As many of you know, biosimilars are, simply, proteinaceous materials, physio-chemically identical to an existing drug substance, merely generated by a differing pathway. There are a number of points of view and opinions on how good or necessary they are:
1. a. They are necessary to keep prices in check. This is always the argument for generics and has a fair amount of validity. Considering a lack of price controls in much of the United States, this is a valid point. Many newer drugs can easily reach more than $100,000 per year, per patient, so any price relief should be applauded.
So, it is claimed, it is in the interest of patients that less expensive alternative sources of a medicine be made available. Since the process of synthesis is different from the name product it should be allowed.
b. They are an infringement on the exclusivity of the innovator. If the final API is chemically identical to the innovator drug, and the patent has not expired, it is an infringement on the innovator’s patent. Small molecule-based products are protected, no matter how different or unique the synthesis of the API is performed by the generic company.
When most people compare generics vs. initiator, they are looking at the structure of the dose, not the (simple) API. The chemical entity (CE) is the material being protected by patent (except in the case of designer dosage forms: osmotic pumps, etc.). Simply put, the “real” chemistry happens during the chemical synthesis, but the majority of development time is spent on developing the “drug delivery system.” So, during the sales portion of a product’s lifecycle, the synthesis of the API is a small portion of the production time; the dosage form takes the majority of effort, time, etc., to produce.
BIOPROCESS CONSIDERATIONS
In a biological product, the making of the product is often quite a time-consuming process, often continuing for days or weeks. Compared to the time needed to make the final dosage form for the bio-product, the bioprocess is the major portion of time and resources. Where most small molecule APIs merely need solvent-based crystallizations, purifying the biological product is complicated and often time consuming.
It is the making of the bio-molecule that the innovator is protecting, not the delivery system. Therefore, allowing a “biosimilar” to market before patent expiry is a financial hardship to the innovator.
2. a. They are just as good/the same as the originator drug. The argument is that additional/parallel clinical testing is not needed because the API is the same. If true, then all that is needed is cursory testing to show equivalency to the name product?
There may be microscopic differences in the minor components, but the major molecule that has been shown to be identical to the original active should be considered “as safe as the original.”
b. They are not the same, biologically, and more testing is needed. Here, the argument goes that, since the biochemical path is different (or there is a patent infringement), the potential byproducts must be different from the originator product.
This argument needs to be examined on a case-by-case basis, not as a general statement. If a drug is used for a disease or condition that is acute, and the treatment schedule is short-lived (less than two weeks, for example), then there is a good chance the minor differences from the innovator molecule are likely not a health hazard.
In the case of a drug that is used for a long-term (chronic) treatment, for example may well be necessary to perform as an anti-rejection drug for transplants, then trace impurities might become an issue. For these type of products, it may be necessary to perform as extensive a clinical study as was done for the innovator product.
It should be apparent that the case for each biosimilar is complex and should be evaluated on a full “risk-benefit” analysis.
