To date, the FDA has approved three biosimilars. The first, Zarxio (filgrastim-sndz), used a meaningful, memorable suffix based on the manufacturers name (Sandoz).
The second two use the random suffixes “-dyyb” and “-szzs” which mean, well, nothing. ASBM’s surveys have shown that physicians (78%) and pharmacists (85%) support memorable names over random because they are easier to recognize and remember.
Yet there’s another reason for the FDA to stick with the original meaningful/manufacturer-based naming system over random: it’s a far better means of promoting manufacturer accountability.
Think of red-light cameras. You probably don’t run many red lights, but do the cameras make you more likely to stop for a red light, knowing that your infraction will be certainly and immediately traced to you? Sure they do. Likewise, manufacturer-based names for biosimilars will incentivize the manufacturer to make a product they can stand by, since a problem with the medicine will certainly and immediately reflect poorly on the company’s name and reputation.
As a former regulator at HHS, part of my job was holding insurers accountable for the decisions they made regarding Medicare beneficiaries. For example, I helped create a system by which patients who were denied Medicare-approved treatments by a private insurer could appeal those decisions. Providers who were found to be abusing the system faced swift consequences- up to and including being banned from further Medicare contracts. We designed a system where the increased likelihood of negative consequences promotes good health outcomes for patients and good behavior among contractors.
Put simply, compliance with regulations is higher when there is a more credible chance of negative consequences – whether it be a traffic ticket, or a reputation as a manufacturer that provides substandard products or services to their patients.
Michael Reilly is Executive Director of the Alliance for Safe Biologic Medicines. He served in the Secretary’s Office at the U.S. Department of Health and Human Services (HHS) from 2002-2008, including three years as Associate Deputy Secretary.
To date, the FDA has approved three biosimilars. The first, Zarxio (filgrastim-sndz), used a meaningful, memorable suffix based on the manufacturers name (Sandoz).
The second two use the random suffixes “-dyyb” and “-szzs” which mean, well, nothing. ASBM’s surveys have shown that physicians (78%) and pharmacists (85%) support memorable names over random because they are easier to recognize and remember.
Yet there’s another reason for the FDA to stick with the original meaningful/manufacturer-based naming system over random: it’s a far better means of promoting manufacturer accountability.
Think of red-light cameras. You probably don’t run many red lights, but do the cameras make you more likely to stop for a red light, knowing that your infraction will be certainly and immediately traced to you? Sure they do. Likewise, manufacturer-based names for biosimilars will incentivize the manufacturer to make a product they can stand by, since a problem with the medicine will certainly and immediately reflect poorly on the company’s name and reputation.
As a former regulator at HHS, part of my job was holding insurers accountable for the decisions they made regarding Medicare beneficiaries. For example, I helped create a system by which patients who were denied Medicare-approved treatments by a private insurer could appeal those decisions. Providers who were found to be abusing the system faced swift consequences- up to and including being banned from further Medicare contracts. We designed a system where the increased likelihood of negative consequences promotes good health outcomes for patients and good behavior among contractors.
Put simply, compliance with regulations is higher when there is a more credible chance of negative consequences – whether it be a traffic ticket, or a reputation as a manufacturer that provides substandard products or services to their patients.
Michael Reilly is Executive Director of the Alliance for Safe Biologic Medicines. He served in the Secretary’s Office at the U.S. Department of Health and Human Services (HHS) from 2002-2008, including three years as Associate Deputy Secretary.
On September 15th, 2016, ASBM held an educational forum at the University of the Sciences in Philadelphia (USciences). The program drew 50 attendees comprised of pharmacists, faculty members, pharmacy students.
The program began with an introduction to biosimilars from USciences Associate Professor of Pharmaceutical Sciences Dr. Zhiyu Li. Dr. Li is Director of Undergraduate Pharmacology/Toxicology Program, where he teaches courses on Biomethods in Pharmacology and Toxicology and Biopharmaceutical Proteins.
