Product Quality Review, Purpose :

Product Quality Review, The objective of carrying out Product Quality Review (APR) is to establish that the product is manufactured as per approved procedures and the trends of results of critical quality attributes are well within acceptable limits.

PQR will also address the review of raw & primary packaging materials used, process validation & revalidation, analytical method validation, cleaning validation & revalidation, stability testing reports, yields, change controls, out of specification results, deviations, failure investigations, CAPAs, rework & reprocessing, market complaints report, trend analysis data, vendor addition/deletion, supplier performance review, retention sample review, batch documentation, drug authority (legal) notices, equipment/utility required, environmental monitoring, etc. done during the review period.

Scope :

[][]This procedure applies to all product manufactured XX Pharmaceuticals Limited (both General & Sterile Block) and is carried out for products manufactured for during calendar year e.g., January to December.

Definition/Abbreviation:

[][]SOP : Standard Operating Procedure
[][]CAPA : Corrective and Preventive Action
[][]PQR : Product Quality Review

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, QA

[][]Responsible to carry out the periodic review of particular product and prepare a report.

Asst. Manager, QA

[][]Responsible to ensure that a formal review of Drug Product / API is undertaken and reported periodically and demonstrate control of the process and effectiveness of any corrective actions required.

Head of Concern Department

[][]To ensure implementation of suggested CAPA.

Head of Quality Assurance

[][]Approval the SOP

Procedure:

Selection of batches

[][]Select the all batches of a product manufactured in the review period.
[][]The batches which are reworked / reprocessed are used must be included in product quality review.
[][]Frequency
[][]Product quality reviews of Drug Products shall be conducted and documented annually.

Schedules for Review

[][]A suitable schedule has to be drawn up by assigning products to person so that review of all products is completed for the stipulated period. The compilation data should preferably to be completed within one month after receiving all data of last batch of evaluation period.
[][]Review of Batch Manufacturing and Packing Records
[][]Review the batch production records for the following particulars:
[][]Review the batch production and packing records of all the batches selected for PQR and record the details like batch numbers, batch production record number and final yields etc.
[][]Review any batch rejections and reprocessing or reworking done during the review period. In such cases highlight the reason, and record the corrective action taken.
[][]Review the process deviation reports are duly adequately investigated, completed and approved.
[][]Record yields of all isolated stages of the product and the yield ranges for all the batches reviewed. Highlight reasons for out of specification yields if any as well as extremes, which are well within limits.
[][]Compile the yield data and prepare the trend charts. Analyze the trend charts, identify and investigate any discernible trends, which are within acceptable upper and lower specifications. Attach the trend charts as in graphical presentation a part of PQR report.
[][]Review in-process control data for key process steps carried out during the manufacture and highlight critical deficiencies.

Review of Environmental Condition

[][]Record the observation for Assurance with environmental condition of manufacturing areas. Critical deviation, if any must be examined in detail to assure how the deviations were taken care of and record observations.

Review of Analytical Reports

[][]For all the batches under product quality review verify all the analytical reports for the following:
[][]Validity of analytical specifications and methods for the products, raw materials and primary packaging materials employed.
[][]Any out of specification analysis and re-testing carried out with explanations for the same.
[][]Review the analytical results for critical parameters like assay, dissolution, loss on drying/water content, related substances etc.
[][]Review any specification changes and also any new analytical instruments added for the testing of the product and raw/primary packaging materials involved in manufacturing the batches for PQR.
[][]Review the calibration /qualification status of instruments used in the analysis of the batches under review.
[][]Review the retention samples randomly for deterioration.
[][]Compile all the critical analytical data (e.g. assay, dissolution) in a graphical presentation as a part of PQR.

Review of Stability Study Program and Data

[][]Stability review data generated for the product during the review period must be verified and critical observations, if any, highlighted with corrective action recommended. On need basis, the review should be extended to previous years as well.

[][]Any recommendations for changes in shelf life must be examined. Record any changes to stability testing protocol and methods during the review period. Any stability failure during the period must be reviewed in detail.

Review of Market Complaints, Returns and Recalls

[][]Market complaints received during the 12 months period of review should be verified for appropriate closure. The corrective & preventive actions taken subsequent to the complaint investigations should be reviewed in detail. Any recall during the period also must be reviewed in detail.

Review of Regulatory Actions

[][]Any regulatory queries with respect to the product under review must be examined in detail. The corrective actions taken and company response to the queries must be examined.

Review of Validation Status

[][]Any validation or revalidation exercises carried out for the process or equipment related to the product under review must be reviewed and findings to be highlighted. Corrective & preventive actions (CAPA) taken, if any, must also be reviewed. Analytical method validation and cleaning validation/revalidation performed during review period must be recorded.

Review of Change Control Documents

[][]Review all the changes made to the system related to the product under review and report the impact on the regulatory and or customer requirements.
[][]Review of Non-conformity and CAPAs
[][]Review the non-conformities and corrective & preventive actions (CAPA), if any, during the internal quality audits.

Review of Critical Equipment & Utility performance

[][]Performance of the critical equipment & utilities used for manufacturing, packaging & testing of the product during the period to be reviewed.

Review of Raw & Primary Packaging Materials

[][]All the batches/ lots of raw materials (active & excipients) and primary packaging materials used for manufacturing & packing of product during the review period to be reviewed.

