As John Adams said, “Facts are pesky things.” And facts that don't reinforce your cognitive mapping are pesky things. But that does not change the fact that nothing deserves truth and accuracy more than the public health.
According to Inside Health Policy:
“While some say an easy solution is to simply add a suffix to distinguish a biosimilar from the innovator product, the compendia group told FDA any change is a change, and regardless of the simplicity of the change, the associated coding would also have to shift. First data bank and two other databanks are sold to stakeholders who assemble them and put overlays on them and then the data are used for different purposes, including for reimbursement.”
But pay heed. As Deming warned, “Change is not required. Survival is not mandatory.”
Giving credit where credit is due, the good people at the USP understand that interoperability is important, but that naming is more of a philosohpical issue. That's why they support differentiation via discrete numerical suffix.
Per Inside Health Policy:
The drug compendia stakeholders told a group of 13 FDA drug policy experts, including drug center chief Janet Woodcock, that changing the traditional naming process would require that each piece of the compendia process be individually rebuilt in order to ensure patient safety and restore functionality to the system. Doing so, while possible, would be difficult and could lead to confusion, errors and misunderstanding, creating a "very real risk to patients," according to slides presented at the May 2 meeting and a June 6 follow-up letter, obtained by Inside Health Policy.
Here are some of the more egregious myths shared by the aforementioned group of compendia stakeholders along with the facts to debunk them.
MYTH
We are concerned that distinguishable naming for every biologic, biosimilar and interchangeable biologic could confuse both providers and patients, and have the unintended effect of slowing the uptake of these cost saving drugs.
FACT
The patient and safety communities, as well as many physician organizations have weighed in on the same issue, and have come out on the opposite side – in favor of transparency, so that patients can know which medication is being put into their bodies and the whole system can quickly connect the dots to stem negative impact when an adverse event occurs. The scope of patient-focused organizations that have come out in support of distinguishable naming is so broad, it covers virtually every single American family.
MYTH
While we agree that it is important to gather data that allows providers to better understand how biologics and biosimilars are performing among various patient groups and to assist in the tracking of adverse events, as we mention above, we believe that the current mechanisms in place (e.g., NDC code, lot number, brand name, manufacturer, etc.) are sufficient.
Traditional naming structures do a good job of tracking post market issues (NDC, lot number, brand name, manufacturer, etc.).
FACT
Other, complementary tracking systems do and should exist, however non-proprietary names are the backbone of pharmaceutical tracking within payment systems, not necessarily for tracking and tracing AEs. The National Drug Code, or NDC, system provides a unique 10- or 11-digit set of numbers for each medication, however payers do not universally use NDC codes.
A lot number alone is not sufficient enough to identify a product and its manufacturer. It is only useful when it is accompanied by an identifier that is linked to the manufacturer. While having brand names is useful for tracking and tracing AEs, they are not always used when prescribing or reporting AEs.
Additionally, there is a lack of standard use in medical benefit setting where the majority of biologics are administered and NDC are not necessarily present in patient records. When are entered there are many instances in patient care where NDC codes have been inaccurately entered.
Current approaches and systems do not allow for adequate collection of data relating to patient subpopulations, such as women, minorities and people with specific genetic problems; depending on the level of additional clinical research that will be required to bring a biosimilar to market, it is very likely there is much we won’t know about how a biosimilar might uniquely impact these subpopulations. Distinguishable names for biosimilars support the patient advocate and medical community’s vital post-approval learning curve to determine which medicines are best for patient subpopulations.
The clarity from distinguishable non-proprietary names will:
· Enable better safety monitoring.
· Promote timeliness in managing adverse events if they occur.
Provide physicians with more information to understand which products are likely to be more effective in specific patient subpopulations.
MYTH
Requiring distinguishable names would segregate the safety data for brand and biosimilar products, making it more difficult to detect rare AEs across classes of products. (Study referenced: 2013 EMA report entitled “Traceability of Biopharmaceuticals in Spontaneous Reporting Systems: A Cross-Sectional Study in the FDA Adverse Event Reporting System (FAERS) and EudraVigilance Databases”)
FACT
The 2013 study referenced in this assertion did in fact find that 96.2% of adverse events could be traced back to biosimilars if either the brand name OR INN or company name were available. However, “…products for which only the INN was available were considered non-identifiable, except for epoetin zeta, for which product the INN differs from the innovator (epoetin alfa),” (pgs. 619-620). This is precisely why there needs to be distinguishable INN/ USAN names: so that products that can only be identified by INN/USAN can still be traced. Furthermore, the 2013 study cited actually found that 1 out of every 10 (90.4%) adverse events related to biosimilars can’t be traced back to a specific product if the biosimilar was given concomitantly or interacted with another medication.
MYTH
WHO has already established a global naming convention, known as the International Non-proprietary Names (INN) system.
FACT
The INN system was established in the 1950’s to identify active ingredients in small molecule chemical compounds, well before highly complex biologics were developed.
