Subsequent Entry Biologics

The term Subsequent-Entry Biologic (SEB) is used by Health Canada to describe "a biologic product that is similar to and would enter the market subsequent to an approved innovator biologic product." The agency is currently considering the regulatory process by which such products would be granted a marketing licence in Canada.

BIOTECanada supports the development of a transparent, predictable regulatory framework for the approval of Subsequent-Entry Bioloigc products. The framework must rigorously ensure patient safety and preserve incentives for the continued introduction of innovative biologics.

What is a biologic?

Biologics are medicinal products created using biologic processes in living cells. The more common small molecule drugs, typically delivered in oral form, are chemically synthesized. Biologics are complex, large molecule drugs manufactured using live cells and are generally administered as an injectable.  Biologics provide new treatment options for serious illnesses, such as cancer, multiple sclerosis, and rheumatoid arthritis, and have enabled treatment where no effective therapies were previously available. 

What is a Subsequent Entry Biologic (SEB)? 

Subsequent Entry Biologics (SEBs), also known as  “biosimilars” or “follow-on biologics” in Europe and the USA, are follow-on versions similar to an original biologic drug, made by different manufacturers after the patent on the innovator drug has expired. SEBs are sometimes mistakenly called “generic” versions of innovative biologics.  Unlike generics, which are identical copies of chemically synthesized drugs, SEBs are similar to, but not identical to the original innovator drug. This is due to the inherent complexities of large molecule drugs and their manufacturing process.

How are biological medicines different?

Biological medicines are made in living systems; their exact characteristics and properties are highly dependent on the manufacturing process meaning each biological medicine is unique. The manufacturing and precise characterization tends to be more difficult when compared to chemical medicines, the ingredients of which are more easily identifiable and can be exactly reproduced.

What is interchangeability?

Generic medicines, which are designated by Health Canada as bioequivalent, are interchangeable with their reference product and often automatically substituted by pharmacists.  Health Canada has stated, “SEBs are not ‘generic’ biologics and authorization of an SEB is not a declaration of pharmaceutical or therapeutic equivalence to the reference biologic drug.”  Health Canada “does not support automatic substitution of a SEB for its reference biologic drug.”

How are SEBs regulated – In the world? In Canada?

In 2004 the European Union was the first jurisdiction in the world to authorize a formal regulatory pathway for biosimilars.  As of July 2011 the EU has so far (December 2010) approved seven biosimilars, in three products classes: human growth hormones, erythropoeitins and filgrastims.

The USA passed the Biologics Price Competition and Innovation Act (BPCIA) in March 2010 creating an abbreviated approval pathway for biosimilars by the Food and Drug Administration (FDA).  No biosimilars had been approved via this pathway as of July 2011.

In Canada, Health Canada issued a final guidance document in March 2010 for approval of SEBs.  An SEB application to Health Canada follows the New Drug Submission Regulation.  This application process partly relies on prior information on the safety and efficacy as deemed relevant to the demonstration of similarity to the original reference biologic drug.  To date Health Canada has approved one SEB, a growth hormone, Omnitrope. 

Find the full Health Canada Guidance can be found here. 

How is the safety of SEBs monitored?

Health Canada has established a safety monitoring system for these products.

How will Canadians get access to SEBs?

Once Health Canada approves an SEB, access is similar to other new drug approvals. Provincial formulary listing or private drug plans cover provinces. They individually decide on patient access and reimbursement.

Will SEBs be cheaper? 

Because of the complexities of biologic drugs, their manufacturing process and the regulatory requirements, it is anticipated that cost savings with SEBs will be much smaller than realized with basic generic drugs.

What you need to know

The complexity of manufacturing biologic drugs, as compared to chemically synthesized drugs, raises safety and efficacy considerations for patients and health care providers.  In order to make informed choices, patients, doctors, and health care providers should understand the complexity of these drugs and the difference between generics and SEBs.