Bills Would Streamline Cellular Therapy Approval

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By John T. Aquino

April 5 — Bills introduced in both the House and Senate would create a conditional, streamlined approval process for cellular therapy treatments, but there are concerns about provisions to allow bypassing some safety and effectiveness studies.

Both bills, which have identical texts, outline a program to approve a cellular therapeutic product for five years, without phase III investigations, if the product's sponsor demonstrates preliminary clinical evidence of safety and a reasonable expectation of effectiveness. The bills are titled “Reliable and Effective Growth for Regenerative Health Options that Improve Wellness (REGROW) Act.”

“There are currently hundreds of cellular therapy products on the market, some of them for years, and there's an uncertainty about whether they fall under Food and Drug Administration regulation,” Chad Landmon of Axinn, Veltrop & Harkrider LLP, Hartford, Conn., told Bloomberg BNA in an April 5 phone interview. “The bills, as I read them, whether you call them hybrids or compromises, are attempts to clarify FDA oversight and at the same time not get in the way of products that are doing or will do good for patients.”

However, in a blog, Paul Knoepfler, associate professor of cell biology and human anatomy at the University of California at Davis, wrote, “REGROW proponents want to rocket forward with stem cells into patients by eliminating Phase III trials and establishing a risky conditional approval paradigm. I haven't seen any evidence that Phase III clinical trials for stem cells are unnecessary nor that the conditional approval paradigm would be safe.”

Nonprofits Support Bills

Sens. Mark Kirk (R-Ill.), Joe Manchin (D-W.Va.) and Susan Collins (R-Maine) March 16 introduced the Senate version of the bill (S. 2689). An identical House bill (H.R. 4762) was introduced the same day by Reps. Mike Coffman (R-Colo.), Mike Takai (D-Hawaii) and H. Morgan Griffith (R-Va.).

The bills were referred to the Senate Health, Education, Labor and Pensions Committee and the House Energy and Commerce Committee.

Proponents of the bills had hoped that they would be reviewed by the full Senate HELP Committee, along with other bills, at an April 6 markup session. The REGROW Act bills weren't included in the list of those to be marked up, but Kirk's office told Bloomberg BNA in an April 5 e-mail that Section 5 of the bill, on standards for regenerative medicine, will be voted on by the committee on April 6.

The Alliance for Aging Research and Patients for Stem Cells supported the bills. AAR President and Chief Executive Officer Susan Peschin wrote in an April 5 e-mail to Bloomberg BNA, “The Alliance for Aging Research supports the REGROW Act because regenerative cell therapy is one of the most promising developments in medicine today. Its potential to restore normal function to damaged cells, tissues and organs offers hope to millions of patients with complex chronic diseases such as diabetes and heart disease, as well as bone and joint conditions that cannot be effectively treated otherwise. However, regenerative cell-based therapies are virtually inaccessible to U.S. patients because the FDA's current statuary framework treats cell-based therapies similar to chemical drugs and biologics.”

She added that because cell-based therapies are highly individualized and rely on patient-specific needs, this makes scaling toward traditional large clinical trials almost impossible.

FDA Issues Guidances, ‘Struggling.'

The focus of the bills is on the FDA's regulation of human cells, tissues and cellular and tissue-based products (HCT/Ps).

Under Section 361 of the Public Health Service Act, if an HCT/P can be minimally manipulated, intended for homologous use, not be manufactured by combining cells or tissues with another article, not have a systemic effect and not be dependent upon the metabolic activity of living cells for its primary function, it doesn't need to go through any review by the FDA prior to marketing under 21 C.F.R. Part 1271.

“The FDA has been struggling—and therefore companies have been struggling—with whether particular products meet the definition of a ‘361 HCT/P' that doesn't need to go through pre-market review,” Landmon said. “In some cases, the agency has gone after companies (see 10 LSLR 02, 1/22/16) and said, ‘You have to file a biologics license application (BLA) [under Section 351 of the PHS Act], which must be supported by clinical data gathered under an Investigational New Drug exemption.' And this is costly and prevents the treatments from being on the market.”

