TABLE OF CONTENTS
| S. NO. | TITLE | Page No. | |
| 1.0 | PRODUCT DETAILS | 02 of 06 | |
| 2.0 | MANUFACTURING FORMULA | 02 of 06 | |
| 3.0 | LIST OF EQUIPMENTS | 02 of 06
|
|
| 4.0 | GENERAL PRECAUTIONS | 02-03 of 06 | |
| 5.0 | MANUFACTURING INSTRUCTIONS | 03 of 06 | |
| 6.0
|
MANUFACTURING PROCESS DETAILS | ||
|
6.1 |
GRANULATION |
03-04 of 06 |
|
|
6.2 |
CAPSULE FILLING |
04-06 of 06 |
|
|
6.3 |
CAPSULE INSPECTION AND POLISHING |
06 of 06 |
|
1.0 PRODUCT DETAILS:
| Product Name | Pregabalin Capsules IP |
| Product Description | Hard gelatin capsules having size ‘2, Green color cap and Yellow color body filled with White to off white color powder. |
| Strength | Pregabalin 75mg |
| Label claim
|
Each hard gelatin capsule contains: Pregabalin – 75 mg |
| Batch Size | 2,00,000 Capsules |
| Average Weight | 270 mg (Avg. Powder Filled)
335 mg (Avg. Weight Filled Capsules) |
| Shelf Life | 24 months |
| Storage | Store in a cool, dry and dark place below 25 0C |
| Drug Category | Anti-Convulsants and Antiepileptic Agent |
2.0 MANUFACTURING FORMULA:
| Material Name | Grade | Category | Quantity per Unit (In mg) | Overages | Batch Qty.
(In kg) |
| Dry Mixing | |||||
| Pregabalin | BP | API | |||
| Starch | BP | Diluent | |||
| Lubricant | |||||
| Talcum | BP | Filler | |||
| Starch | BP | Filler | |||
| Aerosil | BP | Glidant | |||
| Dibasic Calcium Phosphate | BP | ||||
| Hard Gelatin Capsules | |||||
| Capsule Green/Yellow | BP | Empty shells | 65mg/empty caps | – | 204000 Numbers |
3.0 LIST OF EQUIPMENTS:
| Sr. No. | Machineries/Equipments | Capacity | Equipment ID. |
| 1. | Weighing Balance | ||
| 2. | SS Sieves
(with Sieves No’s 40, 60 and 100 ) |
||
| 3. | SS Trays | — | |
| 4. | Halogen Moisture Balance | — | |
| 5. | Double Cone Blender | 100 liter | |
| 6. | SS Containers | r | — |
| 7. | Semi-Auto Capsule Filling Machine | — | |
| 8. | Capsules Polishing and Inspection Machine | — | |
| 9. | Poly-lined HDPE containers with lid | — |
- GENERAL PRECAUTIONS:
- Pregabalin API Description: A white to off white powder.
- All the Manufacturing Activities shall be performed under controlled conditions (temperature NMT 25 0C and relative humidity NMT 60%).
- When working with Active Ingredients and drug product or mixture of Active Ingredients and Excipients, wear gloves and mask to avoid exposure and contact with any body parts.
5.0 MANUFACTURING INSTRUCTIONS:
- All activities shall be performed as per current SOPs.
- Take the line clearance from QA before starting the manufacturing operation during batch to batch and product to product change over.
- Do not overwrite the entry. In case of mistake, cancel the entry by single line with sign & date and make correct entry.
- MANUFACTURING PROCESS DETAILS:
6.1 (GRANULATION):
STEP – I (SIFTING):
- Check Sieve Integrity (before sifting and after sifting).
- Set the Sieve and sieve the Dispensed Materials as per Sieve Sizes mentioned below:
| Material Name | Std. Qty. (kg) | Sieve No. |
| Dry Mixing | ||
| Pregabalin BP | 15.300 kg | 40# |
| Starch BP | 10.000 kg | 60 # |
| Lubricant | ||
| Talcum BP | ||
| Starch BP | ||
| Aerosil BP | ||
| Dibasic Calcium Phosphate BP | ||
- Collect sifted Pregabalin BP (15.300 kg) and Starch BP (10.000 kg) in Polybag.
- Collect sifted Talcum BP (1.000 kg), Starch BP (24.656 kg), Dibasic Calcium Phosphate BP (13.044 kg) and Aerosil BP (1.334 kg) in Polybag
STEP – II (LUBRICATION):
- Load the sieved material of Step-I, Pregabalin BP, Starch BP, Talcum BP, Starch BP, Aerosil BP and Dibasic Calcium Phosphate BP mix properly till uniform mixing of Lubricating Material.
Mixing Time: 40 minutes (20 minutes clockwise direction and 20 minutes anti-clockwise direction)
Mixing Speed: 12 RPM
STEP- X (BLEND SAMPLE ANALYSIS):
- After completion of lubrication, collect the composite blend sample (Qty. 10 gm) and send to QC for analysis according to the table below:
| Test | Specification |
| Appearance of blend
Blend Uniformity Blend Assay Uniformity of Content of Mecobalamin LOD |
White to off white color free flowing fine powder
90 % to 110 % 98 % to 103 % NLT 85% 1.0 % to 1.5 % |
STEP – XI:
- Take Tare weight of two Poly-lined HDPE Containers (capacity: 30 liter each), record the Tare Weight in BMR and unload the above blended material from Double Cone Blender in Poly-lined HDPE Containers (capacity: 30 liter each) and weigh the material with containers and record the Gross Weight of the material and calculate the Net weight of the material as per given formula:
Net Weight = Gross Weight – Tare Weight
- Affix the status label with following details – Product Name, Batch No., Batch Size, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Containers.
