Department Name Filling Building # Page No Page 1 of 27 Issued By (Q.A ) : : Production Manager : : INDEX No Description Page No Summary of Process Summary of Activities Batch Formulation Thawing of Bulk Antigen Lyophilizer Trays Processing Rubber Stopper Processing Processing Product contact Material for Pooling & Filling Vial Processing Room Pressure Recording Preparation of Lyophilizer Verification of Bulk Antigen Container Weights. Pooling & Clarification of Thawed Bulk and Preparation of Final Bulk Integrity Testing of Product Filter Filling Integrity Test of Vent Filters Loading of Lyophilizer Lyophilization Aluminum cap processing Sealing of vials Material Reconciliation record Bulk reconciliation record BMR Certification
Department Name Filling Building # Page No Page 2 of 27 The entire activity has the following major steps: Activity Day No 1 2 3 4 5 1. Thawing of Bulk Antigen 2. Cleaning and Sterilization of Lyophilizer Trays 3. Sterilization and Drying of Rubber Stoppers 4. Cleaning, Preparation and Sterilization of Material Required for Filling and Pooling 5. Cleaning and Sterilization / Disinfection of Lyophilizer 6. Washing and Sterilization of Vials 7. Pooling and Clarification to Prepare Final Bulk 8. Filling of Vaccine into Vials 9. Loading of Filled Vials in the Lyophilizer and Lyophilization 10. Sterilization and Drying of Aluminium Caps 11. Sealing Day 1 Day 2 Day 3 Day 4 Day 5 Day before filling Day of filling Day after filling 2 nd day after filling 3 rd day after filling Sealed vials with lyophilized vaccine are handed over to Screening Dept. for visual inspection. Pages 5 and 6 to be issued to Bulk section who will fill the details and send it back. Pages 25 To 27 to be issued to Lyophilization section who will fill the details and send it back.
Department Name Filling Building # Page No Page 3 of 27 SUMMARY OF ACTIVITIES Target Lyophilizer Number XXXX Lyophilizer Batch Capacity Vials Volume per vial ml (23) Batch Volume as Dispensed Bulk Mfg Dept L (24) of Filling dd/mm/yyyy Fill volume per vial (xx x xx) (Overfill mid point at +X %) ml (25) Batch Volume as Rechecked Filling Dept L Theoretical Batch Size Vials (28) Approx Filling Yield. [Quantity loaded in Lyophilizer] Vials (22) Approx Sealing Yield. [Quantity transferred to screening] Vials (19) Note: Acceptable variation between 24 and 26 which is caused removal of outer packaging / double bagging should not be more than ± X % Activity: BATCH FORMULATION Ref SOP No: Select the bulks for the batch on the basis of bulk Ag titre, volume, filling volume per vial, and batch size. Filling personnel* to cross check in terms of Weights on receipt. Component Bulk Ag No. Antigen Titre Vol. L *Gr Wt kg Tare Wt kg Limit XX L ± X% Actual Vol. L kg kg Set Ag Titre / vial Volume / Formulation: Dt: Weighing: Dt: Product X vial Done Checked Done Checked X ml Remarks:-
Department Name Filling Building # Page No Page 4 of 27 Activity : THAWING OF BULKS Ref SOP NO: The Bulks should be removed for thawing not more than xx Hours prior to estimated time of start of filling. THAWING DETAILS Particulars Product #12 Diluent Removed for thawing on (date) Location of cold room Bldg No CR No Bldg No CR No Removed for thawing at h h Incubator set temp ºC ºC (Range xx to xx C) Thawing completed on (date) Thawing completed at h h No Handling of Bulk Antigen Containers Done By Name Initials 1 2 3 4 Bulk Antigen Containers Received By: Remarks if any:
Department Name Filling Building # Page No Page 5 of 27 Activity : LYOPHILIZER TRAY PROCESSING Ref SOP No : 1. Clean the trays to be used for collecting filled vials using a clean lint free mop wetted with WFI/xx % Isopropyl alcohol. 2. The trays can be processed in either of two ways A) Load the cleaned trays on the dry heat sterilizer (DHS) trolley, as per validated max loading pattern in DHS No xxxx and sterilize at xxx C, xxx minutes B) Load the trays in Autoclave and sterilize at xxx C ± x C for XX minutes No of Trays Pattern No Pattern No 3. If option A above is selected, run the cycle to hold the trays at xxx C for xxx minutes. Normal variation x to + x C 4. Write Product, B.No., Charge No & date on the sterilizer thermograph/printout (for Option A only) sign it and attach it to this BMR No Description of Activity Done By Checked By 1 No of trays cleaned Quantity for batches: 2 Loaded cleaned trays onto the trolley. Loaded in Sterilizer Load pattern no Charge No # xxxxxx xxxx xx # xxxxxx xxxx xx Checked Cycle parameters A) xxx C, xxx minutes B) xxx C ± x C for xx minutes 3 Sterilization temperature xxx C achieved at h (applicable for option A above) 4 Sterilization temperature xxx C maintained till h (applicable for option A above) Remarks:-