Review of Vendor Addition/Deletion and Supplier Performance Report

[][]Vendor addition/deletion and supplier performance reports of raw materials (active & excipients) and primary packaging materials to be reviewed.

Review of Retain Sample

[][]Retain samples (retention samples) of all the batches of the finished products to be reviewed every year by visual examination for any evidence of deterioration and observation shall be documented in respective retention sample register. A summary report to be prepared based on the visual inspection. The same report will go to the PQR.

Review of previous APR Report

[][]Observations/recommendations of the previous Product Quality Review report to be reviewed.

Review of Environmental Monitoring:

[][]Annual review of environmental monitoring summary report to be reviewed and a copy of the summary to be affixed as an annexure with the PQR. Any result exceeds the action limit and the actions against the exceed results to be recorded in the review report.

Report:

[][]An overall summary of the annual product review report shall be prepared by the person conducting the review.

[][]Any other observations or improvements or recommendations for improvements if any shall be given in the report.
[][]The report should include trend charts for all relevant data supporting the review.
[][]The report should include a summary and recommendations for actions to be initiated for any deficiencies.
[][]Document Numbering:
[][]Annual Product Review report shall be numbered as follows:
=>PQR/XX/YYY
=>Where ‘PQR’ represents for Product Quality Review.
=>‘XX’ represents the last two digits of the year (e.g. XX for 20XX).
=>“YYY’ represents for serial number of the PQR report.

Annexure: Product Quality Review

N/A

Disposal of Materials, Purpose:

Disposal of Materials, To establish a system for the authorization and disposal of rejected/expired materials and products. This covers the various steps that are required to be followed for destruction of rejected/expired materials and products in a safe and legal way with proper authorization.

Disposal of Materials, Scope:

This SOP applies to quality related non-complies or undesirable materials in XX Pharmaceuticals Ltd. (Both General & Cephalosporin Block) from any one of the following interface steps.

Rejected Raw & Packaging Materials

[][]Expired Retention Samples
[][]Manufacturing waste and in process waste (Both raw & packaging materials)
[][]Rejected Intermediate/Bulk Products/Batch Tails/Finished Products
[][]Trial sample for product development
[][]Laboratory waste (Reagent, analysis sample etc.)

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]QC – Quality Control
[][]PD – Product Development
[][]BMR – Batch Manufacturing Record
[][]Waste – Materials if they no longer are fit for their originally intended purpose.
[][]Non-Waste – Materials that can be recovered and reused in a process.
[][]Hazardous Waste – Waste is considered to be hazardous if it exhibits any of a number of properties related to flammability, explosivity, water/air reactivity, corrosivity, oxidizing potential, acute or chronic toxicity, ecotoxicity or infection.
[][]Non- Hazardous Waste – Waste is considered to be non-hazardous if it DOES NOT exhibit any of the properties related to flammability, explosivity, water/air reactivity, corrosivity, oxidizing potential, acute or chronic toxicity, ecotoxicity or infection.

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Department

[][]To collect, disposition and proper storage & disposal of rejected materials/products according to this SOP.

Quality Assurance

[][]To review and get prior approval for initial disposition.

HR Executive

[][]To check and monitor regular disposition activities

Senior Executive, Cost & Budget (Factory)

[][]To verifying that all the disposed items and make report for stock adjustment memo.

Head of Plant Operation

[][]Proper follow-up of overall activities

Head of Quality Assurance

[][]Approval of all the disposal activities

Procedure:

Precautions / Special instructions

[][]Wear masks, gloves & safety goggles (eye protective glasses) and other necessary precautions during destruction works and disposal of wastage and expired materials/products.
[][]Avoid scattering after completion of work.
[][]Always keep the plastic bucket/dustbin covered with lids after work.
[][]Wash the container after completion of work.
[][]Do not dispose the waste tablets and capsules directly into drain.
[][]Do not store the in-process waste for disposal for next day.

Disposal procedure for manufacturing & In-process waste from production area

[][]Departmental executives/ operators will ensure that the waste materials are segregated at sources of generation as hazardous & non-hazardous.
[][]Departmental executives/ operators will ensure the waste materials are in their respective designated containers and their physical segregation from passed, approved, quarantined or any finished good materials. They will also separate solid & non-solid waste materials.
[][]In case of new product, Product Development will assess and identify the nature of materials as hazardous & non-hazardous at development stage. Product [][]Development will notify the relevant owners about the disposal procedure of wastes.
[][]The waste packaging materials (polythene bags/cartons/labels/drums/fiber board boxes etc.) will be removed daily from the sections and transferred to salvage yard according to nature of disposal process by service people.

[][]The manufacturing related solid waste materials (waste raw materials, products, IPC materials etc.) will be removed daily from the sections.
Each working area contains separate waste bin with proper labeling for different types of waste as per annexure-V.