In order to demonstrate the size and complexity of biologic medicines, Dr. Li described a small-molecule drug (such as aspirin) as being like a bicycle in terms of complexity, whereas a biologic medicine (such as a monoclonal antibody) is more comparable to an airplane.
Dr. Li describes the greater size and complexity of biologic medicines, relative to traditional chemical drugs.
He then explained that this complexity, and the process by which biologics are grown in living cells, mean that biosimilars can only ever be similar to their reference products- never identical. Even biosimilars grown using an identical sequence as its reference product can result in different end products, likening the two products to twins which look nearly identical yet have different personalities, or the same dish prepared by two different chefs.
ASBM Advisory Board chair Philip Schneider, Associate Dean of the University of Arizona College of Pharmacy, then discussed biosimilars from the perspective of healthcare providers. Dr. Schneider drew upon ASBM surveys of physicians and pharmacists, and more than thirty years’ experience as a professor of pharmacy.
Schneider focused on three main challenges facing policymakers in regard to biosimilars: how they will be named, under what circumstances they may substituted for their reference product, and what information will their labeling include.
Regarding naming, ASBM surveys show that physicians (66%) and pharmacists (68%) overwhelmingly support distinct names for all biologic medicines, including biosimilars. Both the FDA and World Health Organization have proposed accomplishing this by use of a four letter suffix. Of the three biosimilars approved by the FDA, one uses a meaningful suffix derived from its manufacturer’s name-and two use random suffixes.
An informal poll of the audience showed strong support for the meaningful suffix, with most hands raised- by contrast, only one hand was raised in favor of random suffixes. Similarly, an ASBM survey of 400 pharmacists showed 77% support meaningful, memorable suffixes.
“Who here supports random suffixes?” Dr. Schneider asked the audience.
Regarding the labeling of biosimilars, Dr. Schneider emphasized the need for informative, transparent labeling that allows physicians and pharmacists to make informed treatment decisions.
Finally, Dr. Schneider discussed how many states- most recently Pennsylvania- allow substitution of “interchangeable” biosimilars- those shown to provide the same results as the reference product without additional risks. The Pennsylvania law, he explained, reflects the importance of good communication between healthcare providers- so that the physician always knows which medicine is dispensed to the patient at the pharmacy, and the patient’s response to a treatment can be accurately assessed. Currently, 24 states and Puerto Rico have enacted similar legislation.
Dr. Schneider discusses interchangeability. Only interchangeable biosimilars may be substituted by pharmacists.
The final speaker was Andrew Spiegel, Executive Director of the Global Colon Cancer Association. Mr. Spiegel discussed the tremendous benefits that biosimilars will bring patients- including new treatment choices and reduced healthcare costs- but cautioned that the decision to switch must always remain with the patient and physician, rather than a third party such as a government or insurer. Mr. Spiegel provided several examples of how insurance companies can force patients to switch medicines. This is especially worrisome with biosimilars that are not approved by the FDA as “interchangeable” with their reference product. Many patients with the serious, chronic conditions biologic medicines are used to treat struggle for years and try multiple products before becoming stable. Switching a patient’s medicine for reasons other than health and safety is referred to as Non-Medical Switching, and many patient organizations have raised these concerns when testifying before the FDA.
“Patients and physicians should make the treatment decisions” said Mr. Spiegel. “They are concerned only with what’s best for the patient…other entities may have different objectives, including profit or budgetary concerns.”
Additionally, he noted that transparency about how a biosimilar was approved is critical to helping patients make informed choices. For example, the FDA recently approved Inflectra (infiximab-dyyb) for all indications of its reference product for which it applied, despite having demonstrated biosimilarity only in two of the indications- a process called indication extrapolation. By contrast, Health Canada required additional clinical data before granting approval for the extrapolated indications two years later.
Mr. Spiegel discusses the need for caution when approving biosimilars for an indication in the absence of clinical data in that indication.
