PRODUCT DETAIL
PROCESS VALIDATION PROTOCOL & REPORT
CONCURRENT PROCESS VALIDATION FOR RABEPRAZOLE EC AND DOMPERIDONE SR CAPSULES
GENERIC NAME: Rabeprazole EC and Domperidone SR Capsules
LABEL CLAIM: Each Hard Gelatin Capsule contains:-
Rabeprazole Sodium IP 20 mg
(As Enteric Coated Pellets)
Domperidone IP 30 mg
(As sustained release pellets)
BATCH DETAIL:
| Sr. No. | Product Name | Batch No. | Batch Size | Mfg. Date | Exp. Date |
| 01 | Rabeprazole EC and Domperidone SR Capsules | A | 50,000 Capsules | 2 YEARS | |
| 02 | Rabeprazole EC and Domperidone SR Capsules | B | 50,000 Capsules | 2 YEARS | |
| 03 | Rabeprazole EC and Domperidone SR Capsules | C | 50,000 Capsules | 2 YEARS |
TABLE OF CONTENT
| S. No | Particulars |
| 1. | Objective |
| 2. | Scope |
| 3. | Responsibilities |
| 4. | Validation Team |
| 5. | Master Formula |
| 6. | List of Equipment |
| 7. | Reference Documents |
| 8. | Process Control Step |
| 9. | Critical and Non Critical Parameters |
| 10. | Validation Acceptance Criteria |
| 11. | Sampling Plan |
| 12. | Process Parameters monitoring Record |
| 13. | Selection of Batch for validation |
| 14 | Stability Studies |
| 15 | Revalidation criteria |
| 16 | Process validation summary and recommendation |
1.0 OBJECTIVE
The objective of this protocol is to perform a validation study to provide documented evidence with high degree of assurance that the manufacturing process is capable of producing the finished product consistently of required quality, meeting its predetermined specifications and quality attributes.
2.0 SCOPE
This process validation protocol is applicable for process validation of Rabeprazole EC and Domperidone SR Capsules for three consecutive batches manufactured under specified manufacturing conditions at the formulation plant
3.0 RESPONSIBILITIES
Quality Assurance Department: Preparation, review and approval of Process Validation Protocol; review of validation data.
Production: To record the manufacturing data, approval of Process Validation Protocol.
IPQA: Sampling of validation samples as per the sampling plans discussed in Process Validation Protocol.
Quality Control: Testing of all samples; recording and compilation of analytical data and to approve the Process Validation Protocol.
Engineering: To provide support with equipments, facility and manufacturing conditions.
4.0 VALIDATION TEAM
Validation team shall comprise of the representatives from following functions:
• Quality Assurance
• Production
• Quality Control
• Engineering
5.0 MASTER FORMULA
5.1 Master Formula – Raw Material
The following raw materials shall be used during the manufacturing Rabeprazole EC and Domperidone SR Capsules Quantities of raw materials to be used in the manufacturing of various stages of Rabeprazole EC and Domperidone SR Capsules shall be verified and shall be tested as per the standard testing procedures and the result shall comply with the specifications.
| Sr. No. | Ingredient | Specs | Claim | Unit | Qty. Required | |||||
| B. No. A | B. No. B | B. No. C | ||||||||
| Qty | AR No. | Qty | AR No. | Qty | AR No. | |||||
| 1. | Rabeprazole EC and | IP | 20 mg | 13.5 |
||||||
| 2. | Domperidone SR pellets | IP | 30 mg | kg | 13.5 | 13.5 | ||||
| 3. | Dummy pellets | kg | 1.5 | 1.5 | 1.5 | |||||
| 4. | Capsule shells (Pink/CT) | IP | Pcs | 51,000 | 51,000 | 51,000 | ||||
Note: For the manufacturing of Rabeprazole EC and Domperidone SR Capsules blending process not required because enteric coated granules procure from manufacturer/ Supplier which is ready for filling.
6.0 LIST OF MAJOR EQUIPMENTS USED IN VALIDATION
(a) Process Equipment All equipment to be used for the manufacturing must be qualified as per IQ/OQ/PQ acceptance criteria. The following equipments are to be used for manufacturing of Rabeprazole EC and Domperidone SR Capsules
S. No. Name of Equipments Equipment Id. Capacity
1 Cone blender 150 liters
2 Filling Machine 300 holes
7.0 REFERANCE DOCUMENTS
The following documents are used to prepare the validation protocol and to challenge the parameters of the manufacturing process of Rabeprazole EC and Domperidone SR Capsules
7.1 Master Formula Record No. –
7.2 Finished Product Specification No. –
8.0 PROCESS CONTROL STEPS
| Sr. No. | PROCESS STEPS | PROCESS PARAMETERS |
| 1. | Capsule Filling | a. Average Filling
b. Individual weight variation c. Assay (Finished product only) d. Dissolution (Finished product only) e. Yield |
|
2. |
Packing | a. Printing details.
b. Leak test c. Yield |
9.0 CRITICAL AND NON-CRITICAL PROCESS PARAMETERS
| Sr. No. | Process | Process Type |
| 1 | Dispensing | Non-Critical |
| 4 | Capsule Filling | Critical |
| 5 | Primary Packing | Non-Critical |
10.0 VALIDATION ACCEPTANCE CRITERIA:
10.1 Capsule Filling:
10.1.1Average fill weight does not vary by more than 5 % of theoretical average weight.
