Standard Operating Procedure for Sampling Frequency and Quantity Guidelines in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/091/2025 |
| Supersedes | SOP/API/091/2022 |
| 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 uniform guidelines for the frequency and quantity of samples to be collected during various stages of API manufacturing for in-process checks, intermediate testing, and final product evaluation.
2. Scope
This SOP applies to sampling activities conducted by Production and Quality Control personnel during receipt of raw materials, reaction monitoring, drying, milling, blending, and
packing stages of API production.
3. Responsibilities
- Production Chemist: Collect in-process samples as per defined frequency and quantity.
- QC Analyst: Receive and analyze the sample, and log receipt and testing status.
- QA Officer: Review compliance with sampling plan and maintain traceability records.
4. Accountability
The Production Head is accountable for sampling at defined intervals. The QA Head is responsible for approving sampling plans and reviewing deviations.
5. Procedure
5.1 General Sampling Principles
- Use cleaned, labeled, and approved sampling tools and containers.
- Wear appropriate PPE while sampling.
- Ensure samples are representative of the bulk material by collecting from top, middle, and bottom (where applicable).
5.2 Sampling Frequency
- Refer to MFR/BMR for specific instructions. If not defined, use the following general guidance:
- Raw Materials: Each container or as per reduced testing protocol.
- Reaction Monitoring: Every 30–60 minutes or at defined critical stages.
- Drying: Every 2 hours or until LOD is within range.
- Milling/Blending: Start, middle, and end of batch.
- Packing: One sample per 25 kg or per container.
- Additional sampling may be required based on deviations or unexpected results.
5.3 Sampling Quantity Guidelines
- Refer to product specification or method of analysis. If not defined:
- Assay / HPLC: 1–2 g
- LOD / Moisture: 2–3 g
- Identification: 0.5–1 g
- Impurity profiling: 5 g
- Reserve / Retain sample: 25–50 g
- In case of liquids: Collect 5–10 mL using pipettes or sampling bottles.
5.4 Labeling and Documentation
- Label each sample with:
- Product name
- Batch number
- Date and time of sampling
- Stage of sampling
- Sampled by
- Record in the Sampling Logbook (Annexure-1).
- QC to log sample receipt and usage in Analytical Work Log.
5.5 Deviations
- If sampling frequency or quantity deviates from defined protocol, record deviation with justification and obtain QA approval.
- Document deviation in the Batch Record and initiate deviation form if required.
6. Abbreviations
- SOP: Standard Operating Procedure
- QC: Quality Control
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
- MFR: Master Formula Record
- LOD: Loss on Drying
7. Documents
- Sampling Logbook (Annexure-1)
- Batch Manufacturing Record
- Deviation Report (if applicable)
8. References
- ICH Q7 – GMP for Active Pharmaceutical Ingredients
- WHO TRS 986 – GMP Guidelines
- 21 CFR Part 211 – US FDA GMP
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Sampling Logbook
| Date | Batch No. | Stage | Sample Quantity | Sample Type | Sampled By | Remarks |
|---|---|---|---|---|---|---|
| 13/04/2025 | API-20250413 | Post-Reaction | 2 g | LOD & Assay | Sampled as per BMR |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP Release | Standardization of Sampling | QA Head |
| 13/04/2025 | 2.0 | Added minimum sampling quantities and deviation process | Audit Observation | QA Head |