Department Name Filling Building # Page No Page 6 of 27 Activity : RUBBER STOPPERS PROCESSING Ref SOP No : 1. Verify that QC approved stoppers of correct type have been taken for de-cartoning. 2. For RFS stoppers, after de cartoning directly move to sterilization. 3. Load stoppers as per validated loading pattern given below RFS Max No of stoppers / pouches xxxx Pattern No for Autoclave X xxxx Pattern No for Autoclave Y xxxx 4. The stoppers can be processed in either of the two ways: A) Sterilization in Autoclave X (xxx to xxx C) and drying in dry heat sterilizer (DHS) No B) Sterilization and drying in Autoclave Y. In both the cases, carry out sterilization at 121 C for xxx minutes, Write Product, B.No., Charge No and date on the sterilizer printout / thermograph sign it and attach it to this BMR 5. If option A above is selected, then transfer the sterilized rubber stoppers from the autoclave to the DHS from clean room side for drying. Start drying cycle: xxx C for xxx mins. Normal variation - x C to + x C/ ± x min. If option B above is selected then Sterilize stoppers at xxx C ± x C for xxx minutes followed a drying cycle for xxx mins in the autoclave. In case of greater variation in temperature or time, the deciding factor will be the moisture content. Write Product, B.No., Charge No and date on the sterilizer thermograph /printout (for Option A only) sign it and attach it to this BMR. 6. Draw one sample for Moisture content analysis (Limit NMT xxx mg/stopper). In case stoppers of 2 batches are sterilized in 1 load, draw only 1 sample, record both batch nos on TRF, attach copies to both BMRs A) Stopper input: xx mm, Lyo Grey Butyl Rubber 1) Unprocessed b/f: B.No 2) Processed b/f: B.No 3) Fresh quantity issued Actually Loaded for Sterilization 9) No of stoppers Pouches 4) Fresh used from issue 5) Option for Process A =1+2+4 B =1+4 Unprocessed Done Checked Remarks:
Department Name Filling Building # Page No Page 7 of 27 Activity : RUBBER STOPPERS PROCESSING, cont'd Ref SOP No : 7. Load pouches on the Autoclave trolley as per validated loading pattern. Autoclave No. / Equipment No. Charge No. Load Pattern No. Program No. ######## XX XX X ######### XX XX X Quantity for 1 / 2 batches Done Checked DHS No / Equip No #################### Charge X No.: Drying temperature xxx C for xxx minutes for drying in DHS Done Checked Achieved at : h Maintained till: h Sample for Moisture Content (11) Nos. NOTE: Filling activity should not be started before the result of moisture content estimation is received from Q.C. Remarks:
Department Name Filling Building # Page No Page 8 of 27 Activity : PROCESSING PRODUCT CONTACT MATERIAL FOR POOLING AND FILLING Ref SOP No : 1. Use filters based on the following table for B.Size for Filtration> xx L 2. Carry out pre-filtration integrity test using the following data INTEGRITY TESTING OF xx µm FILTER Make Name Part No Quantity/ Bubble Point Diffusion batch A B Tst pr. Rate XXXX xx 1 xx 2 xx 3 YYYY yy 1 yy 2 No bubbles at A, Bubbles should be seen < B, Units: BP, Diffusion Pr: Bar, rate: ml/min A) Pre-Sterilization Integrity Testing Application Stage Method Equipment Equipment No Test Type Step A Presteriliz n Manual XXXX Bubble Pt Auto XXXX Diffusion Filter Details Mfg/ Brand Part No Pore Size Wetting Liq. Test Parameter XXXX xx um WFI XXXX Filter Lot No Filter S.No Observation Result Done Check Bubbles seen at bar Printout attached Remarks:-
