Standard Operating Procedure for DSP Process Validation Sampling in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/190/2025
Supersedes	SOP/BS/190/2022
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 a standardized and GMP-compliant procedure for collecting, handling, and documenting samples for process validation during downstream processing (DSP) of biosimilars.

2. Scope

This SOP applies to all validation batches of biosimilar products undergoing downstream unit operations, including chromatography, filtration, ultrafiltration/diafiltration, and bulk holding, where sampling is necessary for demonstrating process consistency and robustness.

3. Responsibilities

• Production: Execute sampling at designated stages, label and transfer samples as per plan.
• QC: Analyze validation samples and report deviations.
• QA: Review validation sample records and ensure sampling plan compliance.
• Validation Team: Design sampling plan and define critical process parameters (CPPs) and acceptance criteria.

4. Accountability

The Head of Manufacturing and the Head of Quality Assurance are jointly accountable for ensuring the completeness, accuracy, and regulatory compliance of DSP validation sampling activities.

5. Procedure

5.1 Sampling Plan Development

1. Define sampling points based on risk assessment and criticality of DSP operations (e.g., column load/unload, filtration start/end, UF/DF inlets/outlets).
2. Document plan in the approved Process Validation Protocol (PVP), including:
   • Sampling frequency (e.g., hourly, batch-specific)
   • Sample size and container
   • Required tests (purity, concentration, bioburden, endotoxin)

5.2 Sample Collection

1. Use pre-sterilized, labeled containers with tamper-evident seals.
2. Wear appropriate PPE and follow aseptic technique where applicable.
3. Record time, volume, operator initials, and equipment ID in Annexure-1.
4. Ensure homogenous mixing before sampling from bulk pools or intermediate holds.

5.3 Sample Handling and Transfer

1. Store samples at defined temperatures (e.g., 2–8°C) and transfer to QC within defined hold time (e.g., 2 hours).
2. Log sample transfer details in Annexure-2 and maintain chain of custody.

5.4 Testing and Data Recording

1. QC to test samples using validated methods as per PVP (e.g., SDS-PAGE, ELISA, pH, conductivity).
2. Compare results to acceptance criteria for each parameter.
3. Document and report all data with analyst sign-off and date.

5.5 Deviations and Investigations

1. Any out-of-specification (OOS) or abnormal result must be documented as per deviation SOP.
2. Initiate CAPA as required and include impact assessment on process validation conclusions.

5.6 Documentation and Archiving

1. Attach original chromatograms, raw data sheets, and equipment log extracts to the validation batch record.
2. Ensure traceability and retention as per regulatory requirement (minimum 5 years).

6. Abbreviations

• DSP: Downstream Processing
• PVP: Process Validation Protocol
• CPP: Critical Process Parameter
• OOS: Out of Specification

7. Documents

1. DSP Sampling Record – Annexure-1
2. Sample Transfer Log – Annexure-2
3. QC Analysis Summary Sheet – Annexure-3

8. References

• ICH Q8, Q9, Q10 – Pharmaceutical Development, Risk Management, Quality Systems
• FDA Process Validation: General Principles and Practices
• WHO TRS 1004 – GMP for Biotherapeutics

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: DSP Sampling Record

Date	Time	Stage	Volume (mL)	Container ID	Operator
04/05/2025	10:15	Post Protein A	50	SMP-190-A	Ajay Verma

Annexure-2: Sample Transfer Log

Sample ID	Transferred To	Temp (°C)	Transfer Time	Received By
SMP-190-A	QC Lab	4	11:00	Sunita Reddy

Annexure-3: QC Analysis Summary Sheet

Sample ID	Test	Result	Limit	Analyst
SMP-190-A	pH	6.9	6.5–7.5	Dr. Neha Rao
SMP-190-A	Endotoxin	0.06 EU/mg	≤ 0.1 EU/mg	Dr. Neha Rao

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Integrated chain of custody log and expanded sampling points	Validation Protocol Alignment