Standard Operating Procedure for In-Process Sample Collection During Purification in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/177/2025
Supersedes	SOP/BS/177/2022
Page No.	Page 1 of 9
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define the standard procedure for collecting in-process samples during the purification of biosimilar products, ensuring aseptic technique, accurate documentation, traceability, and regulatory compliance.

2. Scope

This SOP applies to all sampling points throughout downstream purification steps, including capture chromatography, intermediate purification, polishing, viral filtration, and UF/DF in biosimilar manufacturing.

3. Responsibilities

• Production: Collect samples as per the Sampling Plan and document in the Batch Record and Annexure-1.
• QC: Receive and analyze samples for parameters such as pH, conductivity, protein content, purity, and contaminants.
• QA: Verify sample traceability, review sampling logs, and ensure deviations are recorded and closed.

4. Accountability

The Manufacturing Manager is accountable for ensuring that all in-process samples are collected and handled per GMP guidelines to support process monitoring and batch release decisions.

5. Procedure

5.1 Sampling Preparation

1. Review the Sampling Plan provided in the BMR and approved by QA.
2. Ensure clean and sterile sampling tools, tubes, PPE, and labels are available.
3. Verify sampling ports or valves are sanitized or pre-sterilized for aseptic withdrawal.

5.2 Sample Collection Technique

1. Label sample containers with the following:
   • Sample ID
   • Batch No.
   • Step Name
   • Date & Time
   • Collected By
2. Wear appropriate PPE and disinfect gloves using 70% IPA.
3. Open the sample port slowly to avoid pressure surge or air ingress.
4. Collect sample (typically 5–20 mL) into sterile tubes using aseptic technique.
5. Immediately close the valve and wipe down surfaces with disinfectant.

5.3 Sample Handling and Transfer

1. Place samples in a secondary containment labeled “In-Process Sample – QC”.
2. Transfer to QC lab within the predefined time limit (typically within 1 hour).
3. Record transfer details in the Sample Transfer Log (Annexure-2).

5.4 Sampling Time Points

1. Typical sample collection points include:
   • Post-harvest clarification
   • Post-capture chromatography (e.g., Protein A)
   • Post-intermediate purification
   • Post-polishing chromatography
   • Post-viral filtration
   • Post-ultrafiltration/diafiltration

5.5 Deviations and Corrective Actions

1. If a sample is missed, compromised, or mislabeled, notify QA immediately and record a deviation.
2. Follow the deviation handling SOP and initiate retesting or re-sampling if required.

6. Abbreviations

• PPE: Personal Protective Equipment
• BMR: Batch Manufacturing Record
• UF/DF: Ultrafiltration/Diafiltration
• IPA: Isopropyl Alcohol

7. Documents

1. In-Process Sampling Log – Annexure-1
2. Sample Transfer Log – Annexure-2

8. References

• ICH Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
• EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
• WHO TRS 999 – GMP for Biotherapeutic Products

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: In-Process Sampling Log

Date	Step	Sample ID	Collected By	Time	Remarks
04/05/2025	Post-Protein A	SMP-BS-024	Ajay Verma	10:10 AM	Clear sample

Annexure-2: Sample Transfer Log

Sample ID	Sent To	Sent By	Received By	Time	Remarks
SMP-BS-024	QC Lab	Ajay Verma	Sunita Reddy	10:35 AM	Delivered on ice

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Clarified sample traceability and transfer controls	Internal audit observation