BATCH MANUFACTURING RECORD OF DRY INJECTION
Table of content
- Batch Details
- General Instructions
- Calculation of API
- Dispensing of raw material
- API transfer record
- Dispensing of primary packing materials
- Component preparation for sterilization
- Steam sterilization record
- Vial de-boxing, Staging, and Inspection record
- Vial washing record
- Vial depyrogenation record
- API Canister weight checking records
- Vial filling record
- In-process checks
- Pre-startup test record for vial filling and sealing
- Vial Sealing record
- Optical testing record for filled and sealed vials
- Material Return record
- Filling Summary
- Material reconciliation record
- Material destruction record
- Packing Summary
- Final Yield statement
- Description of deviation observed during Batch Manufacturing
Date of filling
Theoretical Batch size (No. of vials)
Filling stage
Total no. of vials filled (A)
Total no. of Vials rejected during filling (B)
Total no. good vials transfer to sealing (C)
Sealing stage
Total no. of Vials rejected during Sealing (D)
Total no. of vials transferred to Visual inspection (E)
Visual Inspection
Total no. of vials rejected during Visual inspection (F)
Total no. of Good vials after Visual Inspection (G) = E- F
Semi-Finished Sample (H)
Total no. of good vials transferred to Labelling and Packing (I) = G -H
GENERAL INSTRUCTION:
Follow these general instructions before starting batch manufacturing operations.
All the Standard Operating Procedures are Unit operation based and the current version of the SOPs shall be followed.
Before issuance of materials, check the API and packing material for the correct AR number, QC-approved status label & identity. Record the issued quantity in batch manufacturing record.
Enclose the dispensed material labels to batch manufacturing records.
Ensure that the status boards are updated at all applicable stages before the start of batch manufacturing activity.
Ensure the cleanliness of the equipment and area before the start of batch manufacturing activity.
Ensure that the Temperature, relative humidity, and differential pressure are within the specified limits before the start of the batch manufacturing operation.
Get the line clearance from IPQA Officer.
Carry out the Decartoning, Vial Washing, Depyrogenation, Filling and Stoppering, Sealing, and Inspection activities as per the respective BMR and SOPs.
At the end of the batch manufacturing operation, transfer the unused intact primary packing material to the Store through Material Return Note.
At the end of the batch, manufacturing activity records the destruction details of leftover materials in BMR
Weigh and record the hopper leftover quantity where ever applicable.
CALCULATION OF API (ACTIVE PHARMACEUTICAL INGREDIENTS):
BILL OF MATERIAL
- Material code
- Name of API
- UOM
- Standard Quantity
- API Batch Number
- A. R. Number
- Assay (%)
- LOD(%)
- API Mfg. Date
- API Expiry /Retest Date
For Product Cefotaxime Sodium USP(Sterile) Dry Powder
TARGET FILL WEIGHT CALCULATION
Name of The API – Cefotaxime Sodium USP(Sterile) ,Label Claim = 1.0 g
Composition: Each vial contains: Cefotaxime Sodium Sterile USP equivalent to Cefotaxime 1.0 g.
Calculate the actual target fill weight using the following formula.
Calculation of Assay (%) from Potency (μg) = Potency (μg)X 100 x100/1000
Assay (%) =___________ X 100 /1000 =…………. %
TARGET FILL WEIGHT = 1.0 x100x 100 /Assay (%) as Cefotaxime x (100 – LOD % ) = ________ g/vial.
CALCULATION OF ACTUAL BATCH SIZE
Quantity of API in Kg _______________Target Fill Weight__________g/ vial.
Actual Batch size = Quantity of API in Kg X1000 == ______ No. of vials, Target fill weight in (g)
Actual Batch size =X 1000 = __________ No. of vials.
DISPENSING OF RAW MATERIAL (API)
INSTRUCTIONS: Ensure that all current versions of SOPs are followed at all stages of dispensing.
LINE CLEARANCE: Take Line clearance from IPQA before starting the dispensing activity as per the respective SOP.
