Biosimilars: Some Patient And Prescriber Groups Appear To Warm Up To Arbitrary Suffixes
Executive Summary
Patient and prescriber groups were largely opposed to suffixes for the nonproprietary names of biological products being devoid of meaning when the US FDA first published its nomenclature policy, although a few of these groups may be signaling less of a worry than they once had.
When the US Food and Drug Administration first put out draft guidance in 2015 on the nonproprietary naming of biological products, a slew of prescriber and patient groups felt that the four-letter suffixes that would be attached to the nonproprietary names should be meaningful rather than arbitrary.
But it appears that at least some of these organizations have warmed up to the naming convention to a certain extent.
Several groups who aired this concern in comments on previous versions of the guidance didn’t voice these qualms in comments on the FDA's updated version of the draft guidance, which was released in March 2019. (See sidebar.)
For instance, the Biologics Prescribers Collaborative (BPC) and its parent organization the Alliance for Patient Access (AfPA) look to have reversed their initial position. A 7 May 2019 joint comment from the groups on the new draft guidance states that AfPA "appreciates" the FDA's proposal to, "Continue to apply a naming nomenclature that combines core names with four-letter suffixes that are random and distinguishable for all new approvals."
This contrasts with their comments on the initial 2015 draft guidance, where the groups argued that "our experience as biologics prescribers tells us that the suffix must be memorable, which cannot be easily accomplished when it is meaningless."
"A randomized four-letter code may complicate the achievement of FDA’s goal to improve pharmacovigilance and prevent inadvertent substitution," the groups wrote at the time. "A memorable suffix could identify the manufacturer, which would be easily memorized by those who frequently prescribe biologics."
A BPC spokesperson told the Pink Sheet that the group was hoping to see the use of meaningful suffixes in the new draft guidance, although it was pleased to see the agency call for the use of unique suffixes for biologics, biosimilars, and interchangeable biosimilars.
"This measure will support pharmacovigilance, allowing patients and physicians alike to rely upon accurate tracing of adverse reactions," the spokesperson said.
Meanwhile, the Coalition of State Rheumatology Organization (CSRO) didn't convey any concerns about the suffixes being devoid of meaning in its comments on the 2019 draft guidance. In 2015, the group commented on the initial draft guidance the agency should consider recognizable suffixes "so that a manufacturer can use the same suffix across its portfolio of products."
"This will help the agency and prescribers quickly identify the source of an adverse event," CSRO said in 2015. "In addition, it may increase prescribing confidence and assist with the uptake of biosimilars."
The group echoed this sentiment when commenting on the final guidance issued in January 2017. However, the group released only a one-page comment on the 2019 draft guidance, where it announced support for the FDA's decision to no longer apply the nomenclature retroactively to innovator biologics approved without the suffix.
"The sudden addition of a suffix for a biologic that has been marketed for years without one is confusing to clinicians, as it implies that something has changed about a well-known, older product," CSRO wrote 10 May 2019. "Eventually, as the market progresses towards newly approved biologics and biosimilars, products without suffixes will phase out."
Granted, the FDA didn't change anything related to the content of the nomenclature in the updated draft guidance, as the four-letter suffixes will still be devoid of meaning. But it is notable that CSRO didn't raise any concerns about the suffixesbeing meaningful in its new comments, given that it had done so twice before.
The group didn't respond to a request for comment about whether it still worries about the suffixes being arbitrary.
Similarly, the Alliance for Safe Biologic Medicines (ASBM), which represents a series of patient and prescriber organizations, wrote in its 2015 comments that "the benefits of clear identification are best realized with a memorable, recognizable, and meaningful suffix rather than a random series of letters."
ASBM even cited survey data showing that majorities of physicians and pharmacists prefer a manufacturer-based suffix. Yet, the group did not raise these concerns in its 7 May 2019 comments, instead writing that, "We support the revised guidance and FDA’s decision to apply unique suffixes to biologics at the time of approval."