- Batch Yield of Blend:
Theoretical Batch Yield: 67.000 kg (100 %)
Actual Batch Yield Limit: NLT 99 % (To be established in next batch).
STEP – XII:
- Clean all equipments used in the capsule section as per respective equipment cleaning SOP.
- (CAPSULE FILLING):
STEP – I:
- After receiving QC approval for the blend, verify the Net Weight of the received blend as per status label in Capsule Section.
- Set the Semi-Auto filling machine. Filled the blend as per below parameters and In Process checks and take a sample for Dissolution (Qty. 20 capsules) and send to QC Department for Dissolution Analysis.
- After confirmation of Dissolution result continue the filling of capsules with the blend as per the following parameters and In Process checks under controlled environmental condition
| S. No. | Parameters | Standard | No. of Capsules | In-Process Frequency |
| 1. | Capacity of Hopper of Loader | 20,000 Empty Capsules | —– | 1 Hour |
| 2. | Capacity of Powder Filling Hopper | 3.000 kg (powder) | ||
| 3. | Capsule Size | ‘2ʾ | —– | —– |
| 4. | Product to be filled
|
Powder form | —– | —– |
| 5. | Filling System | Gravity | —– | —– |
| 6. | No. of holes in loading ring | In size ‘2ʾ, 540 holes | —– | —– |
| 7. | Compressed Air Required | NLT 5 kg/cm2
NL- Moisture free |
||
| 8. | Magazine Setting | According to the size of capsules | —- | —- |
| 9. | Machine Speed | 15 RPM | —- | —- |
| 10. | Loader Pressure | 5 inHg | —- | —- |
| 11. | Lock Length size‘2ʾ | 18.00 mm ± 0.76mm | —- | —- |
| 12. | Length of size‘2ʾ | 0.71 inch | —- | —- |
| 13. | Disintegration Time | NMT 30 minutes | 06/Composite | —- |
| 14. | Average Weight of Empty Capsule Shell | 65 mg ± 10 % | 20/ Composite | 30 minutes |
| 15. | Standard Average Weight Powder filled per Capsule | 270 mg ± 3% | 20 Composite | 30 minutes |
| 16. | Standard Average Weight filled Capsules | 335 mg ± 2 % | 20/ Composite | 30 minutes |
| 17. | Weight of 20 filled Caps | 6.700 gm ± 5% | 20/Composite | 30 minutes
|
| 18. | Capsules for Dissolution | 335 mg ± 2 % | 20/Composite | Before staring the filling |
| 19. | Dissolution of Pregabalin | NLT 75 % | 20/Composite | After Completion of Batch |
| 20. | Uniformity of Weight | NMT 02 capsules out of 20 deviate from the standard average weight by more than 3 % and no single capsules deviates from the standard average weight by more than 5 % | 20/Composite | 01 hour |
- Collect the filled capsules in SS Container, when SS container is filled with capsules, transfer the capsules in two Poly-lined HDPE Containers as given in below Step-III.
STEP – II:
- Send the sample of filled capsules (Qty. 30 capsules) to QC department for analysis.
STEP – III:
- Take Tare Weight of three Poly-lined HDPE Containers, record the Tare Weight in BMR and transfer the filled capsules in Poly-lined HDPE Containers and weigh the filled capsules with containers and record the Gross Weight of the filled capsules and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
- Affix the status label with following details – Product Name, Batch No., Batch Size, Avg. Weight, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Containers.
- Batch Yield of Filled Capsules:
Theoretical Batch Yield: 67.000 kg (100 %).
Actual Batch Yield Limit: NLT 99 % (To be established in next batch).
STEP – IV:
- After completion of capsules filling, clean the Semi-Auto Filling Machine as per cleaning SOP.
6.3 (CAPSULE INSPECTION AND POLISHING):
STEP-I:
- Verify the Net Weight of the received filled capsules for inspection and polishing as per status label and after confirmation of received capsule weight for capsule inspection and polishing as per the following parameters and In process checks as given below:
| Sr. No | Parameters | Standard |
| 1. | Vacuum Dust Collector (capacity -20 liter) | Verify for cleaning – Should be satisfactory |
| 2. | Vacuum Flow (100 cfm) | — |
| 3. | Spiral Nylon Brush (Length-3 feet) | Verify for cleaning – Should be satisfactory |
| 4. | Width of Inspection Belt (6″) | Should be defect free and smooth |
| 5. | Vibrator (230 v, single phase) | — |
| 6. | Illuminator (Electronic choke tube light) | Should be working and tube light should be ON |
| 7. | Hopper Capacity | 30,000 caps in one time |
STEP -II: (CAPSULE INSPECTION):
- Transfer the filled capsules into hopper of capsule Inspection Machine.
- Inspect each capsule for any defects and segregate the good and rejected capsules.
- Keep the inspected and polished capsules in double polyethylene bag, weight and record.
- All the rejected capsule should be kept with reject status label and recover the powder from rejected capsule and empty capsule to be destroy.
STEP -III:
- Take Tare Weight of three Poly-lined HDPE Containers, record the Tare Weight in BMR and transfer the inspected capsules in Poly-lined HDPE Containers and weigh the inspected capsules with containers and record the Gross Weight of the inspected capsules and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
- Affix the status label with following details – Product Name, Batch No., Batch Size, Avg. Weight, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Containers.
- Batch Yield of Inspected Capsules:
Theoretical Batch Yield: 67.000 kg (100 %)
Actual Batch Yield Limit NLT 99% (To be established in next batch).
