Thank you for visiting our Information Center. This section is meant to provide you with information on issues surrounding biologic medications and offers links to other valuable internet resources on related topics.
The Alliance for Safe Biologic Medicines works to provide information on the safety and quality of biologics, advocate for policies that keep medical decisions between patients and physicians, and seek solutions that ensure affordability and accessibility of biologic medications while never compromising on patient safety.
Frequently Asked Questions
- What are Biologics?
- What are Biosimilars?
- Why is Patient Safety a Concern?
- Are there places around the world that have already established a so-called “biosimilars pathway?”
- What are biosimilar “interchangeability” and “substitution”?
- What is “pharmacovigilance”?
- What is “Immunogenicity”?
Q: What Are Biologics?
A: Biologics are complex, large molecule drugs that treat serious illnesses, such as cancer, multiple sclerosis, and rheumatoid arthritis. Unlike drugs derived from chemical synthesis, biologics are manufactured using a unique and proprietary process involving living cells. For this reason, no two biologics made from different cell lines or using different processes will be identical. Biologics are also highly sensitive to the manufacturing process. In fact, altering a single manufacturing parameter can change a compound’s identity or the precise effect it has on the human body. Examples of biologics include the cancer drug Avastin and the arthritis drug Enbrel.
Biotech medicine offers the best hope for some of the most devastating medical conditions, such as Alzheimer’s and Parkinson’s disease, for which there are currently no effective treatments. These drugs are also the fastest-growing segment of the pharmaceutical market and are expected to account for half of the new drugs approved by 2015.
Q: What are Biosimilars?
A: Biosimilars (also known as follow-on biologics) are sometimes mistakenly called “generic” versions of innovative biologics. However, unlike generics, which are copies of chemically synthesized drugs, biosimilars are similar to, but not the same as the innovator’s active ingredient. This is an inevitable outcome because they do not utilize the same living cell line, production process, or raw material as the innovator drug.
Q: Why Is Patient Safety A Concern?
A: : Biologics raise some safety concerns above and beyond chemical drugs; commensurately, biosimilars are distinct from oral or injected generic drugs. In contrast to most drugs that are chemically synthesized and their structure is known, most biologics are complex mixtures that are not easily identified or characterized. Small differences in the structure of the innovator and the attempted copy can have effects for patients such as reduced efficacy or changes in safety and tolerance.
In order to make informed choices, patients should understand the complexity of these drugs and the difference between oral or injected generics versus biosimilars and talk with their doctors about the best course of treatment.
Q: Are there places around the world that have already established a so-called “biosimilars pathway?”
A: Yes. In 2004, the European Union authorized the first formal regulatory pathway for biosimilars. The Europeans Medicines Agency (EMA) is the regulatory body of the EU that has guided the implementation of the EU’s biosimilar pathway. The EU’s process overall was science-driven, transparent and sought the input of major stakeholders.
Other countries that have developed a pathway are:
- Japan, 2009
- Canada, 2010
- South Africa, 2010
- And the World Health Organization, 2009
Q: What are biosimilar “interchangeability” and “substitution”?
A: “Interchangeability” is the determination that a patient can be transferred safely from the innovator/reference product to a biosimilar and expect to have the same experience with no change in safety or efficacy. “Substitution” is the legal authority for a pharmacy filling a prescription or hospital to switch the innovator product to the biosimilar or switch the prescribed product to a different product.
Around the world, substitution decisions are largely handled at the local government level; in the US, the decision of whether a biosimilar is substitutable is made at the state level. In Canada, this decision is made at the provincial level, while within the European Union, the decision is made by individual Member States.
South Africa and Japan have similar guidelines for interchangeability and substitution – South Africa does not allow biosimilars to be interchangeable with their reference product and automatic substitution cannot apply to biosimilars. Japan’s approach is similar, but additionally points out that substitution of a biosimilar with it reference or innovator product should be avoided throughout treatment.
The reality, however, is little is known about how the process of interchanging a biosimilar for the reference product and its potential impact on the patient’s immune response.
Q: What is “pharmacovigilance”?
A: Pharmacovigilance is the surveillance of a drug’s performance, particularly of adverse reactions experienced by patients taking the product after it has been released for marketing.
The overall goal of post-marketing pharmacovigilance plans is to accurately and promptly trace a patient’s adverse event to a particular product, manufacturer and lot number. Proper labeling, product tracking and an operational system of reporting and attributing adverse events are all components of a well-functioning pharmacovigilance program.
Labeling remains a concern in the FDA’s implementation of biosimilars moving forward, given the fact that no two biologics are identical. A biosimilar should contain the information needed by the doctor to help the patient make an informed decision. For example, the label should identify trials done with the biosimilar medicine, not the product it is copying.
Part and parcel to the pharmacovigilance process is how to identify the product through its unique name. Only the World Health Organization (WHO) and Japan have laid out clear guidelines that specifically address naming biosimilars:
- The WHO states that biosimilars should be identified with a unique brand name; that where an International Nonproprietary Name (INN) is defined it should be provided and that a lot number is essential for traceability.
- Japan, similarly, states that nonproprietary names should be followed by ‘Follow-on 1’ [or 2, 3, etc] and brand names should be followed by the letters ‘bs’ along with dosage form, dosage and company/manufacturer.
- The European Union, by contrast, does not have a formal guidance regarding naming, however, it does state “in order to support pharmacovigilance monitoring, the specific medicinal product given to the patient should be clearly identified.”
Q: What is “Immunogenicity”?
A: Immunogenicity is a measure of the immune response to a therapeutic drug. Due to the size of the biologic molecule, it is always able to be recognized by the human immune system, where as a small molecule travels through the body unnoticed. Thus the risk of an immune response from a biologic is much more significant than with small molecules. Most health authorities recognize the sensitivity around biologics/biosimilars in causing safety concerns because of immunogenicity.