[][]Put all the tablets checked during in process check (IPC) for hardness, thickness, friability and weight variation in waste bin placed in respective compression room, IPC room. The same procedure will be applicable for capsule, powder for suspension, rejected tablets, and capsule from blister area and bottles which are used for leak test.
[][]Collect the dust from Dispensing, Granulation, Compression, Encapsulation and Powder filling area in the waste bin placed in the respective area except hazardous waste.
[][]Take all the waste in the washing area. Production & QCOM Executive will be present during disposal and follow up the whole activities.
[][]Take approximately 10 – 15 liters of potable water into a bucket. Dissolve any types of waste mentioned above in this water in quantity sufficient.
[][]After dissolving, transfer the dissolved wastes into washing area and dispose them into drain with plenty of water to ensure proper cleanliness of the drain.
[][]Clean the bucket using Sodium bi carbonate & Sodium Lauryl Sulphate (detergent) powder solution.
[][]Dispose the dust or tablets or capsules collected in a vacuum cleaner in the same way as described above.
[][]The manufacturing waste should have to be disposed immediately the same day of waste produced.
[][]Disposal procedure for laboratory waste (Reagent, analysis sample etc.)
[][]For laboratory waste follow the SOP “Waste management in Quality Control Laboratory” Where XX denote current version.
[][]Disposal procedure for waste generated in the Product Development Laboratory
[][]For the waste generated in the PD laboratory follow the SOP “General waste disposal procedure for product development lab.”  Where XX denote current version.
[][]Disposal procedure for intermediate/bulk products/batch tails/finished products/hazardous waste from manufacturing area
[][]When a finished product/ intermediate products/ bulk product/ batch tails, hazardous waste is to be rejected, the concerned department Head shall raise “Disposal Form for Materials & Products” as per annexure-I for write-off in the part-A.
[][]The form is first to be signed by Concerned Department Head followed by concerned personnel of Factory Accounts & Budget, HR & Admin personnel, General Manager plant and approved by Head of Quality Assurance.
[][]After approval of the Disposal Form for Materials & Products, concerned department will attached the “To Be Disposed” label as per Annexure-III with the rejected materials and to be kept in a dedicated area of the respective production department before the schedule for disposal activities.

[][]The disposal activities to be carried out in the concerned department in the respective washing area.

[][]All the disposal activities will be conducted in a dedicated washing area with direct supervision of QA Executive

Tablets, Capsules & PFS : Non-Betalactam

[][]Wear appropriate Personal Protective Equipment/Clothes.
[][]Sort out the blister strips of tablets & capsules.
[][]Tear the blister strips and take out the tablets from the pouches.
[][]For PFS: Open the Alu. Cap & tear the label.
[][]Pour the powder of the bottles into a plastic bucket.
[][]Keep aside the deformed Alu. Cap, LDP stopper & spoon and send to salvage yard.
[][]Keep the Dry powder, tablets and capsules in a bucket; mix/dissolve the tablets/capsules with water and stirring.
[][]Neutralize the liquid (pH 6 – 9) by using acid/alkali. Dilute 10 – 20% of the liquid by fresh water and drain out with plenty of water or burg.

[][]Tear the printed packaging materials and transfer all the torn packing materials to the salvage yard.

Tablet, Capsules and PFS (Cephalosporin)

[][]Wear appropriate Personal Protective Equipment/Clothes.
[][]Make sufficient quantity of 0.4% (v/v) sodium hypo-chlorite solution.
[][]Sort out the products.
[][]Take out the strips from the cartons.
[][]Tear the blister strips and take out the capsules/tablets & keep in a bucket.
[][]Keep the torn blister strips into a polythene bag.
[][]For PFS: Open the Alu. Cap, LDP stopper & tear the label.
[][]Pour the powder of the bottles into a plastic bucket.
[][]Keep aside the deformed Alu. Cap & spoon and send to salvage yard.
=>Dissolve/mix the dry powder, tablets and capsules in a covered plastic bucket with previously made 0.4% (v/v) sodium hypochlorite solution and stir with a rod. Leave it overnight for at least 12 hrs.
=>Neutralize the liquid (pH 6 – 9) by using acid/alkali. Dilute 10 – 20% of the liquid by fresh water and drain out slowly the materials on the following working day.
=>Clean the drain with adequate water flushing.
=>Tear all packaging materials and transfer the torn packaging material for salvage yard.
[][]After disposal of the product/ materials, Part B of the Disposal Form for Materials & Products shall be signed by concerned person with designation who disposed the products and then jointly checked by Executive, QA and Executive, HR & Admin. and finally approved by Head of QA.
[][]All master copy of disposal records shall be maintained and kept by QA department and another copy will be sent to Concerned Department, HR & Admin Department and Cost & Budget (Factory) department.

Expired Retention Samples

[][]For expired retention sample the same procedure to be followed the procedure stated in 7.4 by raising the Authorization and Disposal Form for materials & products.

Waste Packaging Materials

[][]Collect all the in-processed waste produced from packaging area from the waste bin placed in the respective area.
[][]Tear the wastage label, carton, leaflet and put into a polythene bag by attaching “To Be Disposed” label as per Annexure-III.
[][]All wastage of cap, spoon, and dropper are to be deformed and then put into a polythene bag by attaching “To Be Disposed” label. All wastage of foils, films to be cut and put into polythene bag.
[][]All the wastage packaging materials are to be checked by Production and QA Executive daily. Then the daily waste materials sent to the dedicated salvage yard through warehouse with waste material transfer note (Annexure-IV) with proper notification to HR executive.
[][]After receiving of this waste transfer note by HR executive, this copy will be returned to respective department and to be preserved.
[][]All these packaging waste materials are kept in the salvage yard. These wastages are disposed by the third party as per company policy.
This procedure also applicable for the online rejected materials.
[][]In case of large number of online rejected materials the disposal procedure to be followed by prior approval from Head of QA following the Authorization and Disposal Form for Materials & Products.

