MFR of EYE /EAR DROPS
PURPOSE: This Master Formula Record (MFR) is written to describe the formulae, manufacturing procedure, specifications, packing details of dosage form.
SCOPE: This MFR is performed and is applied during the manufacturing of dosage form.
RESPONSIBILITY / ACCOUNTABILITY:
It is the responsibility of Manufacturing Chemist to follow and adhere to this MFR. The Production Manager, QC/QA Manager are accountable for the strict adherence to the master formula.
COPY ISSUED TO:
- Master Copy : Manager Quality Assurance
- Copy No. 1 : Production Manager
- Copy No. 2 : Manager Quality Control
- Copy No. 3 : Small Volume Parenteral Section
|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: OPTHALMIC DOSAGE FORM||STRENGTH: N.A.|
|DEPARTMENT: STERILE PREPARATION||EXPIRY DATE: AFTER 24 MONTHS FROM THE DATE OF MANUFACTURING|
|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|
EQUIPMENTS TO BE USED:
|SR. NO.||NAME OF EQUIPMENT||ASSEMBLING
AS PER SOP NO.
AS PER SOP NO.
|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|
Equipments to be sterilized :
|SR.NO.||NAME OF EQUIPMENTS||STERLIZATION AS PER SOP NO.|
|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|
|S.NO.||INGREDIENTS||STD||Theoretical Quantity Req.||Overages %||Total Quantity Used|
|1.||BORIC ACID||I.P.||0.200||–||0.200 KGS|
|3.||BETAMETHASONE SODIUM PHOSPHATE||I.P.||100.000||15.000||115.000 GMS|
|4.||BENZYLKONIUM CHLORIDE||I.P.||0.02||–||0.02 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|
|9.||SODIUM DI HYD. ORTHOPHOSPHATE||I.P.||0.066||–||0.066 KGS|
|10.||TRI SODIUM ORTHOPHOSPHATE||I.P.||0.040||–||0.040 KGS|
|11.||TWEEN – 80 (SD)||I.P.||0.010||–||0.010 LTRS|
|S.NO.||NAME OF THE MATERIAL||THEORETICAL QUANTITY REQ.||FOR
|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||18.000||–||18.000 NOS|
|6||UNIT CARTONS||10000.000||2.000||10002.000 KGS|
|7||OUTER CARTONS||416.000||2.000||418.000 NOS|
- I) Preparation of Solution:
- Take in SS Batch Mixing Tank (IN-1A) 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 Benzy lkonium 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|
VI) 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|
|Percentage Yield||–||100 ± 2%|
|2||Theoretical Yield||–||10000 x 10ml|
|3||Expected Practical Yield||–||10000 x10ml ± 2%|
- Pack the filled vials in unit carton
- Pack such 24 cartoons in each outer carton
- Seal outer carton with cello tape
- Pack the 24 outer cartons in specified corrugated box to give 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
The following in process controls should be maintained during the processing.
- Check raw material used for manufacturing purpose are all approved materials and have ‘released’ labels fixed on it.
- All weighed Raw materials should be counter-checked by Manufacturing Chemist. If any discrepancy is noticed, it should be immediately brought to the notice of Production Manager and QC/QA Manager.
- Physical characteristics of Raw material like colour, odour and consistency are checked before compounding.
- Final volume should be made as per Standard Operating Procedure.
- pH of the bulk should be checked and it should be with in specified limits.
- 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 interval by the Manufacturing Chemist and 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, net volume should be less than 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 rejected printed material should be destroyed in the presence of QC/QA Manager. Maintain the destruction of the same in the B.M.R.
- It will be ensure that filling or packing equipment has been properly cleaned.
- Filling or packaging of next product should not commence until the ‘Line Clearance’ has been given by the IPQA.
- Carry out bubble test for checking the integrity of membrane filter as per SOP.