Process Validation Protocol [PDF]

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Company Logo Company Name and Address Title: Product Name Type of Validation: Department :



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



Process Validation Protocol For XXXXXXXXXX



Company Name and Address



1. FORMAT/QA/027/01



PROCESS VALIDATION PROTOCOL



Table of Contents



1 of 26



Company Logo Company Name and Address Title: Product Name Type of Validation: Department :



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



2 of 26



1.



Table of Contents.........................................................................................................................................2



2.



Signatories...................................................................................................................................................3



3.



Revision status:............................................................................................................................................4



4.



Aim..............................................................................................................................................................5



5.



Purpose........................................................................................................................................................5



6.



Scope...........................................................................................................................................................5



7.



Responsibility..............................................................................................................................................5



8.



Manufacturing conditions............................................................................................................................6



9.



Process Equipment’s....................................................................................................................................7



10.



Raw Materials and Packing Materials...................................................................................................11



11.



Validation Plan.......................................................................................................................................15



12.



Critical Process Controls, sampling plan and acceptance criteria:........................................................21



13.



Packaging and storage:..........................................................................................................................24



14.



Validation Acceptance Criteria:.............................................................................................................24



15.



Changes and deviations:........................................................................................................................25



16.



Validation summary:..............................................................................................................................26



17.



References:............................................................................................................................................26



18.



Annexure:..............................................................................................................................................26



2. Signatories This document contains 25 pages and is prepared, reviewed and approved by following persons: FORMAT/QA/027/01



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department :



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Prepared By: Designation Mr. XXXXXXXXX



Page No.:



3 of 26



Signature



Date



Signature



Date



Signature



Date



Signature



Date



Signature



Date



Signature



Date



Signature



Date



Sr. Executive-PR Reviewed By: Designation Mr. XXXXXXXX Sr. Manager - PR Designation Mr. XXXXXXXXXXX Dy. Manager - PD Designation Mr. XXXXXXXXX Asst. Manager - QC Designation Mr. XXXXXXXXX Manager- EG Designation Mr. XXXXXXXXXX Executive - QA Approved By: Designation Mr. XXXXXXX Asst. Manager - QA 3. Revision status: Sr. No. FORMAT/QA/027/01



Date



Revision



Changes Made



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department : 1



FORMAT/QA/027/01



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



13/06/2019



R00



Page No.: Initial copy



4 of 26



Company Logo Company Name and Address Title: Product Name Type of Validation: Department :



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



5 of 26



4. Aim The aim of this validation protocol is to provide the validation of (Product Name) manufacturing process as per in line with BMR No. XXXXXXXXXX. 5. Purpose To conduct the process validation of the manufacturing process for the (Product Name) manufactured at the Plant-II and Plant-III The validation study shall be conducted for the generation of sufficient data to establish documentary evidence and to provide assurance that the product can be manufactured with established parameter on a commercial scale meeting all its quality attributes in a consistent manner. 6. Scope This protocol shall be applicable for three consecutive commercial scale up batches manufactured with BMR XXXXXXXXXX with specific batch size, equipment & operating parameter for the process. 7. Responsibility Functional responsibility is with the validation team comprising of:  Quality Assurance Shall be responsible for : 1. Approval & training of validation protocol, review of the data compiled, review of deviation (if any), monitoring of the process as per process parameter & monitoring of withdrawal of validation sample. 2. Review of the facility, equipment qualification & utility validation report. 3. cGMP compliance during the manufacturing process review & evaluation of data /Result generated during validation process. 4. Preparation of process validation summary report, review & its approval.  Production Shall be responsible for : 1. 2. 3. 4.



To execute the batches as per BMR & process validation protocol. Preparation of process validation protocol with the help of QA. Compilation of data related to manufacturing area and furnish the same for review. Review of protocol and summary report.



 Quality Control Shall be responsible for : 1. 2. 3. 4.



Raw material and packing material analysis. Inprocess and finished product sampling and analysis as per sampling plan. Collection and review of Inprocess and finished product analysis data. Submission of data / Result to QA & production for review & evaluation.



