Biosimilars are new versions of existing biopharmaceuticals made in cellular biologic systems and are approved on the basis that they are highly similar to the reference product in terms of quality, safety, and efficacy. The term "biosimilars" is used to describe biologics developed to be highly similar to existing, branded biologics.
Biosimilars are not called generics because biologic drugs cannot be exactly copied. Biologics are derived from living cells or organisms and consist of relatively large and often highly complex molecular entities that may be difficult to fully characterize. Inherent variability of the biologic system and the manufacturing process always exists and any resulting biological product will display a certain degree of variability (microheterogeneity), even between batches of the same product will not be "identical". In contrast, generics are typically identical to the reference product on account of being much smaller and less complex molecules easily characterized and are produced through very standard chemical synthesis.
The real value of biosimilars is that they may reduce the overall healthcare cost burden to the patient, making treatment more accessible. Biosimilars introduce genuine competition into an area that has until now been unhealthily short of it. Such competition can help reduce prices and help free up public funds to broaden overall access to healthcare. In addition, it provides a further incentive for the producers of patent-protected medicines to come up with fresh ideas and genuinely original new products. You could say that competition drives the "virtuous circle" of innovation.
In the next few years, the patents of many major biopharmaceuticals will start to expire, paving the way for biosimilar competition.
The FDA created an abbreviated pathway (351k) for biosimilar development and product registration/approval that relies on a very tailored set of preclinical studies and clinical studies comparing efficacy, safety, and immunogenicity specific to the assessment of biosimilarity.
Unlike generic medicines, which need to demonstrate bioequivalence only, biosimilars need to conduct clinical trials. In general, Biosimilars need to conduct Phase I and Phase III clinical trials to demonstrate biosimilarity. Phase II clinical trial studies do not need to be done due to the fact that the dosing has already been established by the reference product.
Phase I clinical trials are used to show the biosimilarity in PK/PD with the reference product while the robust Phase III clinical trials are used as a confirmatory trial establishing safety and efficacy of the Biosimilar.
Data requirements vary on a case-by-case basis. However, extensive manufacturing, non-clinical pharmacology, toxicology, pharmacokinetics, pharmacodynamics, and clinical data must be generated.
Biopharmaceuticals tend to have a large size and a complex structure and are manufactured from "nature's factory" using a unique line of living cells. This makes it impossible to ensure an identical copy. Inherent variability exists for all biologic products, including the reference product--which will display certain degree of variation (microheterogeneity), even between different batches of the same product.
A biosimilar and the respective originator product will not be entirely identical. However, a high level of similarity to the reference product that must be defined in terms of physicochemical characteristics, efficacy, and safety, based on the results of comparability exercises. This forms the basis for regulatory approval.
Detected differences must be determined to be "clinically irrelevant" and have no impact on therapeutic product safety and efficacy.
Comparability testing involves a stepwise approach to demonstrating biosimilarity, including a comparison of the proposed product and the reference product with respect to structure, function, animal toxicity, human pharmacokinetics and pharmacodynamics, clinical immunogenicity, and clinical safety and effectiveness.
The Biologics Price Competition and Innovation (BPCI) Act, passed in March 2010 as part of the Affordable Care Act, authorized the FDA to create an abbreviated licensing pathway for biosimilars of US-licensed biologics. In February 2012 and March 2013, the FDA issued guidelines on how the agency would implement the biosimilar approval pathway through the fundamental principle that biosimilars must have comparable clinical effects to the reference biologic.
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