Unlike traditional pharmaceutical medicines (small molecule, chemical entities), where the active ingredient of a generic and the originator compound are identical, the active ingredient for biologics (large molecule) is complex, and a biosimilar will not be an exact replica.
WHO has not announced how it may alter its existing INN program to effectively serve biologics including biosimilars, however the organization’s published deliberations on the issue indicate change is likely:
“Compared to a small chemical entity, biotherapeutic proteins are large and complex, with four levels of structure (primary, secondary, tertiary and quaternary). The complexity of their structure is often further augmented by glycosylation and other molecular modifications, whose variability can impact on bio-activity. There are already several different naming policies for SBPs amongst individual regulatory authorities and in some cases, alternative interpretation of INN policy has led different authorities to assign different non-proprietary names for the same product. If prescribers rely on regulatory authority names, this will lack global consistency and could lead to different SBPs having the same name in different countries.
Four approaches are suggested on how to deal with this situation:
· Continue with the status quo
· Treat all SBPs as unique products and provide them with a unique INN
· Create a biosimilar ‘identifier’ to be used for all SBPs (and not just glycosylated ones), e.g. use the original INN and add a fantasy code suffix
· Encourage regulatory authorities to provide an ‘identifier’ under the guidance of WHO”
“The last two approaches fulfill the need for a unique identifier of a biosimilar and it would be preferable for the WHO to perform this (i.e. the third option); if regulatory authorities are involved (fourth option), there is no guarantee that a name will be accepted and adopted globally. The naming of SBPs needs to be addressed globally and soon while the number of registered SBPs remains relatively small and with the INN programme being the best forum to achieve this.” (http://www.who.int/medicines/services/inn/55th_Executive_Summary.pdf)
MYTH
Changing the traditional naming process would require that each piece of the compendia process be individually rebuilt in order to ensure patient safety and restore functionality to the system.
FACT
Comparing biologics to small molecule products that share identical active ingredients misses the crucial point that biosimilars are not generics. If the proper use of biosimilars requires modernizing the existing system of safety alerts, then it is imperative to do so.
Existing INN’s for small molecule medicines and their generic counterparts do not need new naming conventions, only biologics. This significantly reduces the alleged burden on the system.
As medicine and technology evolves, so should our naming and coding process. Patient therapies should be precise and traceable every step of the way; the cost of implementing computer upgrades should never be presented as an obstacle to ensuring the safety of patients.
MYTH
There is already a precedent for shared names that has not resulted in any known issues and are used effectively in EU, Canada, Australia and Japan.
FACT
The non-proprietary naming system in Europe (INN) has mainly been used for first-generation biosimilars, as second-generation products have only recently been approved for marketing in the EU. Historical data that is collected from first generation biologics will be largely irrelevant and will not provide an accurate picture of potential pitfalls as complex second generation biologics enter the marketplace.
Canada has one biosmilar on the market and has stated that it will likely follow guidance issued by WHO as it establishes its naming nomenclature system for biosimilars. Australia and Japan have established their own systems to biosimilars naming, both of which take a distinguishable naming approach. Australia system includes a shared INN and suffix and early evidence indicates successful entry and uptake.
Not mentioned by the cost-centric/anti-safety crowd are the well-documented situation in Thailand, which resulted from the use of shared non-proprietary names. From the Citizen Petition filed January 7, 2014 by Johnson & Johnson with the FDA:
“Between 2004 and 2007, despite our switch to coated stoppers, adverse event reporters worldwide reported 15 cases of erythropoietin antibody-mediated PRCA in patients with chronic kidney disease who had been administered subcutaneous epoetin alfa. Of these 15 cases, 11 occurred in Thailand. The Thai market included multiple epoetin alfa products and hospitals and pharmacists frequently switched patients among them, often with incomplete documentation. Despite an extensive investigation, we were unable to determine which product(s) were responsible for the PRCA in the Thai patients because we could not determine which epoetin alfa product(s) a patient had received or which of several products that a patient had received had caused the problem.
In Thailand, several different erythropoietins were used, some of which shared the same nonproprietary name, and records did not reliably identify which specific product a patient had received. These factors confounded our ability to identify the product(s) responsible for the safety signal. To our knowledge, the product(s) responsible for the increased rate of PRCA in Thailand has never been identified.”
In the early 2000s, Thailand used non-distinguishable names for biological treatment of treat certain diseases, which lead to a dramatic increase in incidences of blood-related adverse events. Some of the products shared the same non-distinguishable name and records did not reliably identify which specific biosimilar a patient had received. These factors confounded the ability to identify the product responsible for the safety signal…When patients are switched between or among products, it can be difficult or impossible to identify the product responsible for an adverse event…contributing to the inability to identify the responsible product for cases of PRCA in the Thailand situation was the common practice of switching patients among the multiple epoetin alfa products available. And even where records identified which product(s) a patient received, it was often impossible to determine the particular product responsible for the PRCA because many patients had received more than one product.”
In order to prevent another life-threatening adverse event, more expensive registries were ultimately required in Thailand to better track these products and related outcomes.
