Patented, Generic, Biologics and Biosimilars Drug Equivalents. What are They?

by: ju-boo lim 

I wrote an explanation recently on metformin, an antidiabetic drug at the request of Dr Jasmine Keys here :

 https://scientificlogic.blogspot.com/2025/01/patented-vs-generic-antidiabetic-drug.html

I  shall now explain in general the differences between patented drugs, generic drugs, and biosimilars. 

Some of the questions medical doctors, healthcare professionals and highly educated  patients often asked in the past few years were :

1.      Is patented dug and its generic equivalent exactly the same in both their chemical formula, and molecular structure, molecular mass and their pharmacodynamics (action of the drug on the body), and their pharmacokinetics (action of body on the drug)?

2.      How long are patented drugs not allowed to be copied by other manufactures?

3.      What about biosimilars? Are they another name for generic similar to the original patented drugs? If not, what  are they? Are they also synthesized chemically, or are they something else?

I’m happy to answer these questions  to explain the distinctions between patented drugs, generic drugs, and biosimilars. I shall  provide some examples and comparisons on their pharmacology.

Let us  begin with patented drugs.

 By definition, patented drugs are new pharmaceuticals developed by a company, protected by patents to give the company exclusive rights to manufacture, market, and sell the drug for a set period.

Patent duration in most countries lasts 20 years from the filing date. However, the effective patent life post-approval (market exclusivity) is often shorter (8–12 years) because clinical trials and regulatory processes consume a significant portion of the patent term. The purpose of a patent is to protect innovation and allow the company to recoup research and development (R&D) costs.

Here are some examples of patented drugs:

 Atorvastatin (Lipitor®, Pfizer). It is used to lower cholesterol. Its patent status expired in 2011, after which generics became available.

By definition generic drugs are chemically identical to their branded counterparts (the original patented drugs) in terms of active ingredient, molecular structure, pharmacokinetics, and pharmacodynamics.

Requirements of generic drugs is, they must demonstrate bioequivalence to the original drug (similar rate and extent of absorption).

The cost is lower-priced because they do not include R&D, marketing, and patent costs. Regulatory approval is a simplified process compared to the original drug.

An example of a patented drug is Prilosec®, AstraZeneca). The generic equivalent is Omeprazole (by multiple manufacturers). Its use is to  treat gastroesophageal reflux disease (GERD).

Let me now come to something most people, including health care professionals do not know and are unfamiliar with. These drugs are called “Biosimilars” What are they?

By definition,  biosimilars are biological drugs that are highly similar but not identical to already approved biologicals  ("reference product"). They are made using living organisms (e.g., bacteria, yeast, or mammalian cells).

They are complex drugs due to the variability of biological systems, biosimilars may differ slightly in post-translational modifications (e.g., glycosylation), which can affect pharmacokinetics and pharmacodynamics.

Their requirements are, they  must demonstrate no clinically meaningful differences in safety, efficacy, and immunogenicity compared to the reference biologicals.

In terms of cost,  biosimilars are less expensive than the original reference biological, but costlier than generics due to more complicated production and testing.

Here are some examples:

Biological: Adalimumab (Humira®, AbbVie).

Biosimilars: Amgevita® (Amgen), Hyrimoz® (Sandoz), Imraldi® (Samsung Bioepis).

Use: Treats autoimmune diseases (e.g., rheumatoid arthritis, Crohn’s disease).

Let me give some key comparisons between Generic Drugs vs. Biosimilars

Feature	Generic Drugs	Biosimilars
Source	Chemically synthesized	Derived from biological systems
Structure	Identical to the original drug	Highly similar, but not identical
Complexity	Simple molecular structure	Large, complex proteins (e.g., monoclonal antibodies)
Approval Process	Bioequivalence studies	Extensive clinical trials to confirm similarity
Cost	Low	Higher than generics, but lower than biologics
Examples	Atorvastatin, Omeprazole	Adalimumab (Humira), Infliximab (Remicade)
Clinical Outcomes	Identical to patented drug	Similar outcomes with potential for minor differences in immunogenicity

What about their pharmacological comparison?

Generic drugs pharmacokinetics are the same as the original drug. The clinical outcome is identical. Here are some examples:

Patented Drug: Viagra®.

Generic: Sildenafil by Teva Pharmaceuticals. Both treat erectile dysfunction and pulmonary hypertension.

Biosimilars pharmacokinetics may vary slightly due to differences in protein folding or glycosylation.