Stock Adjustment Procedure

[][]After approval of Authorization and Disposal Form for Materials & Products for Rejected Intermediate / Bulk Products / Batch Tails / Finished Products and online rejected materials, stock adjust memo to be filled up by Cost & Budget (Factory) personnel as per Annexure-II.
[][]After approval from relevant personnel the main copy to be kept in the Cost & Budget department and another copy will be attached with the relevant Authorization and Disposal Form for Materials & Products.

[][]Finally the adjustment to be done on the ERP.

Annexure:

Annexure I- Authorization and Disposal Form for Materials & Products
Annexure II- Stock Adjustment Memo
Annexure III- Label for “To be disposed”
Annexure IV- Waste Material Transfer Note
Annexure V- Waste Collection & Disposal Procedure

Quality Review Meeting, Purpose :

Quality Review Meeting, To define the Quality Review Meeting requirements to ensure that the review and escalation of quality and. Assurance risks, improvement opportunities and strategy settings are handled effectively.

Quality Review Meeting, Scope :

This SOP is applicable for holding Quality review meeting of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]CAPA : Corrective Action and Preventive Action
[][]IPC : In-Process Check
[][]QMS : Quality Management System
[][]OOS : Out of Specification
[][]PPR : Periodic Product Review

Responsibilities:

[][]The roles and responsibility is as follows:

Manager, Quality Assurance

[][]Facilitate the Quality Review Meeting.
[][]Prepare the yearly calendar for the meeting.
[][]Recommend the participant list.
[][]Prepare the meeting agenda.
[][]Communicate with the participants for the meeting.
[][]Prepare and issue the minutes.

Manager, Quality Control

[][]Update Environmental monitoring/ Laboratory system/ KPI/ Rejection.

Head of Engineering

[][]Update maintenance status of plant/machinery.

Head of Plant Operation

[][]Chair the Quality Review Meeting.

Head of Quality Assurance

[][]Approve the yearly calendar for the meeting.
[][]Approve the meeting agenda.
[][]Approve the participant list.

Procedure:

Overview of Quality Review Meeting:

[][]Quality Review Meeting is an essential part of the governance and improvement framework for Quality and Regulatory Assurance within XX Pharmaceuticals Limited.

Operation of the Site Quality Review Meeting:

Attendance

[][]It is essential to have adequate senior representation of quality, operational, and supporting roles at the QRM. The ownership of this Quality Review Meeting lies with Head of Quality Assurance. The meeting will be chaired by Head of Plant Operation or his designee.
[][]The Team members of Quality Review Meeting will be all technical person of the Plant. It is essential that the members shall be present in all the meetings. To conduct a meeting at least 70% participation of the members is mandatory. However, either one of i e Head of Plant or Head of Quality Assurance must be present in the meeting.

Frequency

[][]The QRM will be held on monthly basis. A yearly calendar will be followed, which will be issued at the beginning of the year. The responsibility lies with Head of Quality Assurance.

Meeting Process and Communication

[][]It is the responsibility of Head of Quality Assurance to notify the members of QRM a week before the meeting with agenda (Annexure I).
[][]The members will give their feedback on their part of actions at least three days before the
[][]meeting to the Head of Quality Assurance. This will facilitate the process of updating the previous meeting.

[][]The minutes will contain the following attributes:

For actions and decisions

=>Owner (a single name in preference to group actions)
=>Content
=>Context for full understanding/reason including related agenda item.
=>Current status of action
=>Target completion date

Record Maintenance

[][]Manager, Quality Assurance will maintain all records of the Quality Review Meeting as per SOP for Document Archiving, Retention, and Retrieval & Destruction. Following records will be maintained:
=>Minutes
=>Actions taken
=>Decisions taken
=>Communications

Brief Description of Agenda items

Review of CAPA status

=>Review actions for most significant CAPAs
=>CAPA update on Level of internal audits
[][]Changes to regulatory requirements
=>Quality Review Meeting will Review of any new regulatory requirement that is to be addressed.
[][]Quality Management System
=>Confirm that the review of current practices/standards gaps versus the QMS is rigorous.
=>Review actual QMS performance versus target.
=>Review significant changes within the QMS.

Risk Management – Governance and Improvement

[][]Risk Register: The Quality Risk Register must be reviewed to ensure
=>Risks are being identified.
=>Risks are being assessed.
=>Action plans are being progressed.

