The term “unbranded biologic” has risen in significance over the past couple of years. On March 23, 2020, the “deemed to be a license” provision of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) shifted many products previously approved via new drug applications (NDAs) to be deemed biologic license applications (BLAs). For many of these products, the change in license type has had minimal impact; however, for products that were previously viewed as having pharmaceutical equivalence, there can be an impact on drug product selection at the pharmacy. Namely, this impacts NDA-to-BLA products that were previously considered “authorized generics” as NDA drugs and are now BLA “unbranded biologics.”
Pharmacists often think of the terms “brand” and “generic” as dichotomous and mutually exclusive, so it is not surprising that unbranded biologics, such as insulin and human growth hormone, among others, seem to be causing confusion for pharmacies when it comes to product selection. We will address how unbranded biologics are being displayed in pharmacy management systems and what pharmacists need to do to make sure they are being reimbursed appropriately.
Unbranded biologics are essentially identical to their branded counterparts, like an authorized generic for small-molecule drugs. As such, unbranded biologics should be therapeutically equivalent and therefore substitutable for the innovator biologic, since they are the same drug. The explanation for this reasoning is similar to this statement that the FDA (Food and Drug Administration) previously issued about authorized generics for small molecules:
“An authorized generic is considered to be therapeutically equivalent to its brand-name drug because it is the same drug. This is true even if the brand-name drug is ‘single source,’ meaning there are no ANDAs [abbreviated new drug applications] approved for that product, or coded as non-equivalent (e.g., BN) by the FDA in the Orange Book. While a separate NDA is not required for marketing an authorized generic, FDA requires that the NDA holder notify the FDA if it markets an authorized generic. The NDA holder may market both the authorized generic and the brand-name product at the same time.”
However, the FDA has not issued this same type of statement for unbranded biologics. Since there are only biosimilars and no interchangeable biologics on the market today, confusion exists about when an unbranded biologic may be substituted for the originally prescribed brand biologic.
Where we see this impact occur is in the pharmacy. We conducted a convenience sample of Walgreens, CVS, Rite Aid, and Walmart pharmacies to understand how their pharmacy management systems display information for unbranded biologics. We talked to pharmacists in a few different states to help account for potential variability based on state pharmacy laws and regulations. While this is a small sample, we found some interesting differences among the major chains. We asked whether substitution options were presented when they entered a prescription for:
- Lantus Solostar, which has branded alternatives of Basaglar KwikPen and Semglee pen.
- NovoLog FlexPen, which has an unbranded biologic of insulin aspart.
- Humalog KwikPen, which has an unbranded biologic of insulin lispro.
Among the CVS pharmacies we spoke to, no substitution options were presented for Lantus SoloStar, NovoLog FlexPen, or Humalog KwikPen. At the Walmart pharmacies, there were not substitution options presented for Lantus SoloStar, but insulin aspart was presented as a substitution option for NovoLog FlexPen, and insulin lispro was presented as a substitution option for Humalog KwikPen. At the Walgreens pharmacies both Lantus SoloStar and NovoLog FlexPen had substitution options presented, but Humalog KwikPen did not. At the Rite Aid pharmacies substitution options were presented for all three, Lantus, NovoLog, and Humalog. This brief exercise illustrated that pharmacies are taking different approaches to substitution options for unbranded biologics. Because this is a small sample size, we cannot guarantee that every store within a chain would display information in this same manner. The authors caution that just because a pharmacy system may display a product as a substitution option, that does not necessarily mean the chain is indicating the product can be legally substituted. Among the comments we heard when making these calls, some pharmacists noted that the insulin products may only be substituted if the prescription notes “substitution allowed.” Similar sentiments included the belief that the products are “not interchangeable without talking to the doctor.” Other pharmacists mentioned that the decision to substitute really depends on the patient’s insurance and which product it will cover.
This variability is likely the result of good intentions to ensure patient safety, preventing nonequivalent products from displaying as substitution options. But an unintended consequence could result in patients not being offered potentially cost-saving alternatives that bear the same active ingredient, strength, route of administration, and dosage form as the original brand product.
