by 1.0 OBJECTIVE
To lay down the procedure for conducting the hold time study of pharmaceutical products during manufacturing at every stage of In – process stage.
2.0 SCOPE
The SOP is applicable to conduct the hold time study of Gel mass, Medicine Paste (bulk) and Quarantine Area in production.
3.0 Responsibility
Production Chemist : To follow the procedure
QA Chemist : To follow the procedure and review &
compilation of results
QC Chemist : Chemical testing of sampl
Microbiologist : Microbial testing of samples
4.0 Accountability:
Head – Quality Assurance : For Review and system Compliance
5.0 Procedure
Definition: Hold-time studies establish the time limits for holding the materials at different stages of Production to ensure that the quality of the product does not deteriorate significantly during The hold time.
- Hold time study shall be conducted to demonstrate that the bulk products and intermediates.
- Retain the appropriate quality before processing to the next stage.
- Meet the acceptance criteria and release specification for the finished products.
- Hold time study shall be conducted but not limited to
- During development or pilot-scale batches
- During scale up.
- During process validation
- As part of the investigation of a deviation that occur during manufacture.
- Any significant changes in processes
- A written protocol shall be prepared which includes the activities to be performed, test parameters and acceptance criteria appropriate to the material or product under test. Annexure I shall be followed to prepare the hold time study protocol.
- Hold time study protocol shall have the unique protocol No.
- Acceptance criteria shall be more stringent as defined in specification of product.
- Hold time study shall be conducted on one batch and if not justified can be extended to other batches.
- A written report shall be prepared which have the provision to record the results.
- Hold time study report shall have the unique protocol No.
- The containers used in which hold-time samples are stored should have the same MOC in which the material is hold in production.
- Where head space is important the hold-time samples should represent the maximum possible head space (worst-case scenario) to bulk stored in manufacturing/quarantine.
- The sample storage environmental conditions should be same as that of the quarantine area/manufacture stage.
- Batches of finished products made from intermediates or bulk products and subjected to a hold-time study should be considered for long-term stability testing.
- Follow the given below table for collection of sample, testing frequency and test parameters:
| Gelatin Mass Preparation | Physical appearance & Microbial test | 0, 12, 24, 36, 48, hours |
| Medicament Preparation | Description, Assay, Related substances, and Microbial test | 0, 12, 24, 36, 48, 60, 72 hours |
| Quarantine Area | Description & Identification, Average Weight, Average fill Weight Uniformity of Weight, Disintegration, assay, Degradation products/ related substance, and Microbial tests. | 0, 30th day, 60th day & 90th day |
- Frequency for the sampling of hold time study samples shall be +3 days. The Frequency shall be applicable for more than 30 days hold time study.
- The results shall be reviewed and a report shall be prepared in hold time study report.
- Any deviation occurred during handling of sample shall be handled through SOP “Deviation Control”.
- Any out of specification results shall be handled through SOP.
- Approved analytical procedure shall be used for analysis of product.
6.0 TRAINING
Trainer : Head – Production Department
Trainees : Staff and machine operator of the gelatin section and QA chemist.
7.0 DISTRIBUTION
Master Copy : Quality Assurance
Controlled Copy : Quality Assurance
8.0 ATTACHMENTS
| Sr. No. | Annexure No. | Title | Format No. |
| 1 | NA | NA | NA |
9.0 REFERENCE
In-house
10.0 ABBREVIATION
| Abbreviation | Extended Form |
| EG | Engineering |
| SOP | Standard Operating Procedure |
| QA | Quality Assurance |
| WH | Warehouse |
| NA | Not Applicable |
| MB | Microbiology |
- REVISION HISTORY OF CHANGE
| Sr. No. | Date | Revision Details | Revision No. |
| 1 | NA | New SOP | 00 |
