Drugs vs. Biologics - What is the Difference?
According to the FDA most drugs can be chemically synthesized since their structure is known, whereas most biologics are complex mixtures that are not easily identified or characterized.
Biologics include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Below are other differences b/w drugs & biologics.
- typically a smaller chemical structure than biologics
- typically manufactured through chemical synthesis, which means that it is made by combining specific chemical ingredients in an ordered process.
- generally have well-defined chemical structures, and a finished drug can usually be analyzed to determine all its various components
- a drug manufacturer can change the manufacturing process extensively and analyze the finished product to establish that it is the same as before the manufacturing change.
- very large, complex molecules, proteins or mixtures of molecules
- manufactured in a living system such as a microorganism, or plant or animal cells
- it is difficult, and sometimes impossible, to characterize a complex biologic by testing methods available in the laboratory, and some of the components of a finished biologic may be unknown
- for biologics, “the product is the process.” Because the finished product cannot be fully characterized in the laboratory, manufacturers must ensure product consistency, quality, and purity by ensuring that the manufacturing process remains substantially the same over time.
Additional Biologics Info
- The living systems used to produce biologics can be sensitive to very minor changes in the manufacturing process. Small process differences can significantly affect the nature of the finished biologic and, most importantly, the way it functions in the body. To ensure that a manufacturing process remains the same over time, biologics manufacturers must tightly control the source and nature of starting materials, and consistently employ hundreds of process controls that assure predictable manufacturing outcomes.
- Process controls for biologics are established separately for each unique manufacturing process/product, and are not applicable to a manufacturing process/product created by another manufacturer. These process controls may also be confidential to the original manufacturer. Therefore, it would be difficult or impossible for a second manufacturer to make the “same” biologic without intimate knowledge of and experience with the innovator’s process.
- A typical manufacturing process for a chemical drug might contain 40 to 50 critical tests. The process for a biologic might contain 250 or more. Biologic production uses specialized processes that do not always resemble facilities, machinery, or equipment used to produce chemical drugs. Construction and validation of new facilities is disproportionately expensive and also time consuming. This helps explain the global shortage of biomanufacturing capacity and the cost differential between biologic and chemical drugs. (source)
Generic Drugs vs. Follow-on Biologics (Biosimilars)
Generic Drug Manufacturing
To be approved as a generic, a drug must have the same active ingredient, strength, dosage form, and route of administration as the reference drug, and it must also be “bioequivalent.” This means that generic drugs are the same chemically as their innovator counterparts and that they act the same way in the body.
Biosimilar Manufacturing (not really possible)
FDA has stated that it has not determined how interchangeability can be established for complex proteins. More here
Historically, FDA has permitted interchangeability only when two products are “therapeutic equivalents.” However, when the follow-on manufacturer establishes a new manufacturing process, beginning with new starting materials, it will produce a product that is different from and not therapeutically equivalent with that of the innovator (i.e. the end product is different). Due to the complexity of biologics, the only way to establish whether there are differences that affect the safety and effectiveness of the follow-on product is to conduct expensive and time-consuming clinical trials.
Case in Point - Premarin® (owned by Pfizer)
Premarin is a vaginal cream biologic the FDA first approved in 1942. It is considered a fairly simple biologic according to Thomas Morrow M.D. as he states below:
“Others [biologics] would include substances that are created in other organisms but are not highly complex, such as the estrogen hormones extracted from pregnant mare urine (Premarin)”
The drug has been a huge money maker for its owner. Other manufacturers and generic drug suppliers have noticed.
One would think that after almost half a century later industry would be able to duplicate a simple biologic. No – that is not the case. In fact despite the knowing source (i.e. pregnant mare urine) not even the manufacture knows its exact chemical makeup.
Despite attempts by 2 manufacturers to duplicate the biologic, the FDA rejected generic ‘alternatives’. See below.
In fact, the site drugs.com says there is no generic version of Premarin currently available. See below.
Could a generic version become available? ‘Not likely’ according to Tori Marsh, MPH of GoodRx. She writes below
Note: There are now many forms of Premarin, not just cream.