FDA Perspective on Biologics
When the FDA recategorized biologicals approved with an NDA or ANDA, it did not create a corresponding term or category akin to authorized generics for small molecules. What makes this even more confusing is that the FDA has specific assignments — biosimilar and interchangeable — in the Purple Book. However, in this question addressing unbranded biologics, the FDA uses the word “equivalent” in its response.
“Q9: How are ‘unbranded biologics’ displayed in the Purple Book?
A9: The term ’unbranded biologic‘ or ’unbranded biological product’ generally describes an approved brand name biological product that is marketed under its approved BLA without its brand name (proprietary name) on its label. Because an unbranded biologic is marketed under the brand name biological product’s BLA and is not different in strength, dosage form, route of administration, or presentation, it is not separately identified in the Purple Book. An ‘unbranded biologic’ is not an ‘interchangeable biosimilar.’ However, an unbranded biologic is considered by the FDA to be equivalent to its brand name biological product because it is the same product as the brand name biological product under the same BLA.”
The FDA does not define “equivalent” in this response, but states it is not an interchangeable biosimilar. Unbranded biologic products typically bear the same chemical/generic name as the innovator biologic, since the FDA (as of today) has not moved forward with its biological naming guidelines, which would require a suffix on all the biologicals previously approved under NDA and ANDA status. This is yet another area where these products differ from traditional biosimilars.
State pharmacy laws and regulations may also have an impact on pharmacists’ authority to substitute these products. In some states, pharmacists may be allowed to exercise professional judgment and document the decision accordingly. In addition to substitution decisions, some states have specific notification requirements around switching biologic products, and notifying the prescriber and/or the patient. If you are unsure what is allowed in your state, consult state pharmacy laws/regulations and/or your pharmacy employer.
Compendia Perspective on Biologics
Each compendium will have its own approach to identifying and grouping biologic products, including the unbranded biologics. For example, Medi-Span lists all BLA-approved products as “single source.” That policy existed long before the March 23, 2020, shift to biologic status for many previously NDA-approved drugs. Medi-Span did announce they would be moving all NDCs that received a BLA assignment to the Purple Book as single source (“N” drugs in Medi-Span terms). As a result, unbranded biologics that were previously authorized generics had been designated as “M” drugs in Medi-Span and had to be changed to “N” drugs in 2020.They still share the same GPI (generic product identifier) as the original brand because they are the same product.
At First Databank, they have renamed the “Authorized Generic Indicator” field to now read “Authorized Generic or Unbranded Biologic,” so that it can be used to identify whether an NDC is either a BLA unbranded biologic or an NDA-authorized generic.
Other compendia may take different approaches to the identification and grouping of unbranded biologics.
Potential Solutions for Pharmacist When Selecting Products
For pharmacists, it is important to be familiar with unbranded biologics and to understand that although they may not be interchangeable biologics, they are equivalent. Some payers may continue to prefer the original brand on their formularies, due to existing agreements, while others may want to encourage their members to switch to an unbranded biologic to save costs.
Pharmacists must be diligent in accurately dispensing the prescribed product to pass retrospective third-party claims audits and use the appropriate dispense-as-written (DAW) code if applicable. If a payer performs an audit comparing the dispensed product to the prescribed product and there is not a match, the payer could void or recoup the reimbursement from the pharmacy. Pharmacists who have been “dinged” on previous audits will know that a call back to the prescriber is a must to avoid future financial penalties.
Until there is more clarity around the interchangeability of unbranded biologics, pharmacies should document when they have contacted a prescriber to authorize dispensing a product, as in the case of an unbranded biologic substituted for the original branded product, and document which product the prescriber intended for the patient to receive. CT
Melissa Sherer Krause, Pharm.D., is VP and partner, and Emmanuel Anderson, is a Pharm.D. candidate, at Pharmacy Healthcare Solutions. The authors can be reached at email@example.com and firstname.lastname@example.org.