scholarly journals 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

2021 ◽  
Vol 10 (13) ◽  
pp. 2878
Author(s):  
Piotr Witkowski ◽  
Jon Odorico ◽  
Jordan Pyda ◽  
Roi Anteby ◽  
Robert Stratta ◽  
...  
Keyword(s):  
Advisory Committee ◽  
Islet Transplantation ◽  
Current System ◽  
Alternative Pathway ◽  
Position Statement ◽  
Cellular Tissue ◽  
Human Islets ◽  
Negative Consequences ◽  
License Application ◽  
The Us

The Food and Drug Administration (FDA) has been regulating human islets for allotransplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA’s position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021. We provided evidence that BLA requirement and drug related regulations are inadequate in reassuring islet product quality and potency as well as patient safety and clinical outcomes. As leaders in the field of transplantation and endocrinology under the “Islets for US Collaborative” designation, we examined the current regulatory status of islet transplantation in the US and identified several anticipated negative consequences of the BLA approval. In our commentary we also offer an alternative pathway for islet transplantation under the regulatory framework for organ transplantation, which would address deficiencies of in current system.

scholarly journals Islets 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

2022 ◽  
Vol 12 ◽  
Author(s):  
Piotr Witkowski ◽  
Louis H. Philipson ◽  
John B. Buse ◽  
R. Paul Robertson ◽  
Rodolfo Alejandro ◽  
...  
Keyword(s):  
United States ◽  
Islet Transplantation ◽  
Organ Procurement ◽  
The United States ◽  
Regulatory Framework ◽  
Human Organs ◽  
Cell Tissue ◽  
License Application ◽  
The Us ◽  
Drug Manufacturing

Clinical islet allotransplantation has been successfully regulated as tissue/organ for transplantation in number of countries and is recognized as a safe and efficacious therapy for selected patients with type 1 diabetes mellitus. However, in the United States, the FDA considers pancreatic islets as a biologic drug, and islet transplantation has not yet shifted from the experimental to the clinical arena for last 20 years. In order to transplant islets, the FDA requires a valid Biological License Application (BLA) in place. The BLA process is costly and lengthy. However, despite the application of drug manufacturing technology and regulations, the final islet product sterility and potency cannot be confirmed, even when islets meet all the predetermined release criteria. Therefore, further regulation of islets as drugs is obsolete and will continue to hinder clinical application of islet transplantation in the US. The Organ Procurement and Transplantation Network together with the United Network for Organ Sharing have developed separately from the FDA and BLA regulatory framework for human organs under the Human Resources & Services Administration to assure safety and efficacy of transplantation. Based on similar biologic characteristics of islets and human organs, we propose inclusion of islets into the existing regulatory framework for organs for transplantation, along with continued FDA oversight for islet processing, as it is for other cell/tissue products exempt from BLA. This approach would reassure islet quality, efficacy and access for Americans with diabetes to this effective procedure.

Heparin induces amyloid formation in cultured human isletss

2007 ◽  
Vol 30 (4) ◽  
pp. 92 ◽  
Author(s):  
K Potter ◽  
K Park
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Islet Transplantation ◽  
Islet Cell ◽  
Human Islets ◽  
Fibril Formation ◽  
Amyloid Formation ◽  
Secretory Product ◽  
Islet Amyloid ◽  
Heparin Sulfate

Background: Pancreatic islet transplantation offers improved glycemic control in type 1 diabetic patients above standard insulin therapy, ideally minimizing macro- and microvascular complications of diabetes mellitus. However success is limited thus far, with fewer than 10% of patients retaining insulin independence at two years post-transplantation. In addition to immune rejection, many non-immune factors may promote long-term graft secretory dysfunction and loss of viable graft mass. One such important non-immune factor may be the formation of islet amyloid, a pathologic lesion of the islet in type 2 diabetes that contributes to the progressive loss of b cells in that disease and that has been shown to form rapidly in human islets transplanted into NOD.scid mice. Amyloid deposits are composed primarily of the b cell secretory product islet amyloid polypeptide (IAPP), are cytotoxic, and develop in environments in which b cells are stressed. Heparin sulfate is used as an anti-coagulant in clinical islet transplantation and to prevent the instant blood-mediated inflammatory reaction (IBMIR), which occurs upon contact between islets and blood and may destroy a substantial proportion of the grafted islet mass. However, heparin is also known to stimulate amyloid fibril formation. Methods: To determine whether heparin may enhance amyloid formation in human islets and contribute to graft failure, we cultured isolated human islets in the presence or absence of heparin sulfate (42 and 420 units/ml) for 2 weeks in 11.1 mM glucose. Results: Histological assessment of sections of cultured islets for the presence of amyloid (by thioflavin S staining) revealed a marked, concentration-dependent increase in amyloid deposition following culture in the presence of heparin. Quantitative analysis of these sections showed that the proportion of islet area comprised of amyloid was increased approximately 2-fold (0.15%±0.12% vs 0.46%±0.15% of islet area) following culture in 42 units/ml heparin, and the proportion of islets in which amyloid was detectable (amyloid prevalence) was also increased (35%±24% vs 68%±10% of islets). At 420 units/ml heparin, the amyloid area was even greater (0.23%±0.15% vs 0.97%±0.42% of islet area) as was the amyloid prevalence (53%±29% vs 81%±14% of islets). To affirm that heparin can stimulate IAPP fibrillogenesis and enhance IAPP toxicity, we incubated synthetic human IAPP in the presence of heparin and measured amyloid formation in real time by thioflavin T fluorescence, and cell toxicity by Alamar blue viability assay in transformed rat (INS-1) ß-cell cultures. Heparin stimulated IAPP fibril formation and increased death of INS-1 cells exposed to IAPP (78.2%±10.9% vs 51.8%±12.2% of control viability), suggesting that heparin stimulates IAPP aggregation and toxicity. Remarkably, preliminary assessment of human islets cultured in heparin did not show increased islet cell death by TUNEL staining or loss of insulin immunostaining. Conclusion: In summary, heparin increases amyloid formation in cultured human islets. Although our preliminary data does not suggest that heparin-induced amyloid formation contributes to islet cell death, we speculate that heparin-induced amyloid formation may contribute to graft dysfunction and that caution should be used in the clinical application of this drug in islet transplantation.