[][]Periodic Review of QRM Plan
=>Schedule adherence of QRM Plan
=>Endorse new Quality Plan and any change in Quality plan

[][]Quality KPI Review
=>Batches Not Right First Time (Process & Testing error)
=>Batches Not Right First Time (Documentation error)
[][]Change Controls
=>Review the overall status of Change Control Tracker and ensure there is no overdue.
=>Endorse the final closing of Change Control
=>Review all critical and major change controls.
=>Check that the closure is timely and the actions taken are effective

[][]Deviations, Out of Specifications, Rejects and Reworks
=>Quality Review Meeting will
=>Review deviations, OOS, rejects and reworks
=>Assure itself that reporting is full and complete and that closure is timely (Investigation will not open more than 30 days).
=>Review overall trends and set strategic improvement actions.
[][]Complaints – Vendor and Customer
=>QRM will Ensure that all vendor and customer complaints are reviewed.
=>Ensure that any ‘unofficial’ complaints or comments are reviewed
=>Review the root cause and proposed CAPA
=>Review overall trends and set strategic improvement actions.
=>Review Recalls and Product Incident Review. .
=>Understand and endorse resultant CAPAs.
[][]Periodic Product Review
=>Quality Review Meeting will review.
=>Schedule adherence for the year, and monitor timely completion.
=>Key findings (executive summary) of PPR.
=>Improvement recommendations (CAPA) in PPRs are actioned and tracked.
=>Adverse quality trends are reviewed and actioned.
=>Positive quality trends are reviewed to ensure sustainability (or transfer of a good practice).
=>Correlate change controls with product quality trends.

[][]Validation
=>Schedule adherence of VMP
=>Issue triggered from validation
[][]Stability Studies
=>Review stability test status.
=>Review any adverse stability data and assess impact on product quality and shelf life
=>Take corrective action to mitigate the risk.
[][]Environmental/Utility Issues
=>Review any adverse trend of environmental monitoring results and results of water testing and to assess impact on product quality.
=>Take corrective action to mitigate the risk.

[][]Training
=>Progress against plan (Schedule adherence)
=>Man-hours utilized Retention & Archiving of Documents
[][]Retention & Archiving of Documents
=>Progress against plan
[][]Preventive Maintenance
=>Schedule adherence
[][]IPC Trending
=>Review the monthly IPC observations for any GMP non Compliance
=>Review the IPC observation trend to minimize the IPC failure/ error.
[][]Review of last minutes
=>Comments on previous minutes from the participants.
=>Track progress of actions in the previous minutes of the meeting.
[][]Any other matters to discuss
=>Any other matters not discussed earlier but have an impact on product quality.
[][]After Action Review
=>At the end of the meeting members will review the meeting process, confirm whether it has met the purpose and identify the needs for its improvement for the next meeting.

Annexure:

Annexure-I: Agenda of Quality Review Meeting

Personnel Movement, Purpose:

Personnel Movement, To define the procedure to be applied for the movement of people & transfer of documents & materials between Cephalosporin & General block.

Personnel Movement, Scope:

This document lays down the guidelines for the movement of people & transfer of documents & materials between the Cephalosporin & General block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]QC – Quality Control
[][]QA- Quality Assurance
[][]QA – Quality Assurance
[][]SOP – Standard Operating Procedure

Responsibilities:

[][]The roles and responsibility is as follows:

All Concerned Personnel

[][]To be responsible to follow the SOP

General Manager, Plant

[][]Proper follow-up of overall activities

Manager, Quality Assurance

[][]Responsible to ensure the Assurance to the procedure.

Procedure:

[][]Where the need arises to move or to transfer documents & materials between the Cephalosporin and General block, care should be taken to prevent contamination, to eliminate the potential sources of contamination. Following provisions have to be maintained in such cases:

Movement of people

[][]Entry of the people working in the Cephalosporin Block is restricted to the General Block during or after their working time. They can enter General Block only before entering the Cephalosporin Block as per requirement.
[][]People working in the General Block can enter into the Cephalosporin Block at any time as per requirement. But it should be maintained that they will not enter again into the General Block at that day.
[][]To transfer any documents / samples / tools / equipment from the General Block to the Cephalosporin Block, the assigned personnel will handover that to the person who work at the lobby area of Cephalosporin Block.
[][]The people working in the lobby area will then handover those to the persons inside the change room.

Transfer of Documents

[][]All the master documents related with Cephalosporin block will be preserved in the document archive room of Cephalosporin Block.
Issuing of BMR, BPR, Logbooks, Forms etc. which control is in the General Block will be done after receiving the requisition from the concerned department to Quality Assurance.
[][]But all the requisition will be performed electronically through mail.
[][]Some common SOPs are shared both by Cephalosporin & General Block. In such cases, all the master copies will be preserved in AGM, QA room of the General Block and controlled copies will be distributed in the Cephalosporin Block.
[][]All signatories will be taken within the Cephalosporin Block.
[][]No documents are allowed to be transferred from the Cephalosporin Block to the General Block. If any document is necessary to be sent to the General Block from Cephalosporin Block (e.g. atomic absorption spectrophotometer reading) it will be sent as an information copy through fax or scan or as a form of soft copy through LAN / Internet.
[][]Before the transfer of materials, the required amount of material is collected & to be placed on a pallet. The material is then transferred manually from General warehouse to the receiving bay of the Cephalosporin warehouse. From the receiving bay, the material is transferred to another pallet (dedicated for Cephalosporin block).
[][]For washed & dried glass bottle or crushed sucrose the same procedure stated in above will be followed.
[][]The pallets/ HDPE drums which were used for transferring materials from the General warehouse can be used only after proper cleaning. These pallets must not be used in the production floor; they will be used only in the warehouse.
[][]For analytical purpose, a set of reference / working standard which is required for analysis must be available in the Cephalosporin QC/ Microbiology laboratory.
[][]Product Development Activities: Any kind of process or product development work related with Cephalosporin product must be conducted within the Cephalosporin block.
[][]Engineering Activities: Any kind of maintenance, calibration activities will be done by the dedicated personnel and equipment’s. In case of single calibration instruments, after finishing the tasks at Cephalosporin Block, all the equipment’s will be transferred to Calibration lab. after proper cleaning and de-contamination.

