By Dr. Sk Sabir Rahaman, MBBS, MD (Pharmacology), DFM(Family Medicine), FCFM, CCEBDM, CCLSD
⚖️ What Are Biologics?
Biologics are complex therapeutic agents derived from living cells using advanced biotechnology such as:
Recombinant DNA technology
Monoclonal antibody engineering
Cell culture techniques
Examples:
Recombinant proteins: Insulin, Erythropoietin
Monoclonal antibodies: Trastuzumab
Cytokines: Interferons
Enzymes & vaccines
Used for chronic and life-threatening conditions like cancer, rheumatoid arthritis, multiple sclerosis, and diabetes.
🔗 What Are Biosimilars?
Biosimilars are highly similar versions of approved biologic drugs (reference products), showing no clinically meaningful differences in safety, purity, and efficacy.
Biosimilars are not generics. They're similar, not identical, due to biologics' complexity.
Synonyms Around the World
| Region | Term Used |
|---|---|
| India | Similar biologics |
| Europe | Biosimilars |
| USA | Follow-on biologics |
| Canada | Subsequent entry biologics |
| Mexico | Biocomparables |
Indian Definition (NDCTR 2019):
“A similar biologic is a biological product similar in quality, safety, and efficacy to a licensed reference biologic.”
🔍 Key Concepts and Terms
| Term | Meaning |
| Reference Product | Original approved biologic (e.g., Neupogen) |
| Biosimilar | Highly similar biologic with no clinical difference |
| Interchangeable | Biosimilar that can be substituted without prescriber approval |
"Highly Similar" ≠ "Exact Copy"
| Criterion | Biosimilar Requirements |
| Structure | Molecular similarity essential |
| Function | Matching bioactivity, receptor binding |
| Clinical profile | Comparable efficacy, safety, immunogenicity |
| Formulation | Minor differences in excipients allowed |
| Trials | Comparative PK/PD + efficacy/immunogenicity (as needed) |
🔬 Development: Biologics vs. Biosimilars
| Step | Biologics | Biosimilars |
| Molecular characterization | ✅ | ✅ |
| Functional assays | ✅ | ✅ |
| Non-clinical studies | Extensive | Limited (if justified) |
| Phase 1 (PK/PD) | Full | Comparative only |
| Phase 3 efficacy trials | Mandatory | May be waived (if justified) |
🚑 Interchangeability: Why It Matters
To be interchangeable, a biosimilar must:
Produce the same clinical effect in any patient
Show no risk in switching from reference to biosimilar
In the US, only FDA-approved "interchangeable" biosimilars can be automatically substituted.
🔹 Biosimilars vs. Generics
| Feature | Generic Drug | Biosimilar |
| Origin | Chemical synthesis | Living cells (biotech) |
| Structure | Simple molecules | Complex proteins |
| Manufacturing | Identical copy | Similar, not identical |
| Size | < 1 kDa | 4–140 kDa |
| Stability | High | Heat & pH sensitive |
| Approval | Bioequivalence | Stepwise comparability |
| Cost | Low | Costly (clinical data needed) |
| Substitution | Automatic | Regulated separately |
🌟 India’s Regulatory Framework
Legal Documents
Drugs & Cosmetics Act (1940)
rDNA Guidelines (1990–2011)
CDSCO + DBT Guidelines on Similar Biologics (2012, 2016)
New Drugs & Clinical Trials Rules (2019)
Regulatory Bodies
| Body | Role |
| CDSCO | Clinical trials, marketing approval |
| DBT/RCGM | Biotech data review |
| GEAC | Environmental approval |
| IBSC | Institutional biosafety clearances |
Approval Steps in India
Quality: Analytical, structural, and functional similarity
Clinical: PK/PD studies; Phase 3 if required
Post-Marketing: Pharmacovigilance mandatory
Extrapolation: Allowed if MoA and evidence support it
🌐 Global Regulation Highlights
Europe (EMA)
Gold standard worldwide
Class-specific guidelines (e.g., G-CSF, insulin)
Requires:
Analytical similarity
PK/PD studies
Efficacy & immunogenicity if needed
USA (FDA)
Purple Book: Lists approved biosimilars
Clear distinction between biosimilar and interchangeable
Labeling must declare biosimilarity
Example: "Filgrastim-aafi is biosimilar to Neupogen"
Other Countries
| Country | Authority | Notes |
| India | CDSCO, DBT | Affordability, fast growth |
| EU | EMA | Global regulatory benchmark |
| USA | FDA | Emphasis on safety & switching data |
| Japan | PMDA | High scientific rigor |
| Canada | Health Canada | Termed "Subsequent Entry Biologics" |
🖊️ Conclusion
Biosimilars are not generics; they are advanced therapies requiring scientific rigor.
India stands out as a global hub, offering affordable access to biologics.
Pharmacovigilance, regulation, and robust quality testing are key to patient safety.
The future of precision, affordable medicine relies heavily on the responsible adoption of biosimilars.
“Biosimilars bridge the gap between innovation and access.”
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