4	History of complaints and response to complainant.
5.2.22	Label Control
5.2.22.1	Checked for proper storage and distribution of labels. Control over coded labels and destruction of the same to avoid misuse.
5.2.23	Training
5.2.23.1	Training to all personnel on basic GMP.
5.2.23.2	All new personnel passed through Induction Training of GMP and relevant job related training.
5.2.23.3	Training need identified with training manuals and media.
5.2.23.4	Annual Training Plans, training schedules and training faculty made periodically.
5.2.23.5	Personal record of persons trained with scope of training.
5.2.23.6	Training Assessment Record of each individual.
5.2.23.7	Specific training records on Health & Safety, First Aid and Fire fighting.
5.2.24	Frequency
5.2.24.1	Full self-inspection shall be undertaken at a frequency of not less than once in a six month and in case of product recall or repeated rejections. Additional inspections may be undertaken as required, where specific issues require.

 

6. Abbreviation:

Abbreviation	Expansion
GMP	Good Manufacturing Practice
QMS	Quality Management System
HVAC	Heating Ventilation and Air Condition
FIFO	First In First Out
SOP	Standard Operating Procedure
CAPA	Corrective And Preventive Action
URS	User Requirement Specification
DQ	Design Qualification
IQ	Installation Qualification
OQ	Operational Qualification
PQ	Performance Qualification

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Annual Product Review

1. Objective:

To lay down procedure for performing Annual Product Quality Review to verify the consistency of the process, assess trends, determine need of change in specification, production, manufacturing and/or control procedures and evaluate the need of revalidation.

2. Scope:

This procedure is applicable to all the products manufactured in the plant. The data shall be used for internal review only.

3. Responsibility:

QA Department: Responsible for compilation and collation of APR documents by assuring that all departments supply the required data and timeline for the receipt of data are met.

QC Department: Responsible for supply of respective data to the QA Department.

Production Department: Responsible for supply of respective data to the QA Department.

Warehouse Department: Responsible for supply of respective data to the QA Department.

4. Accountability:

Head QA Department.

5. Procedure:

5.1  Definitions:

Annual Product Review (APR): Annual Product Review is defined as a total study of a product, considering all the critical parameters to review the trend of analytical and process related data, change control, deviation and market complaints.

5.2  Procedure:

5.2.1	Annual Product Review Procedure:  Annual product review shall be product and site specific. APR shall include at least following reviews:
5.2.1.1	Review of all the batches (Bulk, Finished Product) manufactured whether approved or rejected.
5.2.1.2	Review of complaints, recalls, field alerts, changes including effect upon validation status, error and incident reports, returned or salvaged drug products.
5.2.1.3	Raw Material used, if any changes in source or specification.
5.2.1.4	Review of in-process controls and Finished Product results.
5.2.1.5	Batch that fail to meet established specifications.
5.2.1.6	Changes to process and analytical methods.
5.2.1.7	Review of Marketing Authorization (MA) variations.
5.2.1.8	Review of results for stability programme.
5.2.1.9	Review of commitments for technical agreements.
5.2.1.10	Non conformity, incident reports, rejects.
5.2.1.11	Out of Specification (OOS), deviations.
5.2.1.12	List of validated procedures and revalidation data.
5.2.1.13	List of qualified equipment and requalification data.
5.2.1.14	Change control.
5.2.1.15	Responsible official’s notification.
5.2.1.16	Product variables evaluated.
5.2.2	The Trend Analysis Procedure: A review of trend analysis of following parameters shall be performed for finished products:
5.2.2.1	Batch to batch variation in critical parameters for Finished Products.
5.2.2.2	Review of product complaints, recalls, quality related returned goods, reprocess/rework of product and quality attributes.
5.2.2.3	Evaluation of data.
5.2.2.4	Defined alert limits.
5.2.2.5	Documented investigation of significant variations/deviations.
5.2.2.6	Appropriate corrective action plans/follow-up.
5.2.3.	Annual Product Review Report: The APR report shall include at least following points:
5.2.3.1	Documentation of evaluations including summary and conclusions.
5.2.3.2	Reviewed and approved by designated officials.
5.2.3.3	Personnel responsible for data collection, analysis and reporting.
5.2.3.4	Investigations not completed within the APR period shall be included in an addendum when the investigation is finalized.
5.2.3.5	Review and approval within one months of due date, or two months if other levels of review/approval are required due to observed adverse trends.
5.2.4	Evaluation criteria
5.2.4.1	Valid analytical/microbiological test data (including stability test data)
5.2.4.1.1	Review results for deviations from specifications/guidelines/standards.
5.2.4.1.2	Investigation of deviations /OOS.
5.2.4.1.3	Evaluation of microbiological data (where applicable).
5.2.4.1.4	Methods (including in-process, finished product and stability).
5.2.4.1.5	Review of stability data for : a.  Deviations. b. Any trends showing a decrease or an increase in decomposition products. c.  Evaluation of a possible need to institute an internal release specification to assure conformance to specifications throughout the shelf life.
5.2.5	Primary container / closure changes
5.2.5.1	Identified specific changes.
5.2.5.2	Evaluate effect on product quality.
5.2.6	Formula / process changes
5.2.6.1	Change in source or specification of Raw Material.
5.2.6.2	Changes to formula, Raw Materials quantities, process steps, significant equipment, manufacturing conditions, packaging configurations.
5.2.6.3	Validation data and revalidation data.
5.2.6.4	Stability requirements for trend in potency or decomposition changes.
5.2.7	Complaints
5.2.7.1	Trends – quality and other technical.
5.2.7.2	Type and number attributed to product quality.
5.2.8	Recalls / Field Alerts
5.2.8.1	Stock distribution, market withdrawals, field corrections, stock recoveries.
5.2.8.2	Investigation results.
5.2.8.3	Corrective actions.
5.2.8.4	Reasons for recall or field alert.
5.2.9	Product / process problems
5.2.9.1	Manufacturing variance reports.
5.2.9.2	Review of in-process control and Finished Product results.
5.2.9.3	Rejection reports – (OOS results).
5.2.9.4	Reprocessing or reworks.
5.2.9.5	Process changes.
5.2.9.6	Trends in production.
5.2.9.7	Change control.
5.2.10	Packaging
5.2.10.1	Data on packaging from relevant Master Formula Record.
5.2.11	Follow-up: The product quality review follow up should include:
5.2.11.1	Responsibility of relevant personnel.
5.2.11.2	Appropriate corrective action.
5.2.11.3	Results and conclusion documented.
5.2.11.4	Approval by QA and impacted areas.
5.2.11.5	Tracked and periodically reported to management during management review meeting.