Annexure:

Annexure I- Inter Departmental Materials Transfer Record
Annexure II- Status Label for Inter Departmental Transferred Materials

Document Control, Purpose:

Document Control, To describe the procedure for activities involved in the preparation, control, retrieval and archiving of quality related documents.

Document Control, Scope:

This procedure covers all the documents issued by Quality Assurance and it also includes documents related to regulatory, calibration, qualification and validation activities at XX Pharmaceuticals Limited (Both General & Sterile Block)

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]SOP – Standard Operating Procedure
[][]XX – Current Version of SOP

Responsibilities:

[][]The roles and responsibility is as follows:

Procedure:

[][]This procedure shall be applicable for all the new documents, which are prepared from the effective date of this document. The existing document shall be modified as per this procedure whenever due for periodic review or whenever they need to be revised on need basis.
[][]The layout of the Quality Related documents
[][]The layout of SOPs, calibration, validations, guidelines, QA policies, and qualification should be as per the respective templates.
[][]Formats: The format can be designed according to the data that is to be entered. The document number along with revision number, concerned document reference number shall be placed at the top of each page of the format.
[][]Validation protocols and Reports: The format and contents are described in the procedure for validation protocols and Reports.

[][]Quality related documents are essential documents, which establish the quality systems, and are required as per Good Manufacturing Practices (GMP).
Batch Manufacturing Record (BMR) & Batch Packaging Record (BPR): The format and contents are described in the procedure for Preparation, approval, distribution, control & revision of Batch processing records according to SOP.
[][]Specifications, Method of analysis & analytical work sheet: The format and contents are described in the procedure SOP.

Preparation, review and approval/ authorization of documents:

[][]All documents (new or existing) are to be drafted by appropriately qualified personnel of the concerned department and submit to the head of the department for checking. Before submission for checking, the responsible personnel shall initiate a draft copy.
[][]The department Head shall circulate the draft document to concern section Heads for checking. All the comments / inputs shall be written directly on the draft, signed and dated by the respective persons.
[][]After the draft document has been commented on by all the concerned Heads, a final checking /review is carried out by the QA department.
[][]If there are changes, a further document is prepared and circulated until the final draft is agreed.
[][]Concerned department then shall prepare the final copy and assign sequential number (in case of new documents). In case of existing documents, only the version number will be changed.

[][]The final document shall then be signed by the responsible staff. All the draft copies are to be destroyed subsequently.
[][]Concerned department Head shall send the approved master copy to QA for distribution or Issuance of controlled copies.
[][]QA shall issue the controlled copy of documents to concerned departments.

Standard Operating Procedures

[][]Follow the previous step
[][]Sufficient time is given between issue date and effective date to enable training of concerned people.
[][]Batch Manufacturing Records (BMRs) and Batch Packaging Records (BPRs)
[][]After finalization of Manufacturing Record and Batch Packaging Record shall be prepared by Product Development department.
[][]BMR & BPR shall be drafted by Product Development by using relevant template.
[][]Product Development shall send duly signed master copy of BMR & BPR to QA for distribution or Issuance of controlled copies.
[][]QA shall issue the controlled copy of documents to concerned departments.

Specifications, Method of Analysis

[][]Specification: A list of tests, references to analytical procedures and appropriate acceptance criteria that can be numerical limits, ranges or other criteria to which a material must conform to be considered acceptable for intended use.
[][]Test Procedure: Analytical procedures that are to be followed against any test described in method of analysis.
[][]Each material must have unique specifications and test procedures. The test procedure shall give the details of methods to be carried out against each test parameter defined in the specifications.
[][]QC shall prepare final copy of documents and assign sequential number to all specifications, method and analytical work sheet. These Documents shall be prepared, checked and approved by persons as defined in the responsibility.
[][]QC shall send the duly approved master copy to QA for distribution or issuance of controlled copies.
[][]QA shall issue the controlled copy of documents to concerned departments as per previous step.

Qualification and Validation Documents

[][]Concerned Department shall prepare the Qualification documents by using relevant templates.
[][]After finalization of BMR and BPR concerned QA personnel shall be prepared validation documents by using relevant template.
[][]Other qualification and validation documents shall be prepared, checked and approved by persons as defined in the responsibility.
[][]QA shall issue the controlled copy of documents to concerned departments as per previous step.

Distribution or Issuance of Controlled and Uncontrolled documents

[][]All the GMP documents related to the manufacturing plant will be issued by Quality Assurance. The Controlled copies of documents shall be made by Quality Assurance by photocopying the master copy and sealed as

CONTROLLED
Initial………Date..…

=>in blue ink with initial & date of QA Personnel.

