What is biosimilar medicine? FDA Review and Approval Process
Biologically similar drugs are increasingly attracting attention in the healthcare industry. As a novel and promising type of medication, they hold the potential to bring numerous benefits to patients, healthcare providers, and the overall healthcare system. In this article, let’s delve deeper with GOL into what biological similar drugs are and what the FDA Evaluation and Approval Process for biological similar drugs entails!
What is a biosimilar medicine?
A biosimilar, or biosimilar drug, is a medication with a structure and function similar to a biological drug. Biological drugs, also known as biologics, are medications composed of proteins or protein fragments (whether natural or synthetic). Unlike other types of drugs, biologics are manufactured from living organisms such as yeast, bacteria, or animal cells.
Biological drugs exert their effects in various ways. Depending on the type of drug, they can:
- Stimulate the immune system to better recognize and destroy cancer cells effectively.
- Disable certain proteins within or on the surface of cancer cells, thereby inhibiting the growth of these cells.
- Enhance the body’s immune response.
Immunotherapy and targeted therapy are examples of biological drugs applied in cancer treatment.
Corresponding to certain originator biological drugs, there may be one or several biosimilar drugs. Biosimilar drugs have a similar structure but are not identical to the originator drugs. Biosimilar drugs have a mechanism of action that is similar, with almost no significant difference from the originator drugs. This means that biosimilar medicine are also recognized as safe and effective as the originator biological drugs. Both types of drugs are produced from living organisms.
What is difference between biosimilar and generic?
Generic drugs are copies of brand-name drugs. Generic drugs have a mechanism of action similar to brand-name drugs and can be used as substitutes for them. In other words, generic drugs are alternative options to brand-name drugs for treating specific conditions.
Biosimilar medicine can be considered as the biologic equivalent of generic drugs, although there are still some important differences. For example, unlike generic drugs, biosimilar drugs are not exact replicas of the originator biologic drug.
Some similarities between biosimilar medicine and generic drugs
- Both have been evaluated and compared to the originator drugs in clinical trials.
- The reference drugs used as comparators have been approved by the United States Food and Drug Administration (FDA) for circulation.
- Both undergo FDA evaluation through rigorous processes but are typically shorter than those for their originator drugs.
- Both are safe and equally effective as the originator drugs.
- Both are often more cost-effective treatment options compared to the originator drugs.
Some differences between biosimilar medicine and generic drugs
- Biosimilar medicine have a biological (natural) origin, while generic drugs are synthetic chemical compounds.
- Biosimilar drugs have origins and some characteristics similar to originator biological drugs, whereas generic drugs are identical chemical copies of the originator brand-name drugs.
- When comparing a biosimilar drug to its originator biological drug, the FDA typically requires more data from studies compared to when comparing generic drugs to their originator brand-name drugs. This is because biosimilar medicine have a natural origin and are not exact replicas of the originator drugs.
- FDA approves biosimilar medicine and generic drugs through different processes.
- After receiving marketing approval, biosimilar medicine require an additional approval to be used as substitutes for the originator biological drugs, while this is inherent for generic drugs.
Read more: FDA approved vs FDA cleared: The differences you need to know
Biosimilar drugs have a biological origin (natural)
Generic drugs are exact replicas (with identical active ingredients) of the originator brand-name drugs. This is because the active ingredients of originator brand-name drugs are chemical compounds with well-defined structures that can be easily replicated. However, biological drugs have a biological origin and cannot be replicated 100%. These drugs are produced from highly complex living organisms, and their living environments can easily change. Therefore, although biosimilar medicine are manufactured using processes similar to those of originator biological drugs and share many similarities, structurally, they cannot be identical. Unlike generic drugs, biosimilar drugs are only similar to the originator drugs rather than being exact copies.