It is possible that Center for Drug Evaluation and Research director Janet Woodcock helped to quell some these fears about the suffixes being devoid of meaning. Woodcock previously told the Pink Sheet that she had conducted significant outreach with patient and prescriber groups about the policy. (Also see "Woodcock: Concerns About US FDA's Biosimilars Suffix Policy Detached From Reality" - Pink Sheet, 20 Mar, 2019.)
Is DSCSA A Better Tool?
"We need to know what the patient got, not which different version the pharmacy got," Woodcock told the Pink Sheet. "And that's the problem. Track-and-trace doesn't go down to the patient. It stops at whatever the last receipt of a shipment is. And often, they will get multiple versions."
Don't Apply Nomenclature To Vaccines, Stakeholders Say
But stakeholders who raised the issue in their comments were largely united in their opposition to applying the nomenclature to vaccines.
On the manufacturer side, the Biotechnology Innovation Organization (BIO) and Pfizer Inc. both say that existing identification systems are "sufficiently robust" to ensure safe dispensing practices and pharmacovigilance. BIO specifically points to the FDA's Vaccine Adverse Event Reporting System and Sentinel Post-Licensure Rapid Immunization Safety Monitoring program, along with the Centers for Disease Control and Prevention's Vaccine Safety Datalink and Clinical Immunization Safety Assessment.
"Given that vaccines are not dispensed to patients; instead they are dispensed to, and administered by, healthcare professionals only, there is no danger of a patient unknowingly administering an inappropriate vaccine to themselves," BIO adds. "In addition, healthcare professionals record vaccine administration in patient charts, electronic health records (EHRs), or Immunization Information Systems (IISs), and the currently used vaccine identifiers work well for safety tracking and recall purposes."
Pfizer argues that, "In addition, vaccine names are often abbreviated in a hyphenated string of letters and addition of the four-letter suffix naming convention to vaccines risks causing confusion that the suffix relates to an attribute of the product rather than a distinguishing name; this is particularly true given the random nature of the suffixes."
The Pharmaceutical Research and Manufacturers of America (PhRMA), for its part, favors exempting from the suffix policy vaccines that are subject to the recordkeeping requirements of the National Childhood Vaccine Injury Act of 1986.
"As the Agency notes, the requirements for administration of these vaccines and related documentation are unique: healthcare providers must record in detail the specific vaccine – including manufacturer and lot number – that a patient receives," PhRMA writes. "Thus there are already robust mechanisms for ensuring effective pharmacovigilance and safe use of these products."
Stakeholders on the pharmacy side, many of which oppose adding suffixes to any biological products, offered similar views on applying the nomenclature to vaccines. For example, the American Pharmacists Association opines that "adding a suffix to vaccine names will be confusing and given the importance of vaccines for public health, a variable naming convention could support misinformation efforts that question vaccine quality and safety."
The National Association of Chain Drug Stores agrees that existing identification systems are robust and that the addition of suffixes to the already complex nonproprietary names of vaccines can complicate their identification in health information technology systems.
Split Views On Non-Application To Transition Biologics
Another notable component of the 2019 draft guidance was that the FDA announced it does not intend to attach suffixes to transitional biologics – those that have been regulated as drugs that will be licensed as biologics as of March 23, 2020.
On this front, several biosimilars stakeholders used the decision to support the industry's position that suffixes are not necessary.
The Association for Accessible Medicines (AAM) writes that the move "directly contradicts FDA’s own logic in purporting the requirement supports pharmacovigilance." As an example, the trade group notes there are three insulin glargine products and two insulin lispro products that share the same international nonproprietary name.
"FDA’s new policy would not add a suffix to the names of these products and would seemingly run counter to the reasoning for adding a suffix to other biological products for the purposes of pharmacovigilance," AAM states. "This is particularly contradictory because these products will not be deemed “interchangeable” under the PHSA and none are currently AB-rated for automatic substitution under the FD&C. This will cause confusion amongst patients, prescribers, pharmacists, payers, and pharmacy benefit managers, especially as future biosimilars are approved for the transitional products that share a non-proprietary name."