Department Name Filling Building # Page No Page 9 of 27 Activity : PROCESSING PRODUCT CONTACT MATERIAL FOR POOLING AND FILLING Ref SOP No : 1. Inactivation: Inactivate the Material used for Pooling and Filling in the Autoclave heating it to xxx C for x minutes. Record in the autoclave Log Book. (Variation xx C to xx C) 2. Preparation: Unload the inactivated material from the Autoclave on the Washing room side; Wash inactivated material passing Cooled WFI. Draw a sample from the tanks & check conductivity. Draw samples from Tanks, Silicon tube to header, Header, Syringes, needles & screen for particulates. In case the previous product is Media fill, draw additional samples submit to QC with Product Changeover TRF. On clearance wrap in sterilization pouches. 3. In case the vent filters on BV2 are new, carry out WIT and attach the results on opposite page. In case they continue from the previous day, the Post use integrity test of the previous batch will be treated as the pre-use integrity test of this batch. 4. Check the plan for the next day & select the loading pattern. Load the wrapped material on the autoclave trolley as per validated loading pattern. Attach a list of material sterilized, to this BMR. Write Product, B.No., Charge No and date on the sterilizer printout / thermograph (for Autoclave XX only) sign it and attach it to this BMR. Conductivity check on product tank rinse sample NMT 1 ms/cm Check xx BV1 BV2 Product C/O Done Checked ms/cm ms/cm ms/cm ms/cm NA TRF attached Visual Inspection of Product Contact material rinse sample Item BV 1 BV 2 Silicon tube Header Syringe Needle Fibres Particles Sampled : Screened : STERILIZATION OF MATERIAL FOR POOLING AND FILLING 1 Autoclave No / Equip No ######### / ######## Done Checked 2 Load Pattern number XXX XXX 3 Charge No XX XX 4 Program No XXXXX XXXXX Remarks:-
Department Name Filling Building # Page No Page 10 of 27 Activity : VIAL PROCESSING WASHING Ref SOP No : 1. Verify that QC approved vials of correct type have been taken for de-cartoning. 2. De-carton the Vials, transfer them into clean SS trays and pass them to the washing area. 3. Ensure WFI cooling assembly is sanitized before commencing Washing of x st batch. Ensure pressure of Fresh and Recycled WFI and compressed air, conductivity of Fresh WFI are within limits. Ensure area is free of previous product vials 4. Perform Test for Adequacy using X washed vials. 5. After operation is completed, drain the WFI assembly and clean the machine A) Vial input: x ml, xx mm X xx mm height, (Amber, tubular, USP type-1) 1) Unprocessed b/f: B.No 2) Processed b/f: B.No 3) Fresh qty issued 4) Fresh used from issue Done By Checked 5) Option for A=1+2+4 6) Taken for washing: - Process B=1+4 B Pre-washing and Washing operation checks: Done By WFI cooling Line Clearance WFI WFI Temp ass ly sanitized Checked Conductivity (xx to xx C) (NMT X ms/cm) Yes / No Yes / No ms/cm C Washing Media Outlet Fresh WFI Recycled Comp. Air Pressure (Range Bar ) WFI Set XXXXXXX xx - xx xx - xx xx-xx ########## Observed (Bar) Washing Started at : h Completed at: h Adequacy Sampled Results Time Pass / Fail h C Vial Output (7) Sampled (8) Rejected For Sterilization 6 - (7+ 8) = 9 Unprocessed 18 = 3-4 Remarks Checked
Department Name Filling Building # Page No Page 11 of 27 Activity : VIAL PROCESSING STERILIZATION Ref SOP No : 1. At the start of washing activity, ensure there is enough paper in the printer and a fresh circular chart is placed in the recorder. Ensure that the set points of the Heater Banks of the Tunnel Sterilizer are as per the following chart. Charge no: SET TEMPERATURES OF HEATER BANKS Heater Bank No S1 S2 S3 S4 S5 S6 S7 S8 Done Checked Temperature ºC 2. At the start of washing for the day, after the vials have reached the exit gate of the sterilization zone, the conveyor of the Tunnel shall automatically stop for ten minutes. This event shall be printed the controller. 3. The conveyor speed at the start of the washing i.e. till the vials reach the infeed of the filling machine should be xx Hz. Thereafter it will automatically switch to xx Hz. This event shall be printed the controller. No Description of Activity Time Done By Checked 1 Tunnel sterilizer started at h 2 Minimum set temperature (xxx C) achieved at h 3 xx Minute hold h to h* 4 Tunnel Set to Night operation (Process End) h 4. Attach the printout and circular chart to the BMR. Operators Washing and Sterilization:- Remarks:- * x st / x nd batch of the day.