Biosimilar drugs require additional FDA approval to be interchangeable with the originator drugs
When the FDA approves a generic drug for distribution, it signifies that the drug can be used interchangeably with the originator brand-name drug. No additional information or data is required by the FDA to establish the safety and effectiveness of the generic drug as a substitute for the originator brand-name drug. Due to identical chemical structures of their active ingredients, a prescription written for the originator brand-name drug can be seamlessly replaced with the generic drug. Consequently, patients can expect equivalent efficacy when using the generic drug compared to the originator brand-name drug, allowing for seamless switching between the two without discernible differences.
For biosimilar drugs, FDA approval for distribution does not automatically grant interchangeability with the originator biological drugs. Therefore, although biosimilar drugs may be used in treatment upon receiving marketing approval, they still need specific FDA approval to serve as substitutes for the originator biological drugs. biosimilar medicine without interchangeability status cannot replace originator biological drugs in prescriptions.
The FDA imposes stringent regulations that biosimilar drugs must meet to qualify as interchangeable with the originator drugs. Biosimilar drugs only need to demonstrate safety and effectiveness similar to the originator drugs in treating a specific disease through clinical trials to receive circulate approval. However, if a company seeks their drug to be recognized as interchangeable (and thus automatically substitutable for the originator drugs), they must submit additional clinical trial data to the FDA.
Are biosimilar drugs safe?
Like other medications, a biosimilar drug needs to be evaluated through clinical trials and approved by the FDA before being used in treatment. In these clinical trials, biosimilar drugs are compared to originator biological drugs – the first-invented drugs. Originator biological drugs have undergone clinical trials, been approved for distribution, and used in treatment. Clinical trials are designed to assess the safety and effectiveness of biosimilar drugs compared to originator biological drugs in treating the same specific disease.
Clinical trials assessing drugs in general are very detailed and rigorous. However, clinical trials evaluating biosimilar drugs may be conducted faster than previous clinical trials evaluating originator biological drugs. In studies on biosimilarity, trials are conducted to evaluate the similarity between biosimilar drugs and originator biological drugs on certain aspects. Trials need to demonstrate that both drugs:
- Have the same origin
- Have equivalent dosage and efficacy
- Have the same route of administration (e.g., oral route)
- Provide similar benefits in treating a disease
- Have similar adverse effects
Data collected from these studies will be carefully evaluated by the FDA to ensure that biosimilar drugs are as safe and effective as originator biological drugs.
A biosimilar drug is evaluated in clinical trials to demonstrate safety when used in humans. If a drug has been FDA approved for distribution, it means that it has met stringent standards for safety.
Read more: What are OTC drugs? Differences between OTC and Prescription
Why is the development of biosimilar drugs necessary?
Originator biological drugs often come with hefty price tags due to the extensive research and manufacturing efforts required by companies. These high costs often create barriers to access for many individuals, even though these drugs may offer the most effective treatment for their conditions. In order to enhance accessibility to biological drugs for a wider population, the United States Congress enacted the Biologics Price Competition and Innovation Act (BPCIA). This legislation empowers the FDA to expedite the approval process for biosimilar drugs.
Scientists and policymakers argue that biosimilar drugs have the potential to mitigate medication expenses by expanding treatment options for patients. Some experts have projected that biosimilar drugs could result in significant cost savings, potentially amounting to billions of dollars in medication expenses. However, the realization of these savings depends on various factors, including the number of biosimilar drugs undergoing testing, evaluation, and approval for distribution, as well as their availability in the market. Additionally, it’s crucial to consider the range and prevalence of diseases that can be treated using biosimilar drugs, along with the volume of medication consumption.
How are biosimilar drugs currently used in cancer treatment?
There are several biologic drugs in circulation, such as targeted therapy or immunotherapy drugs, being utilized in cancer treatment, some of which have biosimilar versions. Some biosimilar drugs have been approved for treating specific cancer conditions, and others have been approved for managing the side effects of cancer treatment.
In the coming years, the number of biosimilar drugs approved for cancer treatment is expected to increase. Many experts believe that the introduction of more biosimilar drugs into use could help reduce the cost of treating certain types of cancer.