 

6. Abbreviation:

Abbreviation	Expansion
APR	Annual Product Review
MA	Marketing Authorization
OOS	Out Of Specification
QAD	Quality Assurance Department
QAP	Quality Assurance Procedure
SOP	Standard Operating Procedure
No.	Number

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

SOP Title: Corrective And Preventive Action

1. Objective:

To lay down the systematic procedure for Effective Corrective and Preventive Actions (CAPA) for all type of discrepancies of GMP compliances or Quality System in the premise.

2. Scope:

This procedure is applicable to non-conformances in manufacturing, storage, handling and testing activities and in the implementation of the Quality Management System.

3. Responsibility:

All Departments Heads: Shall be responsible for identifying, notifying and investigating the cause of non-conformance in their departments, timely identifying and taking corrective and preventive actions.

QA Head: Shall be responsible for ensuring the corrective and preventive measures taken and maintaining their records and shall be responsible for responding to customer complaints.

4. Accountability:

QA and All Departments Heads

5. Procedure:

• Definitions:

Correction: Repair, rework or adjustment and relates to the disposition of an existing discrepancy.

Corrective Action: Action taken to eliminate causes of an existing non-conformance, defect or other undesirable situations to prevent recurrence.

Preventive Action: Action taken to eliminate the cause of the potential non-conformance, defect or other undesirable situations in order to prevent occurrence.

Concerned Department: Department in which discrepancy/non conformance have been detected and the responsibility of identifying root cause, suggesting and implementation of CAPA lies with, as per the scope of this SOP.

• Procedure: 

5.2.1	CAPA (Corrective and Preventive Action)
5.2.1.1	Corrective And Preventive Action shall be required if the investigation of the reason for discrepancy reveals a need for identification of root cause and prevent its recurrence. Additionally where, situations may exist for potential non-conformance, preventive action may become necessary to prevent occurrence.
5.2.1.2	The CAPA shall be initiated on the basis of a review of the information collected / received from one of these documents such as: ·         Review of BMR, BPR and QC records. ·         Internal audit reports. ·         Market complaints. ·         Returned goods. ·         Incident reports. ·         Data and risk analysis related to operations and quality system. ·         Trending / trend evaluation. ·         Annual product review. ·         Non-conformance record and report.
5.2.1.3	The CAPA shall be reviewed by the following personnel: ·         Head QA Department. ·         Head QC Department. ·         Head Production Department. ·         Head Warehouse Department.
5.2.1.4	The responsible committee shall review and investigate the root cause of the problem. If trials or experiments are required, they shall be carried out to aid the investigation.
5.2.2.	Corrective Action
5.2.2.1	The need for any action shall be evaluated relevant to the possible consequences on Product Quality, implementation of Quality Management System, GMP compliances and Regulatory Compliances.
5.2.2.2	Possible actions are determined, written, sent for review to the all responsible concerns and a selected action shall be taken within a defined time-frame. Note:  Corrective action is concerned with finding out why any non-conformity occurred and ensuring that the problem does not recur. It focuses on eliminating the root causes.
5.2.3	Preventive Action
5.2.3.1	Preventive action may be taken from a continuous evaluation or analysis of: ·         Customer complaints. ·         Inspection and test reports. ·         Process monitoring data. ·         Audit observations. ·         Non-conformance records and reports. ·         Service reports. ·         Changes in regulatory requirements. ·         Risk analyses associated with operational and quality system processes. ·         Annual Product Quality Review.
5.2.3.2	Preventive action may also sometimes be consequential to Corrective Action. Note: Preventive action is concerned with predicting the likely occurrence of non-conformity and taking action to prevent it.
5.2.4	CAPA report shall be prepared in a specified format with all the available information.
5.2.5	Based on the review of the data and results of experiments (if any), the GMP Committee shall select the most appropriate corrective action to eliminate the cause of the existing non-conformance and to prevent recurrence.
5.2.6	The GMP Committee shall authorize and initiate corrective and/or preventive actions within a defined timeframe.
5.2.7	The effectiveness of the corrective/preventive action shall be reviewed and if it is satisfactory then the corrected procedure shall be continued as regular practice. If it is not satisfactory, GMP committee shall be informed for further necessary action.
5.2.8	CAPA shall be closed out within 30 days of non-conformance.
5.2.9	CAPA shall be alphanumerically numbered, the first four alphabets “CAPA” (stands for Corrective and Preventive action) followed by a slash, and last two digits of the current year followed by a slash and a three digit serial number starting from 001. e.g. the first CAPA of year 2024 shall be numbered as CAPA/24/001.  The CAPA shall be logged in the ‘CAPA Log’ form.

