BATCH PREPARATION OF SVP PRODUCTS
To establish the written procedure for batch preparation of SVP products.
This SOP shall be applicable for batch preparation of SVP products at SVP section
3.0 REFERENCE(S) & ATTACHMENT(S)
3.1.1. USP <797> Pharmaceutical compounding sterile preparation.
3.1.2. PIC/S “guide to GMP for medicinal products (PE-009-8).
3.2 CROSS REFERENCE DOCUMENTS
- Document(s) and Data Control Procedure
- Training Program for Employees
- Preparation, review, approval, issuance & retrieval of standard operating procedure (sops)
3.2.4. CIP & SIP of manufacturing tank, holding tank, product line, filter assembly & FFS machine
3.2.5. Operation & monitoring of mfg. tanks (500 liters, 1500 liters) & holding tank 300 liters.
3.2.6. Transfer of dispensed raw material in manufacturing area
3.2.7. Operation & monitoring of manufacturing Tank (1500 liters, 500 liters) & holding tank (300 liters) .
- DEFINITION & ABBREVIATION(S)
- 1. DEFINITIONS
4.1.1. Batch Preparation: Batch preparation/compounding means processing of batch in a single discrete process by the same individual(s) carried during one limited time period. It is the creation of particular of pharmaceutical product to fit the unique need of patient to perform compounding or preparation, pharmacist combined or process appropriate ingredients using various tools.
4.1.2. Compounding: The process of combining, admixing, diluting, pooling, reconstituting, repackaging or otherwise alerting a drug or bulk product substance to create a sterile medication. Preparing a conventionally manufactured sterile product in accordance with the directions contained in approved labeling provided by the products manufacturer is not compounding as long as the product is prepared for an individual patient & follows the provision of administration.
QA : Quality Assurance
QC : Quality Control
SOPs : Standard Operating Procedures
cGMP : Current Good Manufacturing Practice
SVP : Small Volume Parenteral
NA : Not Applicable
IPA : Isopropyl Alcohol
USP : United State Pharmacopeia
WFI : Water for Injection
CIP : Cleaning in place
SIP : Sterilization in place
BMR : Batch Manufacturing Record
PIC/S : Pharmaceutical Inspection co-operation scheme
SAP : System Application & product in data processing
AHU : Air Handling Unit
COA : Certificate of Analysis
5.1 Originating department shall be responsible:
5.1.1. Preparation of the SOPs.
5.1.2. To perform the operation/cleaning as per the respective SOP.
5.1.3. To perform the activity as per SOP.
5.1.4. To maintain the record & BMR
5.1.5. To provide sample to QA designee.
5.1.6. To provide the training of the SOP to concerned personal.
5.1.7. To get SOP approval from all signatories.
5.1.8. To follow the described here in.
5.1.9. Initiation of change control to modify/revise the SOP.
5.1.10. Co-ordinate with other departments to provide RM as well as utilities.
5.1.11. To maintain the area.
5.2 Head of Originating department/designee shall be responsible for:
5.2.1. Ensure that sub-ordinate, operators are trained before performing any task or operation.
5.2.2. To check the SOP for proper contents/technical parameter as per the equipment.
5.2.3. To get the SOP approval from Quality Assurance or designee.
5.2.4. To provide the training of SOP to the concerned personnel before effective date of the SOP.
5.2.5. To ensure implementation of the SOP on effective date.
5.2.6. To maintain the controlled copies of the SOPs at required location.
5.2.7. To verify that all instruments as well as equipment are in proper working condition.
5.2.8. To provide the planning to other departments & sub-ordinates.
5.2.9. To rectify the troubleshooting.
5.2.9. To verify the records on routine basis.
5.3 Quality Assurance department shall be responsible for:
- 3.1. To verify that all content of SOP are relevant to the concern equipment & process.
5.3.2. To maintain the approved master copy of the SOP of all department for document control.
5.3.3. To issue the required number of controlled copies to the departments and document the same.
5.3.4. To verify that all the instructions are followed properly as per the given SOP.
5.3.5. To ensure implementation of SOP.
5.3.6. To verify that records/log books are maintained as per defined system.
5.3.7. To verify instrument is calibrated before operation.
5.3.8. To verify that instruments & equipment are in proper working condition before performing any task.
5.3.9. To provide line clearance.
5.3.10. Responsible for sampling.
5.3.11. To verify the dispensed raw material.
5.4 Head – Quality Assurance/ Designee shall be responsible for:
- 4.1. To approve new or revised SOP.
- 4.2. Review of draft SOP for technical, function, regulatory and cGMP compliance.
- 4.3. Final approval of the SOP by signing off as approved by.
- 4.4. To ensure the implementation of the defined system.
5.5 Engineering person shall be responsible for:
5.5.1. Co-ordinate with production person for schedule preventive maintenance of equipment.
5.5.2. Perform maintenance of system as per respective SOP.
5.5.3. To provide all utilities for processing.
5.5.4. To maintain the record of preventive maintenance.
5.6 Plant Head shall be responsible for:
5.6.1. To approve new or revised SOP.
5.6.2. To ensure the implementation of the defined system.
6.1.1. Always wear proper sterilized gowning, gloves and masks while performing the batch processing activity.
6.1.2. AHU of the area should be not switch OFF condition at the time of batch processing.
6.1.3. Area sanitization & cleaning activity should not perform during batch preparation & should be complete before activity.