Limit: 290±5%
10.1.2Uniformity of fill weight is within the limit of 10 % of the average fill weight.
10.1.3 The dissolution of Rabeprazole shall be In 0.1 N HCL for 2 hours- NMT: 20%
In Buffer-pH 8.0 for 1 hour- NLT: 70%
10.1.4 Domperidone – In 0.1 N HCL
After 1 hour: 15 to 45 %
After 4 hour: 30 to 75 %
After12 hour: NLT: 70 %
10.1.5 Assay of Rabeprazole and Domperidone Content shall 90% -110%.
11
10.2 Packing:
10.2.1 Physical characteristics of the filled granules, overprinting details and colour of label should not be affected at all time of packing.
10.2.2 Blisters must pass the leak test.
10.3 Batch yield:
10.3.1 Yield after the end of packing is NLT 98.0%.( This is tentative yield , the final yield shall be decided after reviewing the yield data of 10 production batches )
11.0 SAMPLING PLAN
An authorized person will take Production & Validation samples with clean, stainless steel, specified sampling device only. All the samples shall be withdrawn by QA.
Sampling for tests will be done at every process controlling steps as mentioned in the Process Validation Methodology.
Collect the samples from the locations as shown in the sample diagram; label each sample container indicating product name, batch no., manufacturing phase, and sample no., date of sampling and sampler’s name.
Sample size during the blending stage from each sampling point shall be less than or equal to three dosage units.
11.1 Sampling Plan for Capsule Filling:
| Test To Be Performed | Sample Size | Frequency |
| Average filling | 20 caps | Every 30 minutes |
| Individual weight variation | 20 caps | Every 30 minutes |
Note: Assay and Dissolution test performed at final stage of filling because Rabeprazole and Domperidone are available as ready for filling and before process validation carried out Assay and dissolution parameters are tested.
11.2 Sampling Plan for Primary Packing:
| Test To Be Performed | No. of Samples | Total Sample Size | Frequency |
| Leak Test | 10 Strips | 10 x 3 | Slow, optimum & high Speed |
12.0 PROCESS PARAMETER MONITORING RECORD
12.1 Capsule Filling:
| Parameter | Limits | B. No.: A | B. No.- B | B. No.- C | |||
| Min. | Max. | Min. | Max. | Min. | Max. | ||
| Temp. | NMT:27°C | 23°C | 25°C | 24°C | 26°C | 23°C | 25°C |
| Humidity | NMT:50 % | 40 % | 46 % | 42 % | 46 % | 40 % | 47 % |
| Batch No. : A | Date: | |||||
| Sampling At | Uniformity of fill Weight (Lt.:290 mg ±10 %) | Average filling (Lt.:290 mg ±5.0 %) | Average Weight
(Lt. 355 mg±5.0 %) |
Remarks | ||
| Min. | Max. | |||||
| Max Speed | 282.5 mg | 297.6 mg | 289.8 mg | 353.6 mg | Complies | |
| Optimum Speed | 287.2 mg | 296.6 mg | 291.4 mg | 355.7 mg | Complies | |
| Min Speed | 285.5 mg | 297.4 mg | 291.5 mg | 355.3 mg | Complies | |
|
Batch No. : B |
Date: | |||||
| Sampling At | Uniformity of fill Weight (Lt.:290 mg ±10 %) | Average filling (Lt.:290 mg ±5.0 %) | Average Weight
(Lt.355 mg±5.0 %) |
Remarks | ||
| Min. | Max. | |||||
| Max Speed | 287.6 mg | 296.3 mg | 290.8 mg | 355.7 mg | Complies | |
| Optimum Speed | 285.40 mg | 295.60 mg | 291.2 mg | 354.7 mg | Complies | |
| Min Speed | 288.50 mg | 297.20 mg | 289.8 mg | 354.6 mg | Complies | |
| Batch No. : C | Date: | |||||
| Sampling At | Uniformity of fill Weight (Lt.:290 mg ±10 %) | Average filling (Lt.:290 mg ±3.0 %) | Average Weight
(Lt. 355 mg ±3.0 %) |
Remarks | ||
| Min. | Max. | |||||
| Max Speed | 283.4 mg | 297.2 mg | 290.4 mg | 355.4 mg | Complies | |
| Optimum Speed | 282.5 mg | 296.6 mg | 287.5 mg | 351.5 mg | Complies | |
| Min Speed | 285.5 mg | 298.6 mg | 290.5 mg | 355.5 mg | Complies | |
| Dissolution for Rabeprazole Sodium | |||
| Sampling At | Batch No. : | Remarks | |
| For Finished Product Only
|
In 0.1 N HCL for
2 hours- NMT: 20% |
0.00 to 4.91%
|
Complies |
| In Buffer-pH 8.0 for
1 hour- NLT: 70% |
80.8 to 92.8% | Complies | |
| Dissolution for Domperidone | |||
| Sampling At | Batch No. : | Remarks | |
| For Finished Product Only
|
After 1 hour: 15 to 45 %
|
30.09 to 42.5%