FORMAT/QA/027/01



Company Logo Company Name and Address Title: Product Name Type of Validation: Department :



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



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6 of 26



 Process Development Shall be responsible for: 1. To monitor activities related to execution of the process validation in coordination with Production and QA.  Engineering Shall be responsible for: 1. To review the protocol and provide support with equipment’s, facility and manufacturing condition. 8. Manufacturing conditions: Temperature of the manufacturing area is not critical and manufacturing shall be carried out at ambient temperature& for process operations from filtration to packing in ISO Class 8 area. 8.1



Product Details: 1. 2. 3. 4. 5. 6. 7. 8.



Product name



(Product Name)



Generic name



(Product Name)



Chemical name



XXXXXXXXXXXX



Shelf life



5 years



Storage condition



XXXXXXXXXXXXXXX.



Batch size



XXXXXX kg



Packing instruction



Packing style



Use



XXXXXXXX



FORMAT/QA/027/01



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department :



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



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9. Process Equipment’s Sr. No.



1.



2.



Equipment Name



SS Reactor



Glass Lined Reactor



FORMAT/QA/027/01



Equipment Code



XXXXXXX



Qualification Status & Preventive Maintenance ( Due Date)



Qualification Due Date: XXXXXX Preventive maintenance Due Date: XXXXXXX



Qualification Due Date: 20 Oct 2020 R-212



Preventive maintenance Due Date: 16 Aug.2019



Capacity/ MOC/RPM etc. Working Capacity 2000 L MOC SSR RPM 50 Agitator Anchor



Working Capacity 3000 L MOC GLR RPM 102 Agitator Impeller



Details of Control and Measuring Equipment



VG-R-211/01 Range 760 mm Hg – 0 TI-R-211/01 Range 0 to 400⁰C TS-R-211/01 Range 0 to 200⁰C



PG-R-212/01 Range 0 to 7 Kg/cm2 PG-R-212/02 Range 0 to 10.6 Kg/cm2 PG-R-212/03 Range 0 to 4 Kg/cm2 VG-R-212/01 Range 760 mm Hg – 0 TS-R-212/01 Range 0 to 200°C TI-R-212/01 Range 0 to 200°C



Purpose



Sodium hydroxide solution preparation



Reaction



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department : Sr. No.



3.



4.



Equipment Name



Glass Lined Reactor



SS Reactor



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance Equipment Code



Qualification Status & Preventive Maintenance ( Due Date)



Qualification Due Date: 27 Nov 2019 R-213



R-214



Preventive maintenance Due Date: 22June2019



Qualification Due Date: 06 Dec 2019 Preventive maintenance Due Date: 23 June2019



Qualification Due Date: 20 Oct 2020 5.



Centrifuge



FORMAT/QA/027/01



CF-202



Preventive maintenance Due Date: 22June2019



Capacity/ MOC/RPM etc.



Working Capacity 4000 L MOC GLR RPM 98 Agitator Impeller Working Capacity 6000 L MOC SSR RPM 60 Agitator Anchor



Capacity 48” Dia. MOC SS



Page No.:



8 of 26



Details of Control and Measuring Equipment



PG-R-213/01 Range 0 to 7 Kg/cm2 PG-R-213/02 Range 0 to 10.6 Kg/cm2 VG-R-213/01 Range 760 mm Hg – 0 TS-R-213/01 Range 0 to 200°C



Purpose



Reaction



TI-R-213/01 Range 0 to 200°C



VG-R-214/01 Range 760 mm Hg – 0 TI-R-214/01 Range 0 to 400⁰C



Water Washing



TS-R-214/01 Range 0 to 200⁰C



RTM-01 Range 200 to 2000 LPH



Isolation



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department : Sr. No.



Equipment Name



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance Equipment Code



Qualification Status & Preventive Maintenance ( Due Date) Qualification Due Date: 20 Oct 2020



6.



Centrifuge



CF-203



Preventive maintenance Due Date: 23Aug 2019 Qualification Due Date: 24 Jan 2020



7.



8.



9.



Tray Dryer



Multimill



Sifter



FORMAT/QA/027/01



TD-303



Preventive maintenance Due Date: 20 July2019



MM-304



Qualification Due Date 07 March 2021 Preventive maintenance Due Date: 16Aug 2019



SFR-303



Qualification Due Date 20 Dec 2019 Preventive maintenance Due Date: 17June2019



Capacity/ MOC/RPM etc.



