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BioRationality: It Takes 4 to Tango—How US Entities Can Make Biosimilars Accessible


The FDA, Congress, biologic developers, and associations dedicated to evaluating the US biopharmaceutical space will need to work together to overcome challenges to biosimilar accessibility, says Sarfaraz K. Niazi, PhD, in his new column.

FDA role | Image credit: wladimir1804 - stock.adobe.com

Image credit: wladimir1804 - stock.adobe.com

Accessibility means availability and affordability, both of which are out of alignment for today’s biopharmaceutical space. Only 12 out of more than 100 originator biologic molecules have biosimilars on the market, and their prices remains out of reach, in part because of the high cost of development that can be reduced significantly by making 4 key stakeholders “do the tango” together, so to speak. Each of them has a task, and each one has declared commitment to the goal of reducing development costs and drug costs overall.

First, let me break down the tasks for the FDA. With animal toxicology gone with the FDA Modernization Act 2.0, it is time to consider letting comparative clinical efficacy testing go, as the United Kingdom’s Medicines and Healthcare products Regulatory Agency has suggested.

It is not to reduce the development cost but to comply with US 21CFR320.25(a)(13) to avoid human abuse since these trials cannot characterize a biosimilar candidate more than the analytical and clinical pharmacology profiling to prevent unnecessary human exposure. These studies cannot fail, no matter how different the product is. There are better options to ensure the safety and efficacy. The pharmacodynamic comparison is also of little value if, according to the FDA, it need not correlate with the clinical response; this should not be the step-down choice of efficacy testing.

This is within the FDA's power to do, despite the Biologics Price Competition and Innovation Act requirements for testing in at least 1 indication, an irrational clause on several grounds. The FDA cannot remove the interchangeable status but grant it to the first biosimilar approved. This will boost the entry of many new molecules. The FDA can also declare that biosimilars are interchangeable with the reference product and other biosimilars. The FDA has done well by clearing up the immunogenicity issue by saying that if antidrug antibodies do not affect the pharmacokinetics, then such studies are not needed (e.g., insulin).

Now, the FDA must also make it clear that if the primary sequence is the same, then the T-cell immune response must also be the same; these statements are needed to remove the risk perception of biosimilars. The FDA can also remove bridging studies allowing the use of non-US reference products approved using essentially the same dossier; this will enable the global market of approved biosimilars.

One recommendation to the FDA is to remove its objections to the United States Pharmacopeia (USP) creating monographs of biologic drugs. When validated test methods are available, the attributes of the reference products listed in the USP monograph will suffice to establish biosimilarity, removing one of the most significant cost and time barriers to their approval.

Second, let me share the activity in the US Senate; a bill is on the table to remove the interchangeability designations. It is now a bipartisan bill, but it is facing opposition from many, including associations that, in my opinion, shouldn’t be allowed to offer any critique. I am unsure how far this bill will go, but removing the 2 classes of biosimilars is needed to bring more confidence among the prescribers and remove misrepresentations by developers who can afford to conduct additional studies that can never fail. So, in essence, it is just a matter of financial resources, not to bring any benefits to patients.

Congress must also decide how to control the pharmacy benefits managers (PBMs) in controlling the distribution and pricing of biosimilars; dozens of bills are on the table, and none are moving, confirming the lobbying power of the PBMs. The Congress should also remove the “patent dance” now that the Purple Book has been upgraded to include all intellectual properties.

Third, come the developers. Reducing the cost of development requires planning, such as securing approval through a contract development and manufacturing organization (CDMO) and then transferring it under Q5E. This will allow the development of dozens of products simultaneously.

However, knowing what to require as a dossier is pivotal, or the CDMOs can quickly crunch the plan. One area where the developers can get into more significant markets is to repurpose biosimilars for additional indications and ask the FDA to allow the use of the FDA guideline on generally accepted scientific knowledge to reduce testing. Also, developers should consider continuous manufacturing for both prokaryote and eukaryote systems now that the FDA provided a guideline and details of the common technical document required for such submission. Other smart moves involve securing approval at a smaller scale lot and then post-approval using Q5E to upscale commercial manufacturing.

Finally, the developer and other professional associations, dozens of them around the globe, must stop regurgitating the obvious: biosimilars were created to save money; this is not to be advertised—it sounds like buying more to save more. The correct role of these associations is to remove the misconceptions, like favoring interchangeable products and convincing regulatory authorities to become more rational. Holding conferences where one developer tells other developers what to do is a sheer waste of time, in my opinion. The focus should be on prescribers, not the patients or the public.

When it comes to teaching biosimilars, the only direction should be to direct the audience to the grand display of teaching tools and training courses put together by the FDA. There is no need to repeat the claims of the safety and efficacy of biosimilars; if the FDA has approved a product, there should be no question remaining in the mind of any stakeholder. Let the FDA do the job.

Yes, it will work if all can dance together with humility.

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