A Picture is worth a thousand words… Why Memorable Names are preferred by Pharmacists
by Philip Schneider, MS FASHP
Associate Dean, University of Arizona College of Pharmacy
ASBM Advisory Board Chair
Yesterday, I was in Philadelphia with a group of about 50 pharmacy students and faculty speaking about biosimilars and the role they do play and will play in our healthcare system. I explained the differences between a biosimilar and a generic, and why it is important to understand these differences as we develop policy around the substitution and naming of biosimilars. After discussing the FDA’s evolving policy towards naming, I asked those in the room whether it made sense to have a memorable name as was used for the first biosimilar approved by the FDA (zarxio-sndz) with the suffix representing the manufacturer’s name, or a random name like that used for the second FDA approved biosimilar (infliximab-dyyb). Not surprisingly, a single hand went up supporting the random approach. I have conducted similar educational forums on biosimilars over the past few years and have consistently seen that pharmacists overwhelmingly support memorable names. If we could just get that message to the organizations that represent pharmacists, we would all be better served.
A Picture is worth a thousand words… Why Memorable Names are preferred by Pharmacists
by Philip Schneider, MS FASHP
Associate Dean, University of Arizona College of Pharmacy
ASBM Advisory Board Chair
Yesterday, I was in Philadelphia with a group of about 50 pharmacy students and faculty speaking about biosimilars and the role they do play and will play in our healthcare system. I explained the differences between a biosimilar and a generic, and why it is important to understand these differences as we develop policy around the substitution and naming of biosimilars. After discussing the FDA’s evolving policy towards naming, I asked those in the room whether it made sense to have a memorable name as was used for the first biosimilar approved by the FDA (zarxio-sndz) with the suffix representing the manufacturer’s name, or a random name like that used for the second FDA approved biosimilar (infliximab-dyyb). Not surprisingly, a single hand went up supporting the random approach. I have conducted similar educational forums on biosimilars over the past few years and have consistently seen that pharmacists overwhelmingly support memorable names. If we could just get that message to the organizations that represent pharmacists, we would all be better served.
On Friday, July 22nd, The Alliance for Safe Biologic Medicines and MedChi, the Maryland State Medical Society co-hosted a forum entitled “Biosimilars: New Choices, New Challenges”. The event was attended by more than 45 physicians, legislators, patient advocates, healthcare workers, and others.
MedChi’s CEO, Gene Ransom III began the forum with a discussion of the importance of biosimilars in bringing new treatment options to patients. Mr. Ransom demonstrated MedChi’s knowledge of biosimilar issues, and detailed the organization’s history of advocacy for transparency in biosimilar naming and labeling, providing examples of MedChi’s work in urging FDA to support these policies.
Mr. Ransom gives examples of MedChi’s previous advocacy to the FDA in support of distinguishable naming for biosimilars.
In regard to biosimilar substitution, Mr. Ransom discussed MD Senate Bill 0537, which MedChi supported. SB 0537, like substitution bills in many states, requires a pharmacist to communicate to the prescribing physician within 5 days which product- the originator or the biosimilar- was dispensed. The bill passed the Maryland Senate 46-0, but died in the House Committee on Healthcare.
MedChi CEO Gene Ransom III discusses several recent policy issues on which his organization has engaged on behalf of Maryland’s physicians.
ASBM Chairman, Harry L Gewanter, MD then presented a brief overview of biosimilars. He discussed the benefits they can bring to patients, and how their differences from generic versions of chemical drugs (which do copy their reference products identically) create several policy challenges which must be addressed in order for patients to realize those benefits.
ASBM’s surveys of biologic prescribers in eleven countries have aided the World Health Organization in the development of its distinguishable naming system, Dr. Gewanter explains.
First among these are biologic naming. Echoing MedChi’s concerns, Dr. Gewanter emphasized that clear product identification is critical when prescribing, dispensing, and tracking efficacy of all biologic medicines. Dr. Gewanter discussed the naming systems proposed by the FDA and WHO. Dr. Gewanter shared data from ASBM’s surveys of biologic prescribers in eleven countries which show strong and widespread support for distinct naming. In the U.S., 66% of biologic prescribers support the FDA issuing distinct names for all biologics, including biosimilars.