Department Name Filling Building # Page No Page 12 of 27 Activity : VIAL PROCESSING STERILIZATION, continued Ref SOP No : 1. Check the pressures of the three zones of the tunnel, at least once, preferably at start of washing. If the pressures are not within the range given below, immediately stop washing activity and inform the Officer in charge 2. At the end of washing, perform sanitization of the bulk WFI cooling assembly 3. Write the Product, B.No., Charge no and date on the sterilizer printout / graph,sign it and attach it with this page of BMR. CHART SHOWING THE PRESSURES OF THE VARIOUS ZONES OF THE TUNNEL #XXX Drying Zone Sterilization Zone Cooling Done Checked Time Pressure Range (P1) mm wg (P2) mm wg Zone (P3) mm wg Observed Observed Remarks:- xx --xx xx --xx xx --xx Activity : ROOM PRESSURE RECORDING Ref SOP No. 1. Record Room differential pressure before entering the clean area for pooling and filling. No Room & range Observed value (Pa) 1. PAL 1 (xx-xx) 2. PAL 2 (xx-xx) 3. PAL 3 (xx-xx) 4. Filling (xx-xx) 5. Tunnel Room (xx-xx) 6. Sealing (xx-xx) 7. Pooling (xx-xx) Done Checked Time Remarks:
Department Name Filling Building # Page No Page 13 of 27 Activity: PREPARATION OF LYOPHILIZER Ref SOP No.: 1. After Unloading, Carry out cleaning of Lyophilizer and record in the BMR 2. Carry out Sterilization / Disinfection as below: A week 1 denotes 6 working days with the day the Lyophilizer gets Steam Sterilized/Steamed being declared the 1 st day of the week and the batch filled after steam sterilization/ steaming the 1 st batch. If the third batch is to be loaded later than the 6 th day of the week, it is treated as the first batch of the next week. The gap between Sterilization/disinfection step and loading should not be more than xx hours. For Lyophilizer No. A, B, C Batch Before Loading /week 1 1 st batch of week 2 nd batch of week 3 rd batch of week Lyo A Lyo B, C Lyo A, B, C Lyo A, B, C 3 Steam Exposure xxx mins Steam Exposure xxx C, xx mins Disinfection with XXX Disinfection with XXX 2 Steam Exposure xxx mins Steam Exposure xxx C, xx mins Disinfection with XXX 1 Steam Exposure xxx mins Steam Exposure xxx C, xx mins In case there is a change of product, with the virus of the current product not in the present product, the lyophilizer should be sterilized. Display boards: Cleaned, ready for Steam Exposure, and Disinfected with XXX ready for evacuation after Steam Sterilization, Steaming and treatment with XXX respectively. No Description of Activity Done By 1 Lyophilizer No: - Cleaning done after unloading of Product /Batch.No: 2 Remarks:- Strike out what is not used Steam Exposure Steam Exposure xxx mins xxx C, xx mins XX disinfection Checked
Department Name Filling Building # Page No Page 14 of 27 Activity : VERIFICATION OF BULK ANTIGEN CONTAINER WEIGHTS Ref SOP No.: 1. Unwrap the outer packing of the thawed bulk antigen containers 2. Check the Bulk antigen container numbers and record their gross Weights in the Batch Formulation Sheet. 3. Carry out surface disinfection and transfer them to clean room, through hatch. Net Weight of Formulation (Gross Tare on Page 5) Weight in g /ml (B) (From Page 20) (Same as kg /L) Net Volume of formulation (Net Wt / kg/l) kg kg/l (26) L Remarks:- Done Checked Activity : POOLING & CLARIFICATION OF THAWED BULK AND PREPARATION OF FINAL BULK Ref SOP No : 1. The contents of the Bulk antigen containers are pooled in a sterilized, SS blending vessel, with the jacket at a temperature NMT XX C. Start the magnetic stirrer (xxx to xxx rpm) after the level of bulk antigen inside the tank has gone above the impeller. If the temperature of the pool exceeds xx o C, immediately shut off the heating immersion circulator and the magnetic stirrer. 