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Experts: Biologic Product Monographs Do Not Impede On FDA’s Authority

June 18, 2019

Updated Story: This story has been updated to include a comment from FDA.

Some biologics experts are perplexed by the Trump administration’s argument that subjecting biologics products to United States Pharmacopeia (USP) monographs would hamper innovation. FDA argues the monographs set rigid standards for biosimilars to prove they’re highly similar to their reference products, but the experts say the agency is the one with the authority to determine similarity as USP monographs only set up quality standards.

The debate has intensified because the Senate health committee agreed with the administration’s argument and put a provision in its draft health care bill that would exempt biologics from having to adhere to USP monographs. The president’s budget request called for the exemption, and last week FDA officials spelled out their reasons for why biologics should be exempted from USP monographs.

Three years ago, stakeholders were in a similar situation when the Senate considered including the exemption language in the 21st Century Cures Act.

At the time, a USP spokesperson told Inside Health Policy the proposal would preempt stakeholder dialogue on nonproprietary naming solutions for biologics -- a conversation that is still ongoing especially as FDA recently revised its draft guidance establishing nonproprietary naming standards.

Now that the debate has resurfaced, USP, backed by generic drug lobby Association for Accessible Medicines (AAM) and multiple pharmacist groups, wrote to the Senate health committee in an effort to quash the proposed exemption.

In its June 11 letter, USP argues the proposed exemption would have broad negative consequences on public health as product makers would no longer be able to rely upon USP standards for product development.

IHP asked USP whether it still believes that exempting biologics from monograph standards would affect the nonproprietary naming conversation, to which Tony Lakavage, senior vice president of global external affairs and secretary of the USP Convention and board of trustees, reiterated that the proposed exemption has “sweeping impact.”

“[It] would make adherence to all public quality standards optional for all biologics, and that poses a risk to patient safety,” Lakavage said.

In a “CDER Conversation” posted June 12, FDA argued USP monographs could hamper innovation in the biologics space by subjecting them to a “sameness” criteria that products might not be able to meet.

But experts, including USP officials, who spoke with IHP say monographs don’t infringe on FDA’s approval jurisdiction.

Fouad Atouf, vice president of sciences for global biologics at USP, said monographs don’t block innovation, as monographs don’t exist until the first innovator comes to market. After that, companies seeking to develop follow-on products may rely on some of the general standards in the monograph, but ultimately they’re not affected at the approval stage.

He also said USP recognizes that the issue of sameness is not within the scope of a USP monograph.

“What a monograph would do is it would provide a framework for quality attributes for manufacturers that want to bring those products to market,” Atouf said. “In that regard, public standards are supported over multi-manufacturer environments and spaces.”

He added, “Demonstrations of biosimilarity and meeting compendial standards are two different things ... A monograph for a biologic addresses common quality attributes across manufacturing standards and not biosimilarity.”

Nicholas Mitrokostas, partner in Goodwin’s intellectual property litigation group, told IHP he, too, isn’t quite sure why FDA thinks it would be hamstrung by monographs.

“I’m not sure what FDA’s motives are, but I suspect that maybe based on their experience in reviewing applications they feel like it would be easier for them to approve some products if they didn’t feel like the product had to adhere to USP standards,” Mitrokostas said. “On the flip side, FDA has jurisdiction to determine whether something is highly similar or not. Just because there is a USP standard, they don’t have to require a biosimilar product to adhere to it as long as they can show it’s a highly similar product. It’s an interesting position they’re sort of taking.”

Another expert told IHP that USP monographs only focus on identity and quality, and so they don’t affect FDA’s authority over clinical testing.

That same expert noted that many countries in Europe rely on monographs for biologics and that Europe has a more robust biosimilars market than the United States. So why, the source asked, is FDA arguing that monographs hinder competition?

Atouf agreed the European experience with biologic products is a good example of innovation thriving with monographs.

Lakavage said the argument that monographs hamper innovation is a red herring.

“There’s a lot of discussion about the biosimilars market in the United States, and there are a lot of legitimate issues including pricing, prescriber incentives, misinformation. But, public standards for quality are not one of the factors, and it’s simply a red herring,” Lakavage argued. “If anything, public standards for quality in biosimilars would enhance public trust in the products. They are not a problem.”

An FDA spokesperson explained to IHP that while FDA does make the decision on biosimilarity, products can still be misbranded if they don't adhere to USP standards.

"A product that meets the standard for biosimilarity but does not meet an applicable monograph would be misbranded," the spokesperson said. "Compliance with a USP monograph represents an additional requirement that is not necessary for FDA to determine whether a product meets the approval standard, and, therefore, it can impede or delay biosimilar licensure and marketing."

Mitrokostas also noted that, over the past decade, concerns have been raised by some in the biologics industry that USP standards can be used by makers of reference listed products to impose conditions for their products that might make it harder for a generic or biosimilar to meet sameness or highly similar standards for approval.

When asked why AAM would sign on with USP in favor of keeping the monographs if it has potential to hinder biosimilars development, the lawyer made clear he doesn’t know what the group’s thinking is on the topic, but he posited that biosimilars makers would probably rather have the clarity that monographs provide so they at least know what they need to do to gain approval.

IHP reached out to industry groups, including the Biotechnology Innovation Organization (BIO) and AAM, for this story. BIO said it has not taken a formal position on the issue. AAM referred IHP back to USP. -- Beth Wang (bwang@iwpnews.com)