In order to be classified a biosimilar, a medicine must be highly similar to its reference product, and their differences not clinically meaningful.
Regarding biosimilar substitution, Dr. Gewanter showed data from ASBM’s survey of 400 U.S. physicians which revealed that MedChi’s concerns were shared by most physicians. 80% considered it “very important or critical” for a pharmacist to communicate to them when a biosimilar has been substituted at the pharmacy. 82% considered it “very important or critical” to have the authority to block a substitution they deem inappropriate for their patient by indicating “Dispense As Written (DAW)” on the prescription.
Dr. Gewanter explains physician concerns with the prospect of automatic substitution of biosimilars by a pharmacist- substitution of a biosimilar for the prescribed biologic without physician knowledge or involvement.
Dr. Gewanter’s presentation may be viewed here.
ASBM’s Advisory Board Chair, Philip Schneider, Professor and Associate Dean at the University of Arizona’s College of Pharmacy then provided the pharmacist perspective on biosimilars.
Regarding naming, Dean Schneider discussed the long tradition of pharmacists avoiding look-alike or sound-alike names for different medications. Dr. Schneider also noted that while national pharmacy societies such as the American Pharmacist Association (APhA) and the American Society of Health-system Pharmacists (ASHP), (of which Dr. Schneider is a past president) have expressed skepticism, rank-and-file pharmacists have generally been supportive of distinct naming . An ASBM poll of 401 U.S. pharmacists revealed that 68% support the FDA distinct names for all biologics, including biosimilars.
Following initial resistance to communication provisions in the substitution bills in several states, pharmacist perspectives have shifted somewhat, Dr. Schneider explained. The issue has largely faded as a matter of debate among national pharmacy societies, for example.
Finally, Dr. Schneider raised the issue of transparency in biosimilar labeling. ASBM surveys of physicians and pharmacists show these healthcare providers want more informative and transparent labeling than is currently required by the FDA’s Draft Guidance on Labeling of Biosimilars:
The final speaker was Andrew Spiegel, Executive Director of the Global Colon Cancer Association, who gave a patient perspective on biologics and biosimilars.
Mr. Spiegel praised biologic medicines for their role in tripling the life expectancy of patients diagnosed with colon cancer. Biosimilars, Mr. Spiegel emphasized, hold great promise for patients- offering new therapeutic options and doing so at lower cost. However, he cautioned that the benefits of biosimilars will not be realized unless they gain the confidence of providers and patients.
Mr. Spiegel described his experience at recent FDA hearings, where committee members were given an “all or nothing” choice: approve a biosimilar for all the diseases it seeks approval to treat (or indications) for which it applied, or none at all. By contrast, in Canada, biosimilars are approved for each indication separately. The FDA’s “all or nothing” approach is worrying, and does not serve the interest of patients, Mr. Spiegel argued.
The treatment decision-including when to use or switch to a biosimilar- should always remain with the patient and his healthcare team, said Mr. Spiegel.
Finally, Mr. Spiegel raised the emerging issue of Non-Medical Switching. The choice to use an innovator biologic or biosimilar, must always be made by the patient and those who provide him direct care, rather than a third-party payer.
“Treatment decisions, including the decision to switch from one medicine to another should be made for medical reasons that benefit the health and safety of the patient, not for non-medical reasons that might benefit a a company’s shareholders”, said Spiegel. He then outlined practices that payers may use to force a patient to switch to a non-interchangeable biosimilar, such as changing their medical coverage or health care premiums.
On Friday, July 22nd, The Alliance for Safe Biologic Medicines and MedChi, the Maryland State Medical Society co-hosted a forum entitled “Biosimilars: New Choices, New Challenges”. The event was attended by more than 45 physicians, legislators, patient advocates, healthcare workers, and others.
MedChi’s CEO, Gene Ransom III began the forum with a discussion of the importance of biosimilars in bringing new treatment options to patients. Mr. Ransom demonstrated MedChi’s knowledge of biosimilar issues, and detailed the organization’s history of advocacy for transparency in biosimilar naming and labeling, providing examples of MedChi’s work in urging FDA to support these policies.
