Standard Operating Procedure for Process Hold Time and Sample Tracking in API Manufacturing

Department	API Manufacturing
SOP No.	SOP/API/105/2025
Supersedes	SOP/API/105/2022
Page No.	Page 1 of 10
Issue Date	13/04/2025
Effective Date	15/04/2025
Review Date	13/04/2026

1. Purpose

To establish a standardized procedure for monitoring and controlling hold times for in-process materials during various stages of API manufacturing and to ensure traceable tracking of IPC and QC samples from collection to final disposition.

2. Scope

This SOP applies to all hold periods of intermediates, wet cake, dry powder, filtrates, and solutions before further processing, and to all IPC/QC samples drawn and submitted during batch manufacturing in the API facility.

3. Responsibilities

• Production Chemist: Record start and end of hold periods and collect samples as per schedule.
• QC Analyst: Receive and acknowledge samples, track test results, and report timelines.
• QA Officer: Review and approve hold time extensions, ensure hold times comply with validated limits.

4. Accountability

Production Head is accountable for in-process hold time control. QA Head is responsible for procedural compliance and timely oversight of sample tracking.

5. Procedure

5.1 Hold Time Definition

1. Hold time is defined as the duration between the completion of a process step and initiation of the next step.
2. Refer to the approved Master Formula Record (MFR) for allowable hold time limits per stage.

5.2 Types of Hold Times

1. Pre-filtration solution hold
2. Post-filtration (wet cake) hold
3. Crude drying hold
4. Intermediate hold during blending or sieving

5.3 Recording Hold Times

1. Enter the start time when process is stopped or paused.
2. Enter the end time when the next process resumes.
3. Record total duration and reason (if applicable) in Hold Time Log (Annexure-1).
4. If the hold exceeds approved limits, document deviation and QA shall evaluate product quality risk.

5.4 Sample Collection and Tracking

1. Collect IPC or QC samples as per the sampling plan or when hold extends beyond 25% of validated time.
2. Label each sample with unique Sample Code, Batch No., Date, Stage, and Sampler Initials (Annexure-2).
3. Submit sample to QC with completed Sample Forwarding Form (Annexure-3).
4. QC shall enter receipt in the Sample Receipt Log and assign test request reference.

5.5 Sample Status Updates

1. QC to update sample testing status in the tracking log within 2 hours of receipt.
2. Any delay must be informed to QA and Production immediately.
3. For samples under investigation or out-of-spec, QA shall initiate appropriate action.

5.6 Hold Time Extensions

1. In case of unavoidable delay:
   • Production must raise a Hold Time Extension Request
   • QA shall evaluate based on storage conditions, stage, and risk
   • Extension may be granted with justification and supported data
2. Record the extension in the deviation log and Hold Time Logbook.

6. Abbreviations

• QA: Quality Assurance
• QC: Quality Control
• IPC: In-Process Control
• MFR: Master Formula Record
• SOP: Standard Operating Procedure

7. Documents

1. Hold Time Logbook (Annexure-1)
2. Sample Label Template (Annexure-2)
3. Sample Forwarding Form (Annexure-3)

8. References

• ICH Q7 – GMP Guide for Active Pharmaceutical Ingredients
• 21 CFR Part 211 – US FDA cGMP
• WHO TRS 986 – Annex 2 GMP Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Hold Time Logbook

Date	Batch No.	Stage	Start Time	End Time	Duration (hrs)	Reason	QA Verified
13/04/2025	API-20250413	Post-Filtration	11:00	15:00	4	Waiting for QC release

Annexure-2: Sample Label Template

Sample Code
Batch Number
Stage
Sampler Name
Date of Sampling

Annexure-3: Sample Forwarding Form

Date	Batch No.	Sample Code	Test Type	Qty	Submitted By	QC Received By
13/04/2025	API-20250413	IPC105-01	LOD	10 g	Ravi Kumar

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial SOP Release	New Requirement	QA Head
13/04/2025	2.0	Integrated sample tracking and hold time extension protocol	Audit Compliance	QA Head