An official website of the United States government
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Perry T, editor. Therapeutics Letter. Vancouver (BC): Therapeutics Initiative; 1994-.
Therapeutics Letter 123 examines biologics and biosimilars. Conclusions: Biosimilars are not identical to biologics but lie within the variability range of the originator biologic. Government regulators around the world approve biosimilars based on evidence that biosimilars are not inferior to the originator biologic product in terms of safety and effectiveness. Systematic reviews of switching from biologics to biosimilars found no meaningful differences in safety and effectiveness between them. Biosimilars are less expensive than originator biologics.
The term “biologics” can refer to a wide range of therapeutic products, including vaccines, blood products, gene and cell therapies, and bioengineered drugs. Often it is used more restrictively to refer to drugs produced through recombinant DNA technology. Health Canada notes that biologic drugs are “derived through the metabolic activity of living organisms and tend to be significantly more variable and structurally complex than chemically synthesized drugs”.1
Monoclonal antibodies (MAb) comprise one class of biologics. They are created by immune cells that are identical clones of a unique parent cell. MAb are large, complex molecules that have a binding site and may have the same primary, secondary and tertiary structure as a human protein.
According to Health Canada, a biosimilar is a “biologic drug that is highly similar to a biologic drug that was already authorized for sale. There are no expected clinically meaningful differences in efficacy and safety between a biosimilar and the biologic drug that was already authorized for sale”.2 Biosimilars have been approved for use in Canada since 2009 and were developed, similar to generic medications, to reduce the expenditure of healthcare on costly biological treatments and improve patient access to these drugs.
Manufacturing chemical drugs is a controlled, predictable chemical process, allowing identical copies (generic versions) to be replicated exactly. The manufacturing process for biologics is complex, involving several stages of cell selection, cell culture, purification, formulation, production and validation of the final product.
Every biologic manufacturer uses a unique cell line and a proprietary process. No two production batches of biologics are identical. Originator biologics also have intrinsic natural variability because batches can differ and the manufacturing process can itself change.3
During manufacturing, primary amino acid sequences can become modified through glycosylation, changing the shape of a protein because of alterations in the way it folds. These modifications are not controlled by the recombinant DNA inserted into the host cell but are affected by the cell line and the environment in which the cell line is grown.4
Regulators around the world (Health Canada, FDA, EMA) use strict, specific approval criteria to ensure that the biosimilar product lies within the variability range of the originator biologic.
Health Canada, in its submission guidance document, explains: “similarity does not signify that the quality attributes of the two products being compared are identical, but that they are highly similar with two consequences:
Canada, US, Europe, Australia and New Zealand all follow similar scientific principles for the authorization of biosimilars.5 Health Canada accepts use of a reference product from another ICH country and information from other regulators such as the European Medicines Agency (EMA) and the US FDA regarding full biosimilar program development, including analytical similarity, non-clinical and clinical studies.2
Biosimilars can be substantially less expensive than their originator biologics. For example, the biosimilars to infliximab can save Canadians almost 50%, compared with the originator (Remicade).6
Infliximab (Remicade), a chimeric MAb derived from human and mouse DNA, is approved in Canada for treatment of rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease and ulcerative colitis, and psoriasis. Biosimilars Inflectra (CT-P13) and Renflexis have identical approvals.
We identified 12 systematic reviews of studies comparing infliximab with its biosimilars.7 Patients started treatment either as naïve to infliximab or by randomization to continue the originator therapy (Remicade) or to switch to a biosimilar.
We looked for any claim of clinically meaningful differences in rates of disease control, safety or immunogenicity between infliximab and its biosimilars. No such claims were made, so we did not examine the reviews further.
One important RCT and two of the more robust systematic reviews are summarized below. The remainder are described in a summary posted on our website.7
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Your browsing activity is empty.
Activity recording is turned off.
See more...
