BETASONE – N EYE / EAR DROPS – 10 ml
| PRODUCTNAME: BETASONE-N EYE /EAR DROPS | BATCH SIZE: 100 LTRS. |
| PRODUCT REFERENCE CODE: | UNIT SIZE: 10 ml VIAL |
| GENERIC NAME: N.A. | PACK SIZE: 24 x 24 X 10 ML |
| DOSAGE FORM: OPHTHALMIC DOSAGE FORM | STRENGTH: N.A. |
| DEPARTMENT: STERILE PREPARATION | EXPIRY DATE: AFTER 24 MONTHS FROM THE DATE OF MANUFACTURING |
| COMPOSITION: | |||
| Neomycin Sulphate | IP | 0.5% w/v | |
| Betamethasone Sodium Phosphate | IP | 0.1% w/v | |
| Benzalkonium Chloride (as preservative) | IP | 0.02% v/v | |
| Aqueous buffered vehicle | q.s | ||
EQUIPMENT TO BE USED:
| SR. NO. | NAME OF EQUIPMENT |
| 1 | Auto Clave with SS Transfer trolley |
| 2 | Multi-Column Distillation Still |
| 3 | Distill Water Storage Tank |
| 4 | SS Batch Mixing Tank |
| 5 | SS Pressure Vessel – 100 Ltr. |
| 6 | SS Membrane Filteration Assembly (293 mm) |
| 7 | SS Filling Vessel – 100 Ltr |
| 8 | Auto Liquid Vial Filling, Stoppering & Sealing Machine |
| 9 | Auto Vial Labelling Machine |
Equipment to be sterilized :
| SR.NO. | NAME OF EQUIPMENT |
| 1 | S.S Membrane Filter Assembly- 293 MM |
| 2 | S.S Filling vessel |
| 3 | S.S Filling syringes |
| 4 | Sterile dress of operator |
| 5 | Pre Nitrogen Filling needles& POST- nitrogen filling needles |
| 6 | Silicon tubes |
RAW MATERIALS:
| S.NO. | INGREDIENTS | STD | Theoretical Quantity Req. | Overages % | Total Quantity Used |
| 1. | BORIC ACID | I.P. | 0.200 | – | 0.200 KGS |
| 2. | BORAX | I.P. | 0.320 | – | 0.320 KGS |
| 3. | BETAMETHASONE SODIUM PHOSPHATE | I.P. | 100.000 | 15.000 | 115.000 GMS |
| 4. | BENZYLKONIUM CHLORIDE | I.P. | 0.02 | – | 0.02 KGS |
| 5. | EDTA | I.P. | 0.040 | – | 0.040 KGS |
| 6. | DI SODIUM HYDROGEN ORTHOPHOSPHATE | I.P. | 0.280 | – | 0.280 KGS |
| 7. | NEOMYCIN SULPHATE | I.P. | 0.500 | 20.000 | 0.600 KGS |
| 8. | S.M.B.S | I.P. | 0.300 | – | 0.300 KGS |
| 9. | SODIUM DI HYD. ORTHOPHOSPHATE | I.P. | 0.066 | – | 0.066 KGS |
| 10. | TRISODIUM ORTHOPHOSPHATE | I.P. | 0.040 | – | 0.040 KGS |
| 11. | TWEEN – 80 (SD) | I.P. | 0.010 | – | 0.010 LTRS |
PACKING MATERIALS:
| S.NO. | NAME OF THE MATERIAL | THEORETICAL QUANTITY REQ. | FOR RECORD | TOTAL QUANTITY USED |
| 1 | 10 ML PLASTIC VIALS WITH CAP & NOZZLE (PRE-STERILIZED) | 10000.000 | – | 10000.000 NOS |
| 2 | ADHESIVE TAPE ROLL BROWN | 1.000 | – | 1.000 NOS |
| 3 | CELLO TAPE | 2.000 | – | 2.000 NOS |
| 4 | CORRUGATED BOX C – 01 A | 18.000 | – | 18.000 NOS |
| 5 | STICKER LABEL STICKER LABEL | 10018.000 | 3.000 | 10021.000 KGS |
| 6 | UNIT CARTONS | 10000.000 | 2.000 | 10002.000 KGS |
| 7 | OUTER CARTONS | 416.000 | 2.000 | 418.000 NOS |
| 8 | INSERTS | 10000.000 | – | 10000.000 NOS |
MANUFACTURING PROCESS:
- I) Preparation of Solution:
- Take in SS Batch Mixing Tank 70 Lt. of freshly prepared distilled water.
