Biological Drugs
Biological drugs are a class of drugs made from living organisms or contain components of living organisms.
What are biological drugs?
Biological drugs are a class of drugs commonly referred to as biological products or simply biologics. The FDA uses the term biological product to distinguish this type of drug from the more conventional drug made from chemical substances.
• Many of today’s important medications are biological products. They are also some of the most expensive to take.
The global market for biologics is valued at $416 billion in 2023. It is expected to grow to $665 billion by 2030.
It is expected that we will see more oral biologics (pills) over injections in the future.
Demand for biologics is expected to grow due to the coronavirus outbreak.
♦ The top opportunity in the biologics market segment is monoclonal antibodies, which is expected to grow to $75 billion in global sales by 2025.
The biologic market is highly concentrated, with a small number of players.
Major players are:
- Pfizer Inc.
- F. Hoffmann-La Roche
- AbbVie Inc.
- Merck & Co. Inc.
- Johnson & Johnson
- Bristol Myers Squibb Company
- GSK plc. Formerly GlaxoSmithKline Plc.
- Amgen Inc.
- Sanofi S.A.
- Eli Lilly & Company
From living organisms
♦ Biological products are made from living organisms. The material they are made from can come from many sources, including humans, animals and microorganisms such as bacteria or yeast. Biological products are manufactured through biotechnology, derived from natural sources or, in some cases, produced synthetically.
♦ Biological products are among the medications used to treat conditions such as rheumatoid arthritis, anemia, low white blood cell counts, inflammatory bowel disease, skin conditions such as psoriasis and various forms of cancer.
Most biological products are more complex in structure and have larger molecules or mixtures of molecules than conventional drugs. Conventional drugs are made of pure chemical substances and their structures can be identified.
• It is important to understand that most conventional drugs are small molecules and fairly simple in their structure. They are synthesized from chemicals in a consistent process so that manufacturers can be sure that each pill has the same effect every time. This makes them easier to reliably reproduce and copy.
• Most biologics, however, are complex mixtures that are more difficult to identify or characterize. It is virtually impossible to create identical generic biological products, so we have what are called biosimilar or interchangeable biological products.
How safe are biological drugs?
Most biological drugs work on the immune system. Immune system problems such as greater infection risks have been the most common safety issues.
• Almost one-quarter of biological therapies approved in the United States and Europe since 1995 have been the subject of at least one safety-related regulatory action. This usually coming after years of use and documentation of adverse side effects.
The first approved biological drugs in a class are more likely to receive regulatory action. These drugs should be monitored closely. You should report any unusual reaction to your doctor right away.
What are biosimilar and interchangeable biological products?
There are two new types of biological products: biosimilar and interchangeable.
• Biosimilars are a type of biological product that are approved by the FDA because they are highly similar to an already FDA-approved biological product, and have been shown to have "no clinically meaningful differences."
• Interchangeable biological product, in addition to meeting the biosimilarity standard, is expected to produce the same clinical result as the already FDA-approved biological product in any given patient. It can be substituted for the brand-name product without permission from the prescribing doctor.
♦ Since biological products are made using living cells, it's nearly impossible to make an exact copy unless a company follows exactly the same manufacturing process used in the making of the original (brand-name) biological drug.
This information is proprietary information, so making a perfect copy is not really possible, only a close copy.
Biosimilars are similar -- but not identical -- to the brand-name biological product, thus the name biosimilar.
Will biosimilars and interchangeables work in the same way?
The FDA says, yes. Most pharmacists say, no. The FDA says, biosimilars have no clinically meaningful differences in terms of safety and effectiveness from the brand-name product.
Biosimilar products need to have the same mechanism of action as the brand-name product it is compared to.
♦ The biosimilar product is supposed to have the same mechanism of action, route of administration, dosage form, and strength as the original brand- name product. The FDA does not specify that they need to produce the same clinical results as the brand-name product.
♦ An interchangeable biological product, in addition to meeting the biosimilarity standard, is expected to produce the same clinical result as the original brand-name product. FDA approval as an interchangeable biological product is more involved than for a biosimilar product.
How are biosimilars and interchangeables prescribed?
A biosimilar product can be prescribed by a health care provider. The health care professional has to write the specific name of the product on the prescription if they want to prescribe the biosimilar.
An interchangeable biological product may be substituted for the original brand-name product by a pharmacist.
In 2023, patent protection on a third of the drugs will expire, opening the door to biosimilar competition. And hopefully lower prices.
Major suppliers are already working to firm up their customer base by suggesting to physicians, payers and patients that switching drugs is not a good idea if your medicine is working for you.
The battle of the biologicals is already hot.
Are biosimilars generic versions of biological products?
No. Generic drugs are copies of brand-name drugs, have the same active ingredient, and are the same as those brand-name drugs in dosage form, safety, and strength, route of administration, quality, performance characteristics and intended use. That means the brand-name and the generic are bioequivalent.
♦ Biosimilars are highly similar to the original brand-name product they were compared to, but have allowable differences because they are made from living organisms.
Biosimilars are supposed to have no clinically meaningful differences in terms of safety, purity, and potency from the original brand-name biological product.
How are biosimilars approved?
Biosimilars were created under the Biologicals Price Competition and Innovation Act (BCPI) of 2009 and signed into law through The Patient Protection and Affordable Care Act (Obamacare) on March 23, 2010.
♦ Under this law, a biological product may be demonstrated to be biosimilar if data show that the product is highly similar to an already-approved biological product. And the product has to show it has no clinically meaningful differences in terms of safety, purity, and potency from the already-approved biological product.
• The biosimilar approval relies on the FDA’s previous findings that the already-approved biological product is safe and effective. This point has a number of people concerned that the FDA might be rushing approval of biosimilars at the cost of safety.
How is biosimilarity or interchangeability determined?
The manufacturer must submit an application to the FDA for a biosimilar or interchangeable biological product that includes, among other things, information demonstrating biosimilarity based upon data from analytical studies, animal studies, and clinical studies such as the assessment of immunogenicity and pharmacokinetics (PK) or pharmacodynamics (PD).
• If the manufacturer wants its product to be reviewed as an interchangeable product, the application must also include data or information to show that the proposed interchangeable product is expected to produce the same clinical result as the already-approved brand-name biological product in any given patient.
• In addition, when a product will be administered more than once to an individual (as many biological products are), the manufacturer must also demonstrate that the risk in terms of safety or reduced effectiveness of alternating or switching between use of the proposed interchangeable product and the already-approved brand-name biological product is not greater than the risk of using the brand-name product without alternating or switching. This is in addition to the data described above to demonstrate biosimilarity.
• Additionally, the facilities where biosimilars are manufactured must meet the FDA’s standards.
