Biosimilars and Biologics in Pharmaceutical Industries.

Biosimilars and Biologics: Definitions, Differences & Regulatory Pathways

Biological medicines and biosimilars have transformed modern healthcare by enabling the treatment of complex and life-threatening diseases such as cancer, autoimmune disorders, and rare genetic conditions. This article explains biologics and biosimilars in simple yet regulatory-accurate terms, including their development history, scientific differences, and approval pathways in the US and Europe.


What is a Biologic?

A biologic (or biological medicinal product) is a medicine whose active substance is produced using a living system such as bacterial cells, yeast, or mammalian cell lines. Biologics typically consist of large, structurally complex molecules including proteins, monoclonal antibodies, vaccines, and gene-based therapies.

Due to their biological origin, biologics exhibit natural variability and require highly controlled manufacturing processes. Even minor changes in cell lines, raw materials, or production conditions can influence the final product’s quality, safety, and efficacy.


What is a Biosimilar?

A biosimilar is a biological medicine that is highly similar to an already approved reference biologic. Regulatory authorities require that a biosimilar demonstrates no clinically meaningful differences in safety, purity, or potency compared to its reference product.

Because biologics are inherently variable and cannot be exactly replicated, biosimilars are not identical copies like chemical generics. Instead, approval is based on a comprehensive comparability exercise known as the totality of evidence, covering analytical, functional, and clinical studies.


First Biologic and Biosimilar: World and India

First Biologic (World)

The first widely recognized recombinant biologic medicine was recombinant human insulin (Humulin®), approved in 1982. This milestone marked the beginning of large-scale therapeutic protein manufacturing using recombinant DNA technology.

First Biosimilar (World)

The first biosimilar approved under a formal regulatory framework was Omnitrope® (somatropin), authorized in the European Union in 2006. This approval established the foundation for modern biosimilar regulation worldwide.

Early Biosimilar in India

India emerged early in the biosimilar space with the launch of Reditux® (rituximab) in 2007. It significantly improved patient access to monoclonal antibody therapy and positioned India as a global biosimilar development hub.


How Are Biologics Different from Traditional Medicines?

  • Molecular size: Biologics are large and structurally complex, while traditional medicines are small, chemically synthesized molecules.
  • Manufacturing: Biologics are produced in living cells; traditional drugs are manufactured through chemical reactions.
  • Variability: Biologics show natural batch-to-batch variation, requiring advanced analytical control.
  • Immunogenicity: Biologics may trigger immune responses, which must be evaluated during development.
  • Administration: Most biologics are administered by injection or infusion rather than orally.

Difference Between Peptides and Biosimilars in BLA Applications

The regulatory classification of peptides and biosimilars depends largely on molecular size, manufacturing method, and legal definitions.

  • Peptides: Smaller peptides, especially those manufactured by chemical synthesis, may be regulated as conventional drugs rather than biologics. Larger or recombinant peptides may fall under biologic regulations.
  • Biosimilars: Biosimilars are always compared to a licensed reference biologic and are submitted through an abbreviated biologic approval pathway.
  • BLA relevance: Biosimilars are submitted under the biologics license application (BLA) framework, while peptides may follow drug or biologic pathways depending on their characteristics.

Biosimilar BLA submissions emphasize analytical similarity, functional comparability, pharmacokinetic equivalence, and immunogenicity assessment rather than independent full clinical development.


Application Process for Biosimilars

United States (US FDA)

In the United States, biosimilars are approved under an abbreviated pathway that relies on comparison with a reference biologic. The submission demonstrates biosimilarity through a stepwise approach:

  1. Extensive analytical and functional comparison
  2. Manufacturing and quality comparability
  3. Comparative pharmacokinetic and pharmacodynamic studies
  4. Targeted clinical and immunogenicity studies, if required

Some biosimilars may also seek an additional designation allowing pharmacy-level substitution, subject to further evidence requirements.

European Union (EMA)

In the European Union, biosimilars are evaluated through a centralized procedure coordinated by the European Medicines Agency (EMA). Approval is based on the same scientific principles as other biologics but uses a comparability-based development strategy.

EMA allows indication extrapolation when scientifically justified, helping reduce unnecessary clinical trials while maintaining patient safety.


Conclusion

Biologics and biosimilars represent a critical advancement in pharmaceutical science, offering targeted therapies for complex diseases. While biologics require extensive development investment, biosimilars improve affordability and access by leveraging proven reference products. Understanding their scientific and regulatory differences is essential for pharmaceutical professionals, regulators, and healthcare stakeholders.

Read More:

1. What is Contamination Control Strategy (CCS)?

2. What is the difference between NDA vs ANDA vs Orphan Drugs

3. Lyophilized Products Process in the Pharmaceutical Industry: A Comprehensive Guide

4. Nitrosamine Impurities in Pharmaceutical Products

5. Quality Assurance

6. Analytical Evaluation Threshold (AET) in Pharmaceutical

7. Biologics 

This website uses cookies.