6.1.4. All the tanks product line should be properly clean from inside & outside before batch preparation.
6.1.5. After fogging remaining solution should be discard immediately to avoid any rusting of fogger.
6.1.6. Viable & non-viable particle should be in limit.
6.1.7. No other product batch or raw material should be there during batch processing.
6.1.8. All the clamps of WFI loop line to be tighten properly.
6.2 CHECK POINTS PRIOR TO BATCH PREPARATION:
6.2.1. Ensure availability of production plan on weekly basis or monthly basis.
6.2.2. Ensure availability of BMR with approved check list.
6.2.3. Ensure manufacturing area with corresponding air locks is properly clean and sanitized before start batch preparation with schedule disinfectant solution.
6.2.4. Ensure environmental condition (temp./humidity, differential pressure, non-viable & viable particle count are within permissible limit.
6.2.5. Ensure manufacturing tanks, filter assembly, product line & filling machine are clean and sterilized.
6.2.6. Ensure product filters, vent filters are passed in filter integrity test.
6.2.7. Ensure WFI availability, Temperature of WFI maintained above 80ºC & release from QC for chemical & microbiological analysis.
6.2.8. Before collecting WFI for batch preparation in the tank, check vent filter valve mounted on the tank is open & drain valve is close.
6.2.9. Verify that gowning are sterilized & gowning procedure is properly followed.
6.2.10. Line clearance of the area & the machine.
6.2.11. Verify that sterile gloves are worned by concern person.
6.3 MANUFACTURING PROCESS OF STERILE WATER FOR INJECTION
6.3.1. Batches of SWFI prepared in manufacturing room I facility of SVP section & for these product dedicated 1500 liters tanks is installed over there.
6.3.2. To prepare SWFI batch first collect WFI (80-90ºC) in the manufacturing tank (1500) liters by opening the WFI loop valve connected to it as per the standard batch size mentioned in BMR.
6.3.3. Check the fill volume in the tank with level transmitter connect to the tank & volume will be displayed on HMI of the tank.
6.3.4. As the required volume as per BMR filled in the tank close the loop valve of WFI.
6.3.5. Verify the temperature of filled WFI on HMI & start cooling to WFI up to 40-50 ºC with the circulating chilled water in the jacket of manufacturing tank.
6.3.6. As the required temperature achieved collect 50 ml sample, check for pH & conductivity of the same on HMI & verify the same on offline pH meter & conductivity meter.
6.3.7. IPQA person will collect the bulk sample 300 ml in a clean and dried Glass bottle, from the sampling point of the tank & transfer to QC for chemical & microbiological analysis as per the bulk testing specification against duly signed SAP generated bulk sample request slip with proper batch detail.
6.3.8. After getting bulk result with COA, production person will start further process of aseptic filtration & filling.
6.3.9. Duly fill all the steps and attach all intimation slip as well as reports/graph in BMR.
6.3.10. Make entry in production activity log book.
6.4 MANUFACTURING PROCESS OF RESPULES/EYE DROPS PRODUCTS:
6.4.1. During startup the batch processing activity of particular product, BMR of the same should be available.
6.4.2. Follow the steps of BMR.
6.4.3. Manufacturing of respules/eye drops product consist of three main stages.
188.8.131.52 .RM, PM dispensing
184.108.40.206 Batch manufacturing
220.127.116.11 Batch filling
6.4.4. Dispense, Issue approved raw material & packing material on the basis of SAP generated BOM sheet.
6.4.5. Transfer the issued raw material in the manufacturing room or day store room as per SOP
6.4.6. Verify the weight material by production person before compounding of batch.
6.4.7. Batch processing of respules/eye drops will be performed in 500 liters manufacturing tanks in manufacturing room II.
6.4.8. Start the processing of batch preparation as per the standard manufacturing process in BMR & add the ingredients as per the step given in the BMR.
6.4.9. During addition of ingredients be careful there should be no spillage of material.
6.4.10. After addition of all ingredients, proper mixing and stirring time to be followed as per the standard manufacturing process.
6.4.11. After complete addition and dissolution of all ingredients make up the final volume with WFI & verify the final volume with load cell & also with ss dip stick.
6.4.12. Dip stick should be clean properly with WFI before dipping in the solution.
6.4.13. Check & adjust pH on calibrated pH meter.
6.4.14. Continue nitrogen supply in the tank during manufacturing process.
6.4.15. IPQA person will collect the bulk sample 300 ml in a clean and dried Glass bottle, from the sampling point of the tank & send to QC for chemical & microbiological analysis as per the bulk testing specification against SAP generated bulk request slip with proper batch detail.
6.4.16. Mention all the process steps, time, and ingredients quantity in BMR.
6.4.17. After getting bulk release from qc & receiving of COA, start further processing for aseptic filtration & filling.
6.4.18. Filter the solution through sterilized & integrity tested production filter (1.0 micron & 0.22 micron) of 10” in the clean & sterilized holding tank 300 liters with the transfer pump.
6.4.19. During filtration holding tank should be properly closed & vent filter of the same is open.
6.4.20 After filtration & line clearance operate the filling machine as per SOP & start filling as per the desired fill volume.
6.4.21. During filling check all the machine parameters & mention all the activities in the BMR.
6.4.22. Make entry in the production activity log book.
7.0 REVISION HISTORY
|Version No.||00||Effective date|
Detail of revision:
New SOP introduce in system.
Attachment – I
|Company logo||Company Name & address|
|Production activity log book for SVP section|
|Date||Time||B. No.||Activity||Description||Performed by||Checked by||Remarks|