The FDA has issued numerous HCT/P related guidances, one of which in its definition of “homologous use”—which means similarity of position, structure and function—caused two companies' stocks to fall because investors assumed the FDA's definition would mean the companies would have to go through premarket approval (9 LSLR 1284, 11/13/15).

In 2010, Regenerative Sciences LLC sued the FDA in the U.S. District Court for the District of Columbia, arguing that the agency didn't have the authority to regulate a physician-developed procedure utilizing a patient's own stem cells. The district court ruled in favor of the FDA, the company appealed to the U.S. Court of Appeals for the Federal Circuit (7 LSLR 1059, 11/1/13), and the appeals court affirmed the district court's ruling in February 2014 (8 LSLR 106, 2/7/14). The company decided not to seek Supreme Court review.

Bills Build on Policy Center's Report

The bills' sponsors cited a 2015 Government Accountability Office report as saying, “[V]irtually any disease that results from malfunctioning, damaged or failing tissues may be potentially cured through regenerative medicine treatments.”

They noted that in December 2015, the Bipartisan Policy Center published recommendations for advancing regenerative cellular therapies, which aim to “restore health rather than merely treat disease.” The bills' sponsors wrote that the REGROW Act builds on that report by establishing a novel, conditional approval pathway that will ensure products are safe and effective before they can be marketed. It also includes post-market surveillance measures to ensure continued safety during the conditional use period.

Legislation Details

Under the REGROW Act, within one year of the enactment of the legislation, the Department of Health and Human Services would establish a program to conditionally approve a cellular therapeutic product if the product's sponsor demonstrates preliminary clinical evidence of safety and a reasonable expectation of effectiveness, without initiation of phase III investigations.

The product, for a five-year conditional use period, would have to be manufactured, introduced into interstate commerce and used consistent with the regulations in effect at the time of use, including good manufacturing practices, without the approval of an application under Section 351(a) if such cells or tissues:

• are adult human cells or tissues;
• have been evaluated to examine immunogenicity and don't provoke a significant unintended immune response in the recipient;
• are minimally manipulated for a nonhomologous use or more-than-minimally manipulated for a homologous or nonhomologous use, but are not genetically modified;
• are produced for a specific indication; and
• are produced exclusively for a use that performs, or helps achieve or restore, the same, or similar, function in the recipient as in the donor.

 

During the five-year period, the sponsor must submit a BLA as well as annual reports and adverse event reports and an investigational new drug application. The HCT/P would be permitted to remain on the market unless and until the FDA denies approval of the BLA.

The last part of the bill addresses devices involved in the recovery, isolation, processing and delivery of cellular therapeutic products.

Rushing Ahead Will Slow Things, Blog Says

In his blog, Knoepfler quoted Kirk's press release that said, “Unfortunately the Food and Drug Administration (FDA) has identified the current lack of regulatory standards in this area of medicine as an impediment to treatment development. Countries like Japan and England are outpacing the U.S. in regenerative medicine therapy development due to new regulatory policies that the U.S. has yet to mirror. S. 2689 will allow the United States to regain prominence in the field of regenerative medicine science and bring therapies quickly to the patients that need it most.”

Knoepfler blogged that there is “a nationalistic agenda evident in the language that is not scientific. Just because some authorities in Japan have chosen to dramatically weaken regulation of stem cell therapies there and made other questionable decisions such as more widely allowing charging of patients to be in stem cell clinical trials, doesn't mean the U.S. should follow the same somewhat reckless path.”

He concluded, “These practices are highly questionable from a bioethics perspective and also from a simple common sense view that rushing ahead too fast can actually slow things down by leading to catastrophic patient outcomes.”

Landmon responded, “As with any medical product, a balance has to be struck trying to lessen the regulatory hurdles that get in the way of the products getting to market and increase costs while ensuring that the products that are on the market are safe.”

To contact the reporter on this story: John T. Aquino in Washington at jaquino@bna.com

To contact the editor responsible for this story: Randy Kubetin at rkubetin@bna.com