AACT’s Advocacy Platform

FDA Public Hearing Important Information

September 12, 2016
9:00amto 5:00pm

September 13, 2016
9:00am to 5:00pm

The public hearing will be held at the following location:

National Institutes of Health Campus
Masur Auditorium
Building 10
9000 Rockville Pike
Bethesda, MD 20882

Purpose and Scope of the Meeting
The purpose of the public hearing is to obtain comments on the four draft guidance documents relating to the regulation of human cells, tissues, and cellular and tissue-based products (HCT/Ps) from a broad group of stakeholders, including tissue establishments, biological and device product manufacturers, health care professionals, clinicians, biomedical researchers, and the public.  For example, FDA would like comments on the scope of the four draft guidances, including the particular topics covered, the particular questions posed, whether there are additional issues for which guidance would be helpful, and whether FDA’s recommendations for each topic are sufficiently clear and consistent within and across documents to provide meaningful guidance to stakeholders.  In addition, FDA welcomes comments that will enhance the usefulness and clarity of these documents.  FDA recommends that comments exclude discussion of products that do not meet the definition of an HCT/P, such as platelet rich plasma and other blood products.  FDA will consider information it obtains from the public hearing in the finalization of the four draft guidance documents.

Submit electronic comments in the following way:

Federal eRulemaking Portal: http://www.regulations.gov

Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to http://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else’s Social Security number, or confidential business information. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted om http://www.regulations.gov.

If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Dr. Leslie Miller’s Presentation to the FDA Public Hearing

Dr Witten, Members of the Panel, Ladies and Gentlemen,

My name is Leslie Miller, and I am the Chairman of the Executive Committee of the Alliance for the Advancement of Cell Therapy. This organization is composed of patients, clinicians, and scientists interested in not only the advancement of this field, but the very responsible use of cell therapy. I speak today as a practicing cardiologist and clinical trialist with experience in over 100 FDA-approved clinical trials, including four current actively enrolling cell therapy trials.

I want to begin by thanking the FDA for responding to the very large interest demonstrated in this hearing by postponing the original date to today, doubling the time allotted for the Hearing from 1 to 2 days, utilizing this expanded venue, and allowing me to speak.

There is clearly very significant interest in the proposed Guidelines for Cell Therapy, largely because it involves the treatment of the biggest problem in US health care, and that is Chronic Disease. More money is spent on chronic disease care than any other single item in Federal or private health care, and also accounts for the greatest disability and loss of productivity. It is also a Worldwide problem, as the WHO last year changed their Number One priority for action from Acute Infection to Chronic Disease, based on the unparalleled pain, suffering, disability, and economic burden that now afflicts hundreds of millions of patients, and will impact many millions more with the advancing age of the population. This cost is not sustainable, and requires new solutions. Unlike drugs, which only treat symptoms of a disease, cell therapy attempts to harness the body’s native repair mechanisms to actually repair and regenerate damaged tissue and organs, with a goal of not only stabilizing, but reversing disease progression, and hopefully move toward cures. As such, it represents one of the most promising treatment options for most chronic diseases.

We acknowledge that the FDA is facing a very significant challenge in how to optimize the many rapid advances taking place with many diverse uses and types of cell therapy, while maintaining the health and the safety of products. We share this commitment to safety and highest standards for cell therapy. However, under the current regulations, research has become slow and almost prohibitively expensive, leading to trials that have often been under-powered to answer critical questions on efficacy, which delays and impedes progress in the field. We believe that the very pressing health problem of chronic disease warrants new approaches to regulation in order to meet this pressing challenge, and provide benefit for the millions of patients in need.

One new approach is embodied in the REGROW Act, which is about to be considered by Congress. This Bill is not intended to alter FDA’s oversight role over cell therapy, but provides enhanced flexibility and much quicker access for patients to only those cells and strategies that are shown to be both safe and reasonably effective in randomized Phase II trials, with increased numbers of subjects enrolled to really test the therapy being evaluated, and avoid the extremely high cost of Phase III trials.