2. The pool of bulk antigens is clarified using a sterilized xx µm filter capsule/s. The outlet of the xx µm filter/s is connected to a 2 nd sterilized SS blending vessel with the jacket at a temperature of XX XX C. Clarification should be started only after the temperature of the pool is in the range of XX XX C for xx minutes. The contents of the second SS blending vessel will be the final bulk for the batch. No Particulars Done Checked 1 Bath temp before Pooling Pooling: xx-xx C Start End Blending vessel C h h A 2 Clarification: Temperature of Stirrer A, B Pool Final Bulk RPM Start time End time xx - xx C xx - xx C xxx-xxx C C h h 3 Filtration Residue (29) Sampled Bulk (30) ml XX ml x X bottles = XX ml Remarks:- B
Department Name Filling Building # Page No Page 15 of 27 Activity : POOLING & CLARIFICATION OF THAWED BULK AND PREPARATION OF FINAL BULK Ref SOP No : 1. Check the integrity of xx µm filter capsule bubble point method. Connect the SS blending vessel with the final bulk to the glass header only after the integrity test is done and the filter capsule has passed the test. 2. Inactivation: Inactivate the Material used for Pooling in the Autoclave heating it to XXX C for X minutes. (Variation permitted XX C to XX C) 3. Perform the environmental monitoring activities as per SOP No. This includes exposing settle plates, contact plates and Air sampling as per location map, Swabs of critical surfaces, Finger dabs of operators involved in pooling & filling operation FILTER INTEGRITY TESTING Application Stage Method Equipment Equipment No Test Type Clarification Post-Clarific n XXXXX XXXXX ######## Bubble Pt Filter Details Mfg/ Brand Part No Pore Size Wetting Liq. Test Parameter Filter Lot No Filter S.No Observation: bubbles @ bar Pooling material Autoclave No: Charge no: Inactivation Result Done Checked Done Checked Remarks:-
Department Name Filling Building # Page No Page 16 of 27 Activity : FILLING Ref SOP No.: 1. Volume per vial (23) is indicated on page 5 of this BMR. The Volume per vial is the lower limit of the permitted volume range. The upper range is calculated adding X % of the Volume per vial. The weight range is derived from this volume range multiplying it with weight/ml of the bulk. Calibrate the balance to be used for verifying the Fill volume. 2. Check for absence of previous product components. Carry out the priming of the header and the pumps, collect the priming liquid and send as sample of final bulk to Q.C. No Description of Activity 1 Volume / vial (23), Pg 5 XX ml 2 Weight per ml Calculation Volume Wt (Bulk WFI) (C) XX ml g 3 Volume Range to weight range setting Lower Vol. Limit (23) Upper Vol. Limit (23) x XXX=(E) Balance Calibrated YES / NO Wt (Final bulk) (D) g Lower Wt Limit (23) x (B) Line Clearance: Wt/mL (D/C) = (B) Upper Wt. Limit (E) x (B) Done Checked 4 XX ml XX ml g g Sampling for Visual Inspection (Sample size: XX vials) Fibre Black Part. White Part. Glass Total (%) 5 Filling activity : Filling machine XXXXXXXXX Room Started at Room Completed at Temp C Temp C Rh % h Rh % h Remarks:
Department Name Filling Building # Page No Page 17 of 27 Activity : FILLING Ref SOP No.: Rejection Quantity Vials (12A) Sample to QC Stopper (12B) (13) XX Total Loaded in Lyophilizer Done By Filled Appr. Vials Trays Vials (F) F- (G) (12A+13)=22 Checked Stoppers rejection details (12B=R1+R2) Balance processed (17) During filling (R1) Balance in hopper (R2) Vials Nos Stoppers Nos No Description of Activity Done By Checked 6 Rejection Inactivation details Autoclave No: Charge No: Operators: I Shift II Shift III Shift ID numbers of syringes used for filling STATION NUMBER 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Remark :
Department Name Filling Building # Page No Page 18 of 27 Activity : FILLING Ref SOP No.: 1. At the start of filling, reject the vials used for checking the centering of filling needles, volume setting etc. (Reject Not less than first xx vials) Syringe Number Attach Fill Volume Print or record manually, on weight basis, every xx Minutes Time (h) 1 2 3 4 5 6 7 8 9 10 11 12 Water bath temp xx-xx 0 C Done *Checked * Fill in case no printout is available, otherwise sign on printout Remarks:-
Department Name Filling Building # Page No Page 19 of 27 Activity : INTEGRITY TESTING VENT FILTERS Ref SOP No.: 1. On completion of the Filling activity, carry out integrity testing of the two vent filters (XXXX) of the Blending vessel tank attached to the filling machine WIT method. 2. Fill the upstream side with WFI at xx-xx o C. A hold at xxxx mbar should not produce an intrusion rate greater than xxx ml/min 3. Attach printouts below:- Remarks:-
Department Name Filling Building # Page No Page 20 of 27 Activity : LOADING OF LYOPHILIZER Ref SOP No.: 1. Ensure that the Lyophilizer to be loaded has been cleaned and Sterilized/disinfected, the date of loading should not be later than the date on the board (Pg.no 16) 2. The trays containing filled and half stoppered vials are to be transported to the Lyophilizer in a mobile class 100 trolley 3. Ensure that the temperature of the Lyophilizer shelves is xx ºC before loading of trays containing filled and half-stoppered vials. 4. After all the trays have been loaded in the lyophilizer, inform lyophilizer operator on duty. He will check the loading of the lyophilizer, insert product temperature probes and close the door of the lyophilizer. No Description of Activity Done By Checked 1. Checked, that Lyophilizer is Sterilized / Disinfected 2. Checked that Class 100 trolley is Switched ON 3. Vials Loaded in Lyophilizer No: Remarks:- Vol. Per Vial (23) xx ml Lyo. No:- Loading date Recipe No. Sterilization Details (see page 15) For Filling Dept: Lyophilizer B, C: 1 st Batch Steam Steriliz n. Lyophilizer A: 1 st Batch Steaming. 2 nd Batch / 3 rd Batch All Lyophililzers XX disinfection
Department Name Filling Building # Page No Page 21 of 27 LYOPHILIZER CHAMBER CLEANING, DISINFECTION AND STERILIZATION: 1. For Lyophilizers B and C, If Status board Cleaned, Ready for Steam exposure is displayed on clean room side, evacuate chamber to xxx mbar (Water ring vac pump: WP), followed steam exposure at xxx - xxx C for xx minutes. 