 

6. Abbreviation:

Abbreviation	Expansion
GMP	Good Manufacturing Practice
CAPA	Corrective And Preventive Action
SOP	Standard Operating Procedure

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Control of Non-Conforming Products

1. Objective:

This procedure deals with the disposal of products that do not conform to specification.

2. Scope:

Applicable to non-conforming, set-up, on-line, off-line of Bulk, Semi-Finished and Finished products and general non-conforming.

3. Responsibility:

Concerned Department: to fill no-conformance form, reporting and participate in investigation, initiating CAPA and implementation.

QA Head: to allocate non-conformance report number, investigation, CAPA, follow up and close out.

4. Accountability:

Head QA/ Head Production

5. Procedure:

• Definitions:
• Non-conformance: A non-conformance is, in essence or something that does not meet specifications.

 

• Procedure:

5.2.1	If a product is found to be failing to meet its specification either during manufacturing or testing it shall be reported to the Head of Quality Assurance Department in “Non-Conformance Report”.
5.2.2	Isolate the product-in-process that is likely to have been affected by the discrepancy noticed.
5.2.3	The non-conforming part of the product or, the batch shall be quarantined and the production shall be temporarily suspended.
5.2.4	Enter the details of non-conformity in the “Non –Conformance Log” and allocate number starting with the letters NCR, followed by a slash and a three digit serial number 001,002,003 etc.
5.2.5	Investigate the non-conformity by reviewing the batch record. He/she shall also review the laboratory investigations related to the non-conforming test results.
5.2.6	Assessment of significance of the non-conformity and suggest remedial measures which may include correcting the non-conformity, allowing the product to proceed or, rejecting the product. The review of the non-conformity and the action to be taken shall be recorded as per SOP.
5.2.7	The remedial action shall be taken and necessary batch records shall be filled. The required Batch Manufacturing Record (BMR) forms shall be obtained from QA after authorization.
5.2.8	The products shall be reprocessed, only after authorization and permitted within the scope of Master formulation.
5.2.9	If the corrective action of the non-conformity indicates the need for preventing recurrence the instruction given in the SOP “Corrective And Preventive Action”.
5.2.10	Trending of non-conformities shall be done on yearly basis. If frequent non-conformity is observed on a particular product, then refer SOP (Corrective And Preventive Action) shall be followed to take necessary preventive action to avoid recurrence.
5.2.11	For General Non-Conformance in plant shall be recorded in prescribe format.
5.2.12	Record the details of general non-conformity in the “Non –Conformance Log” and allocate number starting with the letters GNCR, followed by a slash and a three digit serial number 001,002,003 etc.

 

6. Abbreviation:

Abbreviation	Expansion
QAD	Quality Assurance Department
NCR	Non-Conforming Report
GNCR	General Non-Conforming Report
CAPA	Corrective And Preventive Action

 

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SOP Title: Procedure for Stability Study of Drug Products

 

1. Objective:

To assure that products remain within specification for their shelf life it is necessary to have a systematic stability programme.

2. Scope:

Product stability can be affected by changes to the formulation, method of manufacture, storage conditions and both raw material and contact packaging components.  The procedure is applicable to all new / existing products manufactured.

• Products covered by stability requirements:

New Products

• Products where there is a significant change in:

Formulation

Manufacturing process

Packaging components

• Existing products kept as control samples.

3. Responsibility:

QC Chemist: Responsible for analysis of stability samples and documentation as per SOP.

Head QC Department: Responsible for review of stability study data.

Head QA Department:   Responsible for review, approval and ensure compliance of stability procedure.

4. Accountability:

Head QC and QA Department

5. Procedure:

5.1.  Definitions:

Drug Product: The dosage form in the final immediate packaging intended for marketing.

Impermeable Containers: Containers that provide a permanent barrier to the passage of gases or solvent. e.g. sealed aluminum tubes for semi solids, sealed glass bottles for liquid preparations.

Semi permeable Containers: Containers that allow passage of solvent, usually water while preventing solute loss.  Examples include plastic bags and semi rigid, low density polyethylene pouches and bottles.

New Product: New products are formulations, which does not exist in company .

Existing Product: Existing products are products which are existing in  for a period of more than 2 years/ or for which minimum 10 production batches at manufacturing location has been completed whichever is earlier.

Existing products also include products with change in RM source of active/ excipients, change in process.

Long term stability study: This is a stability study set up to provide data to meet local regulatory requirements. It is to be set up to meet the requirements of stability study protocols as per ICH specifications.

Accelerated stability study: Used where an early indication of stability is required, or where a minor change in formula or packing is made. Also this test may be applicable to batches where the impact of reworking is being assessed.

Intermediate stability study: This method is used for the ongoing samples tested at an interval of 3 months up to 12 months due to specific changes to ensure that product is stable throughout its shelf life.

