Although the BPCI Act has a provision for declaring a biosimilar interchangeable with its reference, it is unlikely that many drugs will achieve this designation. In the EU, automatic substitution is banned because of the dangers of switching between similar biologics, for example, switching between brands of antiepileptic drugs can cause seizures.
The largest fear that many have is that biosimilars will induce immunogenic reactions. The formulation of the erythropoietin biologic Eprex (indicated for anemia caused by chronic kidney disease and chemotherapy) was slightly modified, causing the formation of neutralizing antibodies that reacted with endogenous erythropoietin. This caused red blood cell aplasia, meaning that the bone marrow ceased to produce red blood cells.
Drugs such as Eprex that can suddenly become dangerous due to minute differences between batches raise dire safety concerns for follow-on biologics, which will have unavoidable differences from the original. Aside from the more dramatic side effects, immunogenicity can also cause reduced efficacy and delayed serum sickness-like symptoms.
One study found that by using a battery of assays, the biosimilars Binocrit and Retacrit had comparable quality to Eprex and Dynepo. However, they also found significant differences in potency from what was printed on the packaging, which could create problems in prescribing the correct dosage for patients.
Another study focused only on epoetin alpha raised concerns about the higher level of mannose in the biosimilar and the need for more extensive and sensitive studies to detect any possible clinical implications.
Even in the small molecule field, generic forms of brand-name drugs can have potentially clinically meaningful differences. According to one study, generic paclitaxel and brand name Taxol have significant potency differences. Though both inhibit the growth of cancer cells by arresting their development in a specific stage of mitosis, the generic had a higher severity of these effects.
This is problematic because the FDA mandates that all generics be clinically equivalent to their references at the same dosage. When this is not true, the interchangeability of the two drugs is called into question.
The R&D cost of a new drug is estimated to be about $1.2 billion. Biopharmaceuticals manufacturers claim that building manufacturing facilities costs up to $450 million more. Without adequate mechanisms to recoup this cost, the incentive to bring new innovative drugs to the market is greatly reduced.
For this reason, the BPCI Act grants a 12-year exclusivity period during which the innovator company does not have to share its clinical data and no biosimilars can be approved. Interestingly, this development cost figure varies widely from source to source.
Shapiro claims that the average cost is only $530 million. Groups like the AARP, the American Medical Student Association, and the National Women’s Health Network, support a five year exclusivity period. This would allow more competition and bring down the prices of biologics much more rapidly.
In addition, it is the same period of exclusivity permitted for small molecule drugs before generics can be made. Biosimilars and generics manufacturers argue in favor of a reduced exclusivity period, claiming that the competition will encourage innovator companies to create new biologics in order to continue to profit.
One biosimilar company Hospira, also states that in Germany, where legislation is more favorable to biosimilar companies, the company has seen a 20–30% price drop in erythropoietin drugs because of competing biosimilars. For this reason, President Obama proposed a compromise of seven-year market exclusivity in his 2012 budget proposal. This proposal will be seriously debated by advocates of both sides as it could potentially compromise return on investment by innovator companies.