Capacity 48” Dia. MOC SS



Capacity 96 Trays MOC SS



Page No.:



9 of 26



Details of Control and Measuring Equipment



Purpose



RTM-01 Range 200 to 2000 LPH



Isolation



PG-TD-303/01 Range 0 to 7 Kg/cm2 TS-TD-303/01 Range 0 to 200⁰C



Drying



TI-TD-303/01 Range 0 to 200⁰C



Working Capacity 125 Kg/hrs. MOC SS Mesh Size 0.5 mm



NA



Milling



NA



Sifting



Working Capacity 36”. MOC SS Mesh Size 10 mm



Company Logo Company Name and Address Title: Product Name Type of Validation: Department :



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



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Details of QC instruments : Sr. No.



Equipment Name



Equipment ID



Make



1.



HPLC



M/QC/I/003



AGILENT



2.



HPLC



M/QC/I/004



AGILENT



3.



HPLC



M/QC/I/076



AGILENT



4.



HPLC



M/QC/I/097



SHIMADZU



5.



UV Spectrophotom eter



M/QC/I/104



Shimadzu



6.



GC



M/QC/I/013



PERKIN ELMER



7.



GC



M/QC/I/077



AGILENT



8.



IR



M/QC/I/023



SHIMADZU



9.



Auto Titrator & KF Titrator



M/QC/I/107



Metrohm



10.



Vacuum oven



M/QC/I/017



SHEETAL



11.



Drying oven



M/QC/I/016



12.



Muffle Furnace



M/QC/I/056



13.



Muffle furnace



M/QC/I/079



FORMAT/QA/027/01



PATHAK ELECTRICALS GALAXY SCIENTIFIC EQPT. NA



Calibration Status Cal. Due date: 18/08/2019 Cal. Due date: 15/08/2019 Cal. Due date: 16/06/2019 Cal. Due date: 30/06/2019 Cal. Due date: 18/06/2019 Cal. Due date: 14/06/2019 Cal. Due date: 19/06/2019 Cal. Due date: 09/08/2019 Cal. Due date: 21/08/2019



Purpose Analysis Analysis Analysis Analysis Analysis Analysis Analysis Analysis Analysis



Cal. Due date: 02/12/2019



Analysis



Cal. Due date: 02/12/2019



Analysis



Cal. Due date: 02/12/2019



Analysis



Cal. Due date: 02/12/2019



Analysis



Company Logo Company Name and Address Title: Product Name Type of Validation: Department : 10. 10.1



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



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Raw Materials and Packing Materials Raw Material



Sr. No .



Code



1.



XXXXXXX



XXXXXXX In-house



2.



-



XXXXXXX In-house



3. XXXXXXX



4.



XXXXXXX



5.



XXXXXXX



FORMAT/QA/027/01



Ingredient



XXXXXX X



XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXX XXXXXXX X XXXXXXX XXXXXXX



Vendor Name



XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX



Spec No



Rationale



XXXXXXX



Key Raw material Washing



XXXXXXX XXXXXXX



Solvent for reaction



XXXXXXX Reagent XXXXXXX



Acid



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department : Sr. No .



6.



7.



10.2 Sr. No.



Code



XXXXXXX



XXXXXXX



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance Ingredient



XXXXXX X



XXXXXX X



Vendor Name M/s. Heetu chemicals & alkalies ltd. XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX



12 of 26 Spec No



XXXXXXX Reagent



XXXXXXX



Solvent for washing



Code



Ingredient



Vendor Name



XXXXXXX



XXXXXXX



Spec No



Primary packing



XXXXXXX



XXXXXXX



Black Polythene bag (33” x 66”)



XXXXXXX XXXXXXX XXXXXXX XXXXXXX



XXXXXXX



Primary packing



XXXXXXX XXXXXXX XXXXXXX



XXXXXXX FORMAT/QA/027/01



XXXXXXX



Rationale



XXXXXXX



XXXXXXX



02



Rationale



Packing Materials XXXXXXX



01



Page No.:



XXXXXXX



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department :



04



05



06



07



08 09



10



11



Documents No. XXXXXXxXX Prospective Validation Quality Assurance HDPE full open top drum (120 lit.)