- Dissolve Boric Acid and Borax in 10 Ltr. Of water and add to Batch Mixing Tank Stir it properly.
- Dissolve Betamethasone sodium phosphate and stir properly.
- Dissolve Di Sodium Orthophosphate and monosodium orthophosphate & Tri-Sodium phosphate and add to the mixing tank stir it properly.
- Dissolve SMBS & EDTA in water and pour in BMT.
- Dissolve Benzylkonium Chloride and to the mixing tank.
- Dissolve Neomycin Sulphate and add to the mixing tank.
- Dissolve Tween – 80
- Adjust the pH to 7.1 (pH RANGE: 6.8 TO 7.2)
- Make up the volume to 100.00 Ltr.
- Shift the solution from batch mixing tank to pressure vessel and do membrane filtration.
- II) Filtration
Filtration is done with the membrane assembly by using the appropriate pre-filter and post filter i.e. membrane
| Pre Filter | 1.5 µ | |
| B | Membrane Filter | 0.2 µ |
III) Aseptic Filing
After the process of washing, sterilization Filteration filing of Aseptic filing is carried out in class 100 area under the laminar flow. The machine adjustment is carried out for the appropriate vials.
| Filling Station Adjustment | Yes/No | Yes | |
| B | Butyl Bung Station Adjustment | Yes/No | No |
| C | Sealing Station Adjustment | Yes/No | Yes |
- IV) Volume variation is checked intermittently, volume prescribed 5ml, and volume filled 5.05 ml, percentage variation 10%.
- V) Labeling
Labeling of vials is done with the help of auto vials labeling machine.
- VI) Packing
| Open Packing | Yes/no | Yes | Pack Size | 24x24x10ml | |
| 2 | Blister Packing | Yes/no | No | Pack Size | NA |
- Yield
| Percentage Yield | – | 100 ± 2% | |
| 2 | Theoretical Yield | – | 10000 x 10ml |
| 3 | Expected Practical Yield | – | 10000 x10ml ± 2% |
Quarantine Stores
The packed and labeled vials send to the Quarantine store for an observation period of fourteen days till the Q.C. report is completed.
Finished Goods Stores
After the completion of the Quarantine period and labeled vials, send to the finished goods store.
MANUFACTURING SPECIFICATION:
- The average fill of each vial is 10 ml.
- The weight variation limit allowed in each filled vial is 10.0 ml to 10.2 ml.
- Use the accurate quantity of water to make up the final volume of the solution.
- Filter the completely charged batch using membrane Filteration apparatus using appropriate membrane filter & pre-filter.
- Transfer the solution from the mixing tank to the pressure tank after the complete charging of the batch.
- The temperature should be kept at 25°c for the entire operation, relative humidity should be kept at 40% for entire operation
Packing Details:
- Pack the filled vials in a unit carton
- Pack such 24 cartoons in each outer carton
- Seal outer carton with cello tape
- Pack the 24 outer cartons in the specified corrugated box to give a pack size of 24 x 24 x 10 ml.
- Seal the corrugated box with adhesive tape and label it properly by affixing the specified label
IN-PROCESS CONTROLS:-
The following in-process controls should be maintained during the processing.
- Check raw materials used for manufacturing purposes are all approved materials and have been ‘released’ labels fixed on them.
- All weighed Raw materials should be counter-checked by Assistant Manufacturing Chemist. If any discrepancy is noticed, it should be immediately brought to the notice of the Production Manager and QC/QA Manager.
- Physical characteristics of Raw material like color, odor, and consistency are checked before compounding.
- The final volume should be made as per Standard Operating Procedure.
- the pH of the bulk should be checked and it should be within specified limits.
- The bulk sample should be sent for analysis to Q.C. Department before starting the filling and sealing stage.
- Intermittently filled volume should be checked at 30 minutes intervals by the Assistant Manufacturing Chemist and the record for the same should be kept in Batch Manufacturing Record.
- The net volume should be checked for all the filling nozzles and in no case, the net volume should be less than the volume claimed on the label. (Limit for volume variation: volume claimed + 5%
- The labels and cartons should be checked thoroughly for proper batch coding.
- Intimation should be sent to Q.C. Department for finished product sampling and testing.
- After the completion of labeling and packaging, the coded labels and cartons should be accounted for, and rejected printed material should be destroyed in the presence of the QC/QA Manager. Maintain the destruction of the same in the B.M.R.
- It will ensure that filling or packing equipment has been properly cleaned.
- Filling or packaging of the next product should not commence until the ‘Line Clearance’ has been given by the Q.C. Analyst.
- Carry out bubble test for checking the integrity of membrane filter as per SOP.