What are biologics and biosimilars?

Biologics are essentially large drugs with complex proteins made from living cells such as humans, plants, microorganisms, and animals, through a multifaceted manufacturing process.

These complex products must be handled and administered through a carefully evaluated and inspected process. Biologics include a wide array of products across multiple therapeutic areas, including gene and cell therapies.

On the other hand, a biosimilar is conceptualized as a copy of biologic medicine similar but not identical to the original drug. Biosimilars have no clinically significant differences from their reference FDA-approved biologic. 

History

The late 1800 and early 1900 was a biotechnological era where scientists such as Shibasaburo Kitasato and Emil Von Behring advanced medical science and biotechnology by developing a "serum treatment" or "antitoxin therapy."

These therapies were developed with serum from animals— typically sheep or horses—injected with the right antigens to produce the required antibodies.

This drastic development in medicine during this era brought about the Biological Control act that mandated the National Institutes of Health (NIH) to oversee the production and advancements of biologics. Biologic inception stages featured transplantable tissues, blood products, and vaccinations.

The history of biosimilars is fairly new as the FDA ran a legislative campaign in 2009 to permit the Pathway for Biosimilars Act, allowing the agency to authorize biosimilars. 

This is when the history of biosimilars began. The Biologics Price Competition and Innovation Act (BPCI ACT) helped pharmaceutical companies to expedite the approval of these treatments without the need for repeating their clinical research on people or animals.

The creation of nearly any recombinant DNA-based biologic for medication development has been made possible by replicating human genetic information while also advancing production techniques of these biologics.

These advancements in regulation and production techniques have opened the door for the cost-effective biosimilars. In 2013, the first biosimilar (infliximab) was licensed in the EU. The United States followed shortly after, approving filgrastim in 2015 as the first approved biosimilar in the nation.

We will discuss the approval and post-market monitoring processes for both biologics and biosimilars, review cost differences between the two, and explain the roles of MSLs and pharmacists in educating patients within the field.

Approval Process

Biologic Approval. Before producing and supplying biologics for mass consumption, every entity involved in the production of biologics or in charge of the regulatory compliance of a biologic requires  FDA permission.

Therefore, manufacturers must submit a Biologics License Application (BLA) in order to produce and supply these therapies. 

The Center for Biologics Evaluation and Research (CBER) is a component of the FDA that ensures the safety, efficacy, and availability of biologics. Essential elements like clinical trial methods, a product description summary, and manufacturing techniques must be included when submitting documents for review by CBER.

Biosimilar Approval. To enhance patients' confidence in the biosimilars, the safety and quality of all products must undergo a rigorous review process. A suggested biosimilar product is contrasted with a reference product, a single biological product that has already received FDA approval.

A "separate" application is used to approve reference products, and it must include all the data and details required to substantiate their efficacy and safety. Therefore, an organization seeking FDA approval must thoroughly test its product to ensure relatively similar standards to a reference drug before requesting consent.

A manufacturer will submit an application to the FDA for licensure if it can independently demonstrate that its biosimilar development program, which creates a proposed biosimilar product, is comparable to its reference product.

After that, the FDA will conduct extensive research to validate the authenticity of the information provided for the proposed drug. If it meets the standards comparable to the already approved FDA drugs, the organization will receive approval for mass production.

If it does not meet the expected results, the FDA will offer to rescind the proposal until the organization can achieve the standards provided by the FDA.

Post-Market Monitoring

With the growth of sophisticated data investigation tools in the past few years, the evolution of biopharmaceutical processes has advanced dramatically. As biologic and biosimilar medications have become increasingly popular over the past decade, robust platforms for assuring the delivery of quality products are becoming essential. 

Companies use Quality by Design techniques to further promote the safety and efficacy of drugs on the market. Real-time monitoring and advanced process control have become the most utilized tools for monitoring biological drugs. 

Real-time data collection utilizes the use of sensors integrated into the bioprocess chain. Data collection is done without removing samples from the processes and is recorded in various databases for evaluation.

Additionally, process monitoring tools made possible by modern data analytics and simulation enable manufacturers to gain full statistical representations of advancements in their pharmacological capabilities, side effects, and unfavorable consequences.

This data is stored in special databases that provide insight into further development of biologic and biosimilar drugs.

Cost Difference

Healthcare expenditures worldwide are impacted by the significant expense of medications, particularly biologics. Biologics are more complicated to create than conventional small-molecule generics.

This is because biologics are bigger and more complex molecules that cannot be made using traditional chemical processes but must be made in living tissues, with purification crucial in developing these drugs.

In contrast, biosimilars are mostly made using chemical compounds predicated on biologics studies. Hence, the cost of biologic drugs is more expensive compared to biosimilar drugs.

References

• Center. Updated 2019. Biosimilar Development, Review, and Approval. U.S. Food and Drug Administration. Accessed 1st July 2022. 

• State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars. Updated 2022. 2020. Accessed 1st July 2022. 

• Wasalathanthria, D. P., Ding, J., & Jian Li, Z. Real-Time Process Monitoring in Biologics Development [Review of Real-Time Process Monitoring in Biologics Development]. Updated 12th May 2020. Accessed 1st July 2022.