03



Validation Protocol XXXXXXXX



HDPE full open top drum (60 lit.) Black XXXXXXX Polythene bags (50[L]X30[W]) Transparent XXXXXXX Polythene bags (50[L]X30[W] )



Page No.:



13 of 26



XXXXXXX Secondary packing



XXXXXXX XXXXXXX XXXXXXX



XXXXXXX



XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX XXXXXXX



XXXXXXX



XXXXXXX



XXXXXXX



Secondary packing



XXXXXXX



XXXXXXX



Secondary packing



XXXXXXX



XXXXXXX



Secondary packing



XXXXXXX



Secondary packing



XXXXXXX



XXXXXXX



Fiber Board Drums (18X28)



UN No. HDPE XXXXXXX Drum Capacity 120 L-SEA UN No. HDPE XXXXXXX Drum Capacity 120 L-AIR UN No. HDPE Full Open 1200001443 Drum CAP – 60 L SEA UN No. HDPE Full Open 1200001444 Drum CAP – 60 L AIR



XXXXXXX XXXXXXX



XXXXXXX



Note:  Raw material and packaging material shall confirm to the In-house specifications.



FORMAT/QA/027/01



Secondary packing Primary packing Primary packing Secondary packing



Company Logo Company Name and Address Title: Product Name Type of Validation: Department : 11. 11.1 11.1.1



0



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



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Validation Plan



Process Details for Manufacturing of (Product Name): Dissolution of XXXXXXX in XXXXXXX: Apply vacuum to the reactor R-212 / R-213 and charge XXXX L XXXXX in to reactor. Release the vacuum of Reactor. Open the manhole Charge XXXX Kg. of XXXX Slowly in Reactor R-212/ R-213 under stirring, after the charging close the manhole properly. Charge XXXXXX XXXX Kg in Glass Flask GF-208/GF-213 from Tank ST-207 by gravity. Charge slowly hydrochloric acid XXX Kg at XXXX°C in R-212/R-213 under stirring. Stir the reaction mass for XX Min. at XXXX°C. After charging of XXXXXXX clean the Glass Flask GF-208/GF-213 with XXXXXX till Neutral pH. Check the pH on pH paper. Withdrawn the sample and check clarity of Reaction mass from reactor. Reaction mass should be Clear. If Reaction mass is not clear then stir the reaction mass for further XX min at XX °C.



11.1.2



Preparation of XXXXXXXXX Solution: Take XX L. purified water in cleaned HDPE drum & add XX Kg XXXXXXXXX slowly. Stir with HDPE/Teflon rod. (XXXXXXXX should not expose with MS, SS item and solvent vapor). Apply vacuum to the Glass Flask GF-208/GF-213 and charge XXXXXXX solution in Glass flask. Slowly start addition of XXXXXXX solution in R-212/R-213 under stirring in allow to raise the temp. and maintain between XXXXX °C in XXX Hrs. After the complete addition of XXXX solution, maintain reaction mass at XXXX°C. (if temp below XX°C then apply hot water to the jacket of reactor to achieve temp XXXX°C). Stir th reaction mass at XXX°C for XX min. Withdraw the sample from reactor R-212/ R-213 for HPLC test. (To check XXXXXXX content (NMT 1.0 %) & XXXXXXXXXX (NMT 3.5 %). If HPLC results is not complies add XXXXXXX solution (XXXXXXXXX & water in the ratio 1:2) as per reaction requirement and continue reaction monitoring up to XXXXXXXX content within the limit. Cool the reaction mass to XXXXXX C.



FORMAT/QA/027/01



Company Logo Company Name and Address Title: Product Name Type of Validation: Department : 11.1.3



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



15 of 26



Preparation of XXXXXXXXXXXX Solution in to reactor & pH adjustment: Charge XXX L. Water in reactor apply chilling to reactor and keep water under stirring Open manhole and charge XX Kg XXXXXXXXXX slowly under stirring in reactor. Chill solution to XX – XX C. Transfer the above chilled caustic solution to receiver V-208A/V-213. Add slowly prepared XXXXXXXX solution at XX –XXC to R-212 / R-213 and adjust the pH X-X by using Sodium Hydroxide solution. Record the temperature. After complete addition stir the reaction mixture and cool to XX – XX C and maintain for XX min.