MYTH
Distinguishable names would be “Contrary to Sound Economic Healthcare Policy and Congressional intent in BPCIA.”
FACT
The patient and safety communities, as well as many physician organizations have weighed in on the same issue, and have come out on the opposite side – in favor of transparency, so that patients can know which medication is being put into their bodies and the whole system can quickly connect the dots to stem negative impact when an adverse event occurs. In the views of these stakeholders:
· “If untraceable biosimilars become the norm and should the hypothesis of biotherapeutic equivalency not prove to be correct it would likely cause significant morbidity and mortality and thus irreparably damage this market and consumer and practitioner confidence in this class of products.” – From January 30, 2014 comments submitted the FTC by Salvatore J. Giorgianni, Jr., PharmD, BSc, CMHE and chair of the American Public Health Association Caucus on Men’s Health and president of the Griffon Consulting Group, Inc.
· Distinguishable names can prevent delays in determining the cause of an AE by creating a more expeditious route back to the origin of the problem and may avoid the recall of an entire class of biologics (which would be necessary if the specific medicine causing the adverse effect could not be readily identified.)” - From a January 7, 2014 letter to the FDA signed by the Maryland State Medical Society.
Additionally, Australia opted for distinguishable codes for all biologics, and they appear to be experiencing successful rollout and uptake of biosimilars.
MYTH
The incident surrounding ado-trastuzumab shows the risk of confusion with prefixes and can cause patient safety concerns.
FACT
Safety and quality experts concluded that the lesson learned by the ado-trastuzumab incident is not that prefixes present a patient safety risk but instead that strong coordination is needed between FDA, USAN, National Library of Medicine (NLM), USP, Compendia, and HIT stakeholders regarding naming for all biologics, including biosimilars.
MYTH
Applying different names for the same biological drug ingredients:
• Introduces confusion and unnecessary complexity
• Is contrary to historical FDA practice and policy
• Is opposed by virtually all pharmacy association stakeholders because it conflicts with normal pharmacy practice - employing an electronic database to recognize products by identifiers
• Is unnecessary for product recall or other patient safety considerations
• Undervalues the ability of existing systems (NDC- and Lot- based recalls) and new regulatory structures (track and trace) to provide adequate safeguards
FACT
The patient and safety communities, as well as many physician organizations have weighed in on the same issue, and do not believe distinguishable naming would introduce confusion and complexity, nor do they believe distinguishable names would hinder product recalls. They have come out on the opposite side – in favor of transparency, so that patients can know which medication is being put into their bodies and the whole system can quickly connect the dots to stem negative impact when an adverse event occurs.
Due to the fact that the FDA will characterize its assessment of biosimilarity (based on comparative analytical data) into one of four levels -- not similar, similar, highly similar or highly similar with a fingerprint-like similarity – it will become even more critical to provide transparency as to which biologic or biosimilar is being prescribed. Additional pharmacologic studies would be required to show that the identified difference is "within an acceptable range to consider the proposed biosimilar product to be highly similar to the reference product." FDA said only products in the top two tiers would meet the statutory requirement for analytical similarity under the Biologics Price Competition and Innovation Act of 2009.
The American Society of Health-System Pharmacists in a February 27 letter to the FTC that “…we do not oppose the addition of suffixes (e.g., alpha, beta) to the INN name if experts believe this approach is needed to facilitate pharmacovigilance.”
The Hematology/Oncology Pharmacy Association (HOPA) has stated its support for distinguishable naming in a published position paper: “Health care providers, patients, manufacturers, and regulatory agencies must be able to identify that a product is biosimilar to the original branded medication, and they must be able to associate the medication with the appropriate therapeutic class to assure appropriate prescribing. Naming is important to avoid prescribing and dispensing errors. Further, biosimilars must be able to be easily tracked to monitor safety and quality. Pharmacists are uniquely positioned to understand the important role that naming will have in ensuring appropriate medication substitutions take place when biosimilars are used.”
Nowhere are the issues of safety, efficacy, and traceability more important than to those with Orphan Diseases. And nowhere are biologics more important for treatment. So let’s end this missive with the position of NORD.
In a letter submitted to FDA Commissioner Margaret Hamburg, NORD asks that the agency give serious consideration to the concerns of the rare disease community when setting policy regarding official names for biologics, including biosimilars. NORD President and CEO Peter L. Saltonstall writes,
With over 7,000 rare diseases identified and 30 million Americans affected, the patient population represented by NORD is extraordinarily heterogeneous, the letter notes. Without thoughtful and consistent naming protocols for biologics, there is the potential for significant confusion among treatment options and increased adverse events, both of which could jeopardize patient safety. Distinguishable naming of all biologics is imperative for health care professionals to deliver the degree of customized care that is routinely required for patients with complicated, uncommon and less well-studied diseases. Every patient deserves the care best suited for their medical situation and most likely to give them the best outcomes. Biologics are often the most advanced and effective treatments for patients we represent and everyone in the treatment continuum should be able to readily identify the specific drug product a patient was given.
… and you will know the truth, and the truth will make you free.