5.2  Procedure:

5.2.1	General Procedure
5.2.1.1	Incubators shall be maintained at ± 2° C of the specified temperature and ± 5% of the specified RH. This shall be monitored by use of chart recorders/ data loggers or recording in a logbook. The data loggers shall be reviewed fortnightly basis and as and when excursion takes place and any deviations as follows must be assessed for impact, recorded and reported to the Head of QA.   Deviations of > ± 2°C to ± 5°C from the set point for 48 hours. Deviations of > ± 5% RH to ± 10% RH from the set point for 48 hours. Deviations of > ± 5°C from the set point for 24 hours. Deviations of > ± 1 0% RH from the set point for 24 hours.
5.2.1.2	The deviation if any should be discussed with the Head QA and informed to Contract Giver, if required.
5.2.1.3	Additional test stations may be added where required.
5.2.1.4	If the test is being set up to investigate a change to an existing formulation / process / packaging where possible at least one batch of the existing equivalent shall be set on concurrent test as a control sample.
5.2.1.5	A sufficient number of samples should be maintained at each time/temperature point to allow for retesting of any parameter of batch found out of specification.
5.2.1.6	Samples shall be collected from manufacturing area at defined staged as specified in the product BMR/BPR.
5.2.1.7	The batches shall be charged for stability at both accelerated and long term conditions as per the regulatory requirement and technical agreement.
5.2.1.8	Sampling shall be retrieved at defined time points.
5.2.1.9	Analysis of the samples shall be carried out as per the finished product specification and method described in the current testing protocol and / or relevant pharmacopoeia.
5.2.1.10	The Samples shall be withdrawn from the respective chambers at stated interval ± two days of the due days and tested as per specification. The samples shall be stored at 250C ± 20C until the completion of analysis. Remaining samples if any shall be destroyed as per SOP. Deviations must be recorded, reviewed and approved by the Head of QA.
5.2.2	Type of Batches Subjected for Stability Studies
5.2.2.1	New product: For all new products minimum three pilot batches with same batch formula shall be kept for accelerated as well as long term stability testing. First three production batches shall be kept for accelerated as well as long term conditions in the original marketed pack.
5.2.2.2	Change in the Active Raw Material source/Excipients source: Three production batches shall be kept for accelerated as well as long term stability studies and one production batch for change in excipients source.
5.2.2.3	Existing products with New Pack: Minimum one batch shall be kept for stability for both accelerated and long term testing.
5.2.2.4	Existing product: Minimum one batch of existing product annually shall be subjected for routine stability studies (25°C ± 2°C / 60% RH).  To ensure that one batch is picked each year the first batch of the year should be picked for stability study.
5.2.2.5	Pack: All new as well as existing products has to be kept in final pack for stability studies
5.2.3	Storage Conditions
5.2.3.1	General Case (applicable for oral dosage forms – Tablets & Semi-solids – Ointments / Creams preparations packed in impermeable containers). Study Storage Conditions Long term * 25°C ± 2°C / 60% RH ± 5% RH OR 30°C ± 2°C / 65% RH ± 5% RH Intermediate ** 30°C ± 2°C / 65% RH ± 5% RH Accelerated 40°C ± 2°C / 75% RH ± 5% RH   * Storage conditions for long term studies depend on the contract giver requirement of the particular agent.   ** If 30°C ± 2°C / 65% RH ± 5% RH is the long term condition, there is no intermediate condition.
5.2.3.2	If long-term studies are conducted at 25°C ±2°C/60% RH ±5% RH and “significant change” occurs at any time during 6 months testing at the accelerated storage condition, additional testing at the intermediate storage condition should be conducted. In general, “significant change” for a drug product is defined as: ·         A 5% change in assay from its initial value; or failure to meet the acceptance criteria for potency when using biological or immunological procedures. ·         Any degradation product’s exceeding its acceptance criterion. ·         Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g., color, phase separation, re-suspendibility, caking, hardness, dose delivery per actuation); however, some changes in physical attributes (e.g. melting of creams) may be expected under accelerated conditions; and, as appropriate for the dosage form. ·         Failure to meet the acceptance criterion for pH. ·         Failure to meet the acceptance criteria for dissolution testing at 12 dosage unit.
5.2.4	Testing Frequency
5.2.4.1	New Products : Study   Accelerated 0 1 2 3 6 – – – – – – – Long term 0 1 2 3 6 9 12 18 24 36 48 60*   * or up to after one month of expiry of product
5.2.4.2	Existing Products: For change in raw material / excipients source change in manufacturing location : Study   Accelerated 0 3 6 – – – – – – – Long term 0 3 6 9 12 18 24 36 48 60#   # For existing products long term study shall be performed above six months period of the shelf life.
5.2.5	Stability Protocol
5.2.5.1	Stability protocol shall comprise ·            Objective ·            Scope ·            Responsibility ·            Procedure ·            Testing frequency ·            Testing parameter ·            Sample quantity ·            Test specification and method of analysis ·            Acceptance criteria ·            Report
5.2.6	Analytical Testing Method
5.2.6.1	In case of contract manufacturing products stability samples shall be analyzed by Contract Giver reference, there given finished product specification and validated analytical methods and should be stability indicating. The test and methods of analysis applicable along with reference to the specification number shall be indicated in the analytical section of the protocol. If any additional tests are required to be performed they shall be indicated in the analytical section of the protocol.
5.2.7	Control of Studies
5.2.7.1	A stability study may comprise several related batches, e.g. the first three production batches, current and modified pack/formulation etc.
5.2.7.2	For each stability study a ‘Stability Study Set-up Record’ is to be prepared and should include the following information: ·         Purpose ·         Batch nos. ·         Date of manufacture. ·         Date of primary packaging. ·         Date placed on stability ·         The number of units set on storage as determined using the table on the form. ·         The test methods are to be specified by reference to the approved procedure
5.2.7.3	The number of units set on storage shall be determined using the table on the form. Sample removal at each time point and subsequent stock levels must also be recorded on the Stability Stock Record Sheet.
5.2.7.4	When the stability test is set up a Stability Result Record is to be initiated for each batch/pack forming part of the stability study.
5.2.7.5	Stability samples are to be clearly labeled with: ·         Stability Study Number or Reference Number ·         Batch Number ·         Storage Conditions ·         Testing frequency due and placed in the relevant incubator.
5.2.7.6	Regulatory approval shall be taken for the products which are under regulatory submission.
5.2.7.7	The Set up and Results Records shall be passed to the responsible QC chemist for controlling stability tests. From these documents an annual test plan is drawn up. This plan is kept in the QC laboratory and is used to check the completion of testing. According to annual test plan a monthly test schedule shall be specified format.
5.2.7.8	The chemist responsible for stability testing shall carry out or arrange the testing of the samples within 30 days of the due date. The analytical data, calculations and results shall be reported on the stability analysis record. Supporting data shall also be attached.
5.2.7.9	The analysis record with associated print outs etc shall be checked by the QC Head or Senior Chemist and returned to the chemist responsible for stability studies.
5.2.7.10	The analyst/chemist shall records the results on the Stability Results Record, which shall be checked by the QC Head or Senior Chemist and then forwarded to QA Department for review. This is to be done at each test point.
5.2.7.11	The stability analysis records with associated data shall be filed with specific document number by the person designated for Stability Studies.
5.2.8	Data Evaluation and Reporting
5.2.8.1	The Head of QA shall review the stability results record at each test point. If the data shows little variation or degradation the results are accepted. If there is evidence of a trend statistical extrapolation is to be used particularly where accelerated testing is employed. The results record is returned to the analyst.
5.2.8.2	For long term monitoring and where applicable accelerated testing, at each test Point, a report shall be submitted to the Head QA for evaluation and review of proposed shelf life. The report shall include: ·         General product information. ·         Specification. ·         Test methods. ·         Study design and conditions. ·         Stability data and analysis of (including trend analysis). ·         Conclusions.
5.2.8.3	For long term monitoring where a result outside the existing or proposed specification is found, an OOS report shall be initiated as per SOP.
5.2.8.4	If a failure is confirmed, additional batches or increased test frequency shall be implemented.