11.1.4



Isolation of the Crude Product by Centrifuge (CF-202 & CF-203): Apply continuous Nitrogen pressure to the Centrifuge for XX minutes and check oxygen percentage. (Limit- NMT X %). Open the bottom valve of the R-212/R-213 & feed the material to the Centrifuge CF-202/CF-203. Collect the mother liquor in centrifuge receiver. Spin dry the wet cake by running the centrifuge at high speed for XX-XX Min. Switch off the centrifuge and allow to stop completely. Stop centrifuge for XX-XX min. for Relaxation time. Unload the product (Wet cake) in HDPE drums lined with new polybag. Transfer the material to Reactor area for slurry.



11.1.5



Preparation of Slurry in Reactor: Charge XXX L water in reactor R-212/R-213. Open the manhole and charge wet cake in Reactor R212/R-213 under stirring, after the charging close the manhole properly. Heat the reaction mixture at XX-XX°C & Stir for XX min.



11.1.6



Hot Purified water Charge XXXX L Purified water to Reactor R-214. Heat the purified water up to XX to XX and use the same hot water for washing in Centrifuge.



11.1.7



Isolation of the Product in Centrifuge & water wash: Apply continuous Nitrogen pressure to the Centrifuge for XX minutes and check oxygen percentage. (Limit- NMT X %). Open the bottom valve of the R-212/R-213 & feed the material to the Centrifuge



FORMAT/QA/027/01



Company Logo Company Name and Address Title: Product Name Type of Validation: Department :



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



16 of 26



CF-202/CF-203. Collect the mother liquor in centrifuge receiver. Drain the ML to ETP. Wash the cake in centrifuge with hot water from R-214 (XXX L). Wash the cake with Purified water (XX L) from R214. Spin the centrifuge till complete removal of washing ML. Drain the ML to ETP. 11.1.8



Washing with Fresh XXXXXXX : Wash the cake in centrifuge with fresh XXXXX from CFT-203 (90 L). Note the XXXXX ML Quantity. Spin dry the wet cake by running the centrifuge at high speed for XX-XX Min. switch off the centrifuge and allow to stop completely. XX-XX min for relaxation then Unload the product (Wet Cake) in HDPE drums lined with new polybag. Transfer the material to Tray Dryer TD-303for drying.



11.1.9



Drying of the (Product Name) in Tray Dryer (TD-303): Open the door of tray dryer and take out the trays. Charge the wet cake in the trays with the help of SS scoop and place the trays in trolleys. Switch on the fan & allow to air drying for XX-XX Min. Start heating to the Tray Dryer by opening the steam valve heat to XXX-XXXC. Maintained at XX-XXC for XXX min. and record the temp details. Cool the product at Room Temperature. Unload the dried product in HDPE drums lined with polybag.



11.1.10 Milling of (Product Name) (MM-304): Place the HDPE drums with polybag below the outlet of Multimill for collecting the milled material. Slowly charge the dried material in to the Multimill charging hopper by SS scoop and switch on the Multimill. Continue the milling operation till batch quantity completes. Check the integrity of mesh visually after completion of milling. Integrity: Satisfactory / Not Satisfactory. 11.1.11 In process Sample: Send the In process Sample intimation note given to QC for composite sample of milled (Product Name) for Description, color value &pH.



11.1.12 Sifting (SFR-303): Place the HDPE/Fibre board drum lined with poly bag below the outlet nozzle of sifter for collecting the sifted material. Switch ON the Sifter and slowly charge the material in to the Sifter by SS scoop. FORMAT/QA/027/01



Company Logo Company Name and Address Title: Product Name Type of Validation: Department :



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



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17 of 26



Continue the sifting operation till batch quantity complete. Check the integrity of sieve visually after completion of sieving. Integrity: Satisfactory / Not Satisfactory. Note: If the integrity is not satisfactory, replace it with a new one and sieve the entire batch quantity again. 11.1.13 Packaging: Product shall be packed in transparent Polythene bag Qty. Qs then placed in Black Polythene bag Qty. Qs and then placed in HDPE/Fiber Board Container.