|
Complies |
| After 4 hour: 30 to 75 % | 46.9 to 55.0%
|
Complies | |
| After12 hour: NLT: 70 % | 82.9 to 91.2% | Complies | |
| Dissolution for Rabeprazole Sodium | |||
| Sampling At | Batch No. : | Remarks | |
| For Finished Product Only
|
In 0.1 N HCL for
2 hours- NMT: 20% |
0.00-5.67% |
Complies |
| In Buffer-pH 8.0 for
1 hour- NLT: 70% |
94.5 to 102.7% | Complies | |
| Dissolution for Domperidone | |||
| Sampling At | Batch No. : | Remarks | |
| For Finished Product Only
|
After 1 hour: 15 to 45 %
|
29.9 to 44.0%
|
Complies |
| After 4 hour: 30 to 75 % | 46.7 to 54.8%
|
Complies | |
| After12 hour: NLT: 70 % | 82.6 to 90.9% | Complies | |
| Dissolution for Rabeprazole Sodium | |||
| Sampling At | Batch No. : | Remarks | |
| For Finished Product Only
|
In 0.1 N HCL for
2 hours- NMT: 20% |
0.0-8.1%
|
Complies |
| In Buffer-pH 8.0 for
1 hour- NLT: 70% |
82.4 to 94.9% | Complies | |
| Dissolution for Domperidone | |||
| Sampling At | Batch No. : | Remarks | |
| For Finished Product Only
|
After 1 hour: 15 to 45 %
|
30.7 to 43.7%
|
Complies |
| After 4 hour: 30 to 75 % | 45.4 to 50.6%
|
Complies | |
| After12 hour: NLT: 70 % | 77.0 to 96.5% | Complies | |
| ASSAY | |||
| Sampling At | Batch No. : | Remarks | |
| For Finished Product Only
|
Rabeprazole Sodium IP |
20.30 mg i.e.101.5 %
|
Complies |
| Domperidone IP | 31.2 mg
i.e. 104.0 % |
Complies | |
| ASSAY | |||
| Sampling At | Batch No. | Remarks | |
| For Finished Product Only
|
Rabeprazole Sodium | 20.52 mg
i.e.102.6 %
|
Complies |
| Domperidone | 29.5 mg
i.e. 98.3 % |
Complies | |
| ASSAY | |||
| Sampling At | Batch No. : | Remarks | |
| For Finished Product Only
|
Rabeprazole Sodium | 20.51 mg
i.e.102.55 %
|
Complies |
| Domperidone | 31.65 mg
i.e. 105.5 % |
Complies | |
12.2 Capsule Packing:
Leak test (No any Strip should be leak) |
|||
| Batch Detail | Slow Speed | Optimum Speed | High Speed |
| B. No.: A | Passes | Passes | Passes |
| B. No.- B | Passes | Passes | Passes |
| B. No.- C | Passes | Passes | Passes |
13.3 Yield :
| Yield ( % ) | ||||
| Sr.No. | Limits | B. No.: A | B. No.- B | B. No.- C |
| Capsule Filling | NLT 96.0 % | 99.0% | 96.8% | 48.4% |
| Packing | NLT 95.0 % | 98.6% | 95.0% | 97.6% |
13.0 SELECTION OF BATCH FOR VALIDATION
| Batch No. | Batch Size | Mfg Date | Exp Date | Date of commencement | Date of completion |
| B. No.: A | 50,000 Capsules | ||||
| B. No.- B | 50,000 Capsules | ||||
| B. No.- C | 50,000 Capsules |
14.0 STABILITY TESTING
The stability study of the batch under process is to be carried out as per stability study.
15 .0 REVALIDTION CRITERIA
Once process has been validated, the manufacturing process of Rabeprazole EC and Domperidone SR Capsules shall be revalidated if there is change in following parameters
• Change in manufacturing formula and formulation.
• Change in batch size.
• Major change in equipment.
• Change in source of active pharmaceutical ingredient.
• Any customer / regulatory specific requirement.
• Any recommendation from annual product review.
• Sequential batches that fail to meet product and process specification on the basis of trend analysis.
16.0 PROCESS VALIDATION SUMMARY & RECOMMENDATIONS:
Process validation of Rabeprazole EC and Domperidone SR Capsules has been performed as per approved protocol no X for three consecutive batches for 50,000 capsule batch size of batch no A, B and C, During process validation of Rabeprazole EC and Domperidone SR Capsules collect the sample and analyze the all parameter as per finished product specification of product and fount that all parameter are complies with respect to specification. So base on process validation report of product we are concluded that manufacturing process of Rabeprazole EC and Domperidone SR Capsules mg has been validated. And finally concluded that,
• Capsule filling is carried out at minimum and optimum speed.
• Primary packing is carried out at slow and optimum speed of machine.
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