FDA Denies Par Generic Epinephrine Injection Request
FDA has denied a Par Sterile Products petition asking that it not approve any ANDA for an epinephrine injection 1 mg/mL product in a 1 mL vial, ampule, pre-filled syringe, or similar parenteral administration modality that does not contain the same inactive ingredients in the same amounts as Par’s recently reformulated Adrenalin (epinephrine injection). In the alternative, the petition said, FDA should require generic products to have the same or lower levels of impurities as reformulated Adrenalin, as demonstrated through testing commensurate with studies performed by Par for a postmarketing commitment.
The agency’s denial letter says that in general, FDA expects that an ANDA referencing Adrenalin as its reference-listed drug (RLD) would contain the same inactive ingredients in the same concentrations as the RLD. However, it says, agency regulations specifically permit an ANDA for a parenteral drug product to differ in terms of certain inactive ingredients such as preservatives, buffers, and antioxidants.
FDA said it does not agree with Par’s conclusion that a generic epinephrine injection product referencing Adrenalin as the RLD that does not have the same inactive ingredient composition as reformulated Adrenalin would necessarily have a higher level of impurities, as many factors can affect the formation of impurities. FDA also disagreed with Par that such a generic product would have “less-than-optimal efficacy” or a “less-than-optimal risk profile.”
“As reformulated,” the letter says, “Adrenalin’s inactive ingredient composition results in a different, but not proven to be better, impurity profile than the original formulation. For instance, reformulated Adrenalin contains new impurities that the original formulation did not contain. Par has not established that the impurity profile of reformulated Adrenalin results in a more effective or a safer product for the emergency treatment of allergic reactions…. For these reasons, we deny your request that we refrain from approving any ANDA referencing Adrenalin as its RLD with inactive ingredients that differ in any way from reformulated Adrenalin. As stated, we will review any proposed generic product on a case-by-case basis to determine if the applicable legal and regulatory requirements are met.”
Likewise, FDA rejected Par’s idea that it should require every ANDA applicant seeking approval of a generic version of Adrenalin to engage in the full range of activities that Par did in connection with its post-marketing commitment, noting that while the sponsor agreed to conduct the studies, they are not required by FDA.