2. For Lyophilizer A, If Status board Cleaned, Ready for Steam exposure is displayed on clean room side, evacuate chamber to xxx mbar (WP), followed steaming for xx mins. 3. Above steps are followed drying of chamber with WP for minimum xx mins. 4. For all Lyophilizers, If status board Disinfected with XXX, Start evacuation is displayed on clean room side, carry out evacuation as per SOP (XXX cycle: xx min evacuation vacuum pump with shelf at xx C) No Description of Activity Done By 1. Status board: Lyo B and C:'Cleaned, Ready for Steam Exposure Process xxx - xxx C maintained Process Start Start End End h h h h 2 Status board: Lyo A:Cleaned, Ready for Steam Exposure Vacuum Pull down Started xxx min Exposure Drying Start End Steam Start End End h h h h h h Drain temperature at the end of Steaming: C 3 Status board: Disinfected with XXX, Start evacuation Shelf temp. +xx C Evacuation with vac pump attained at Start End h h h 4. Display Board: Ready for Loading up to: 5. SHELF PRE-COOLING: (Set Shelf temperature: -xx C). yy C attained: h. Inform production dept. the achievement of yy C displaying the status board indicating time of attaining temperature 6. CHECK LOADING OF VIALS ON SHELVES (SOP No. ) No of shelves Loaded Loading end Time No. of product Door closing temp. Probes time h h
Department Name Filling Building # Page No Page 22 of 27 7. LYOPHILIZATION CYCLE DETAILS Step Freezing Condenser Chamber Primary Sec. Drying cooling Evacuation drying Shelf Temp - xx C NA NA -xx to xx C xx C Start Time End Time Duration X / X x ± x h x h x h xx ± x h x ± x h Norm X x ± x h x h x h 8 BATCH STOPPERING AND UNLOADING Ensure the following parameters before stoppering the vials. Avg. Product Temp Spec: xx ± x C Vacuum Spec: xx ± xx µbar Condenser Temp. Spec: - xx C C µbar C Stop the cycle and stopper the vials as per SOP No.. Time of Stoppering: h. 9 Chamber vacuum released sterile air at h. Instruct production department to unload the vials after breaking the vacuum air. xx h xx min ± x h Done / Checked By x ± x h DEVIATIONS DURING LYOPHILIZATION (if any) :
Department Name Filling Building # Page No Page 23 of 27 Activity : ALUMINUM CAPS PROCESSING Ref SOP No : 1. Verify that QC approved Aluminum Caps of correct colour have been taken for decartoning. 2. Remove the outer package and transfer the inner plastic bag to the sterilizer loading area. 3. The caps can be processed in either of the two ways: A) Sterilization in Autoclave X and drying in dry heat sterilizer (DHS) XX; B) Sterilization and drying in Autoclave Y. If option A is selected, then transfer the caps into clean SS trays, load into the autoclave as per validated loading pattern and Sterilize it at XXX C to XXX C for xx minutes. Pattern No 1 II No of Caps/trays 4. After sterilization, transfer the trays containing the Aluminium caps from the autoclave to the DHS via clean room side for drying at xxx C for xx mins Normal variation x C to + x C 5. If option B is selected then process the caps at xxx C ± x C for xx minutes in the autoclave. 5. Write /verify Product, B.No., Charge No and date on the sterilizer thermograph / printout (for Option A only) sign it and attach it to this BMR A) Aluminum Cap input: 13 mm, Colour Done 1) Unprocessed b/f: B.No 5) Option of Process No A =1+ 2 + 4 B =1+ 4 Description of Activity 2) Processed b/f: B.No 3) Fresh quantity issued 4) Fresh used from issued Nos Nos Nos Nos Unprocessed quantity from this batch (18) (3-4) Nos 6) Taken for Sterility = 9 (For 1 / 2 batch/es) B) Loaded in Autoclave No. ################ Charge No. Load Pattern No Prog No. Checked C) Aluminum Cap Drying at xxx C in DHS No: ########### Charge No. xxx C Achieved at xxx C Held till h h Remarks:-.
