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 organs for transplantation as in all other developed countries worldwide..." 

...scientific evidence strongly supports need for the urgent regulatory update in the US, and the need for the islet regulation as organs... 

 

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


 
Pancreatic islets are micro-organs, yet 
FDA has been regulating human islets for transplantation as drugs

 

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

  • Islets are micro-organs, with own unique anatomy, 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 remain preserved- exactly like for whole organ transplantation.

The "Islets for US" Collaborative

Our collaborative is composed of over 50 experts and leaders in the field of islet and pancreas transplantation deeply concern about over 20-year lack of  the access to life saving islet transplantation for Americans with type 1 diabetes, severe hypoglycemic episodes and hypoglycemia unawareness

 

Therefore:

1. We have prepared a comprehensive report, which included a root-cause analysis of the existing problem.

2. We have identified major deficiencies in the current regulatory approach to the islets in the US, which lead to  the imminent demise of the entire field of islet transplantation, or alternatively to unsafe and detrimental for the field and patients, commercialization of the human pancreas and islets for clinical transplantation. 

3. Based on our analysis, we identified critical elements of the necessary regulatory update, which we propose to the FDA and HHS for considerations.

4. Instead of deficient islet regulation as drugs, we propose islet regulation under the existing regulatory framework for organ transplantation in the US ,under the UNOS and OPTN, along with components of the FDA regulations for human cell and tissue for transplantation exempt from the drug regulations. Proposed regulatory updated can be easy implemented by the decision of the Secretary of the HHS, as it was done previously for vascularized composite tissue.

 

5. Unfortunately, despite evidence and rationale we provided,  regulators do not see the need for the regulatory update. 

We wrote  several letters to the FDA, HHS, HRSA, CMS, UNOS and published 6 articles in peer -reviewed scientific journals voicing our concerns and providing arguments for the regulatory update.

We presented our position during the FDA Experts Advisory Committee Meeting in April 2021 and during the Scientific Sessions of the  American Diabetes AssociationCongress in June 20021. (see below)

 

Key negative consequences of the deficiencies in the current islet regulations

Imminent demise of islet transplantation in the US

Over last 10 years, we have witnessed a decline of  islet transplantation in the US, as the procedure remained limited only to experimental settings due to outdated islet regulations, Regulations of human islets as drugs preclude safe transition of the islet transplantation to the standard of care procedure available to diabetic patients in the US. Lack of the financial support system and reimbursment precludes any islet transplantation activity.

 

Reference:

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update. Am J Transplant, 2021, 21:1365–1375.

Deficiency of drug manufacturing procedures and regulations in the reassurance of islet quality and sterility. 

Recent scientific evidence and FDA's own report clearly indicate that the current regulation of human islets as drugs does not reassure safety and effectiveness of the therapy as intended to. Islet sterility and quality prior to transplant cannot be reassured despite the application of the drug manufacturing procedures and regulations during islet preparation for the transplantation. 

Reference:

Pancreatic Islets Quality and Potency Cannot be Verified as Required for Drugs. Transplantation 2021, Jul 1, 

 

Imminent threat of the commercialization of human pancreas and islets for clinical transplantation without proper reassurance of islet quality and patient safety

Despite above,  the FDA still considers granting a Biological License to a single for-profit company  to market human islets for transplantation in the US, which would further compromise patient safety, lead to unsafe and detrimental commercialization of human pancreas and islets for clinical transplantation in the US .  

 

The continuation the islet regulation as drugs has multiple negative consequences for the future of islet and organ transplantation and diabetes care for the US public.

 

Reference:

  1. Regulatory updates are needed to prevent the commercialization of islet transplantation in the United States. Am J Transplant (2021) 21:2620–2622.

  2. Islet transplantation in the United States – Quo Vadis? An interview with Camilo Ricordi (CR), Ali Naji (AN), Peter Stock (PS), Piotr Witkowski (PW). Transpl Int (2021) 34:1177–1181.  

  3. Arguments against the Requirement of a Biological License Application for Human Pancreatic Islets: The Position Statement of the Islets for US Collaborative Presented during the FDA Advisory Committee Meeting. J Clin Med (2021) 10:2878.

  4. 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, 2022 in press. 

 
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

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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.

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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Letter to the Secretary of Health and Human Services with

the request to regulate human islets as organs for transplantation

                                                                                                                       

May 4, 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

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

FDA Advisory Committee Meeting

 

April 15th, 2021

 

Our recommendations against BLA approval by the FDA for allogeneic pancreatic islet.                                                                                                         

Our publications

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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

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Our Mission

  •  To educate about the negative consequences of the current regulations of the pancreatic islet for transplantation in the US and

  • To promote an appropriate regulatory update for safe and effective islet transplantation in the US

 

Our goal​

 

To stimulate the FDA and the U.S. Government to introduce appropriate 

regulatory update  regarding islets for transplantation under the regulatory framework developed for organ transplantation in the US.

 

This would: 

  • allow for safe and effective islet transplantation in the US

  • promote safe, effective, and affordable access to islet transplantation for millions of Americans with diabetes.

  • preserve the human pancreas and islets as public resources for the public good preventing from unsafe and detrimental commercialization of human islet  transplantation. 

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 !

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 8 years later

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