There is ample precedent internationally for accelerated pathways and conditional approval for cell therapy in countries like Japan, China, many countries in Europe, and most recently, Canada. We are now behind these countries in our response to this important problem, and there does not seem to be a comparable sense of priority or urgency by the FDA. Acceleration of the approval process is feasible based on the substantial record of high degree of safety of particularly autologous cell therapy, with many meta-analyses having shown only a 2-4% incidence of any safety issue, which is 3-4 fold lower than the 15% average intolerance to any new drug.

The problem in this field is that the use of cell therapy has evolved rapidly from being available only in FDA-approved clinical trials, to essentially unregulated use in well over 500 clinics in this country, as well as a large number outside the US, by practitioners with highly variable training and competence. This has led to many valid criticisms of this unregulated use of cell therapy, although critics wrongly imply that all clinics are of similar and poor quality. These concerns and criticisms have led the FDA to seek an all-inclusive set of guidelines which would essentially shut down clinical access to cell therapy in the U.S. This would drive thousands of patients who are seeking cell therapy to offshore clinics, which are not easily accessible, and therefore disadvantage the poor and those with limited resources, and markedly diminish the chances of gaining the much needed increased data on the safety and efficacy of cell therapy.

We believe that there is a very reasonable alternative to the total suppression of cell therapy, which is the creation of a Registry of Cell Therapy. There is ample precedent of using a well-curated Registry even as a control group for many Phase II and III trials, including mechanical assist devices, as well as their very important value in providing important non-protocol, real-world experience with a given treatment, that may show outcomes that may differ from clinical trial data, both better and worse than reported.

Importantly, we believe that such a Registry could address most of the valid criticisms and concerns about the current unrestricted use of cell therapy.
In order to participate, a clinic would have to meet the following rigorous criteria:

1. TO ADDRESS CONCERNS ABOUT INCOMPLETE DATA: Agree to enroll every patient treated for every indication and provide de-identified data on indication, symptoms, demographics, etc.

2. TO ADDRESS THE VARIABLE QUALITY OF CELLS DELIVERED: Must obtain certification of cell prep lab (on-site) or vendor, with complete data on source, prep, type and number, quality and route of delivery.

3. TO ASSURE USE OF VALID TREATMENTS STRATEGIES: Use of only IRB approved protocols for every indication based on published data.

4. TO ADDRESS THE MAJOR CONCERN THAT PATIENTS GET VARIABLE AND POTENTIALLLY INFLATED EXPECTATIONS OF THERAPY: Propose the use of a novel, scripted narrative that can be reviewed and approved by the FDA, which would then be video taped and provided to each patient to assure fair and balanced information is given to every patient, with time to allow family members to review and ask questions of the provider to much more uniform and informed consent process. It would also include a consent to provide required follow-up data.

5. TO ADDRESS THE LACK OF RELIABLE/MEANINGFUL DATA:  Use of end points/metrics utilized in published clinical trials at uniform time points in every patient by trained/objective observers, to document both good and adverse outcomes for each indication.

6. TO ASSURE RELIABILITY AND INDEPENDENCE OF THE DATA:  Use of an independent company to control all data acquisition, storage and use.

7. TO ASSURE COMPLIANCE WITH DATA SUBMISSION: Agree to submit all data within 1 month of each uniform time or be subject to temporary suspension from further therapy until data is up to date.

8. ONE OF THE MOST IMPORTANT ASPECTS OF THE DATA IN THE REGISTRY: Complete transparency and the ability for the FDA to audit every aspect of the data including outcomes, as well as access for patients who are seeking cell therapy and identify the highest quality centers and their outcomes with real-time data available.

We have little doubt that this would significantly reduce the number of clinics providing cell therapy initially, but we believe that this could provide the FDA with the much needed high quality data on safety and efficacy of cell therapy, and allow continued access for patients at those clinics that are willing to meet these very high standards with enhanced confidence of providing a very high standard of care. The need is rapidly increasing and the time for a new approach is at hand.

We hope that the FDA will give serious consideration to this proposal.