Introduction to Biosimilars
As clinical guidelines are published and the pharmaceutical industry innovates, the practice of pharmacy changes. At the fore front of innovation is the biologic. These medications are capable of achieving clinical outcomes that traditional small chemical medications cannot. Biologics are not without disadvantages. In addition to being more challenging to create, these medications are also orders of magnitude more expensive. This cost has kept biologics as an alternative or not even an option to patients who would greatly benefit from their use. In order to solve this issue, the pharmaceutical industry is developing biosimilars, or medications that are similar to existing biologics and are offered at a lower cost.
Most medications that are found in a pharmacy are small molecule products. These drugs are synthesized chemically and have been relatively cheap to produce. When a small molecule drug is first offered on the market by a single proprietary manufacturer, they are known as brands drugs. The costs of these products are typically high for a regulated period of time, that proprietor is the only entity legally allowed to produce that drug. This creates a temporary monopoly, allowing the proprietor to sell at a price with no competition. After that period of time is up, other manufacturers are allowed to create what is known as generics. This system of proprietor creation and then generic competition is regulated by the Hatch-Waxman Act. This legislation has two goals. The first is to create an incentive for new drug creation by allowing innovator manufacturers enough of a monopoly to make a profit despite high research and design cost. The second is to lay down a framework where generics can come in and make prices reasonable for patients. When both goals are met, a balance is struck between continuing innovation and low drug costs. Hatch-Waxman has created a model that works well for the brand-generic model which for the time being describes the inventory of most pharmacies.
For biologics, this model cannot be applied. The reason for this difference is due to the method of how biologics are synthesized. Biologics are made from genetically engineered cells. These cells then create proteins which are then isolated. As you can imagine, this process is much more complex and difficult. The process for engineering these cells may be trade secrets which means non-proprietary manufacturers must come up with a different way to arrive at a similar protein. The fact that the active pharmaceutical ingredient is a protein makes replication more challenging for non-proprietary manufacturers. A protein’s function is in part derived from its tertiary structure, the way in which the protein is folded. Slight alterations in the amino acid chains which make up the protein could alter tertiary structure and therefore alter is function. In other words, the creation of generics for biologic proprietary medications are nearly impossible.
This is where biosimilars come into the picture. Biosimilars are highly similar medications to a reference product. A reference product is like the brand product of the original model. The sponsors of the biosimilar must go through a new legal route before they can market the product. Thus far, that legal pathway has been through the Biologics Price Competition and Innovation (BCPI) Act. This act is designed to work similarly to the Hatch-Waxman Act. The BCPI is not the complete story however, leaving the path biosimilars must go through unclear. The amount of research needed for a biosimilar and the time that it will take to develop a biosimilar for example are still unknown.
In conclusion, biosimilars are medications that are clinically similar to proprietary biologics and can be produced and sold at a lower cost. Due to the complex nature of biologics themselves, biosimilars will not be the new generics but could lower health care costs and bring innovative pharmacotherapy to more patients.
Robert Bond, PharmD '18