What about their clinical outcome? They are comparable in clinical efficacy and safety, but minor immunogenicity differences are possible. Examples are biologicals like  Filgrastim (Neupogen®, Amgen) for neutropenia. Its biosimilar is  Zarxio® (Sandoz).

Let me now show examples of clinical applications of biosimilars.

In Oncology and cancer treatment the biological use is  Trastuzumab (Herceptin®) for HER2-positive breast cancer. Another biosimilar is Ogivri® (Mylan/Biocon).

For the management of Autoimmune Diseases, the biological is  Etanercept (Enbrel®) and the biosimilar is  Erelzi® (Sandoz).

For the management of diabetes, the biological is  insulin glargine (Lantus®), compared with the biosimilar Basaglar® (Eli Lilly).

Let me now answer the following as to why biosimilars may act differently?

In immunogenicity,  biosimilars can provoke slightly different immune responses due to subtle structural differences. There are also glycosylation patterns.  Post-translational modifications in biosimilars can influence how they interact with receptors or are metabolized.

What about the history of all these drugs?

Synthetic drugs were first introduced by Rockefeller over a 100 years ago, using petroleum products.  But when were biosimilars introduced?  Was it during the time when biotechnology came into existence? Let’s have a look at some history.

The Origin of Biosimilars:

First Introduction: The concept of biosimilars emerged much later than synthetic drugs, primarily as an extension of advancements in biotechnology in the late 20th century.

The first biosimilar was approved in 2006 in the European Union (EU). It was Omnitrope® (a biosimilar of somatropin, a recombinant human growth hormone), developed by Sandoz.

Development Timeline:

1970s–1980s:

The Biotechnology Revolution  became a field of practical application with the development of recombinant DNA technology (e.g., cutting and recombining DNA to produce desired proteins).

This led to the creation of the first biological drug -  recombinant human insulin (Humulin®, by Genentech in 1982), produced using genetically engineered Escherichia coli bacteria.

1980s–1990s: Biological Era:

Biologicals like erythropoietin (EPO) for anaemia and filgrastim (Neupogen®) for neutropenia became standard therapies, driven by advancements in genetic engineering and cell culture technologies.

2000s: Emergence of Biosimilars:

As patents for early biologicals expired, the pharmaceutical industry began developing biosimilars to offer lower-cost alternatives while maintaining similar efficacy and safety.

The EU pioneered regulatory frameworks for biosimilars, introducing guidelines in 2005, making it the first region to approve biosimilars (starting with Omnitrope® in 2006).

2015: First Biosimilar Approved in the U.S.

The U.S. FDA approved its first biosimilar, Zarxio® (biosimilar to filgrastim), developed by Sandoz.

The next question people may ask is, why did biosimilars come much later?

My answer is, this is because  they are unlike small-molecule synthetic drugs (developed around 1900, following Rockefeller’s establishment of the pharmaceutical industry).

Biologicals are inherently complex. Their production requires living organisms, advanced biotechnological processes, and precise control of cellular environments.

Biosimilar development is challenging.  It requires sophisticated analytical tools and clinical studies to ensure similarity in efficacy, safety, and immunogenicity.

Connection to Biotechnology:

Biosimilars are a direct result of the biotechnology revolution, which began in the 1970s. 

(I studied biotechnology only after I obtained my PhD in medicine which was part of my in-service postdoctoral medical research in the mid-1980’s).

 The ability to manipulate DNA and produce therapeutic proteins using living cells laid the foundation for biologicals, and eventually for biosimilars. Without these advancements, the concept of "highly similar but not identical" alternatives to biologicals would not be feasible.

Summary

Synthetic drugs began in the early 20th century (e.g., aspirin in 1899, followed by Rockefeller’s promotion of pharmaceuticals).

Biologicals emerged in the 1980s (e.g., recombinant insulin).

Biosimilars was first approved in 2006 (Europe) and later in 2015 (U.S.), made possible by biotechnology advancements.

I hope I managed to explain in a very brief way, and using very simple non-technical language some of the differences between patented, generic and biosimilar drugs. For medical doctors who are interested to learn more, here are the references for further reading

1. Biosimilars and Their Role in Health Care
   U.S. FDA - Biosimilar Basics
2. Generics and Patented Drug Comparisons
   World Health Organization (WHO) - Generic Drugs
3. Scientific Review of Biosimilars
   McCamish M, Woollett G. "The state of the art in the development of biosimilars." Clin Pharmacol Ther. 2012.
4. Biosimilar Pharmacology
   Weise M et al. "Biosimilars: What clinicians should know." Blood. 2012.