By Bob Roth
Virginia recently enacted legislation which would regulate interchangeability of an approved biosimilar drug and its reference biologic, the net effect of which is certainly to limit substitutability at the pharmacy level. This law would require a pharmacist to adhere to recordkeeping requirements, and patient and prescriber notification requirements, if a biosimilar product was dispensed in lieu of the prescribed innovator biological product. It is not at all clear if pharmacists would readily accept such responsibilities, and if there is scientific evidence to require these additional requirements. Further, as a result of the way the law is written, it is likely that Virginians will rarely, if ever, see biosimilars substituted for the innovator product.
The legislation requires that in order for a biosimilar product to be substituted for the innovator biologic drug, the interchangeability standards discussed in the Biologics Price Competition and Innovation Act of 2009 (BPCIA) must be met. Specifically, meeting the BPCIA standards will almost certainly require convincing arguments proving that the risk of switching between the biosimilar and the innovator product, in terms of reduced efficacy or altered safety, will not exceed the risk of using the innovator product without switching. Discussion of such requirements, briefly mentioned in FDA’s recent Guidance for Industry “Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009,” suggests the FDA may require prospective clinical experience in order to make this argument. However, implementing this concept is particularly nebulous since FDA has yet to define the clinical data that would be required to support the safety and effectiveness of substituting one marketed biologic formulation for the other. The Act suggests that assessing the potential risks of alternating or switching between use of the biosimilar biologic product and the reference biologic product will necessitate a multiple switch clinical protocol. However, such studies are not routinely conducted, and criteria for acceptable switch findings are not clear. There is no reason to believe that a mathematically defined “clinical equivalence” criterion similar to bioequivalence for generic drug products approved through the Abbreviated New Drug Application [505(j)] pathway would be required. However, it will certainly be necessary to have data supporting a conclusion that any observable differences between products during switching are of no greater magnitude than the variations one can expect over time with one formulation alone.
We have previously summarized the extensive development work that has been undertaken, and is likely to continue to be required, for approval of a biosimilar drug. The very extensive and costly development programs for the presently approved biosimilar proteins would only become more of a factor if interchangeability was the ultimate goal.
Finally, it should be noted that the price discount for a biosimilar product is estimated to be only approximately 20-30% off the innovator price, a far smaller discount than is typical for a generic small molecule drug with many approved products commercially available. This lack of a strong financial impact on the consumer is likely to further discourage pharmacists from undertaking the paperwork requirements of the new Virginia law. We anticipate that this new law will substantially limit the potential market share of biosimilars as they come on the market in Virginia, and that public health savings from these new products will be less than hoped.
Bob Roth is Vice President and Worldwide Medical Director and Nick Fleischer is Vice President at The Weinberg Group, the world’s leading food and drug consulting firm. If you have any questions or thoughts on this blog post or others, please contact us.