Mr. Ransom gives examples of MedChi’s previous advocacy to the FDA in support of distinguishable naming for biosimilars.
In regard to biosimilar substitution, Mr. Ransom discussed MD Senate Bill 0537, which MedChi supported. SB 0537, like substitution bills in many states, requires a pharmacist to communicate to the prescribing physician within 5 days which product- the originator or the biosimilar- was dispensed. The bill passed the Maryland Senate 46-0, but died in the House Committee on Healthcare.
MedChi CEO Gene Ransom III discusses several recent policy issues on which his organization has engaged on behalf of Maryland’s physicians.
ASBM Chairman, Harry L Gewanter, MD then presented a brief overview of biosimilars. He discussed the benefits they can bring to patients, and how their differences from generic versions of chemical drugs (which do copy their reference products identically) create several policy challenges which must be addressed in order for patients to realize those benefits.
ASBM’s surveys of biologic prescribers in eleven countries have aided the World Health Organization in the development of its distinguishable naming system, Dr. Gewanter explains.
First among these are biologic naming. Echoing MedChi’s concerns, Dr. Gewanter emphasized that clear product identification is critical when prescribing, dispensing, and tracking efficacy of all biologic medicines. Dr. Gewanter discussed the naming systems proposed by the FDA and WHO. Dr. Gewanter shared data from ASBM’s surveys of biologic prescribers in eleven countries which show strong and widespread support for distinct naming. In the U.S., 66% of biologic prescribers support the FDA issuing distinct names for all biologics, including biosimilars.
In order to be classified a biosimilar, a medicine must be highly similar to its reference product, and their differences not clinically meaningful.
Regarding biosimilar substitution, Dr. Gewanter showed data from ASBM’s survey of 400 U.S. physicians which revealed that MedChi’s concerns were shared by most physicians. 80% considered it “very important or critical” for a pharmacist to communicate to them when a biosimilar has been substituted at the pharmacy. 82% considered it “very important or critical” to have the authority to block a substitution they deem inappropriate for their patient by indicating “Dispense As Written (DAW)” on the prescription.
Dr. Gewanter explains physician concerns with the prospect of automatic substitution of biosimilars by a pharmacist- substitution of a biosimilar for the prescribed biologic without physician knowledge or involvement.
Dr. Gewanter’s presentation may be viewed here.
ASBM’s Advisory Board Chair, Philip Schneider, Professor and Associate Dean at the University of Arizona’s College of Pharmacy then provided the pharmacist perspective on biosimilars.
Regarding naming, Dean Schneider discussed the long tradition of pharmacists avoiding look-alike or sound-alike names for different medications. Dr. Schneider also noted that while national pharmacy societies such as the American Pharmacist Association (APhA) and the American Society of Health-system Pharmacists (ASHP), (of which Dr. Schneider is a past president) have expressed skepticism, rank-and-file pharmacists have generally been supportive of distinct naming . An ASBM poll of 401 U.S. pharmacists revealed that 68% support the FDA distinct names for all biologics, including biosimilars.
Following initial resistance to communication provisions in the substitution bills in several states, pharmacist perspectives have shifted somewhat, Dr. Schneider explained. The issue has largely faded as a matter of debate among national pharmacy societies, for example.
Finally, Dr. Schneider raised the issue of transparency in biosimilar labeling. ASBM surveys of physicians and pharmacists show these healthcare providers want more informative and transparent labeling than is currently required by the FDA’s Draft Guidance on Labeling of Biosimilars:
The final speaker was Andrew Spiegel, Executive Director of the Global Colon Cancer Association, who gave a patient perspective on biologics and biosimilars.
Mr. Spiegel praised biologic medicines for their role in tripling the life expectancy of patients diagnosed with colon cancer. Biosimilars, Mr. Spiegel emphasized, hold great promise for patients- offering new therapeutic options and doing so at lower cost. However, he cautioned that the benefits of biosimilars will not be realized unless they gain the confidence of providers and patients.