The process for approving biosimilar products
Biosimilars undergo FDA approval via an abbreviated pathway. The primary objective of a biosimilar development program is to establish biosimilarity between the proposed biosimilar and its reference product, rather than independently proving the safety and efficacy of the proposed biosimilar. This typically translates to fewer costly and time-consuming clinical trials for biosimilar manufacturers.
Read more: A Guide to Drug Master Files
What information is necessary for the approval of a biosimilar product?
The FDA assesses each proposed biosimilar product individually and provides guidance to manufacturers regarding the extent and type of testing required to establish biosimilarity.
An application for a proposed biosimilar typically needs to include data demonstrating its biosimilarity to a reference product. Here are details on the data typically required in such an application:
- Analytical studies: Comparative analytical data form the cornerstone of biosimilar development. These studies furnish data supporting the structural and functional similarity of the proposed product to the reference product, and assess any identified differences.
- Animal studies: These studies may provide toxicological or pharmacological information.
- Clinical study or studies: Pharmacology studies may illustrate that the proposed biosimilar behaves in the body similarly to the reference product and elicits similar effects. An immunogenicity assessment evaluates a patient’s immune response to the proposed biosimilar. Additional comparative clinical studies may be conducted after other studies to address any remaining uncertainties about potential clinically meaningful differences from the reference product.
The FDA retains the discretion to determine whether a particular element is necessary in a proposed biosimilar application. It evaluates all evidence based on comparisons between the biosimilar and the reference product, within the context of the Agency’s previous determination of the reference product’s safety and efficacy.
Is it possible for a biosimilar to receive approval for an indication that is approved for the reference product, even if the biosimilar has not been directly studied in that indication?
A biosimilar may fulfill the criteria for approval, at least in part, through data from clinical studies demonstrating its safety and efficacy in an appropriate condition of use. Consequently, the FDA might grant approval for indications or populations without direct clinical studies if the manufacturer provides sufficient scientific rationale. This justification is based on factors including:
- All available information in the biosimilar application
- FDA’s assessment of the safety and efficacy of the reference product for approved indications
- Evaluation of various scientific factors relevant to each indication
Are there additional data requirements for interchangeable biosimilar products?
An interchangeable biosimilar refers to a biosimilar that can be substituted for the reference product without the involvement of the prescribing healthcare provider, subject to state pharmacy laws. It’s important to note that not all biosimilars are interchangeable. Manufacturers must specifically seek FDA approval for a product to be classified as interchangeable.
The approval process for interchangeable biosimilars includes additional requirements regarding substitution potential. Patients who obtain their medications from pharmacies may transition between a brand-name biological product and an interchangeable biosimilar, akin to how generic drugs can replace brand-name drugs at pharmacies.
Apart from establishing biosimilarity, manufacturers of interchangeable biosimilars must submit data demonstrating that the proposed product is expected to produce equivalent clinical outcomes to the reference product in any patient. Additionally, for certain interchangeable biosimilars, the FDA evaluates information on the effects of switching between the reference product and the interchangeable biosimilar. Consequently, manufacturers typically conduct switching studies where patients alternate between the reference product and the interchangeable biosimilar, comparing them to patients solely treated with the reference product.
While this additional information aids the FDA in determining the classification of a biosimilar as interchangeable, it’s important to understand that being labeled as interchangeable does not inherently imply superior safety or efficacy compared to other biosimilars. Both biosimilars and interchangeable biosimilars are held to the same stringent standards for quality and similarity to the reference product. All biological products receive FDA approval only after meeting these rigorous standards.
We hope that this article has provided you with a better understanding of biosimilar medicine, as well as the FDA’s evaluation and approval process for this type of medication.
If you need more detailed information or require assistance with consulting on FDA, please don’t hesitate to contact GOL. Our experienced team of experts is always ready to address any inquiries you may have and provide you with the most enthusiastic support.