[][]If an additional copy of document is required by any department for operational use then Quality Assurance dept. shall issue an additional copy only after written approval from Head of Quality. Such requests shall be obtained through the Request Form as per Annexure – I.
[][]The controlled copies of new documents shall be distributed to the concerned departments and sufficient time should be given before the effective date of the document to enable training of the concerned people.
[][]All formats shall be controlled by QA. The required number of working format shall be copied from control copy by respective department head or his nominee and reconciliation of copied format shall be done by respective department head or his nominee.

Revision of existing documents

[][]Documents such as SOPs, BMR, BPR etc which requires revision due to change control shall be revised by concerned department.
[][]Revised documents shall be given sequential revision No. and controlled by Quality Assurance.
[][]Documents undergoing change due to regulatory requirements / audit Assurance shall also be revised through proper change control by the concerned department.
[][]QA shall distribute the controlled copies of revised documents to concerned departments as per previous step.

Document Archive

[][]All the master documents will be archived at QA end at the document archiving room of both two blocks. At the archiving room, master documents will be kept after recording the archiving no. in the document archive register as per annexure-V.
[][]In the archive room, master document will be kept in a departmental manner as per allocated area for the individual department.
=>Document archive no. will be given as the following format-
=>GDA/XXXX/YYYY
=>Where, GDA represents as General Document Archive. For Sterile block it will be CDA that’s represents as Sterile Document Archive.

=>XXX represents as the Departmental Code as per following List-

[][]Quality Assurance/QA
[][]Quality Control/QC
[][]Engineering/ENG
[][]Production/PRD
[][]Product Development/PD
[][]Microbiology/MICRO

=>YYYY- represents as sequential number which starts from 001.

[][]Document archive room will be lock & key controlled system. Only authorized personnel of QA department will enter in this room for documents preservation. Any other will take authorization from Head of QA to enter this room for document checking or reviewing.
[][]Retrieval or Recall of Obsolete Controlled copies and Superseding of Obsolete Master documents
[][]When the document has been revised following a change request, the older version must be superseded.
[][]Obsolete versions of documents are retrieved and reconciled and entries are made in the specific obsolete register.
[][]All retrieved controlled copies of documents shall be destroyed immediately & recorded.
[][]The Master Copies of the superseded documents along with document change /approval request form shall be archived in the QA department stamped as in Red Ink maintaining the a register.

OBSOLETE
Initial………Date..…

=>in RED ink with initial & date of QA Personnel.

Document Retention

[][]The Retention period of quality related documents is mentioned in Annexure – II.
[][]All quality related documents should be stored securely and safely with controlled access, protected from damage and mutilation. The storage areas and access restriction to the retention of these documents are in the documents archiving room.
[][]The documents related to legal proceeding should be securely kept till the legal proceeding are over.
[][]All documents relevant to quality of the in-house manufactured products must be included in the documents archiving register having a archiving no.

[][]Quality Assurance shall maintain all the Master documents
[][]Responsible Quality Assurance executive shall maintain a log register for taking & re-archiving of documents from Documentation Archiving Room of QAD.
[][]A log register shall be maintained by responsible Quality Assurance executive to archive the Batch Production Records.

Destruction

[][]QA department shall destroy the documents after the retention period is over and maintain a record of the same.
[][]The destruction may be performed by shredding, cutting, tearing, to make the documents non-usable.
[][]A file note will be prepared. A list of documents with sufficient information like document number, effective date, review date etc. (or manufacturing date, expiry date, batch number or lot number of the materials or products etc.) will be attached as an annexure in the file note. Destruction approval will be given by GM, Plant and Manager, Quality Assurance.

Annexure:

Annexure-I: Request for Issuance of Additional Copy of Documents
Annexure-III: Retention Period of Quality Related Documents.
Annexure-III: Document Control Register
Annexure-IV: Log Register for Obsolete Documents
Annexure-V : Document Archive Register

Hold Time Study, Purpose:

Hold Time Study, To establish a procedure for determination of in-process holding time limits.

Hold Time Study, Scope:

This procedure is applicable for all products to be manufactured at both General block and Sterile block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]RH – Relative Humidity
[][]NMT – Not more than
[][]QA – Quality Assurance
[][]SOP – Standard Operating Procedure

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure proper handling & storage of hold time sample following this SOP.

Executive, Quality Control

[][]To be responsible to provide analytical support

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]Hold time study for dispensed materials (Active materials), blended granules, bulk tablet, coated tablets, bulk capsules, blister strips, filled bottles to be done.

[][]The sampling & testing frequency will be 7 days and 15 days. In addition for blister and filled bottles-60 days study to be performed. Based on the holding time study the holding period will be fixed.
[][]During holding time study all products were considered withstand the controlled environmental condition (The environmental condition is; %RH: NMT 55.0% and Temperature NMT 25deg.C).
[][]If the holding period of dispensed active materials, blended granules, bulk tablets/capsules, filled bottle and blister strips is more than the time period specified in this SOP then further assessment/retesting to be conducted before further proceeding.
[][]However in case of recoverable residue consumption of capsule products the h. study will be conducted up to four months and based on the analytical data the holding period will be fixed.
[][]The numbering of hold time study report for individual products shall be assigned as per
=>HSR/PXXXXX/YY
=>Where, HSR means Hold time Study Report
=>PXXXXX means the product code
=>YY means the version number of the study report.
[][]Sampling, analytical testing shall be conducted according to annexure- I.
[][]Hold time test of dispensed active materials for a product of different strengths will be done once.
[][]Data shall be compiled and used for establishing in-process holding time limits for different stages of product manufacturer.
[][]The  H. study for equipment should be performed and both clean and unclean state of equipment also be considered. Based on the documented data the equipment holding time period will be established.
[][]After collecting all data the H. time study report will be generated for each product following the annexure-II.

