PURPOSE:This Standard Operating Procedure is written to describe the formulae, manufacturing procedure, specifications, packing details of dosage form.
SCOPE:This procedure is performed and is applied during the manufacturing of dosage form.
RESPONSIBILITY / ACCOUNTABILITY:It is the responsibility of Assistant Manufacturing Chemist to follow and adhere to this SOP. The Production Pharmacist, 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 Pharmacist
- Copy No. 2 : Manager Quality Control
Copy No. 3 : Non-β Lactam Capsule Section
|PRODUCT NAME: TORZYME CAPSULES||BATCH SIZE: 10.0 LACS|
|PRODUCT REFERENCE CODE: 229||UNIT SIZE: 10 X 30|
|GENERIC NAME: N.A.||PACK SIZE: 36 ´ 10 ´ 30|
|DOSAGE FORM: CAPSULE||STRENGTH: N.A.|
|DEPARTMENT: NON β-LACTAM DEPARTMENT||EXPIRY DATE: AFTER 12 MONTHS FROM THE DATE OF MANUFACTURING|
Each Capsule contains:
Lactobacillus Sporogenes 40 X 106 Vitamin B2 I.P. 2.5 mg
Diastase (1:800) 25 mg Vitamin B6 I.P. 0.5 mg
Papain I.P. 20 mg Simethicone I.P. 40 mg
Vitamin B1 I.P. 1mg Folic Acid I.P. 75 mcg
D-Panthenol I.P. 1 mg Niacinamide I.P. 15 mg
EQUIPMENTS TO BE USED:
|SR. NO.||NAME OF EQUIPMENT||ASSEMBLING
AS PER SOP NO.
AS PER SOP NO.
|1||Tray Drier Machine|
|3||Roto Cube Blender|
|4||Automatic Capsule Loading Machine|
|5||Semiautomatic Capsule Filling Machine|
|6||Feeder, Sorter & Capsule Polishing Machine With A.D.U.|
|7||Triple Track Blister Packing Machine|
|S.NO.||INGREDIENTS||STD||Theoretical Quantity Req.||Overages %||Total Quantity Used|
|2.||D – PANTHENOL||I.P.||1.000||20.00||1.200 KGS|
|3||DI CALCIUM PHOSPHATE||I.P.||250.000||250.00 KGS|
|4||EC PINK / BLACK (SIZE: 0)
BLACK / PINK (O)
|5||FOLIC ACID||I.P.||0.080||50.00||0.120 KGS|
|6||FUNGAL DIASTASE||I.P.||10.000||25.00||12.500 KGS|
|7||LACTC ACID BACILLUS||I.P.||6.600||65.00||10.890 KGS|
|8||MAGNESIUM STEARATE||I.P.||3.000||3.000 KGS|
|14||VITAMIN – B2 PLAIN||I.P.||2.500||2.00||2.550 KGS|
|15||VITAMIN – B1 (MONO NITRATE)||I.P.||1.000||40.00||1.400 KGS|
|16||VITAMIN – B6 HCl||I.P.||500.000||20.00||0.600 KGS|
|S.NO.||NAME OF THE MATERIAL||THEORETICAL QUANTITY REQ.||FOR
|TOTAL QUANTITY USED|
|1||220 MM CLEAR (PVC)||180.000||18.000 KGS|
|2||ADHESIVE TAPE ROLL BROWN||2.000||2.000 NOS|
|3||CORRUGATED BOX B -15||92.000||92.000 NOS|
|4||CELLO TAPE||10.000||10.000 NOS|
|5||ALUMINIUM FOIL ( 3 TRACK)||40.000||40.000 KGS|
|6||UNIT CARTON ( 10 X 30)||3333.000||2.000||3335.000 NOS|
- Use number zero size Pink – Black Capsules.
- Moisture content of powder should be less than 2.0 %.
- Average fill of each capsule is 500 milligrams.
- Weight Variation Limit for average weight of 20 Capsules is +5 %
- Disintegration time for each Capsule is not more than 15 minutes.
- Average weight of twenty filled capsules is 11.9 grams.
- Mix the batch, Fill and Polish the Capsules and also perform the primary packing of Capsules at temperature not more than 27° C and Relative Humidity not more than 45 %.
Yield : Theoretical Yield is 10.0 LAC capsules. Expected Practical Yield is 10.0 LAC ± 2% capsules
- Blister Pack the filled and polished capsules by using Triple Track Blister Packing Machine as per its SOP.
- Put 10 strips each containing 30 capsules into the carton.
- Seal the carton from both ends with cello tape.
- Pack the 36 cartons in specified corrugated box B-15 to give a pack size of 36 x 10 x 30 capsules.
- Seal the each corrugated box with adhesive tape and label it properly by affixing the specified label.
- Fit the mesh # 40 Stainless Steel Sieve on the Sifter as per its SOP . and place Stainless Steel Container below the discharge hopper.
- Sift the 1.0 kgs of Aerosil through 40 mesh Stainless Steel Sieve on the sifter and let it to collect in the container kept below the discharge hopper.
- Mix D-Panthenol 1.2 kg with above sifted Aerosil thoroughly and sift both through mesh no. 40.
- Sift the 0.120 kgs of Folic Acid through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 3.0 kgs of Magnesium Stearate through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Dry 16.5 kgs of Niacinamide in tray drier at 60° C for 45 minutes and sift it through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 24 kgs of Papain through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 3.0 kgs of Talcum through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 1.4 kgs of Vitamin B1 Mono Nitrate through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 2.550 kgs of Vitamin B2 Plane through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 0.600 kgs of Vitamin B6 HCl through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 12.5 kgs of Fungal Diastase through 40 mesh Stainless Steel Sieve on the sifter and collect in the separate container.