 

6. Abbreviations:

Abbreviation	Expansion
RM	Raw Material
ICH	International Conference on Harmonization
FIFO	First In First Out
RH	Relative Humidity
OOS	Out of Specification
AWR	Analytical Work Record
BMR	Batch Manufacturing Record
BPR	Batch Packing Record
0C	Degree Centigrade

 

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SOP Title: Release of finished products

1. Objective:

To lay down procedure for release of finished products for sale or distribution.

2. Scope:

This procedure is applicable for release of finished products for sale or distribution of all formulations manufactured at the site.

3. Responsibility:

Production department: To complete and review BMR, BPR, attached respective documents and follow the procedure.

QA department: To review BMR, BPR, analytical test report, inspection of finally packed batch, daily production report and release of batch for sale or distribution as per procedure.

QC department: Analysis of bulk/semi finished and finished product and submit the report to QA department as per procedure.

4. Accountability:

Head QA Production/QC department

5. Procedure:

• Definitions:
• QA Associate: Executive, officer of quality assurance department or the person trained to perform job as per this SOP.
• Production Associate: Executive, officer of production department or the person trained to perform job as per this SOP.
• QC Associate: Executive officer of quality control department or the person trained to perform as per this SOP.
• Finished product: A finished dosage form, for example a tablet, capsule or solution that contains an active pharmaceutical ingredient, generally but not necessarily, in association with inactive ingredients in a final marketed pack.
• Procedure:

5.2.1	The finished goods which are finally packed and supported with documents BMR/BPR, batch analytical record (BAR) of the particular batch shall be submitted to Quality Assurance department as soon as completed.
5.2.2	Before sending BMR, BPR to QA department production head/designee shall check and review the batch documents as per Annexure.
5.2.3	Before sending Analytical Test Report to QA department, it shall be checked and reviewed as per specification to ensure the results are within specifications and satisfactory.
5.2.4	After receiving the particular BMR, BPR, analytical test report etc from production and QC departments, all the batch documents shall be comprehensively reviewed.
5.2.5	Final or terminal inspection of finished products shall be carried out as per procedure given in step 5.5
5.3	Review of Batch  Manufacturing Record (BMR) and Batch Packing Record (BPR)
Following points shall be checked for BMR and BPR
5.3.1	The product name with dosage, batch number, batch size, date of manufacture and expiry date mentioned on the BMR & BPR is correct.
5.3.2	The Raw material/ Packing materials used for the manufacturing / Packing are in the list of approved vendors. The raw materials and packing materials used are tested and approved by Quality control department.
5.3.3	Before dispensing, line clearance of dispensing booth is carried out.
5.3.4	Active Pharmaceutical Ingredients and excipients are issued and checked by authorized personnel as per the BMR & BPR and if there is any potency based calculation it is counter checked by the QA manager.
5.3.5	Before initiating manufacturing, line clearance is taken for area and equipment from QA wherever necessary. The environmental conditions are maintained during the manufacturing process and packing (i.e. RH, Temperature).
5.3.6	Manufacturing operations are followed as per the instructions given in master formulation record. The manufacturing operations are counter checked by competent technical manufacturing staff.  (Wherever applicable).
5.3.7	The critical process parameters are well within the limits and critical in-process controls are done as per the frequency mentioned in the BMR & BPR and are well within the limits and the in-process quality control analytical reports are enclosed Batch card.
5.3.8	If there is any process deviation, it is recorded and it is investigated and approved by Quality Assurance department.
5.3.9	The correct packing components are used as per packing material requisition slip which is authorized by the department head.
5.3.10	The line clearance is carried out during packing operation as per the BPR.
5.3.11	Over printing/coding details are correct and appropriate as per the BPR.
5.3.12	Blister packing in-process checks are performed as per the frequency mentioned in the BPR and counter checked by competent technical staff.
5.3.13	The reconciliation records of packing materials are well within the limits.
5.3.14	The specimen of coded /printed aluminium foil/ blisters, cartons or product label and shipper label attached to BPR which are duly signed by the production personnel and counter checked by Quality Assurance personnel.
5.3.15	The batch is manufactured and packed under the supervision of a competent technical staff.
5.3.16	All these above points shall be ensured and filled as per Annexure.
5.4	Review Batch Analytical Record (BAR)
Following points shall be checked for BAR
5.4.1	Drug products at all stages are analysed as per the established specifications and are well within the specified limits and analysis shall be carried out by certified analyst.
5.4.2	The raw data/ protocols/ HPLC & GC chromatograms, UV/ IR spectrum are enclosed with the analytical report and counter checked by competent technical staff.
5.4.3	Working standard is standardized and is within validity period.
5.4.4	The certificate of analysis is prepared by analyst and checked by Quality Control head.
5.4.5	The microbiological analysis of finished products (Wherever applicable) shall be carried out as per the established specifications and the results are well within the limits.
5.5	Final  or terminal inspection of finished products
5.5.1	When the finished products are finally packed, the daily production report shall be generated in triplicate which is forwarded to Quality Assurance department.
5.5.2	On receipt of the daily production report, In-process Quality Assurance (IPQA) personnel or QA designee shall  contact the concern chemist of production department & check the packed products
5.5.3	It shall be ensured that the batch manufacturing record is complete and signed before inspecting the packed finished products
5.5.4	The finished product shall be transferred to Finished Goods Store only after release for sale or distribution
5.5.5	Quantity specified on the daily production report shall be checked and verified physically same as mentioned on the daily production report. Following method shall be followed for inspection of finished products- 10 % of the batch size (total number of boxes/shippers) with defined number and three additional boxes/shippers shall be inspected for final inspection. The boxes/shipper to be inspected shall be identified and 100 percent units shall be inspected from these selected boxes. Example: If there the total lot or batch size is 90 shipper/boxes, then the total number of shipper to be inspected shall be 9 + 3 (10 % + 3 additional boxes).To ensure uniform sampling of batch every 9th number box shall be identified for inspection along with additional boxes.
5.5.6	The selected boxes/shippers shall be opened and checked for the following: ·         Product name ·         Batch no. ·         Date of manufacturing ·         Date of expiry ·         MRP, if any ·         Special marking, if any ·         Quantity of units per box/shipper ·         Unit or blister/strip per carton/units. ·         Physical checks ·         Any discrepancy/defects Subsequently the cartons shall be replaced in their respective shipper after inspection. If any discrepancy is not found, the shipper shall be immediately packed.
5.5.7	If any discrepancy is found, it shall be noted down, informed to production head, QA head and necessary correction shall be taken.
5.5.8	Finally all the packed boxes/shipper shall be checked for outer label, adhesive tape, physical status, any defects and strapping wherever required.
5.5.9	If the checked finished goods comply with the stated requirement of the batch manufacturing record and daily production report,  A final inspection report of finished product shall be prepared as per Annexure and submitted to QA head/delegate.
5.6	Release of finished products
5.6.1	The inspected finished goods shall be kept in Finished Goods Quarantine and labelled as ‘Quarantine’ after final inspection till QA release.
5.6.2	When BMR, BPR, batch analytical records, Daily production report and final inspection of finished pack product report are found satisfactory, then the finished product shall be released by Authorized person (Head QA or his authorized delegate) for distribution/sale and the respective documents shall be signed.
5.6.3	Once finished product is released for sale/distribution, the status label on the CBs/shippers shall be changed as “QA RELEASE” and the goods shall be transferred to Finished Goods Store with complete batch record.
5.6.4	The released finished product entry shall be made in Annexure ‘Finished Product Release Register’
5.6.5	The release shall be conveyed to Production head or his authorized designee and commercial store in-charge through preparing a report in “Daily Production Report” from specified booklet filling all details under “QC detail “column. Copies of the report shall be kept as following: Sr. No. Copy No. Department to be Issued 1 First (original) Purchase and account 2 Second (pink) BMR 3 Third Production

 

6. Abbreviation:

Abbreviation:	Expansion
BMR	Batch Manufacturing Records
BPR	Batch Packing Records
SOP	Standard Operating Procedure
CB	Corrugated Box
i.e.	Id est (that is)
RH	Relative Humidity

 

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SOP Title: Sampling of In-process and Finished Products

1. Objective:

To lay down procedure for sampling of in-process and Finished Products in routine manufacturing practice.

2. Scope:

This procedure is applicable to all products manufactured at the site.

3. Responsibility:

Production Department: To intimate QA person for sampling at defined stage of manufacturing and follow the procedure.

QC Department: To receive, log and analyse the sample as per specified procedure and prepare test report.

QA Department: To sample the in-process and Finished Products per instructions at defined stages of manufacturing.

4. Accountability:

Head QA Department.

5. Procedure:

5.1  Definitions:

Inprocess material: In-process material means any material fabricated, manufactured or blended that is produced for, and used in, the preparation of the finished product.

Finished product: A finished dosage form, for example a tablet, capsule or solution that contains an active pharmaceutical ingredient, generally but not necessarily, in association with inactive ingredients in a final marketed pack.

QA Associate: Officer/Executive or any personnel of Quality Assurance Department trained to perform duties as per this SOP.

Production Associate: Officer/Executive or any personnel of Production Department trained to perform duties as per this SOP.

QA Associate: Officer/Executive or any personnel of Quality Control Department trained to perform duties as per this SOP.

