Why is islet transplantation
still not available to the patients with Type 1 Diabetes in the US?
 
 

Islet transplantation is approved for clinical use worldwide... 

... Why not yet in the US?

"...because, human islets have been regulated as drugs, instead of being regulated as organ for transplantation in other developed countries worldwide..." 

...scientific evidence strongly supports need for the urgent regulatory update 

 

Dr. Camillo Ricordi

Professor of Surgery, Medicine, Biomedical Bioengineering, Immunology  at University of Miami

Director of the Diabetes Research Institute (DRI) and the Cell Transplant Center

expert, inventor and "father" of the field of islet transplantation 

"...anyone who is involved in the science, to say: "you should never change your mind", does not understand what  science is..." 

 

Dr. Anthony Fauci

Director of National Institute for Allergy and Infectious Disease

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  • Pancreatic islets are located in the human pancreas surrounded by the exocrine tissue.

  • Islets are micro-organs, with own unique structure and function, they are made of many different type of cells.

  • They have own blood vessels and nerves.

  • They are retrieved (isolated from the pancreas) and transplanted while their structure and function remains preserved- exactly like for whole organ transplantation.

Letter to the Secretary of Health and Human Services with

the request to regulate human islets as organs for transplantation

                                                                                                                       

May 4, 2021

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Letter to Editor: Pancreatic islet quality and potency cannot be verified as required for drugs: Reflection on the FDA review of the Biological Islet Application for Human Islets.

Transplantation 2021

                                                                                                                       

June 17, 2021

Islet Transplantation at a Crossroads - Need for Urgent Regulatory Update in the United States: Perspective Presented During the Scientific Sessions 2021 at the American Diabetes Association Congress 

Frontiers in Endocrinology in press

                                                                                                                       

December 2021

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American Diabetes Association Congress 2021

Regulatory and clinical hurdles facing Islet Transplantation in the US                                                                                                                                    

June 28th, 2021 

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watch the presentation below

Our reports and recommendation against BLA approval by the FDA for allogeneic pancreatic islet during the FDA Advisory Committee Meeting.                                                                                                                                    

April 15th, 2021 

  • During the Open Public Hearing Dr. Witkowski and Dr. Ricordi presented our report. 

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These are the reasons, why this is an urgent problem 

and need to be addressed immediatelly:    

 

  1. Patients with type 1 diabetes mellitus can die suddenly due to low blood sugar despite modern insulin therapy

Some diabetic patients and their families live in constant fear of sudden death due to low blood sugar. Their daily life is severely compromised. They are afraid to drive, work and live independently. 

They develop severe anxiety and depression.

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2.   Islet Transplantation can save those patients and prevent from      

      low blood sugars 

                                                                                                                               watch Stacy' story below 

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Islet transplantation restores normal blood glucose control. eliminates dangerous low blood sugars and allows patients to resume fully independent personal and professional life.

3.   FDA’s outdated regulations have created unnecessary barriers to access to islet transplantation and need to be updated

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In other countries Islet Transplantation has become a standard of care but this treatment is still not available in the USA

The "Islets for US" Collaborative

Recognizing an imminent demise of islet transplantation in the US:

Over last 10 years, we have witnessed a decline of  islet transplantation. More recently, access to this life saving therapy is threatened by the possibility of the commercialization of human pancreas and islets for clinical transplantation in the US .  

The FDA treating human islets as a biologic drug, is reviewing and likely grant a Biological License to a single for-profit company  to market human islets for transplantation in the US.

We are convinced that  this scenario will have negative consequences for the future of islet and organ transplantation and diabetes care for the US public,

We strongly believe that the regulations governing islets, their processing, and their transplantation need to urgently updated.

Our Goal

  • ·    Our collaborative is composed of over 50 experts and leaders in the field of islet and pancreas transplantation with a special interest in the treatment of type 1 diabetes mellitus who decided to stand up against the demise of islets transplantation in the US. Known as the "Islets for US" Collaborative we prepared a comprehensive report proposing solutions based on the most up-to-date research and state-of-the-art clinical experience.

  • ·    Our goal is to urgently motivate the FDA and the U.S. Government to change the current outdated regulations and policies. We propose that human islets be regulated as any other organ for transplantation- we want to protect them from commercialization and preserve the human pancreas and islets as public resources for the public good. We believe our proposal will also promote safe, effective, and affordable access to islet transplantation for millions of Americans with diabetes. It sounds ambitious but in reality we are just playing catch up to other developed countries, such as Canada, Europe, Japan, and Australia which already offer clinical islet transplantation to their patients !