- Sift the 10.89 kgs of Lactic Acid Bacillus through 40 mesh Stainless Steel Sieve on the sifter and collect in the same container.
- Sift the 50 kgs of Di-Calcium Phosphate through 40 mesh Stainless Steel Sieve on the sifter and collect in the separate container
- Sift the 200 kgs of Di-Calcium Phosphate through 40 mesh Stainless Steel Sieve on the sifter and collect in the separate container and perform the following:
- Divide it into five equal parts i.e. 5 x 40 kgs.
- Take 42 kgs of Simethicone and divided into 5 equal parts i.e. 5 x 8.4 kgs.
- To one part of D.C.P. Add one part of Simethicone. Mix thoroughly to make a dough using the Mass Mixer.
- Similarly mix the rest 4 parts of D.C.P. in 4 parts of Simethicone individually by using Mass Mixer.
- Now prepare the granules of the dough by passing it through the granulator.
- Dry the granules in the Tray drier at temperature not more than 70° C.
- Sieve the dried granules through the mesh # 30 Stainless Steel Sieve on the Sifter as per its SOP No-SOP-P-NPM-02 and collect in the Stainless Steel Container kept below the discharge hopper.
- Re-dry the granules in Tray drier.
- Moisture content of these granules should not be more than 2.0%.
- Add these granules to the sifted bulk batch.
- Transfer all the ingredients sifted to Roto Cube Blender. Mix 131.240 kgs of Calcium Sulphate granules to these ingredients and allow to blend together for 1 hour by operating Roto Cube Blender as per its SOP Weigh the whole batch. The weight of whole batch should be in range of 495.0 kg – 500.0 kg.
- Send the sample to Quality Control Department for bulk testing.
- Start filling of Empty Hard Gelatin capsules, 500 milligrams of blended powder in each capsule shell by using Automatic Capsule Loading Machine and Semiautomatic Capsule Filling Machine as per their SOP.
- Polish the filled capsules by using Feeder, Sorter & Capsule Polishing Machine With A.D.U. as per its SOP.
- Blister pack the filled capsules by using Triple Track Blister Packing Machine as per its SOP.
- The following in-process controls should be maintained during the processing:
- heck Raw materials used for manufacturing purpose are all approved materials and have ‘Released’ labels fixed on it.
- 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 Production Pharmacist and QC/QA Manager.
- Physical characteristics of Raw material like colour, odour, and consistency are checked before compounding.
- Humidity and temperature should be maintained during the manufacturing, filling, polishing and packaging of the capsules.
Relative Humidity – Less than 45 %
Temperature – 25 0C ± 2 0C
- The total weight of blended powder should be checked in the presence of Assistant Manufacturing Chemist and record the same in Batch Manufacturing Record.
- Bulk sample should be sent for analysis to Quality Control Department before starting the filling of hard gelatin capsules.
- Intermittently the Assistant Manufacturing Chemist should check weight variation of filled capsules at interval of 30 minutes and record for the same should be kept in Batch Manufacturing Record.
- Detect out of limit capsules by Weight Variation Method as follows:
- Take the average weight of 20 Capsules on the calibrated balance and calculate the upper and lower limit as per the table given below in accordance with IP/BP:
|AVERAGE WEIGHT OF CAPSULES
|MAXIMUM PERCENTAGE DIFFERENCE ALLOWED|
|less than 300 mg||10|
|300 mg or More||
- Take the weight of individual Capsules and check if all the Capsules are lying with in the limits.
- Select the Capsules only if no more than two Capsules are out of percentage limit and if none Capsule differs by more than 2.5 times the percentage limit, otherwise reject the Capsules.
- Capsules taken for testing and In-process control should not be added to the bulk batch to avoid mix-ups and cross-contamination.
- Inspection, sorting and polishing of filled capsules should be done as per SOP.
- Disintegration of filled capsules should be done using Disintegration Testing Apparatus
- Disintegration is the time required for the group of capsules to disintegrate. Disintegration Test should be carried out at regular interval of 1 hour by using Disintegration Test Apparatus.
- The tube assembly unit is removed from the glass beaker and from each tube the plastic discs are removed.
- The glass beaker is filled with water. The water in the beaker is retained at the temperature of 37+1˚C through out the test by suitably setting the thermostat.
- Introduce a tube assembly unit into glass beaker in such a way that wire mesh at the base of each tube is atleast 2.5cm below the surface of liquid when the basket is at highest position.
- Switch on the apparatus to move the basket assembly containing the capsules up and down through a distance of 5 to 6 cm at a frequency of 28 to 32 cycles per minute. Start the stopwatch.
- Disintegration Time of filled capsules = Not more than 15 minutes
- The strips and cartons should be checked thoroughly for proper batch coding.
- Assistant Manufacturing Chemist and Production Pharmacist should randomly check that the correct no. of strips are being packed in each cartons and also the number of cartons in each shipper is exactly the same as that shown in proof.
- Intimation should be sent to Quality Control Department for finished product sampling and testing.
- After the completion of labelling and packaging, the coded cartons should be accounted for and rejected printed material should be destroyed in the presence of QC/QA Manager. Fill the destruction sheet and attach the same in the Batch Manufacturing Record.
- It will be ensure that filling or packaging equipment has been properly cleaned after the completion of batch.
- Filling or packaging of next product should not commence until the Quality Control Analyst has given the ‘Line Clearance’.
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