FDA’s Gottlieb Wants to Make It Easier to Obtain and Study Biologic Samples

Over the next couple of weeks, I’ll be further analyzing some details of the Food and Drug Administration’s (FDA’s) new Biosimilars Action Plan.


biosimilar developmentMuch has been made of the difficulties biosimilar manufacturers have been having in obtaining reference product samples. These are used for the most basic biosimilar development tasks: (1) the reverse engineering of the molecule, (2) physiochemical comparison of the originator and the new biosimilar, and (3) clinical testing in humans to compare the effects of the new product with the originator.

Manufacturers of the originator biologics have not made it easy. A couple of strategies used to protect access to the samples include exorbitant pricing and withholding products based on Risk Evaluation and Mitigation Strategies (REMS) mandates. These and other creative methods can delay the supply of samples to biosimilar manufacturers, and thus access to competitive products.

Legislative attempts to bypass these tactics include the CREATES Act, which is making its way through the Senate. However, at the rollout webinar of the Biosimilars Action Plan on July 18, FDA Commissioner Scott Gottlieb suggested a sensible solution: allowing the prospective biosimilar developer to purchase samples of the originator product outside the US.

He noted, “The FDA is seeking to strengthen its partnerships with regulatory authorities in Europe, Japan and Canada. Such partnerships can enable greater efficiency in developing safe and effective biosimilars.” Dr. Gottlieb continued, “For example, we’re actively exploring whether data sharing agreements could give us better insights into biosimilars’ real-world safety and efficacy and, in some circumstances, facilitate the increased use of non-US-licensed comparator products in certain studies to support an application under Section 351(k).”

Within the framework of the biosimilar approval pathway, biosimilar manufacturers had been permitted to use “bridging studies.” These allow drug trials using the EU-licensed version of a biologic after comparator studies have demonstrated the similarity of the EU- and US-licensed samples. The idea, in simplest terms, is that an EU-approved version of Remicade® is not exactly the same as the US-approved version. In biologic manufacturing, lot-to-lot differences in some structural elements are common, but they do not seem to affect the clinical outcomes of the product. Dr. Gottlieb has allowed that the differences between the two versions may be insignificant, and this could spur biosimilar development.

“We know that when those developing biosimilars use biologics sourced ex-US as their comparator product, it can lower the cost of clinical studies since many of these products can be procured more easily, and cheaply, in European and Asian markets,” Dr. Gottlieb said.

Furthermore, the Biosimilars Action Plan states that FDA will also explore “ways to reduce the number of lots of the reference product required for testing.” Overall, this can make the initial steps in biosimilar development less expensive.

Action at the Capitol to Improve Access to Biologic Samples by Biosimilar Developers?

The Trump Administration has indicated a desire to streamline marketplace rules to improve the efficiency of the Food and Drug Administration (FDA) and to enhance manufacturers’ access to the marketplace. “President Trump issued an executive order to this effect,” said Mary Jo Carden, RPh, JD, Vice President of Legislative and Pharmacy Affairs, Academy of Managed Care Pharmacy (AMCP). But “what that means is still a question.”Image result for Mary Jo Carden

Efforts are underway to clear away a roadblock to manufacturers who are trying to bring a competitive biosimilar to the marketplace. Step 1 in the process of building a biosimilar, before a drugmaker can begin to develop and characterize a biosimilar version of an originator, is to obtain samples of the licensed biologic. This is not as simple as it sounds. Those companies producing the originator may be unwilling to provide samples or charge extremely high rates for the use of their product, as a way of stalling competition. Some manufacturers have used REMS and internal distribution restrictions as a reason not to sell to biosimilar drug developers.Image result for US Capitol

Reginia Grayson Benjamin, JD, Director of Legislative Affairs for the Academy, said that two separate initiatives are being developed in Congress to address this problem. First introduced in June 2016 by Senator Patrick Leahy (D-VT) (S. 3056), the Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act, will need to be reintroduced in 2017. It is an effort to assist competition in the biologics market, by facilitating entry of biosimilars (and small-molecule generics). The CREATES Act,” according to Ms. Grayson Benjamin, “seeks a legal solution to the sample access problem, by creating a right to a civil cause of action for failure to provide sufficient quantities of a covered product.”

Second is the Fair Access to Safe and Timely Generics (FAST) Act, which may be reintroduced into the House of Representatives. It was first brought to Congress in June 2015 by Representative Steve Stivers (R-OH) as H.R. 2841, and did not make it out of the Subcommittee on Health. Ms. Grayson pointed out that it is not a companion to the CREATES Act, but it “would create a regulatory solution,” she said.

However, these proposals, which have not yet been formally debated or sent to committee, and other health care–related bills that have been introduced, have received little consideration because of actions surrounding and the ultimate vote to reject the American Health Care Act.

UPDATE: On April 6, H.R. 2051 was introduced in the House by Representative David B. McKinley (R-WV). This is a reboot of the FAST Act, and has been referred to the Referred to the House Committee on Energy and Commerce.