5.2  Procedure:

5.2.1	Sampling at the Granulation stage
5.2.1.1	Generally sampling of the blend (and as per instruction given in BMR/SPC/STP) shall be done at granulation stage.
5.2.1.2	After completion of the blending process, Production person shall refer the sampling instruction in BMR and intimate QA person for sampling of the blend (lubricated granules) by filling Intimation Slip.
5.2.1.3	QA person shall refer the BMR instruction and verify the record and Intimation Slip.
5.2.1.4	It shall be ensured that cleaned sampling tools (spatula, thief or rod etc), clean sampling bags are available for sampling of blend.
5.2.1.5	It shall be ensured that lubricated blend has been completely unloaded from the blender into cleaned double polythene lined HDPE drums. All the containers shall be inspected physically before sampling.
5.2.1.6	Generally a composite 10 gram sample (and/or as per instruction given in BMR/SPC/STP) shall be taken from all containers of unloaded granules (blend) by using appropriate tool.
5.2.1.7	The sample along with Intimation Slip shall be sent to the QC Department for analysis.
5.2.1.8	The blend shall be kept properly in the Quarantine till test report come.
5.2.2	Sampling at the compression stage
5.2.2.1	After completion of the compression process, Production person shall refer the sampling instruction in BMR and intimate QA person for sampling of the compressed tablets by filling Intimation Slip.
5.2.2.2	QA person shall refer the BMR instruction and verify the record and Intimation Slip.
5.2.2.3	It shall be ensured that the batch has been completely compressed and the tablets are kept in cleaned double polythene lined HDPE drums. All the containers shall be inspected physically before sampling.
5.2.2.4	QA person shall take sample from the container which contains tablets representing whole batch taken by the operator/chemist at every half an hour interval for weight variation checks within the compression cubicle.
5.2.2.5	QA person shall mix the tablets manually then take the tablets quantity 60 tablets (and/or as per instruction given in BMR/SPC/STP) and enclose in the sample poly bag.
5.2.2.6	The sample along with Intimation Slip shall be sent to the QC Department for analysis.
5.2.2.7	The compressed tablets shall be kept properly in Quarantine till test report come.
5.2.3	Sampling at the coating stage
5.2.3.1	After completion of the coating process, Production person shall refer the sampling instruction in BMR and intimate QA person for sampling of the coated tablet by filling Intimation Slip.
5.2.3.2	QA person shall refer the BMR instruction and verify the record and Intimation Slip.
5.2.3.3	It shall be ensured that the coating process is completed and the coated tablets are kept in cleaned double polythene lined HDPE drums. All the containers shall be inspected physically before sampling.
5.2.3.4	QA person shall take composite 60 tablets (and/or as per instruction given in BMR/SPC/STP) sample into clean sample poly bag from each drum and label the sample poly bag.
5.2.3.5	The sample along with Intimation Slip shall be sent to the QC Department for analysis.
5.2.3.6	The coated tablets shall be kept properly in the Quarantine till test report come.
5.2.4	Sampling at capsule filling stage
5.2.4.1	After completion of the capsule filling process, Production person shall refer the sampling instruction in BMR and intimate QA person for sampling of the filled capsule by filling Intimation Slip.
5.2.4.2	QA person shall refer the BMR instruction and verify the record and Intimation Slip.
5.2.4.3	It shall be ensured that the capsule filling process is completed and the filled capsules are kept in cleaned double polythene lined HDPE drums. All the containers shall be inspected physically before sampling.
5.2.4.4	QA person shall take composite 60 capsules (and/or as per instruction given in BMR/SPC/STP) sample into clean sample poly bag from each drum and label the sample poly bag.
5.2.4.5	The sample along with Intimation Slip shall be sent to the QC Department for analysis.
5.2.4.6	The filled capsule shall be kept properly in the Quarantine till test report come.
5.2.5	Sampling of finished products
5.2.5.1	After completion of the packing operations, Production person shall refer the sampling instruction in BPR and intimate QA person for sampling of the finished product by filling Intimation Slip.
5.2.5.2	QA person shall refer the BPR instruction and verify the record and Intimation Slip.
5.2.5.3	It shall be ensured that the packing operation is completed and BPR is filled properly.
5.2.5.4	QA person shall take sample from the container which contains strips/blisters representing whole batch taken by the chemist at one hour interval in the packing line.
5.2.5.5	QA person shall take a composite of 60 tablets/capsules (and/or as per instruction given in BMR/SPC/STP) as such packed in the strip/blister for chemical analysis.
5.2.5.6	For retention/control sample, at least twice of complete analysis sample shall be taken from three time point sampling stage (initial, middle and end) of packing operation and the sample shall be taken as such in the carton.
5.2.5.7	The Finished Product sample along with Intimation Slip shall be sent to the QC Department for analysis.
5.2.5.8	The Finished Product shall be kept properly in Quarantine till test report come.
5.2.6	Labelling of samples
5.2.6.1	The sample shall be labelled properly at least with the contents like Product Name, Batch No., Batch Size, Mfg. Date, Exp. Date, Stage, and Sample Quantity.
5.2.6.2	Label shall be duly verified by QA person with respect to correct information clearly written on it.
5.2.6.3	The sample shall be enclosed properly to avoid any chances of contamination and mix up.
5.2.6.4	Samples shall be sent to the QC Department without any delay and logged in specified register.

 

6. Abbreviation:

SOP	Standard Operating Procedure
BMR	Batch Manufacturing Record
BPR	Batch Packing Record
SPC	Specification
STP	Standard Test Procedure
HDPE	High Density Polyethylene

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Product Reprocessing

1. Objective:

This procedure demonstrates the details of reprocessing/reworking of manufactured /packed batches of products that conform to the required quality.

2. Scope:

Applicable to only those products, where reprocessing/packaging rework is required.

