scholarly journals Navigating the Regulatory Pathways and Requirements for Tissue-Engineered Products in the Treatment of Burns in the United States

2020 ◽  
Author(s):  
Kimberly Belsky ◽  
Janice Smiell
Keyword(s):  
United States ◽  
The United States ◽  
Biologically Active ◽  
Class Iii ◽  
Skin Substitutes ◽  
Burn Treatment ◽  
Regulatory Pathways ◽  
Biologics License Application ◽  
License Application ◽  
Promotional Materials

Abstract In the burn treatment landscape, a variety of skin substitutes, human tissue-sourced products, and other products are being developed based on tissue engineering (ie, the combination of scaffolds, cells, and biologically active molecules into functional tissue with the goal of restoring, maintaining, or improving damaged tissue or whole organs) to provide dermal replacement, prevent infection, and prevent or mitigate scarring. Skin substitutes can have a variety of compositions (cellular vs acellular), origins (human, animal, or synthetically derived), and complexities (dermal or epidermal only vs composite).The regulation of tissue-engineered products in the United States occurs by one of several pathways established by the US Food and Drug Administration, including a Biologics License Application, a 510(k) (Class I and Class II devices), Premarket Approval (Class III devices), or a human cells, tissues, and cellular and tissue-based products designation. Key differentiators among these regulatory classifications include the amount and type of data required to support filing. For example, a Biologics License Application requires a clinical trial(s) and evaluation of safety and efficacy by the Center for Biologics Evaluation and Research. Applicable approved biologic products must also comply with submission of advertising and promotional materials per regulations.This review provides a description of, and associated requirements for, the various regulatory pathways for the approval or clearance of tissue-engineered products. Some of the regulatory challenges for commercialization of such products for the treatment of burns will be explored.

Comparison of regulatory pathways for the approval of advanced therapies in the European Union and the United States

Cytotherapy ◽  
2021 ◽  
Vol 23 (3) ◽  
pp. 261-274
Author(s):  
Carolina Iglesias-Lopez ◽  
Mercè Obach ◽  
Antonio Vallano ◽  
Antonia Agustí
Keyword(s):  
United States ◽  
European Union ◽  
The United States ◽  
The European Union ◽  
Regulatory Pathways ◽  
Advanced Therapies

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.

Use of Skin Substitutes in Adult Canadian Burn Centres

1997 ◽  
Vol 5 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Richard A Hopper ◽  
Judy Knighton ◽  
Joel Fish ◽  
Walter Peters
Keyword(s):  
United States ◽  
Donor Site ◽  
The United States ◽  
Human Cadaver ◽  
Research Development ◽  
Skin Substitutes ◽  
Private Companies ◽  
Pig Skin ◽  
Human Cadaver Skin ◽  
Cadaver Skin

Seventeen Canadian adult burn centres were surveyed to determine the pattern of use, cost and availability of nine skin substitutes. An equal number of centres in the United States with comparable bed capacities were approached for comparison. Eighty-eight per cent of the Canadian centres and 76% of the United States centres responded to the questionnaire. Human cadaver skin, pig skin and Biobrane were used by approximately twice as many United States centres as Canadian centres. Cultured epidermal autografts (CEAs) were used by 20% of the Canadian centres and 15% of the American centres. Opsite, Tegaderm and Duoderm were used widely in both countries. Alloderm was used only in the United States, and amnion was not used in either country. The most common use of each substitute varied among centres, however, the pattern of use was comparable between the two countries, with the exception that Biobrane was not used in Canada to cover donor site wounds. In the United States, 60% of cadaver skin and all CEAs were purchased from private companies, whereas use of these two relatively expensive skin substitutes in Canada was restricted to centres with access to hospital-affiliated skin banks or laboratories. With the dependence of Canadian centres on noncommercial sources of biological skin replacements, research development in established skin banks should be encouraged, and regional discrepancies regarding access to these facilities addressed.

