CEFEPIME AND AMIKACIN FOR INJECTION 1.25GM
PRODUCT PROFILE
Generic Name: CEFEPIME & AMIKACIN FOR INJECTION
Strength :.25 GM
Lot size: 70500 units
Average Filled Weight: 2.15 gm/vial
Label Claim: Each vial contains:
Cefepime Hydrochloride USP
equivalent to Cefepime ___________ 1000 mg
Amikacin Sulphate IP
equivalent to Amikacin _____________250 mg
Shelf Life: 2 Years
Dosage Form: Dry powder for Injection ( For IV Use ).
OPERATING PARAMETERS: Room Temperature : 23 + 2°C and Relative Humidity : 25 + 5 %
MANUFACTURING FORMULA
| S.No | Ingredient | Standard Quantity | Compensation Factor | Required Quantity |
| 01 | Cefepime Hydrochloride USP | 70.500 KG | 80.00% | 126.90 KG* |
| 02 | Amikacin Sulphate IP | 17.625KG | 40.00% | 24.675KG* |
* Exact Required Quantity depends upon Assay and Moisture / LOD content of Raw Materials.
1. Required Quantity of Cefepime Hydrochloride:
= Lot Size in No. X 1.0 gm X 10 / Assay on anhydrous basis X (100 – Moisture) = _________________
2. Required Quantity of Amikacin Sulphate:
= Lot Size in No. X 0.25 gm X 10 / Assay on anhydrous basis X (100 – Moisture) = _________________
PACKING MATERIALS :
| Item | Specification | Quantity |
| Vials | 10 ml Vial ( Tubler ) White type I | 72262 |
| Seal | 20mm F/O White ( Button Type ) | 74025 |
| Plugs | Rubber Plugs 20mm Grey Butyl ( RFU ) | 72262 |
GMP CHECKLIST
- The area is free from unwanted material as well as the material from the last batch/ product.
- All equipment and containers used in processing in this batch are cleaned to the required standard.
- The wash water analysis report is available in case of product change over.
- The product is labeled at all stages with all details such as the name of the product, Lot no., and Mfg. date, Exp. date.
- All the instructions of manufacturing procedure are strictly followed and any deviation is made only after consultation of manager Q.A and recorded.
- The temperature and relative humidity of the manufacturing area is 23 + 2°C & 20% – 30% respectively and these parameters are checked and recorded every 1 hour by operation and 2 hours by QA during the process.
- Sterile dress is worn during the manufacturing process.
- All the critical parameters are to be recorded as per BMR.
PRECAUTIONS:
a) All parts in contact with the product must be of inert material.
b) Wear proper dress and accessories while handling raw materials.
c) Check that the Blender is thoroughly cleaned.
d) Keep the sample collected at each stage separately till the batch manufacturing is Completed.
f) Check autoclave load indicators (chemical) of sterile loads before using every individual.
g )Check all print out of equipment.
EQUIPMENT CHECKLIST :
S.No. Equipment Previous prod. Cleaned by Checked by
- SS Hopper
- L inner vial machine
- Vial filling and stoppering machine
- Vial sealing machine
- SS Treys
- Sterilization and depyrogination Tunnel
- Autoclave
- Electronic balance
DISPENSING PROCESS :
Manufacturing chemist shall punch material requisition slip in ERP and take a print out Singed and shall give it to store incharge.
Store Incharge dispenses the approved raw material in the presence of the production person and IPQA person.
IPQA person shall tally the weighed quantity with requisition slips and shall sign on dispensing sheet and BMR.
The storekeeper shall fill the issued quantity and analytical control number on BMR and sign it & transfer the dispensing raw material to the blending section.
Issue the required quantity of primary packing material from the store.
MIXING :
Mix both the raw material in a blender for 4 hours at 20 rpm.
If the product is new the sample of mixed raw materials is sent to QC for testing.
If the result ensures that the material is homogeneously mixed then the material is ready for filling.
If the material is not homogeneous then mix it again for 2- 4 hours.
WASHING AND STERILIZATION PROCESS OF VIALS AND RUBBER PLUGS :
Remove approved empty vials from the boxes in de-carooning area and load the vials on conveyor of vial washing machine.