scholarly journals Regulatory updates are needed to prevent commercialization of islet transplantation in the US

2021 ◽  
Author(s):  
Piotr Witkowski ◽  
Rolf N. Barth ◽  
Anthony Japour ◽  
Gail Javitt ◽  
Jordan S. Pyda ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
The Us

scholarly journals Private in-patient psychiatry in the USA

2014 ◽  
Vol 38 (5) ◽  
pp. 230-235 ◽  
Author(s):  
L. Mark Russakoff
Keyword(s):  
Managed Care ◽  
Healthcare System ◽  
Affordable Care Act ◽  
Private Practice ◽  
Psychiatric Care ◽  
Current System ◽  
Baby Boomer Generation ◽  
Current State ◽  
The Us ◽  
The Usa

SummaryThe US healthcare system is in the midst of major changes driven by four forces: the growing consensus in the country that the current system is financially unsustainable; managed care and parity legislation; the Affordable Care Act 2010; and the ageing of the ‘baby boomer’ generation. How these forces will combine and interact is unclear. The current state of in-patient psychiatric care and trends affecting the private practice of in-patient psychiatry over the next few years will be described.

Effective Use of Industrial Advisory Boards

1997 ◽  
Vol 11 (4) ◽  
pp. 236-238
Author(s):  
Walter W. Buchanan ◽  
Willard D. Bostwick
Keyword(s):  
Advisory Committee ◽  
Growth And Development ◽  
Engineering Technology ◽  
Advisory Boards ◽  
Engineering And Technology ◽  
The Us ◽  
Effective Use

The Technology Accreditation Commission (TAC) of the US Accreditation Board for Engineering and Technology (ABET) stipulates that each accredited programme must have an industrial advisory committee composed of industrial representatives. However, how do we ensure that these committees contribute significantly to the growth and development of engineering technology programmes as a means of ensuring technical currency of the programme and the maintenance of close liaison with the employing industries?

scholarly journals Controversial advertising of medicines. A comparison between Poland and the United States

2018 ◽  
Vol 21 (5) ◽  
pp. 67-79
Author(s):  
Marta Makowska
Keyword(s):  
United States ◽  
Prescription Drugs ◽  
The United States ◽  
The European Union ◽  
Negative Consequences ◽  
Direct To Consumer ◽  
Law And Ethics ◽  
The Us ◽  
The Law ◽  
Direct To Consumer Advertising

For many years, the subject of aggressive marketing campaigns conducted by pharmaceutical companies has been raised in Poland. Drug ads are everywhere, on television, the radio, magazines and on the Internet. Therefore, it is extremely important is to ensure both their legal and ethical dimension. This article will present the differences between direct-to-consumer advertising of medicines in Poland and in the US. The dissimilarities result mainly from differences in legislation. In Poland, the law is much stricter than in the US. For example, in the United States companies are allowed to advertise prescription drugs directly to patients. In the whole of the European Union, and thus in Poland, it is strictly prohibited. The article will also present other regulations existing in Poland and in the United States and it will compare them. It will offer examples of violations of the law and ethics in the advertising of medicine in both countries. Lastly, it will briefly outline the negative consequences of unacceptable pharmaceutical marketing.

scholarly journals EVOLUTION OF US POLICY TOWARD IRAN’S NUCLEAR PROGRAM IN XXI CENTURY: FROM PRESIDENT BUSH TO PRESIDENT TRUMP

2020 ◽  
pp. 23-33
Author(s):  
P. Sinovets ◽  
V. Gergiieva
Keyword(s):  
Negative Consequences ◽  
International Treaties ◽  
Future Prospects ◽  
Donald Trump ◽  
Nuclear Program ◽  
George Bush ◽  
Comprehensive Plan ◽  
The Us ◽  
Nuclear Issue ◽  
President Bush