 

Proposed solutions

Option 1

 

Regulation of allogeneic islets (micro organs) as any other organ for transplantation instead of as biologic drugs

 

Not only pancreas but also allogeneic islets as subparts of human organs are protected from the commercialization by the law in the US ( 1984 National Organ Transplantation Act, 42 U.S. Code § 274e (Prohibition of organ purchase). FDA's position is in conflict with that law, since it mandates conversion of the human organ (pancreas), or subparts of human pancreas (pancreatic islets), into a biologic drug for the purpose of the transplantation. FDA position would allow commercial, for profit manufactures of the human islets to benefit from altruistic human organ donation.

Based on the same act, allogeneic islets as subpart for human pancreas for transplantation should be regulated not by FDA but by the HRSA/OPTN/UNOS as other organs for transplantation in the US.

  • The Department of Health and Human Services may introduce reinforcement of the regulation of human pancreatic islets as any other organ and its parts for transplantation by the HRSA/OPTN in the next two of months, before a biological license for islets as a drug is issued by the FDA.​​

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Option 2

Introduction of the regulation of allogeneic islets as a tissue for transplantation solely under  the Section 361 of the Public Health Service (PHS) Act with the exemption from the Section 351 of the PHS.

This would require the FDA to update the interpretation of the regulations based on the current scientific knowledge and clinical practice in regard to allogeneic islets for transplantation. Unfortunately, the FDA has been reluctant and again, only the Secretary of the Department of Health and Human Services may direct the FDA to pursue the updates.

 

 

Specifically, experts call on FDA to:

1.   Recognize that short-term incubation of islet allografts prior to infusion does not alter their relevant        

       biological characteristics and that these cells are therefore not “more than minimally manipulated”;

2.   Update its regulations to allow islet allografts from suitably-matched unrelated donors to be regulated in the same manner as autologous or related-allogeneic donor cells.  

         

The substantially higher burden for unrelated islet allografts is not justified by the science and is not necessary to protect patients, but serves only to prevent patients from accessing this treatment in the U.S.

 

Specifically, 21 CFR 1271.10(a)(4)(ii)(b), which currently states: “Is for allogeneic use in a first-degree or second-degree blood relative” should be revised to state: “Is for use in immunologically-compatible donors and recipients.”  This language is more consistent with current clinical standards.

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Other countries

Contrary to the United States, many other countries regulate allogeneic islet cells as minimally-manipulated human tissue for transplantation .  In particular, according to the European Medicines Agency:

"...If the enzymatic digestion leads to isolation of functionally intact tissue units (e.g. pancreatic islets) or there is scientific evidence that the original structural and functional characteristics are maintained, the procedure is NOT considered substantial  manipulation..." (EMA ref)

Moreover, in 2011, European Committee for Advanced Therapies (CAT) considered that

  • autologous/allogeneic human islets of Langerhans were not an ATMP but are considered to fall under the provisions of the Tissues and Cells legislation.

  • Under this legislation, islet cells are neither considered a medicinal product, since the active substance, i.e., human tissues, cannot be commercialized or manufactured on an industrial scale for ethical and legal reasons. (ref)

What will happen after proposed regulatory update?

Experts highlight the numerous predicted positive effects of updating the regulation including:

  • Unnecessary and outdated regulatory requirements will be removed, but regulations necessary to protect patient safety will remain in place.

  • Main regulatory barrier will be eliminated for the implementation of the islet transplantation as a standard of care procedure.

  • Clinical oversight by the OPTN/UNOS as for any other organ transplantation would be implemented improving overall safety and efficacy of the procedure.

  • Islet transplantation would be more affordable by eliminating need for redundant and  unnecessary costly processing systems related to drug manufacturing control.

  • As more transplant centers would be able to meet the requirements, islet transplantation will be much more accessible for the patients.  

  • Human pancreas and islet for transplantation remain public resources which will promote organ donation and life-saving transplantation.

  • Research being more affordable will lead to further progress not only in islet transplantation but in cellular therapies and regenerative medicine overall.

Executive action required

The FDA has refrained from the required regulatory update, exemption of the allogeneic islets from drug related regulations​

Therefore in our opinion, the  shortest route to changing FDA’s current outdated policy is through the decision of  the Secretary of  the Health and Human Services to include and reinforce regulation of the allogeneic islets as subparts of human organ for transplantation under the National Organ Transplantation Act, and not by the FDA but by the HRSA/OPTN/UNOS as any other organ transplantation in the US.

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2015 University of Chicago

14 patients participated in islet transplantation clinical trial so others Americans could get access to this treatment one day too.

Some patients still do not need any insulin injections (off insulin) more than 7 years later

READ THOSE PATIENT STORIES