FORMAT/QA/027/01



Company Logo Company Name and Address Title: Product Name Type of Validation: Department :



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance Process Flow



FORMAT/QA/027/01



PROCESS VALIDATION PROTOCOL



Page No.:



18 of 26



Company Logo Company Name and Address Title: Product Name Type of Validation: Department : 11.2



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



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Batch details: Batch operation shall be carried out as per approved Batch Manufacturing record. Three consecutive batches shall be taken for validation studies. Batch number, Batch size in kg. Shall be recorded in validation report.



FORMAT/QA/027/01



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department :



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



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3.6



4.6/ 5.6



Reaction monitoring



During Addition of XXXXXXX Solution



Remove the sample from the reactor through Sampler



10 ml



pH adjustment



During Addition of XXXXXXX Solution



NA



NA



Isolation



After spin drying the Reaction Mass



FORMAT/QA/027/01



Sample solid material from Centrifuge



10 gm



--



Temp. 4550ºC and Time 60 min.



XXXXXXX content (NMT 1.0 %) Production Till & & QC Complies XXXXXXX XX (NMT 3.5%) pH 7- 8 Temp. 25-35ºC



30-60 min



Production



Once



HPLC- For Production Information & Sulphated & QC Ash- For Information



Remarks CPP



Acceptance criteria



Responsibility Production



30-45°C



CPP



NA



Every 60 Production min



CPC



NA



Frequency



NA



CPP



2.6 2.7



NA



None



Stir reaction Temperature mass at 452.5 and 50ºC for 60 Time min.



Quantity of sample



During Temperature Addition of 1.2 and XXXXXX Time Solution



Method Of Sampling



Process



Parameter



Critical Process Controls, sampling plan and acceptance criteria:



BMR Step No.



12.



Validation Protocol XXXXXXXX



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address



12.4



Loss on drying



Draw ~3g from Top, Middle, and Bottom trays of TD and then send to QC.



As per 14.2 After milling Specification



FORMAT/QA/027/01



Every 60 min



Production 100 - 105 0C



80 gm



At time interval Production LOD Limit: & QC of 6, 8 NMT: 0.5 % &10 hrs.



Once



QC



As per BMR



Remarks



Acceptance criteria



NA



Sample the material from tray dryer ~3g x 3 As per below fig. no. 1 & 2



Draw the one Composite sample from all drums.



Responsibility



Once



None



NA



10 gm



HPLC- For Production Information & Sulphated & QC Ash- For Information



10 gm



None



During Drying



9.3 Temperature



Once



HPLC- For Production Information & Sulphated & QC Ash- For Information



CPP



Sample solid material from Centrifuge



XXXX Wash



21 of 26



None



9.7/ 11.7



After completion of XXXX wash



Sample solid material from Centrifuge



Page No.:



CCP



8.6/ XXXXXX 10.6 wash



After completion of XXXXX wash



Quantity of sample



Method Of Sampling



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Process



Parameter



BMR Step No.



Type of Validation: Department :



Validation Protocol XXXXXXXX



Frequency



Title: Product Name



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address



FORMAT/QA/027/01



Remarks



Productio n & QC



Complete Analysis as per specification



None



22 of 26 Acceptance criteria



Quantity of sample 80 gm



For Complete analysis & stability



Draw sample from all containers make composite sample for complete analysis & stability



Page No.: Responsibility



Method Of Sampling



Finished 17.1 product Analysis



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Process



Parameter



BMR Step No.



Type of Validation: Department :



Validation Protocol XXXXXXXX



Frequency



Title: Product Name



+ 1.0 kg for each batch



After Sifting



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department :



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



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Drawing: Sampling of Tray dryer as per below Figure: b e c



a d Fig no. 1. Single Tray Top



Middle



Bottom Fig. No. 2 Tray Dryer (TD-304) 13.



Packaging and storage:



13.1



Product Containers: Product shall be packed in transperent Polythene bag [33x66] OR [30x50] Qs then Placed in Black Polythene bag [33x66] OR [30x50] Qs and then placed in HDPE/Fiber Board container.



13.2



Storage: Store in a well-closed container protect from light.