Wash the vials in an automatic liner vial washing machine as per the validation cycle and SOP.
Checking of washed vials done by production and IPQA Incharge at frequent intervals.
After washing vials are automatically transferred in the sterilization and depyrogination tunnel for sterilization and depyrogination. Check the pressure of different zone of the tunnel, sterilization temperature, and conveyor speed of the tunnel every hour. After sterilization vials are automatically transferred to the filling area.
If rubber stoppers are not Ready for use then wash and sterilized rubber plug in bung processor with HPW and transferred the washed and sterilized rubber plug to the filling area.
FILLING AND SEALING
Maintain the temperature and relative humidity of the filling area before doing the filling process and record at frequent intervals.
Take the Blended raw materials under sterile conditions.
Fill the blended sterile powder in the hopper and start filing operation.
Adjust the fill weight of the powder ( Range – 2.15gm ± 2% )
After filling rubber plugs are automatically bunged on the filled vial by an automatic plugging machine.
Seal the vials with the help of an automatic vial sealing machine.
Check the weight variation, Temperature, RH %, Pressure differential, and sealing of vials after every hour.
VISUAL INSPECTION:
Check the filled vials for the presence of any foreign partials.
Keep the good vials separate with a label containing the product name, lot No., Mfg.Date, Exp.Date.
Keep the rejected vials in separate tray labels of the type of rejection.
Transfer the good vials to the Quarantine Section.
IPQA Incharge does the random sampling of products for final analysis by QC.
LABELLING AND PACKING INSTRUCTION :
The packing area is free from unwanted material as well as material from the last batch/product.
The line equipment and containers are properly identified.
Care is taken to avoid mix up during all stages of packing.
PROCEDURE :
Take the dispense packing material that is labeled, carton, literature, inner carton box, outer carton box, etc.
Take the vials from the quarantine area for labeling, and paste the printed labels on the vials with the help of a labeling machine.
Check the initial coding of labels for batch No. Mfg.Date, Exp.Date and MRP.
Check the labeled vial and packing carton with the packing insert.
The packing supervisor and IPQA Incharge shall randomly inspect the quality of labeling and coding every two hours.
Pack the final product in corrugated boxes.
After the QA approval transfer the finished product to the store.
STANDARDS AND IN-PROCESS CHECK
| S.No | Parameters | Standards | Frequency | Person Responsible |
| 1 | Colour of reconstituted solution | Clear colorless or light yellowish solution. | At the time of reconstitution | Mfg. Chemist
IPQA Incharge |
| 2 | Fill Weight Check | 2.15gm ±2% | 2 Hours | Mfg. Chemist
IPQA Incharge |
| 3 | Cleanliness of filled vial | Should be clean | 2 Hours | Mfg. Chemist
IPQA Incharge |
| 4 | Seal Check | 20mm F/O White
(Button type) |
2 Hours | Mfg. Chemist
IPQA Incharge |
| 5 | Mould Defect | All the Vials should pass | 2 Hours | Mfg. Chemist
IPQA Incharge |
| 6 | Overprinting on Labels and
other Packing material. |
At the time of packing | 2 Hours | Mfg. Chemist
IPQA Incharge |
| 7 | pH | 4.5 – 7.5 | At the time of finished product testing | QC in-charge |
| 8 | Assay | Between 90% to 110% of label claim | At the time of finished product testing | QC in-charge |
| 9 | Water/LOD/Moisture | NMT 7.25 %w/w | At the time of finished product testing | QC in-charge |
YIELDS
| S.No | Process | Theoretical | Permissible |
| 1 | Bulk | 100 % | 98 – 99.5% |
| 2 | Filling | 99.0% | 97 – 99.0% |
| 3 | After visual inspection and packing | 97% | 96 – 97% |
EQUIPMENT, MACHINERY, AND ACCESSORIES
| S.No. | Equipment | Purpose |
| 1. | Weighing Balance | Weight Adjustment |
| 2. | Blender | Mixing of material |
| 3. | Vial Washing Machine | Washing of Vials |
| 4. | Sterilizing Tunnel | Sterilization & Depyrogenation of Washed Vials |
| 5. | Autoclave | Sterilization of Dresses, filling item,s and accessories |
| 6. | Filling and sealing Machine | Filling of powder into Vials |
| 7. | External Vial Washing machine | External washing of vial |
| 8. | Visual Inspection Table | Visual inspection |
| 9. | Labeling Machine | Vial Labeling |
ANALYSIS:
Raw material analyzed and released by Q.C for filling.