Regulatory Assessment of Premarket Approval of Medical Devices in US and EU

2017 ◽  
Vol 9 (04) ◽  
Author(s):  
M.P. Venkatesh ◽  
Divya Bandla
Keyword(s):  
United States ◽  
European Union ◽  
Medical Devices ◽  
The United States ◽  
The European Union ◽  
Class Iii ◽  
Risk Class ◽  
Class Iib ◽  
Set Up ◽  
Premarket Approval

The demand for medical devices globally has raised the attention of government regulatory bodies to ensure the safety and effectiveness of these products. Developed markets, such as the United States and European Union, have set up wellestablished regulatory systems for medical devices, which have consistently been amended to accommodate the changing requirements of safety and the trend of globalization. The way in which devices are regulated in the European Union is very different from that of United States, especially in terms of the clinical data required for premarket approval. This has introduced significant differences in time-to-market approval for both United States and European Union, particularly in the case of high-risk Class III and Class IIb implantable devices. Systems for approving new medical devices must provide pathways to market important innovations besides ensuring that patients are adequately protected. To achieve these goals, the United States and the European Union use a combination of premarket testing and postmarket vigilance but with some marked contrasts in their approaches. Features of both environments require reform, as well as continuing research to assess policy changes which will benefit device manufacturers to develop devices which can be marketed both in US and EU simultaneously

The Status of Acellular Pertussis Vaccines: Current Perspective

PEDIATRICS ◽  
1991 ◽  
Vol 88 (2) ◽  
pp. 401-405
Author(s):  
Keyword(s):  
United States ◽  
Pertussis Toxin ◽  
Recombinant Dna ◽  
The United States ◽  
Biologically Active ◽  
Current Status ◽  
Chemical Agent ◽  
Protein Antigens ◽  
Recombinant Dna Technology ◽  
Acellular Vaccines

Clinical studies of component ("acellular") pertussis vaccines have been undertaken in recent years, and several acellular vaccines have been used in Japan for 10 years. The Committee has reviewed these trials and related data and herein provides its assessment regarding the current status of the acellular vaccines and their possible use in the United States. The pertussis vaccines in current use in the United States are prepared from whole cells of a strain of Bordetella pertussis that is grown in broth medium, harvested by centrifugation, and killed or partially detoxified by heat or by the addition of a chemical agent, such as thimerosal, or by a combination of these methods. In contrast, the acellular vaccines developed in Japan and used in that country since 1981 contain one or more antigens derived from biologically active components of the B pertussis organism.1 An inactivated form of lymphocytosis promoting factor (LPF), also known as pertussis toxin and a variety of other synonyms, is a frequent component of acellular pertussis vaccines, as are filamentous hemagglutinins (FHA). Other constituents included in acellular vaccines are agglutinogens, a term denoting a variety of protein antigens on the surface of the B pertussis organism. Of the agglutinogens, a 69-kd outer membrane protein, when injected into neonatal mice, protects against B pertussis challenge.2 Acellular vaccines also have recently been derived from mutant pertussis toxin molecules prepared with recombinant DNA technology.3 The acellular vaccines produced in Japan have been classified into two types: B type, which contains LPF and FHA in roughly equal amounts; and T type, which contains mostly FHA but some LPF and agglutinogens.1,4

Evaluation of Commercially Available Knee Cartilage Restoration Techniques Stratified by FDA Approval Pathway

2021 ◽  
pp. 036354652110372
Author(s):  
Andrew Scott Gudeman ◽  
Betina B. Hinckel ◽  
Lasun Oladeji ◽  
Taylor E. Ray ◽  
Wayne Gersoff ◽  
...  
Keyword(s):  
United States ◽  
Cartilage Repair ◽  
The United States ◽  
Regulatory Pathway ◽  
Knee Cartilage ◽  
Level Of Evidence ◽  
Regulatory Pathways ◽  
Levels Of Evidence ◽  
Pubmed Database ◽  
Level 1