Mylan NV similarly argues that, "FDA’s decision to not require suffixes for already approved biologics and transitional biologics further undermines FDA’s assertions that meaningless suffixes are necessary, and implicitly acknowledges that different proprietary names are not needed to ensure safe use."
Among innovators, Pfizer also questioned the FDA's decision, albeit for a different reason. The drug giant, which also develops biosimilars, believes it is practical to attach suffixes to transitional products.
"It is unclear how FDA made the determination that unique nonproprietary names were necessary for biosimilars and prospectively approved biological products, but not transitioning biological products," Pfizer says. "Further, the burden on transitional biological product sponsors to implement this change would be minimized given the holder of a deemed BLA will need to revise the product labeling to conform to labeling requirements for biological products regulated under section 351 of the PHS Act. Suffix implementation could be planned to coincide with other necessary labeling and packaging changes incurred due to the transition."
Overall, Pfizer supports the use of suffixes, although the company thinks they should resemble the name of the license holder and supports their retroactive application to innovator products with biosimilars.
Vizient, meanwhile, applauded the agency's decision not to add suffixes to transitional biologics.
Other Disputes Abound
The new comments additionally show that innovator companies who also market biosimilars are not in complete alignment over the new suffix policy.
While Pfizer supports the FDA's naming system to a certain extent, Novartis AG, which develops biosimilars through its subsidiary Sandoz Inc., restated its belief that the suffix convention is unnecessary and should not be applied to any biological products.
Novartis, along with several other stakeholders across the spectrum, point to data showing that more than 99% of adverse event reports for biosimilars feature the brand name rather than the nonproprietary name, indicating that the suffixes are not useful for pharmacovigilance purposes. (Also see "Biosimilar Suffixes Appear Superfluous In Adverse Event Reporting" - Pink Sheet, 10 Oct, 2018.)
But Amgen Inc. flaunted support for the FDA's new suffix policy in its comments on the 2019 draft guidance. The drugmaker posits that suffixes facilitate effective pharmacovigilance efforts and agrees with the agency that retrospective application of suffixes to previously approved innovator products is not necessary.
Amgen also uses data to make the point that suffixes are useful in adverse event reporting. According to the company's comments, a search of the FDA Adverse Event Reporting System (FAERS) shows that over the two-year period of 2017-2018, there were 531 reports for infliximab products submitted using the nonproprietary name, 21 (4%) of which contained Celltrion Inc.'s -dybb suffix and three (0.6%) of which contained Samsung Bioepis Co. Ltd. and Merck & Co. Inc.'s -abda suffix. The remainder of the reports used the nonproprietary name without the suffix.
The company contends that these figures are consistent with the market shares of the biosimilars at the time, which were 5% for infliximab‐dyyb and 0.3% for infliximab‐abda. However, this calculation assumes that all the adverse event reports without the suffix are for the brand Remicade product.
Further disagreements materialized over the FDA's decision to approve interchangeable biosimilars with the naming convention. The biosimilars industry has decried the move, citing concerns that the presence of a suffix will create inferiority perceptions about their products and inhibit their uptake.
Pfizer agreed that the presence of a suffix on the name of the interchangeable biosimilar name but not the reference product "creates a perceived difference and disingenuous exploitation of this perception could undermine the biosimilars pathway," although the drugmaker thinks the solution is retroactive application of suffixes to reference products rather than their elimination. (Also see "Biosimilar Leaders Compliment Pfizer For Calling Out Fellow Innovators, But Should FDA Play A Role To Dispel Misinformation?" - Pink Sheet, 20 Sep, 2018.)
Conversely, Amgen and AbbVie Inc. both support the FDA's decision to attach the nomenclature to interchangeable biosimilars and all future innovator biologics prospectively, and do not believe that the agency should apply the suffixes retroactively.
Several patient and prescriber groups also agreed that the suffixes should be applied to interchangeable biosimilars, including CSRO, the National Kidney Foundation and the International Cancer Advocacy Network.