As India accelerates its leadership in biosimilar development, regulatory expectations are evolving rapidly. The Central Drugs Standard Control Organization (CDSCO) has updated its guidelines in 2025 to align with global agencies like the EMA and USFDA.
A key area of emphasis? Assay validation and customization.
If your assay is not CDSCO-compliant, your biosimilar program could face delays, rejections, or re-validation cycles that cost time, money, and credibility.
In this blog, we break down step-by-step how to build an assay that meets the latest CDSCO standards while optimizing for speed, reproducibility, and clinical success.
Step 1: Understand CDSCO’s Updated Expectations
CDSCO’s 2025 draft guidelines focus heavily on:
- Orthogonal analytical validation
- Reduced dependency on in vivo models
- High-quality in vitro data (e.g., ELISA, LFA, ADA/NAb assays)
- Regulatory documentation & traceability
Pro Tip: Align your design with ICH M10, WHO TRS guidelines, and Indian-specific bioanalytical validation standards.
Step 2: Start with a Defined Analytical Objective
Before designing the assay, clarify:
- What are you measuring? (e.g., PK, ADA, NAb)
- In what matrix? (Serum, plasma, cell supernatant)
- What level of sensitivity and specificity is required?
- Will the assay be used for both preclinical and clinical phases?
Why this matters: CDSCO wants to see context-specific assay design, not repurposed generic kits.
Step 3: Select a Validated Reference Biological Product (RBP)
Your comparability relies on:
- Using an RBP approved in ICH countries (EU, US, Japan)
- Maintaining the same lot across your comparability study
- Documenting scientific justification for your RBP choice
Mistake to avoid: Using multiple RBPs without clear bridging data – this is often flagged by CDSCO reviewers.
Step 4: Build the Assay Using Orthogonal Tools
Use a combination of complementary methods to strengthen your case:
- ELISA + LC-MS/MS for PK
- Bridging vs direct-binding ADA formats
- Functional neutralization + competitive inhibition for NAb
Also, include:
- Linearity curves (R² > 0.99)
- Recovery studies (80–120%)
- LOD, LOQ, and intra/inter-assay CVs (<10%)
Step 5: Incorporate Cryopreserved Reference Standards
Denovo recommends using vapour-phase liquid nitrogen (-196°C) storage for standards. Why?
- Avoids batch-to-batch drift
- Enables repeat analysis over extended timelines
- Strengthens your long-term comparability package
CDSCO expects traceable, long-term controls for clinical translation.
Step 6: Prepare for a Regulatory Review (Documentation)
Your assay dossier should include:
- Assay SOPs and raw validation data
- Reagent traceability and certificate of analysis (CoA)
- Rationale for matrix selection
- Performance specs across sample types and time points
- Tech transfer documentation if using a CRO partner
Checklist:
- Validation summary with statistical data
- Visual plots of dilution linearity and recovery
- Stability testing data for samples and reagents
Step 7: Engage CDSCO Proactively
India’s regulators are increasingly collaborative. Consider:
- Pre-submission meetings
- Query resolution support via your CRO
- Including supplemental validation packages proactively
This is especially useful for novel assay formats or LFA-based kits.
Conclusion
Building a CDSCO-compliant assay in 2025 is not just about ticking validation boxes.
It is about designing with intent, documenting with rigour and anticipating regulatory expectations.
At Denovo Biolabs, we specialize in biosimilar-focused assays – from ELISA to ADA and LFA – all aligned with Indian and global standards.
Need help validating your biosimilar assay? Let’s build it right, the first time.