Since 2002 until now, the Iranian nuclear program remains one of the hottest international problems despite the efforts of three US presidential administrations, which ruled during this time to solve the Iranian issue. This article analyses and compares the policy toward Iran of three US presidents George Bush, Barack Obama, and Donald Trump, discusses the positive and negative consequences of their attempts to solve the Iranian nuclear issue, and outlines the future prospects of US-Iran communication over the nuclear deal. President Trump's policy on Iran was somewhat similar to that of President Bush, both presidents rejected the policy of any concessions to Iran and focused on the policy of pressure. The US withdrawal from the JCPOA influenced not only the relations between the US and Iran, but also the relations of European countries, as since its release in 2018, Europe has tried to save the JCPOA and deter Iran from resuming its nuclear program. In general, Trump's policies not only canceled the nuclear deal, which was the result of long negotiations by the Obama administration, but also complicated further negotiations with Iran. Despite the victory of Democrat Joe Biden, who is a follower of Obama's policies, signing a new agreement with Iran may be even more difficult than it was in 2013-2015, because Iran's missile program has become even more developed, as well as distrust of international treaties as well. The article analyzes the possible consequences of Trump's policies and options for returning to dialogue and agreement. The next crucial stage in Iran-US relations is the upcoming elections in Iran in 2021, the results of which will affect the readiness of any concessions to ease sanctions and establish a dialogue. Key words: Iranian nuclear program, Joint Comprehensive Plan of Action (JCPOA), Nonproliferation Treaty (NPT), economic sanctions.

scholarly journals Warlords, the United States, and the state of anarchy in Afghanistan

2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Ahmad Shah Azami
Keyword(s):  
United States ◽  
The United States ◽  
State Building ◽  
The State ◽  
Negative Consequences ◽  
Human Rights Abuses ◽  
Illegal Mining ◽  
The Us ◽  
The Government ◽  
The Impact

As part of its “War on Terror”, the United States (US) provided immense sums of money and advanced equipment to Afghan warlords in order to defeat and dismantle the Taliban and al-Qaeda in Afghanistan. Nearly two decades after the 2001 US-led intervention in Afghanistan that toppled the Taliban regime, the US continues supporting the warlords in various ways. As the intervention was also aimed at establishing a functioning state and reconstruction of the war-torn country, the US needed the support of local warlords to achieve its goals. However, over time, warlords and warlordism became a major challenge to the postTaliban state-building project and in many ways undermined the overall security and the state monopoly on violence. These warlords, who had been mostly expelled and defeated by the Taliban regime, returned under the aegis of the B52 bombers, recaptured parts of the country and reestablished their fiefdoms with US support and resources. They not only resist giving up the power and prestige they have accumulated over the past few years, but also hamper the effort to improve governance and enact necessary reforms in the country. In addition, many of them run their private militias and have been accused of serious human rights abuses as well as drug trafficking, arms smuggling, illegal mining and extortion in the areas under their control or influence. In many ways, they challenge the government authority and have become a major hurdle to the country’s emerging from lawlessness and anarchy. This paper explores the emergence and reemergence of warlords in Afghanistan as well as the evolution of chaos and anarchy in the country, especially after the US-led intervention of late 2001. It also analyzes the impact of the post-9/11 US support to Afghan warlords and its negative consequences for the overall stability and the US-led state-building process in Afghanistan.

Biosimilar epoetin for cancer and chemotherapy-induced anaemia in the US

2021 ◽  
Vol 10 (3) ◽  
pp. 122-122
Author(s):  
Charles L Bennett
Keyword(s):  
Advisory Committee ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Safety And Efficacy ◽  
Biological Drug ◽  
Drug Products ◽  
Fda Approval ◽  
The Us ◽  
Approval Letter

Biosimilars are biological drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety and efficacy. Biosimilar epoetin received US Food and Drug Administration (FDA) approval in 2018 [1]. The manufacturer received an FDA non-approval letter in 2017, despite receiving a favourable review by the FDA’s Oncologic Drugs Advisory Committee (ODAC) and an FDA non-approval letter in 2015 for an earlier formulation.

Predicting Measles Susceptibility

PEDIATRICS ◽  
1984 ◽  
Vol 73 (6) ◽  
pp. 871-873
Author(s):  
LORING G. DALES ◽  
JAMES CHIN
Keyword(s):  
Public Health ◽  
Health Service ◽  
Advisory Committee ◽  
Virus Vaccine ◽  
Measles Virus ◽  
Public Health Service ◽  
Measles Vaccine ◽  
Measles Outbreak ◽  
The Us ◽  
History Of

Elsewhere in this issue, Scott et al1 present results of their study which found that the historical criteria developed by the US Public Health Service Immunization Practices Advisory Committee (ACIP) for detecting students who were susceptible to measles performed very poorly in a school measles outbreak. The ACIP criteria designate as susceptible persons born since 1956 who have no documentation of immunization, who have no physician-Venified history of measles infection, who last received measles vaccine before their first birthday, or who were last immunized (at age 12 months or older) before 1968 with measles virus vaccine that could have been either live or inactivated.

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