- Check the following: Area Cleanliness
- Temperature and Relative Humidity is within specified Limits
- The intactness of all API canisters to be issued
- Material Code and Material Name of the API
- Approval status and AR. No. of API
- API canisters number
- The gross weight of all API canisters
- Manufacturing and Expiry / Retest date of the API Issued.
After Line clearance, dispense the Raw materials as per Respective SOP
RAW MATERIAL DISPENSING
- Material Code
- Name of the Ingredient – Cefotaxime Sodium USP(Sterile)
- Quantity Required
- Quantity Dispensed
- AR No.
- Dispensed by (Ware House)
- Checked by(Production)
- Verified by(IPQA)
VERIFICATION OF API CANISTER WEIGHTS
No. of Canisters Issued – Canister No. ,Gross Wt.(kg) ,Canister No.Gross Wt.(kg)
TOTAL API QUANTITY DISPENSED (No of canisters x Net Qty per canister)
= {______ X ______ } + {______ X ______ } = ___________Kg
Received By (Production)_______Verified By_______(IPQA)
API TRANSFER RECORD
INSTRUCTIONS:
(1) Transfer the dispensed API canisters from stores to IRM (Interim Raw Material) store as per SOP.
(2) Disinfect the outer surface of the canister with 20 % Virosil.
(3) Keep the disinfected canisters in the Dynamic pass box.
(4) After 30 minutes of UV exposure unload the canisters from the aseptic side.
(5) Disinfect the canister using 70% IPA solution.
(6) Place the disinfected canisters below the LAF in the sampling room till transferred to the vial filling room.
LINE CLEARANCE: Take Line clearance from IPQA before the API transfer as per respective SOP.
Check the following:
- IRM store Area cleanliness
- Availability of Disinfectant
- Removal of previous Product / Batch material
- Cleanliness of the pass box
- Ensure proper working of the pass box
Total No. of API Canisters received
Date of Transfer
Number of canisters
Outer surface of Canister cleaning and sanitization with 20% Virosil
Hold time in Dynamic pass box ( NLT 30 minutes)
Date of receipt
After unloading of canister clean and sanitization with 70 % IPA solution
Done by____Checked by______Verified by_____
DISPENSING OF PRIMARY PACKING MATERIAL
INSTRUCTIONS:
(1) The material should be Dispensed by a Warehouse person as per the respective SOP.
(2) Ensure affix the tags in all dispensed materials
(3) Production person shall check the dispensed material before transfer to the production area.
(4) IPQA person shall cross-verify the dispensed material before transfer to the production area.
(5) Attach the dispensed labels to the BMR.
LINE CLEARANCE: Take Line clearance from IPQA before starting the dispensing activity as per the respective SOP.
Check the following:
- Area Cleanliness
- Temperature and Relative Humidity are within specified Limits
- The intactness of all materials to be issued
- Material Code and Material Name
- Approval status and AR No. of primary packing materials
- Ensure that the shipper is not damaged or deformed.
- Material Code
- Name of the material
- #Std. Batch Qty (No.)
- Batch Size
- Actual Quantity Required
- Qty Issued (No.)
- Manufacturer / Supplier
- A. R. No.
- Dispensed by Warehouse
Rubber Stopper: 20 mm Grey Bromo butyl rubber stoppers
Vial: 20 ml Moulded Glass Vials Type – III (USP)
Seal:20 mm Royal Blue colour
PP disk Aluminium Seal (Plain).
Note: Issuing Quantity will vary depending on the individual pack sizes. A loose quantity shall not be issued.
#Standard batch size is considered as 10000 vials for calculation purposes. Quantities are inclusive of 2% excess.
COMPONENT PREPARATION FOR STERILIZATION
Name of the Equipment
- Table Mounted LAF
- Ceiling Suspended LAF
- Filter Integrity Test Apparatus
- Pouch sealing Machine
INSTRUCTIONS:
(1) Transfer the machine parts & accessories to the washing area.