3. Responsibility:

Head Logistics: Responsible for receipt and transfer of goods to warehouse

Head Warehouse: Responsible to transfer of goods to production department with transfer note for reprocessing.

Head Production: Responsible for reprocessing/reworking

Head QA: To approve reprocessing/rework

4. Accountability:

Head QA / Head Production

5. Procedure:

• Definitions:
• Rework/Reprocessing: Rework / reprocessing is the execution of an operation in existing batch due to minor packaging variation.
• QA Associate: Officer, Executive of Quality Assurance Department or any personnel trained to perform duties as per this SOP.
• Production Associate: Officer, Executive of Production Department or any personnel trained to perform duties as per this SOP.
• QC Associate: Analyst, Supervisor, Executive of Quality Control Department or any personnel trained to perform duties as per this SOP.
• Warehouse Associate: Officer, Executive of Warehouse Department or any personnel trained to perform duties as per this SOP.
• Procedure:

5.2.1	Rework or Reprocessing of the product may be carried out for various reasons such as wrong Batch No. & Expiry Date, Improper or incorrect labelling, Defects in packaging components, additional labelling requirement.
5.2.2	The batches for rework will be returned to Production Department by the Warehouse Department along with Transfer Note.
5.2.3	The batch will be shifted to the manufacturing area under appropriate controlled conditions.
5.2.4	Prior to start of the rework to ensure that working conditions are maintained and approval from contract giver is obtained for rework.
5.2.5	Hand over the old BPR, along with the new BPR to the Production Head.
5.2.6	QA shall draw bulk sample and send request to QC Department for analysis as per  “Test Request for Bulk Product”.
5.2.7	The QC Department shall examine the Bulk with relevant product specification.
5.2.8	After completion of analysis and approval by QC Department the rework will be carried out as per relevant BPR.
5.2.9	On completion of the rework a Finished Product sample shall be drawn for analysis.
5.2.10	The Batch Packaging Record shall be clearly marked as rework / reprocessing along with the comments for reason of rework.
5.2.11	The rework Batch Packaging Record and initial Batch Packaging Record shall be placed together.
5.2.12	Reworked /reprocessed batches shall be kept for stability study if requires.
5.2.13	Finally reworked batch shall be released by the QA Department.

 

6. Abbreviation:

Abbreviation	Expansion
BPR	Batch Packing Records
QA	Quality Assurance
QC	Quality Control
No.	Number

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Product Recovery

1. Objective:

This procedure provides the details for the recovery of earlier batches of products that conform to the required quality by incorporation in subsequent batch.

2. Scope:

Applicable to only those products where permitted in Master Formulation.

3. Responsibility:

Production Head: To request test of additional recovery residue, addition of recovery, reconciliation and record the recovery in BMR/BPR.

QA Head: To approve recovery.

QC Head: To carry the relevant test and release the recovery residue.

4. Accountability:

Head QA/ Head Production

5. Procedure:

• Definitions:
• Recovery: Recovery is the introduction of all or part of previous batches of the required quality into a new batch at a defined stage of manufacture.
• Residue: Residues are the rejections collected at various stages of processing of a product.
• QA Associate: Officer, Executive of Quality Assurance Department or any personnel trained to perform duties as per this SOP.
• Production Associate: Officer, Supervisor, Executive of Production Department or any personnel trained to perform duties as per this SOP.
• QC Associate: Analyst, Supervisor, Executive of Quality Control Department or any personnel trained to perform duties as per this SOP.
• Procedure:

5.2.1	During the processing of a batch rejections may arise for various reasons such as chipping of tablets, improper locking of capsules, cut pockets in strip pack, less filled jars etc. The quantity of recoverable residue generated at various stages shall be recorded in the process history sheet of the BMR/BPR.
5.2.2	The quantity of residue to be utilized in a subsequent batch shall be entered in the second part of BMR/BPR Register.
	Note: a)   The addition of residues to the subsequent batch shall be done not later than three months from the date of manufacture of the earliest batch. b)        The quantity of the residue from earlier batch in the subsequent batch shall not exceed 10% of the next batch or as permitted according to Master Formulation. c)         The residues generated from recovery added batches shall not be added to the subsequent batches. d)     The expiry date of the batch shall not be changed after addition of   recovery.
5.3	Tablets (To be added to the subsequent batches):
5.3.1	A “Test Request Form” shall be sent to the QC Department requesting them to examine, identify and approve the addition of recovery to the subsequent batch. The batch number, quantity of the recovery, Mfg.  Date and Exp. Date shall be recorded on the “Test Request Form”.
5.3.2	Examine the recovery with relevant product specification for critical test of assay, identification or any impurity profile (if any).
5.3.3	After obtaining QC Approval, the recovery shall be processed as per steps mentioned in the relevant Batch Manufacturing Record and added at Granulation Stage.
5.4	Capsules (to be added to the subsequent batches):
5.4.1	Refer the points 5.3.1 and 5.3.2
5.4.2	After obtaining QC Approval, the recovery shall be processed as per steps mentioned in the BMR and added at Blending Stage.
5.4.3	The batches containing recoveries shall be subjected to Stability Studies.
5.4.4	The batches containing recoveries shall be mentioned specifically in APR.
5.4.5	The batches containing recoveries shall be subjected to additional testing, if required before release.
5.4.6	The process of adding recovery shall be validated, a Process Validation Protocol shall be generated simultaneously.
5.4.7	QA Department shall fill the Format “Test Request For Stability” the batch of the product in which recovery added.

 

6. Abbreviation:

Abbreviation:	Expansion
BMR	Batch Manufacturing Records
BPR	Batch Packing Records
APR	Annual Product Review

 

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.