Filled Vials are drawn online for analysis by IPQA.
All the analytical tests are performed by QC Chemist from Quality Control. The batch is released after 14 days.
CONTROL SAMPLES
10 labeled and duly packed Vials are collected online by IPQA Incharge during packing and sent to QC for storage in the control sample room.
WASTAGE / REJECTION DISPOSAL
Control samples are destroyed 3 months after the expiry of the batch as per the standard operating procedure. Destruction records are to be maintained. Filled rejected Vials are first inactivated by using suitable chemicals and then destroyed by crushing as per the standard operating procedure. Printed packing material is destroyed by shredding it into small pieces.
DOCUMENTATION CHECK
All the documents are Checked by the department head or concerned person and duly signed by authorized Q.A. personnel.
Batch records are to be preserved for 5 years after manufacturing in the record room.
TRANSFER
Packed finished goods are transferred to FGS after proper entry in ERP. Dispatched after finished good inspection by IPQA and release by QA HEAD.
Distribution records are maintained at finished goods stores.
TECHNICAL DIRECTION
Generic name : Cefepime and Amikacin
Party Name : IPCA Labortories
Claim: Each vial contains:
Sterile Cefepime + Amikacin ………………………………………………….. 1.25gm
Description of Product: White-colored crystalline amorphous powder filled in glass vials and sealed with rubber plug and Button-off aluminum seal.
| S. No. | Component | Brief Description | Qty./ Master | Packaging Instructions |
| 1. | Glass Vial 10 ml | 10 ml type I white Vial tubular. | 72 No. | Fill Sterile powder as per required weight aseptically. |
| 2. | Rubber plug | 20 mm bung grey buty RFU Stopper. | 72 No. | Plug the vial using a sterile rubber plug aseptically. |
| 3. | Button-off seal
( White– Code-A) |
20mm standard virgin Button-off aluminum seal with White color plastic Button. | 72 No. | Seal the vial properly using a Button-off aluminum seal. |
| Solvent | ||||
| 4. | Vial 10 ml | White type III | 72 No. | One in each Tray |
| 5. | Bung 20mm | Grey Butyl | 72 No. | Plug the vial using a sterile rubber plug aseptically. |
| 6. | Aluminum Seal
( White ) |
Flip–Off 20 mm | 72 No. | Seal the vial properly using Flip – off aluminum seal. |
| 7. | Label
|
Sticker Label for vial printed as per the party artwork given.
Size : 70 x 28mm ± 1 mm |
72 No. | Paste one label on each vial duly coded with batch No. Exp. date & Mfg. Date. |
| 8. | Label for solvent | For a 10 ml vial | 72 No. | One on each solvent |
| 9. | Plastic tray | For 10 ml vial + 10 ml solvent | 72 No. | Put1 vial of powder and solvent in each tray |
| 10. | Unit carton
|
Unit carton made up of 300 GSM ± 10% laminated art card, printed as per approved text, color, and design.
Size :74x32x85 mm ± 1 mm |
72 No. | Put 1n tray in each unit carton duly coded with all batch details. |
| 11. | Literature | As per party artwork | 72 No. | Put 1 in each unit carton .
|
| 12. | Shrink pack
|
Shrink pack made from 9-inch polythene roll. | 12 Nos
|
6 unit cartons in each shrink pack |
| 13. | Master Carton
|
Corrugated box made up of 5 ply as per approved design, color and text,100 GSM.
Size: 325x220x268 mm ± 3mm |
01 No. | 12 Shrink packs in each box |
| 14. | Gum/Tape/Patti
|
48 mm ±1 mm wide self-adhesive BOPP , Plain | As per Requirement | Close the corrugated box flaps and seal them using BOPP tape. |