Standard Operating Procedure for Intermediate Holding Studies in Elixir Manufacturing

Department	Elixir Department
SOP No.	SOP/ELX/074/2025
Supersedes	SOP/ELX/074/2022
Page No.	Page 1 of 8
Issue Date	11/04/2025
Effective Date	15/04/2025
Review Date	11/04/2026

1. Purpose

To establish a procedure for conducting intermediate holding studies in elixir manufacturing to determine acceptable holding durations and ensure product quality, stability, and compliance with regulatory expectations.

2. Scope

This SOP applies to all intermediate and bulk elixir solutions held during manufacturing processes such as post-mixing, pre-filtration, and pre-filling in the Elixir Department where studies are required to validate the maximum allowable holding time.

3. Responsibilities

• Production Department:
  • Provide samples and document time points for intermediate stages.
• Quality Control (QC):
  • Conduct physical, chemical, and microbiological testing at specified time intervals.
• Quality Assurance (QA):
  • Review results, approve holding time based on data, and update manufacturing guidelines accordingly.

4. Accountability

The Head of Quality Assurance is accountable for the evaluation, approval, and documentation of holding study results and updating validated parameters in the Master Manufacturing Record.

5. Procedure

5.1 Study Design

1. Select representative batches of elixir products based on formulation type (sugar-based, alcohol-based, or aqueous).
2. Define holding stages to be studied:
   • Post-mixing, pre-filtration
   • Post-filtration, pre-filling
3. Set holding durations at defined intervals (e.g., 0, 4, 8, 12, 24 hours).

5.2 Sampling and Storage Conditions

1. Store samples under standard manufacturing conditions:
   • Temperature: 20–25°C
   • Closed container with appropriate labeling
2. Label each sample with batch number, stage, time point, and date/time of sampling.

5.3 Testing Parameters

1. At each time point, test samples for:
   • Appearance (clarity, color, odor)
   • pH
   • Assay of API (Active Pharmaceutical Ingredient)
   • Preservative content (if applicable)
   • Microbial limits (Total Viable Count, Yeast and Mold Count)

5.4 Data Analysis and Approval

1. Compare results with initial (0-hour) values and product specifications.
2. Determine the maximum time for which the intermediate retains its integrity and complies with specifications.
3. Document findings in the Intermediate Holding Study Report (Annexure-1).
4. QA to review and approve the finalized holding times for inclusion in the manufacturing process.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• QC: Quality Control
• API: Active Pharmaceutical Ingredient

7. Documents

1. Intermediate Holding Study Report (Annexure-1)
2. Sample Tracking Log (Annexure-2)
3. Raw Data Sheets (Annexure-3)

8. References

• WHO TRS 1019 – GMP Guidelines for Pharmaceutical Products
• ICH Q8(R2) – Pharmaceutical Development
• 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: Intermediate Holding Study Report

Time (hrs)	Appearance	pH	Assay (%)	Microbial Status	Remarks
0	Clear	5.6	100.2	Complies	Initial
12	Clear	5.5	99.8	Complies	Acceptable
24	Slight haze	5.4	98.6	Complies	Limit reached

Annexure-2: Sample Tracking Log

Sample ID	Batch No.	Stage	Time Collected	Collected By
HLD-1015-12	ELX-1015	Post-mixing	11/04/2025 – 12:00 PM	Rajesh Kumar

Annexure-3: Raw Data Sheet (Sample)

Parameter	Method	Result	Limit	Status
pH	Potentiometry	5.5	5.0–6.0	Pass
Assay	HPLC	99.8%	95–105%	Pass

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial SOP Release	New Document	QA Head
11/04/2025	2.0	Expanded Test Parameters and Annexures	Enhanced Validation Compliance	QA Head