Biologics are the complex molecules obtained from the natural source. They are used for treating diseases majorly in the therapy areas like cancers, immunology, and endocrinology.

  • These drugs are mostly proteins

  • Biologics are generated from complex procedures including the sophisticated biological procedures

  • Sophisticated methods are used for the characterizing the molecules

  • While manufacturing, there might be small changes from batch to bath, however, there shouldn’t be any difference in terms of safety and efficacy. Small changes in the steps like glycosylation don’t impact the efficacy of the biosimilar

  • In Europe, the safety, efficacy, purity, sterility, and stability should be properly established between the batches in order to release the batch



Biosimilars are the drugs which are similar to the reference molecule. As the biosimilars are obtained from living beings, slight changes from the original molecule are accepted. However, safety and efficacy should be the same as the original molecule.

Requirements from biosimilars

 The same standards of structure, efficacy, and safety are expected from biosimilar compared to the reference molecules.  So, biosimilars should have biosimilars with the reference molecule. By showing the bio-similarity, conducting- clinical trials can be avoided. A further extrapolation of the data can be based on scientific evidence.




FDA conducts a rigorous procedure to evaluate the safety, efficacy, and quality of reference products and biosimilars. 


Biosimilar product is highly similar to the reference compound in terms of safety, purity, and potency with the reference compound. Biosimilars show biosimilarity with the reference compounds. 


The manufacturer submits the data comparing the biosimilar with the reference compounds, starting from analytical data, animal studies if required and clinical trials. The manufacturer of the biosimilar has to prove the similarity between the reference product, with no major differences in safety and efficacy. This avoids the requirement of rigorous clinical trials, thereby reducing the cost of development. This eventually results in low price products. 



The data requirements for biosimilars include

  • Analytical data: To demonstrate the similarity with the reference compound

  • Animal studies: For toxicity assessment

  • Clinical data: To demonstrate the safety, efficacy, and purity 

 FDA evaluates each biosimilar differently. FDA can waive off the requirements if it is scientifically appropriate. 



The act created an abbreviated pathway for proving better access of biologics to patients. This doesn’t mean that substandard products will be approved by the FDA. If the manufacturer could able to scientifically convince the safety and efficacy, the FDA will waive off the study.



Biosimilars can be extended for all the indications of the reference molecule if the biosimilar can show similar therapeutic activity for one indication. This is based on the availability of

  • Available information of biosimilars

  • Safety and efficacy of other approved indication

  • Knowledge on other scientific factors

FDA expects the supporting data from the manufacturer for exploration. The knowledge on the other factors includes PK studies, PD studies, immunogenecity, efficacy and safety of the approved indication. FDA evaluates the scientific evidence to assess if the extrapolation can be done for those indications for which the manufacturer has not conducted clinical trials. 

FDA works in closely with the manufacturer for indication extension. The manufacture has to submit the scientific evidence to prove the safety and efficacy of the biosimialr for extrapolation. 



Europe is far ahead of the biosimilars approvals compared to the rest of the world. The first biosimilar was approved in 2006 in Europe.


Characteristics of biosimilars:

  • Similar to the reference molecule: Physical, chemical and biological properties should be very similar to the reference drug molecule

  • No variation in clinical effect compared with the reference drug molecule

  • Scientific evidence should be presented that minor change doesn’t impact the physical, chemical and biological properties of the drug

  • Biosimilars and biologics should contain the same 3D structure

Differences between biosimilars and generics



  • Obtained from a biological source

  • There will be slight changes from reference molecules and changes from batch to batch

  • Tough to characterize

  • Requires additional data with structure and biological activity

  • Obtained from chemical synthesis

  • Can be synthesized exactly

  • Easy to characterize

  • Required data on biological activity


Approval of biosimilars in Europe

The rules for the approval of biologicals was developed in 2004.

The biosimilars are approved centrally however, some small molecules are approved at the national level as well. 


Data requirements for approval:

  • Quality studies

  • Comparing the efficacy data with the reference compound

  • Comparing the pharmacokinetic, pharmacodynamic and immunogenic studies with the reference compound

  • Also, a risk management plan needs to be submitted



Steps for biosimilar approvals

Compare quality studies: Protein structure and biological function are being studied.

Non-clinical studies: Performs the pharmacodynamics of the drugs

Clinical studies: The main target establishes the biosimilarity of the biosimilars with the reference compound.


Immunogenicity studies

Immunogenicity studies are important for the biologics as they can trigger the immunological responses within the body.  Immunogenicity is not considered as a safety concern. Immune reactions are influenced by a range of factors including age, sex, and genetic factors. It is important to make sure that, with the batch changes there shouldn’t be any impurities or factors that can trigger immune responses. Immunogenicity is studied after marketing the products.


Humira (adalimumab)


Humira is TNF blocker used to treat several

  • Rheumatoid arthritis

  • Juvenile Idiopathic Arthritis

  • Psoriatic Arthritis

  • Ankylosing Spondylitis

  • Adult's Crohn's disease

  • Pediatric Crohn's disease

  • Ulcerative colitis

  • Plaque psoriasis

  • Hidradenitis Suppurativa

  • Uveitis


Biosimilars of Humira

Amgen: Amjevita in the US and Europe Solymbic in Europe

Boehringer Ingelheim: Cyltezo 

Hetero Drugs: Mabura

Samsung Bioepis:  Imraldi,  Hadlima 

Sandoz: GP2017


Remicade (infliximab)


Infliximab is a monoclonal antibody which acts by blocking tumor necrosis factor. It is used to treat the following diseases:

  • Rheumatoid arthritis

  • Psoriatic Arthritis

  • Ankylosing Spondylitis

  • Adult's Crohn's disease

  • Pediatric Crohn's disease

  • Ulcerative colitis

  • Pediatric ulcerative colitis

  • Plaque psoriasis

Biosimilars of Remicade

 Amgen/ Cellitron: Remsima/Inflectra/  Flammegis

 Pfizer: Ixifi 

 Samsung Bioepis: Flixabi

 Sandoz: Zessly