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Regulatory Policy: CBER Importance Boosted With Attention To Biologic Drugs, Biosimilars, Speakers Say

May 04, 2012

Increasing attention to development and use of biologic drugs, biosimilars, and companion diagnostics is boosting the importance in health care of the Food and Drug Administration's Center for Biologics Evaluation and Research, speakers said April 24 at a drug law conference.

Stephen Paul Mahinka of Morgan, Lewis & Bockius LLP noted that until recently it has been easy to think of CBER as a small actor in the medical product arena.

"But one thing that is changing in this arena is the importance of CBER. It is at the heart of the FDA's work on biosimilars and preparation for pandemics. In the upcoming years, it will have a huge impact on the range of medical products available and the economic impact of these products," Mahinka said at the Food and Drug Law Institute's 55th Annual Conference in Washington.

Three CBER office directors outlined the center's future strategies during the session, while attendees sought answers for questions involving the co-approval of a drug and its companion diagnostic and whether FDA is attempting to regulate the practice of medicine.

'Looking to Be Innovative.'

In the initial presentations, the CBER directors discussed their offices' accomplishments and priorities.

Diane Maloney, CBER's associate director for policy, noted that the center's strategic goals for the next four years are to:

  • increase national preparedness to address threats from bioterrorism, pandemics, and emerging infectious disease;
  • improve global public health through international collaboration;
  • enhance the ability of science and technology to facilitate the development of safe and effective biological products;
  • ensure the safety of biological products;
  • advance regulatory science and research; and
  • manage for organizational excellence and accountability.

"In facilitating product development, we are looking to see how we can be innovative, and in ensuring the safety of biological products we are using computational models to better inform ourselves on safety issues," Maloney said.

Discussing recent CBER product approvals, Maloney highlighted Hemacord, the first licensed hematopoietic progenitor cells-cord (HPC-C) cell therapy, which is indicated for use in hematopoietic stem cell transplantation procedures in patients with disorders affecting the hematopoietic (blood-forming) system. Maloney noted that Hemacord's approval was based on reliance on safety and effectiveness data submitted to a public docket and data submitted in the license application demonstrating compliance with other regulatory requirements. "This is the first approval of a license application for cord blood," Maloney said.

Mary Malarkey, director of CBER's Office of Compliance and Biological Quality, said CBER has a small inventory compared to FDA's Center for Drug Evaluation and Research and Center for Devices and Radiological Health. However, "We're seeing more and more actions and problems as a result of our bioresearch monitoring inspections and have issued more Notices of Initiation of Disqualification Proceedings and Opportunity to Explain than CBER has seen in 20 years," Malarkey said. "So we need to devote more time to these issues."

Dr. Celia Witten, director of CBER's Office of Cellular, Tissue and Gene Therapies, said her office has been averaging 120 to 140 annual submissions for investigational products. In December 2011, it finalized its guidance document Current Good Tissue Practices (CGTPs) for Manufacturers of Human Cells, Tissue and Cellular and Tissue-Based Products (HCT/Ps).

"Perhaps the most critical work we will do in FY 2012 is our draft guidance Preclinical Safety Assessment of Investigational Cellular and Gene Therapy Products. This is our year to make a big push to get it out. If it's not out this year, it'll be next year. It's a high priority," Witten said.

Defining 'Practice of Medicine.'

Panel member Mahinka said that for personalized medicine there has been an increased emphasis on the importance of a diagnostic to accompany a new biologic drug. "But there has been little guidance from FDA on the sequencing of review of the biologic and the targeted diagnostic. These reviews have been difficult because the usual situation is that the biologic and the diagnostic have been developed by different companies," Mahinka said.

In response, Maloney said FDA has issued draft guidance on companion diagnostics and recommended coapproval of drug and diagnostic, which she acknowledged has generated some concern (6 LSLR 323, 3/23/12).

"We agree the issue comes up," Witten said. "One thing worth thinking about is that just as we expect products to be defined by phase III review, we expect the same thing of devices. People may want to continue to develop the device during phase III for the drug, and FDA views it differently."

An audience member asked if FDA had issued or would issue better definitions of the difference between the "practice of medicine" and the development and manufacture of therapies that are subject to FDA review. He specifically referenced FDA's March 13, 2012, warning letter to New York-based IntelliCell Biosciences Inc. (6 LSLR 377, 4/6/12).

The letter stated that the company recovers and processes adipose tissue from donors for autologous use. Using ultrasonic cavitation, the company processes the lipoaspirate into a stromal vascular fraction known as IntelliCell adipose-derived stem cells. The IntelliCell product is administered to patients intravenously, or is injected into specific areas of the body, such as the lips, cheeks, knees, scalp, and/or buttocks. In the letter, FDA said that IntelliCell was required to have valid biologic license to market this product.

Pending Litigation

Malarkey said that from FDA's perspective the practice of medicine is the use of FDA-approved drugs. Since there is pending litigation, however, she said she would not comment further.

FDA filed suit Aug. 6, 2010, seeking an injunction in the U.S. District Court for the District of Columbia against Regenerative Sciences LLC, citing violations of current good manufacturing practice in the company's stem cell treatment for musculoskeletal and spinal injuries, which expands and reinjects a patient's stem cells (4 LSLR 761, 8/13/10). FDA has filed for summary judgment (5 LSLR 68, 1/28/11).

The Bloomfield, Colo., company argued that it was only engaged in the practice of medicine and said it welcomed the opportunity to determine whether the government has the right to restrict a patient and his or her physician from using a person's own stem cells to treat disease.

Witten noted that FDA has a "Tissue Reference Group" in place to answer questions on pre-Investigational Drug Application issues. "An individual wanting clarification as to whether an IDA or BLA is required could start there. There are a lot of case-by-case situations in biologics," Witten said.

Maloney concluded by stating that CBER is scheduled to join other parts of FDA in the White Oak offices in Silver Spring, Md., in 2014 and that it is beginning preparations for the move.

Reproduced with permission from Life Sciences Law & Industry Report, 6 LSLR 524 (May 4, 2012). Copyright 2012 by The Bureau of National Affairs, Inc. (800-372-1033) <>