Standard Operating Procedure for Identification of Holding Time and Conditions in Elixir Manufacturing
| Department | Elixir Department |
|---|---|
| SOP No. | SOP/ELX/073/2025 |
| Supersedes | SOP/ELX/073/2022 |
| Page No. | Page 1 of 8 |
| Issue Date | 11/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 11/04/2026 |
1. Purpose
To define the procedure for determining and monitoring acceptable holding times and conditions for intermediates, bulk solutions, and in-process elixir formulations to ensure product quality and stability.
2. Scope
This SOP applies to all intermediate and final bulk elixir solutions held during manufacturing stages such as post-mixing, pre-filtration, post-filtration, and pre-filling in the Elixir Department.
3. Responsibilities
- Production Operator:
- Record holding start and end times, and monitor environmental conditions.
- Production Supervisor:
- Ensure batch is held within validated time limits and specified conditions.
- Initiate deviation process if holding time exceeds permissible limits.
- QA Officer:
- Review holding logs and environmental data; provide approval for batch continuation or disposition.
4. Accountability
The Head of Production is accountable for ensuring that product intermediates and bulk elixirs are not held beyond validated times and are maintained under controlled conditions.
5. Procedure
5.1 Determination of Holding Times
- Holding times for each product stage shall be defined based on development studies and validated data.
- Typical holding times include:
- Post-mixing (pre-filtration): ≤ 8 hours
- Post-filtration (pre-filling): ≤ 12 hours
- Intermediate syrup stages: ≤ 24 hours (if applicable)
5.2 Storage Conditions
- Intermediate and bulk solutions shall be stored in closed, labeled stainless steel tanks or containers.
- Conditions shall include:
- Temperature: 20–25°C or as per product-specific requirement
- Protection from light for light-sensitive formulations
- Nitrogen blanketing for alcohol-based volatile solutions (if applicable)
5.3 Documentation and Monitoring
- Record start and end times of each holding stage in the Holding Time Log (Annexure-1).
- Monitor and record temperature every hour using calibrated temperature display units.
- Use the Holding Condition Checklist (Annexure-2) to verify compliance.
5.4 Handling Deviations
- If holding exceeds the validated time:
- Immediately inform QA and initiate a deviation report.
- Hold product under “Quarantine” status pending investigation.
- QA will evaluate the impact on product quality and recommend disposition.
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- °C: Degrees Celsius
- CFU: Colony Forming Units
7. Documents
- Holding Time Log (Annexure-1)
- Holding Condition Checklist (Annexure-2)
- Deviation Report (if applicable)
8. References
- WHO TRS 986 – GMP for Pharmaceutical Products
- 21 CFR Part 211.111 – Time Limitations on Production
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Holding Time Log
| Date | Batch No. | Stage | Start Time | End Time | Duration (Hrs) | Recorded By |
|---|---|---|---|---|---|---|
| 11/04/2025 | ELX-1015 | Post-mixing | 09:00 AM | 04:30 PM | 7.5 | Rajesh Kumar |
Annexure-2: Holding Condition Checklist
| Condition | Compliance (Yes/No) | Remarks | Checked By |
|---|---|---|---|
| Temperature maintained at 20–25°C | Yes | Within range | Sunita Reddy |
| Container closed and labeled | Yes | Tag updated | Sunita Reddy |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial Release | New SOP | QA Head |
| 11/04/2025 | 2.0 | Included separate holding limits for intermediate and bulk | Process Optimization | QA Head |