(2) Transfer the machine parts to the LAF workstation & clean them as per SOP.
(3) Pack the cleaned parts and accessories for sterilization as per Respective SOP
(4) Check the integrity of the filters before loading them into the sterilizer as per SOP.
(5) Load sterilizer as per the validated load pattern for sterilization and drying as per SOP.
LINE CLEARANCE: Take Line clearance from IPQA before the component preparation & sterilization as per respective SOP.
Check the following:
Cleanliness of preparation and sterilization area
Cleanliness of Equipment in preparation and sterilization area
Cleanliness and working of the LAF workstation
Manometer reading of the LAF (8 to 15 mm of Water column)
Availability of wrapping material
Availability of Utility
Availability of clean and dry garments
Machine parts□, Miscellaneous items, and Rubber stoppers.
Status labeling
Working on the Integrity testing apparatus
Availability of WFI / P.W for cleaning of machine parts
Availability of Equipment (Tools) for Opening machine parts (disassembling) before washing.
FILTER PRE-INTEGRITY TESTING: BEFORE USE (PRE-FILLING)
FILTER PRE-INTEGRITY TESTING: BEFORE USE (PRE-FILLING)
Filter – 0.2 µ Hydrophobic filter
Function – Sterilizing grade filters for compressed gases
Filter Lot no.
ROOM NAME: PREPARATION AND STERILIZATION ROOM
(Compressed air) & 0.2 µ Hydrophobic filter (Nitrogen gas) – Water Intrusion Test (WIT) Limits: _____ml/min
(Compressed air) & 0.2 µ Hydrophobic filter (Nitrogen gas)- Observed value_____ml/min
WASHING AND PREPARATION OF MACHINE PARTS AND ACCESSORIES
Filling Machine Parts
Garments
Disinfectant Filtration accessories
Rubber Stoppers
Rinse water samples for machine parts
Rinse water samples for rubber bungs
Note: Attach Rinse water (Machine parts, Rubber bung) and swab sample reports to BMR, as required.
STEAM STERILIZATION RECORD
Name of the Equipment
- Bung Processor cum Steam Sterilizer
- Ceiling Suspended LAF
- Mobile LAF
INSTRUCTIONS:
(1) Clean the sterilizer.
(2) Load the sterilizer as per the validated load pattern
(3) After the completion of sterilization unloads the sterilized articles.
(4) Attach the printouts to the BMR.
(5) Ensure that the LAF workstation is in operation.
LINE CLEARANCE: Take Line clearance from IPQA before sterilization as per respective SOP.
Check the following:
- Preparation and sterilization area cleanliness
- Working and Cleanliness of Equipment
- Availability of Utility
- Previous Product/Batch material Removal
- Status labeling
- Completion of Equipment logbook / Sheet
- Manometer reading of the LAF (8 to 15 mm of Water column).
STERILIZATION RECORD:
Date
Load details
Load Number
Start time
Pre pulses
Sterilization Hold – From______To____
Post pulses
End time
Note: Verify each Sterilization cycle printout after sterilization is complete and attach it to BMR
Sterilizer load pattern and sterilization cycle parameters
loaded by______Unloaded by______
ASEPTIC AREA ACTIVITY DETAILS
INSTRUCTIONS: Before startup of batch processing (on the day of filling) verify the following activities.
Previous Day Activity
- Day end Cleaning
- Disinfection / Fogging
Machine Parts Assembly
- Assemble dosing disc
- Assemble side guards
- Assemble Intermediate hopper
- Assemble the main hopper
- Assemble the Rubber stopper chute and stoppering head
- Assemble rubber stopper bowl
- Assemble connecting tube
- Assemble the pack /canister with butterfly assembly to the connecting tube
- Rubber Stopper transfer from cooling zone to filling room
- Microbiological Monitoring
- Ensure Media Plates Expose during the operation
- Centrifugal air Sampling / Personnel Monitoring