Biosimilars Handbook

Affordable Care Act (ACA)

The ACA is a law passed in March 2010 that laid out many changes to the American health care system. Among the many provisions, it includes the Biologics Price Competition and Innovation Act (BPCIA), a measure to pave the way for biosimilar development, licensure and distribution in the United States via FDA approval.


Biological products, or biologics, are medicines made from a variety of natural sources (human, animal or microorganisms) that can be used in the treatment, prevention or diagnosis of diseases and medical conditions. Biologics can include a wide range of products; vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and proteins. Examples include growth hormones to treat growth failure, cytokines to treat anemia, monoclonal antibodies to treat cancer. Unlike most traditional, small-molecule prescription drugs that are made through chemical processes, biological products are generally made from human and/or animal materials. Biological products are usually larger and have a more complex structure than most small-molecule prescription drugs.

Biologics Price Competition and Innovation Act (BPCIA)

The BPCIA creates an abbreviated licensure pathway for biological products approved by the FDA as biosimilar to, and/or interchangeable with, an FDA-licensed biological reference product. The objectives of the BPCIA are similar to those of the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98–417) (commonly referred to as the “Hatch-Waxman Act”), which made safe and affordable generic drugs available to consumers through establishing an abbreviated pathway for their approval under the Federal Food, Drug, and Cosmetic Act (FD&C Act).


A biosimilar is a biologic medicine that is approved by stringent regulatory pathways in the E.U., Japan, Canada, and Australia showing that the biosimilar is highly similar to a previously-approved brand biologic. Biosimilars are approved for use and made available following the expiration of patents or regulatory exclusivity on an original biological product. These products are often available to patients at a lower-cost than expensive brand biologic medicines. FDA is approving biosimilar therapies based on the pathway laid out in the Biologics Price Competition and Innovation Act (BPCIA,) as part of the Affordable Care Act of 2010.

Center for Biologics Evaluation and Research (CBER)

CBER is the Center within FDA that regulates biological products for human use under applicable federal laws, including the Public Health Service Act. CBER protects and advances the public health by ensuring that biological products are safe and effective and available to those who need them. CBER also provides the public with information to promote the safe and appropriate use of biological products.

Center for Drug Evaluation and Research (CDER) The Center for Drug Evaluation and Research (CDER) within FDA that regulates drugs under the Federal Food, Drug and Cosmetic Act. CDER performs an essential public health task by making sure that safe and effective drugs are available to improve the health of people in the United States. CDER regulates over-the-counter and prescription drugs, including some biological therapeutics and generic drugs.

Clinical Trial

An investigation to discover or verify the clinical, pharmacological, and/or other pharmacodynamic effects of a pharmaceutical product to ascertain its safety and/or efficacy. Clinical trials in drug and biologic development are a series of controlled tests following a pre-determined plan or protocol in humans that determines the safety and efficacy of the tested product or treatment. Clinical trials in biosimilar and interchangeable biologic development are controlled tests following a pre-determined plan or protocol in humans that confirms the high similarity established in analytical tests.

Dosage Form

Pharmaceutical products in the form that they are intended for administration to or by the patient (i.e., injectable, capsule, tablet, liquid).


A measure of the ability of a medicine or treatment to achieve a desired result.

United States Food and Drug Administration (FDA)

The FDA is the federal agency responsible for protecting the public health by assuring the safety, efficacy and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medicines and foods to maintain and improve their health.


Guidance documents represent a regulatory agency’s current thinking on a particular subject. According to the FDA, guidance does not “create or confer any rights for or on any person and do not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both.”


The ability of a substance, such as an antigen, to elicit immune responses in the body. Immunogenic reactions could occur in all therapies that contain antigens, including biologic and biosimilar therapies. Immunogenicity can be triggered intentionally, like a vaccine, where antigens are introduced into the body to produce a specific, desired immune response, such as immunity to pathogens (e.g., smallpox or polio). Unintentional immunogenicity occurs when a person’s immune response to an antigen is unforeseen. Some immune systems are sensitive to specific antigens in the environment, leading to allergies and some can mount a response, in some cases with clinical manifestations, to antigens contained in biologic and biosimilar therapies. Most immunogenic responses are not clinically relevant, but some immunogenic responses can raise very significant and potentially severe safety concerns. It is therefore important to monitor the immunogenicity of all biologics, whether they are originator branded products or biosimilars.

Interchangeable Biologic

Interchangeability is the FDA designation made once it has been determined that substituting, or interchanging, a reference product with its equivalent will produce the same clinical result for patients, with no difference in safety or efficacy. Federal law states that interchangeable products can be substituted at a pharmacy without the intervention of a physician.

International Nonproprietary Names (INN)

According to the World Health Organization (WHO), the INN is the name given to an active pharmaceutical substance or active pharmaceutical ingredients to facilitate identification. Each INN is a unique name that is globally recognized and is public property. A nonproprietary name is also known as a generic or proper name.

No Clinically Meaningful Difference

No clinically meaningful difference refers to the scientific concept that a biosimilar will treat the same disease with generally the same safety and efficacy as the brand biologic product. This includes data and statistical analysis showing that the drug is safe, potent and pure.


The pharmacological science relating to the monitoring, detection, assessment, and prevention of adverse events in humans pursuant to treatment from pharmaceutical products.

Pharmacy Practice Act

Pharmacy practice acts are the laws, regulations and rules that govern the practice of pharmacy in each state.


A measure of drug activity expressed in terms of the amount required to produce an effect of given intensity.

Public Health Service (PHS) Act

Most, but not all, biologic products are licensed under the PHS Act. Small-molecule prescription drugs are approved under the Federal Food, Drug and Cosmetic Act (the FD&C Act).

Reference (original) Product

Medicine developed and distributed by an originator company that has been approved and is being referenced in the creation of a biosimilar therapy.


A determination made by the FDA based on a rigorous scientific process that includes testing and analysis to confirm that there is no clinically meaningful difference between a biosimilar or interchangeable biologic and the corresponding reference product.


The pharmacy practice of dispensing an equivalent and interchangeable medicine to the prescribed medicine without requiring consultation with the prescriber. “Automatic substitution” refers to medicines identified as equivalent and interchangeable that the private or public entity paying for the medication has requested be substituted by the pharmacist.