Annexure:

Annexure-I: Sampling stage and testing frequency for hold time study
Annexure-III: Hold time study Report format

Retention Sample, Purpose:

Retention Sample, To establish general guidelines for sampling, handling and storage of Retention sample of finished products for regulatory testing and for resolution of customer complaints.

Retention Sample, Scope:

This procedure is applicable for both General block and Sterile block at XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]BPR: Batch Packaging Record
[][]QA: Quality Assurance
[][]QA: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure proper handling & storage of retention sample following this SOP.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]At the start of packaging operation, retention sample of every batch for different dosage form shall be taken by the Quality Assurance personnel engaged in In-process checking as follows-

[][]Tablet: Not less than 60 Tablets (Equivalent to unit packs)
[][]Capsule: Not less than 60 Capsules (Equivalent to unit packs)
[][]Powder for Suspension: Pack size is 35ml or less- 6 unit packs & Pack size is above 35 ml- 4 unit packs
[][]Kidney Dialysis Fluid: 1 Pack (10 L)
[][]Liquid Sterile: Not less than 60 ml (Equivalent to unit ampoule or pack)
[][]Sterile Powder for Injection: Not less than 10 unit packs

[][]Retention samples of finished product shall be collected from each part (i.e., each type of pack -commercial, trial aid, export, institutional, etc.) of a batch. During collection of retention sample followings shall be considered –
[][]Full retention sample shall be collected from first time packaging whether it is commercial or export.
=>One or two unit packs shall be collected from next each part.
=>Representative samples shall be collected from any pack of export or trial aid pack.
[][]Quantity of the retention sample shall be recorded and signed with date on Batch Packaging Record by the concerned Quality Assurance executive.

[][]Quantity of the retention sample shall be recorded and signed with date on Batch Packaging Record by the concerned Quality Assurance executive.
[][]The samples shall be sent to retention sample store after keeping record into the “Annexure-I: Retention Sample Archiving Log Book” of specific Quality Assurance station.
[][]Before archiving the retention sample in the specific rack, entry shall be given for Product name, quantity, Batch No., Mfg. Date and Exp. Date. At the same time, Serial No. shall be given on the outer side of the carton/pack of retention sample for easy identification.
[][]Serial number of retention sample shall be given as follows-

GR/XX/YYY
Where,
=>“GR” stands for General Retention (For Sterile Block it will be CR)
=>“XX” stands for the last two digit of the year. It will be changed for next year.
=>For example- AA for year 20AA, BB for 20BB and so on.
=>“YYY” is the sequential number. In every new year it will be started from 001 and so on.

[][]Retention sample of each batch shall be kept up to the product shelf life plus one year (minimum).
[][]The Retention samples shall be stored under ambient temperature of the retention sample store (Temperature should be NMT 30ºC). For sterile powder for Injection products this room temperature will be controlled as not more than 25º C.
[][]Temperature of Retention sample store shall be recorded in “Annexure-II: Temperature Record Sheet” regularly (at least two times in a day i.e. at 9:00 AM and 4:00 PM) using calibrated thermo hygrometer. At the same time maximum and minimum temperature shall be recorded at 8:30 AM in each day.
[][]Requisition for Retention sample shall be raised through Annexure-III: Requisition Form for Retention Sample. Samples/Documents shall be provided to requester dept. after getting approval of Head of Quality Assurance. No of supplied retention samples to be recorded in the retention sample register.
[][]After the stipulated storage time (Shelf life plus one year), all the retention samples will be discarded through the SOP of “Procedure for disposal of material and products”, SOP.

Annexure:

Annexure-I: Retention Sample Archiving Log Book
Annexure-II: Temperature Record Sheet
Annexure-III: Requisition Form for Retention Sample

Batch Issuance, Purpose :

Batch Issuance, The purpose of this SOP (Standard Operating Procedure) is to provide a documented procedure for issuance of BMR and BPR.

Scope :

Batch Issuance, This procedure is applicable for issuance of BMR and BPR at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]BMR: Batch Manufacturing Record
[][]BPR: Batch Packaging Record
[][]QCOM: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Assurance

[][]To ensure implementation of the SOP.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]Issuance Procedure of Batch Manufacturing and Packaging Record (BMR/BPR).
[][]Fill up the respective BMR/BPR details in requisition form (Annexure-II) with signature of user and send to C for the issuance of respective BMR/BPR.
[][]On receipt of BMR/BPR requisition form from production department, QA shall enter the issuance entry in BMR/BPR issue register and then, photocopy the required copy of respective product BMR/BPR from the master copy of BMR/BPR.
[][]QA personnel shall enter the information related to Batch like Batch Number, Manufacturing Date, Expiry Date to photocopy of BMR/BPR.
[][]Send the photocopy of BMR/BPR to production department.

Annexure:

Annexure-I: Batch Issuance Register
Annexure-II: Batch Requisition Form