Regulatory Uncertainty Can Hurt Biologic Innovation

Life Sciences Law & Industry Report connects the dots among the many disciplines that make up the burgeoning life sciences industry, with biweekly updates on current regulatory, legislative,...

May 5 — Regulatory uncertainty about cellular and tissue products has become a hindrance to innovation, the FDA's top biologics official told a conference audience May 5.

“We need more clarity about the regulatory requirements” for human cell, tissues and cellular and tissue-based products (HCT/Ps), said Peter W. Marks, director of the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER). “It has been slower in coming than we would have liked.”

“There's black, and there's white, but there's also a gray area in between that's sometimes difficult to define,” Marks said at a session at the Food and Drug Law Institute's Annual Conference in Washington. “And when we do, and I'm speculating here, but I think we will make some people happy and some people very unhappy.”

CBER's mission is to protect and enhance the public health through the regulation of biological and related products including blood, vaccines, allergenics, tissues and cellular and gene therapies.

Level of Ambiguity

Marks was responding to a Bloomberg BNA question about the FDA extending the deadlines for public comment on four HCT/P draft guidances and rescheduling the public hearing to discuss them (10 LSLR 09, 4/29/16).

The extensions reflect the controversial nature of the topic. One of the draft guidances caused two companies' stocks to fall because investors assumed the definition meant the companies would have to go through premarket approval for their HCT/P products (9 LSLR 1284, 11/13/15).

“The draft guidances have become controversial,” Marks acknowledged. “And there are spirited discussions going on. A lot of people have different ideas of where the field will go. There is some disagreement about the definitions of ‘minimal manipulation' of cells and tissue and ‘homologous use' [which refers to similarity of position, structure and function]. Our major concern is that we have safe and effective products. And it's nice to be in an area that people care about.”

Session panelist Daniel A. Kracov, of Arnold & Porter LLP, said, “I'm on the other side of that controversy in my representation of clients, and I feel there's a level of ambiguity around cell-based products and about enforcement that is retarding the ability of companies to generate money to develop innovative, safe and effective products. It has gone on too long, I think.”

‘Killing Technology.'

Panelist Sheldon Bradshaw of King & Spalding LLP took up the argument that some of the FDA's actions have discouraged innovative research.

He brought up the case of United States v. Regenerative Scis., LLC, in which the FDA sued two physicians who had developed a treatment for bone pain that extracted, manipulated and reinserted a patient's stem cells. The physicians argued that the treatment was the practice of medicine, which the FDA can't regulate. The agency countered that the mixture was a biological product that was subject to the agency's regulations. The U.S. District Court for the District of Columbia found in favor of the FDA (8 LSLR 106, 2/7/14).

“There was a lot of feeling it was a misguided prosecution,” Bradshaw said. “And after the FDA won, it didn't seem to know what to do. It has curtailed research, and doctors don't know how much they can do in taking cells out of patients and then reinserting them. It's killing technology in the bud.”

Marks said the FDA encourages sponsors of drugs and biologics to have early conversations with the agency. “And we have become aware of the need to be in tune with sponsors who have a drug or biologic for a small population and may want to use novel trial designs, novel statistical designs and novel ideas.”

FDA's Goal: Safe, Effective Products

But, Marks added, regenerative medicine is ripe with people who want to take cells and manipulate them and put them back without very much science to support them.

“They ‘know' that if they take cells from your ear and put them in your brain or in your eye that it will help your brain or your vision, and they make the claims without any data to say there is efficacy,” he said. “Some people say that stem cell injections in their joints have helped them tremendously. But at least two people have gone blind from eye injections and there are reports that the insertion of stem cells has caused hemorrhaging in the brain.”

Marks continued, “We want to make sure that the products that get out there are for the benefit of patients, that they aren't just innovative but have some hope of getting the results patients are looking for.”

Flexible on Immunotherapy

Edward Li, associate professor of pharmacy practice at the University of New England College of Pharmacy, said that clinicians are excited about using oncology immunotherapies, which boost the body's natural defenses to fight the cancer.

Marks said, “We have come to realize with immunotherapies that we have to change our paradigm. Traditionally, we want to first see a good response rate, then a halt to tumor progression pre-survival, and then a better survival rate. Immunotherapies don't work that way. The tumor doesn't change in size, but people live longer. It's going to get more complicated as we look at combinations of these things. But we will take a more flexible approach.”

Marks concluded by alluding to rumored changes to the CBER as a result of the cancer “moonshot” initiative that is being led by Vice President Joe Biden (10 LSLR 09, 4/29/16).

“CBER is the now the smallest of FDA's centers. But we do pride ourselves on having the ability to interact with sponsors and have dialogues in real time. It's nice to have a kind of boutique for biologics. As for any upcoming changes, I think we can still keep the best of what CBER is.”

To contact the reporter on this story: John T. Aquino in Washington at

To contact the editor responsible for this story: Randy Kubetin at