Mr. Spiegel described his experience at recent FDA hearings, where committee members were given an “all or nothing” choice: approve a biosimilar for all the diseases it seeks approval to treat (or indications) for which it applied, or none at all. By contrast, in Canada, biosimilars are approved for each indication separately. The FDA’s “all or nothing” approach is worrying, and does not serve the interest of patients, Mr. Spiegel argued.
The treatment decision-including when to use or switch to a biosimilar- should always remain with the patient and his healthcare team, said Mr. Spiegel.
Finally, Mr. Spiegel raised the emerging issue of Non-Medical Switching. The choice to use an innovator biologic or biosimilar, must always be made by the patient and those who provide him direct care, rather than a third-party payer.
“Treatment decisions, including the decision to switch from one medicine to another should be made for medical reasons that benefit the health and safety of the patient, not for non-medical reasons that might benefit a a company’s shareholders”, said Spiegel. He then outlined practices that payers may use to force a patient to switch to a non-interchangeable biosimilar, such as changing their medical coverage or health care premiums.
On July 12th and 13th, the FDA’s Arthritis Advisory Committee, held two meetings, to discuss proposed biosimilars to adalimumab (July 12th) and etanercept (July 13th).
Nine ASBM members provided oral or written testimony at one or both of the meetings.
Many of those testifying expressed concern with the FDA’s practice of approving biosimilars in indications in which they were not clinically evaluated, based on extrapolation from clinical data in other indications. Said ASBM’s Chairman Harry Gewanter, MD, in a statement:
“We believe the approval of a biosimilar should be decided on a case-by-case basis for each potential indication based on sufficient supporting data rather than justifying an automatic blanket extrapolation to all indications. Ultimately, the burden of proof must be on the biosimilar manufacturer to demonstrate that their product is highly similar in structure, function and in patient response to the reference product.”
Andrew Spiegel, Executive Director of the Global Colon Cancer Association (an ASBM Steering Committee Member), expressed concerns with the approval process in his statement:
“Extrapolation is also an area of concern to the patient community. At a minimum, approval for each indication should be granted individually, rather than an all-or-nothing approach. We don’t suggest that safe extrapolation is not possible, we simply think each indication should be approved individually based on solid data. This panel should have flexibility, and not be forced to approve the drug for all or no indications.”
Mr. Spiegel cited the more cautious approach taken by Health Canada to approve a biosimilar to infliximab. While approved for Rheumatoid Arthritis (RA) and Ankylosing Spondilitis (AS), additional clinical data was required before approval was granted for IBD indications (Ulcerative Colitis and Crohn’s Disease) two years later.
Mr. Spiegel also joined other patient advocates in urging the FDA to oppose the practice of Non-Medical Switching, particularly with non-interchangeable biosimilars:
“Treatment decisions, including the decision to switch from one medicine to another should be made for medical reasons that benefit the health and safety of the patient, not for non-medical reasons that might benefit a a company’s shareholders”, said Spiegel.
NMS is the switching of a patient from one treatment to another, typically by a third party such as a Pharmacy Benefit Manager (PBM) or insurance company, for reasons other than a patient’s health and safety.
Unlike generic versions of chemical drugs, biosimilars are not identical to their reference products, and these differences can produce unexpected effects in patients, including unwanted and harmful immune responses. In the case of biologic treatments such as those used to treat autoimmune disorders, switching a patient (who may have worked for years to find a treatment that effectively manages his or her condition) can cause the patient to lose that hard-won stability.
NMS is the switching of a patient from one treatment to another, typically by a third party such as a Pharmacy Benefit Manager (PBM) or insurance company, for reasons other than a patient’s health and safety.
Unlike generic versions of chemical drugs, biosimilars are not identical to their reference products, and these differences can produce unexpected effects in patients, including unwanted and harmful immune responses. In the case of biologic treatments such as those used to treat autoimmune disorders, switching a patient (who may have worked for years to find a treatment that effectively manages his or her condition) can cause the patient to lose that hard-won stability.