14.



Validation Acceptance Criteria: Manufacturing process of (Product Name) is considered as validated if three consecutive batches Manufactured as per approved Batch Manufacturing record, the following criteria are met. 1. Critical process controls are within defined acceptance criteria.



FORMAT/QA/027/01



Company Logo Company Name and Address Title: Product Name Type of Validation: Department :



PROCESS VALIDATION PROTOCOL



Validation Protocol XXXXXXXX



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



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24 of 26



2. Product meets the defined specification. 3. Yield of product is within defined acceptance range 14.1 Revalidation Criteria. 1. 2. 3. 4. 5. 6. 14.2



Any major change in manufacturing process which may affect the quality of product. Any change in batch size & batch formula. Manufacturing site Any modification in any critical equipment and major modification in utility system. Any change in source of Key starting material. Change in Primary packaging material.



Critical Process Controls: Critical process controls for (Product Name) shall conform to predefined acceptance criteria as per section 12.0



14.3



Yield Acceptance Criteria: 85.71 to 102.85 % on Input of XXXXXXXXX.



14.4



Stability Study: If acceptance criteria at all the stage of 3 batches are satisfied, the process to be accepted as validated for manufacturing the product at the site, sequent the validation batches shall be introduced for complete stability study as per stability protocol.



14.5



Conclusion: Based on the result of all the 3 batches suitable conclusion will be drawn with respect to the suitability of proposed process of manufacturing for the (Product Name) conclusion about the suitability of the validation batches for stability testing could be drown.



14.6



Report Approval: Process validation data shall be compiled and report shall be prepared by officer or Executive –QA this report shall be checked by Asst. Manager - QA, Manager - QC, Manager - Production and approved by Head -QA



15.



Changes and deviations: Any changes or deviations during the process of validation batches shall be documented and reported in the process validation report and Batch manufacturing Records.



FORMAT/QA/027/01



Company Logo



PROCESS VALIDATION PROTOCOL



Company Name and Address Title: Product Name Type of Validation: Department : 16.



Documents No. XXXXXXxXX Prospective Validation Quality Assurance



Page No.:



25 of 26



Validation summary: In the Process validation report present a summary of validation discussing Stability equipment suitability, input materials, critical process control parameters, product quality and yield. Draw appropriate conclusions on the validation and present any recommendations as a result of the validation including recommendation to correct any deficiencies observed.



17.



References: Sr. No. 1 2



18.



Validation Protocol XXXXXXXX



Document



Reference



Batch Manufacturing Record



: XXXXXXXXX XXXXXXXXXX



Specifications and Test Methods for Final product



:



Annexure: Annexure-01



: Training



Annexure-02



: List of standard operating procedures



Annexure-03



: Abbreviations



Annexure-04



: Specification for (Product Name)



FORMAT/QA/027/01



XXXXXXXXXXXX



Annexure-01



Annexure-02



LIST OF STANDARD OPERATING PROCEDURE S. No.



Title of SOP



SOP No.



1



Operating procedure for Reactor



XXXXXX



2



Operating Procedure For Centrifuge



XXXXXXX



3



Operating Procedure For Tray Dryer



XXXXXX



4



Operating procedure for Multimill



XXXXXX



5



Periodic cleaning Procedure for Dedicated Equipments



XXXXXX



6



Process Validation



XXXXXX



Annexure-03



ABBREVIATIONS S. No.



Code



Abbreviation



1. 2.



BMR MFR



Batch Manufacturing Record Master Manufacturing Record



3.



RBZ



(Product Name)



4. 5.



QA PDL



Quality Assurance Process Devlopment Lab



6.



SSR



Stainless Steel Reactor



7. 8.



GLR CF



Glass Lined Reactor Centrifuge



9.



TD



Tray Dryer



10.



MM



Multimill



11.



SOP



Standard Operating Procedure



12. 13.



PPE NLT



Personnel Protective Equipment Not Less Than



14.



NMT



Not More than



15.



ETP



Effluent Treatment Plant



16.



HDPE



High Density Polyethylene



17. 18.



PR COA



Production Certificate of Analysis



19.



RT



20.



CPC



Room Temperature Critical in process control



Annexure-04