Department Name Filling Building # Page No Page 24 of 27 Activity : SEALING OF VIALS Ref SOP No : Lyophilizer Unloading: 1. After the lyophilization operator on duty has informed you about completion of lyophilization cycle, open the door of the Lyophilizer &unload the trays containing the lyophilized vaccine 2. Clean and Sterilize/disinfect the lyophilizer. Record the same in the BMR of the batch to be loaded. Sealing Operation: 1. Carry out sealing operation on the vials unloaded from the Lyophilizer. 2. The trays containing the good sealed vials should be transferred to visual inspection department through the material transfer hatch. 3. The sealing rejection should be loaded in autoclave and heated at xxx ºC (xx to xxx o C) for x minutes and then unloaded from the autoclave from the washing room side. Unloading & line Clearance: Rejection in Lyo Sensor (14) Vials Rejection & inactivation details Empty vial (15A) Bad seal (15B) Approx. Vial for sealing (22)-(14) = (H) Description of Activity Sealing machine used XXXXXX XXXXXX Autoclave No: Breakage (15C) Vial, Stopper Rej 15A to 15C =(15D) Started (h) Charge No: Cap rej (15E) Sealing Completed (h) Processed Caps (17) Done By Checked nos nos nos nos nos nos Approx No of Vials Handed Over To Visual Inspection Department H-15D= Trays Vials Vials Received screening: Name: : (for Screening Dept)
Department Name Filling Building # Page No Page 25 of 27 Activity: MATERIAL RECONCILIATION RECORD No Description Vial Stopper Caps 1 Bal. Unprocessed Material b/f (18) Quantity Prod / Batch No 2 Bal. Processed Material b/f (19) Quantity Prod / Batch No 3 Fresh Material Issued Quantity 4 Quantity used from Fresh material Res. Doc No. 5 Option for washing/sterilizing [A: 1+2+4, B: 1+4] A / B A / B A / B 6 Total Quantity for Washing or Transfer based on (5) 7 Sampled for Adequacy of Washing XX X X 8 Rejected during Washing or Transfer X X 8A Rejection in % [(8/6) x 100] Limit: 2% 9 Sterilized [6-(7+8)] 10 Quantity for Filling/Sealing (If 5: A, 10=9) (If 5: B, 10=9+2) 11 Sampled- Post Sterilization x x 12 Rejection- Filling stage x 13 Sampled- Filling stage xx xx xx 14 Rejection: Lyophilization stage x 15 Rejection: Sealing stage 16 Post Sterilization Sample and Rejection (Sum 11 to 15) 17 Bal. Processed Material Quantity c/f Prod/Batch No or ICN 18 Bal. Unprocessed Material Quantity [3-4] c/f Prod/Batch No or ICN 19 Quantity of vials for visual inspection 20 Variance* In No: [(1+2+3)-(7+8+16+17+18+19)] In percent: [(In no)/(10-17)] x 100, 21 Consumption (1+2+3)-(17+18) *Permissible variance ± X % Vial and Cap, ± X % Stoppers
Department Name Filling Building # Page No Page 26 of 27 Activity: BULK RECONCILIATION RECORD After the sealing activity is over, reconciliation on the basis of final bulk should be done to determine the percentage yield for the batch. No Description (A) (B) 22 Quantity of vials Loaded in Lyophilizer Vials 23 Volume per Vial as declared Bulk Mfg Dept X ml 24 Batch Vol. dispensed Bulk Mfg Dept L 25 Fill Volume X ml 26 Batch Vol. rechecked Filling Dept L 27 Post Clarification Yield [26-(29/1000)] L 28 Theoretical yield [(26) x 1000]/ (25) Vials 29 Blending & Filtration residue (29A=26-27) 29B=29A/25 ml Vials 30 Sample in Liquid Form [Filling stage] XX ml 31 Excess Volume Balance in Tank after filling ml 32 Total Liq Samples /Losses [32A=29+30+31] 32B =32A/ 25 ml Vials 33 Total Loss/Samples as vials (32B+16) Vials 34 Expected Yield 28-33B Vials 35 Final yield [(19) / (28B) x 100] (not less than XX%) % 36 Percentage Reconciliation [(19) / (34B) x 100] % Stage: Post Clarific n Filling Lyophiliz n and Sealing Total Calc x 100 29B / 28 [(28-29B)-22]/(28- (22-19) / 22 Sum of all 29B) Norm (NMT) x % x % x % x % Actual: Remarks: DEVIATION: Yes / No. If yes, Report date/s:
Department Name Filling Building # Page No Page 27 of 27 01. MANUFACTURING DEPARTMENT : BMR CERTIFICATION The contents of this Document have been checked and verified me. The information contained herein is complete and true to the best of my Knowledge. Deviations if any are reported. Hence submitted to Quality Assurance department. Signature of Production Officer : of Completion of Submission : : 02. QUALITY ASSURANCE DEPARTMENT : I here certify that, this batch record is reviewed me, to ensure that the above mentioned batch process has been carried out according to the Authorized Master formula and processing instructions. All operational steps have been scrutinized and approved according to the checklist (attached ) and have been found to be complete. Signature of Quality Assurance Review Officer : of Receipt of Approval : :