Background: Commercially available products used in knee cartilage reconstructive and restorative surgical practices fall under unique US Food and Drug Administration (FDA) regulatory pathways that determine the level of evidence required to market each product. Purpose: To evaluate the levels of evidence in the literature supporting commercially available cartilage repair procedures stratified by FDA regulatory pathway (section 351 vs section 361 of “Human Cells, Tissues, and Cellular and Tissue-Based Products” [HCT/P] in the Code of Federal Regulation) with the hypothesis that products requiring approval under a stringent regulatory pathway (351 HCT/P) have higher levels of evidence in the literature supporting use and that products with a less stringent regulatory pathway (361 HCT/P) have a higher number of products available for use in the United States. Study Design: Systematic review; Level of evidence, 4. Methods: A search of the PubMed database was performed to identify all peer-reviewed articles pertaining to either allograft or autologous cartilage repair technologies. Predefined inclusion and exclusion criteria were used to find clinical, preclinical, and laboratory studies while excluding duplicates, systematic reviews, and products not available in the United States. Articles were categorized by regulatory pathway (351 and 361 HCT/P), and variables including publication year, type of publication, level of evidence, and number of publications were analyzed. Results: After application of predefined criteria, 470 of 1924 articles were included in this study. The 351 HCT/P group was composed entirely of autologous chondrocyte implantation (ACI) technology; 94% of the 361 HCT/P group was composed of osteochondral allografts (OCA). The articles regarding 351 HCT/P were more likely to be clinical in nature than the articles on 361 HCT/P (80% vs 48%, respectively; P = .0001) and entailed significantly more level 1 studies (25 vs 0, respectively; P < .0001). Twice as many articles in the 351 HCT/P group were published in the American Journal of Sports Medicine compared with the 361 HCT/P group (71 vs 38, respectively; P = .18). Conclusion: Both ACI and OCA have robust evidence supporting their use, whereas the remaining regulated products have little or no supporting evidence. Technologies regulated by 351 HCT/P were more likely to be level 1 clinical studies and published in the highest impact journal. The 361 HCT/P pathway regulated many more products, with fewer articles supporting their use.

Neurophysiological and Behavioral Responses of Ixodes scapularis to host odors

2020 ◽  
Author(s):  
Tanya Josek ◽  
Jared Sperrazza ◽  
Marianne Alleyne ◽  
Zainulabeuddin Syed
Keyword(s):  
United States ◽  
Ixodes Scapularis ◽  
Land Development ◽  
The United States ◽  
Biologically Active ◽  
Impact Factors ◽  
Sensory Physiology ◽  
Olfactory Sensilla ◽  
Haller's Organ ◽  
Different Doses

ABSTRACTThe black-legged tick, Ixodes scapularis (Ixodida, Ixodidae), is one of the major disease vectors in the United States and due to multiple human impact factors, such as decreasing forest size for land development and climate change, it has expanded its range and established across the United States. Throughout the life cycle, ticks locate hosts for their blood-meal and although the ecologies of this tick and their hosts have been studied in depth, the sensory physiology behind host location largely remains unexplored. Here we report establishing a robust paradigm to isolate and identify odors from the natural milieu for I. scapularis. We performed single sensillum recordings (SSR) from the olfactory sensilla on the tick tarsi, and used the SSR system as biological detector to isolate natural compounds that elicited biological activity. The SSR setup was further tested in tandem with gas chromatography (GC) wherein the ticks’ olfactory sensillum activity served as a biological detector. The GC-SSR recordings from the wall pore sensilla in the Haller’s organ, and further identification of the biologically active deer glad constituents by GC-mass spectrometry (GC-MS) revealed methyl substituted phenols as strong chemostimuli, as compared to ethyl or propyl substitutions. Strongest electrophysiological activity was elicited by meta-cresol followed by para-cresol. Ethyl- and propylphenols with any of the three, ortho, meta or para substitutions, did not induce any neurophysiological activity. Finally, a behavioral analysis in a dual-choice olfactometer of all these phenols at three different doses revealed no significant behavioral response, except for p-cresol at −3 dilution Overall, this study contributes to our understanding of I. scapularis tick’s neurophysiology and provides a robust platform to isolate and identify natural attractants and repellents.

The Wilderness Experience Program Industry in the United States: Characteristics and Dynamics

1998 ◽  
Vol 21 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Greg Friese ◽  
John C. Hendee ◽  
Mike Kinziger
Keyword(s):  
United States ◽  
Organizational Development ◽  
Personal Growth ◽  
The United States ◽  
Multiple Sources ◽  
Wilderness Experience ◽  
Promotional Materials ◽  
Wilderness Experience Program ◽  
Outdoor Programs

Wilderness experience programs (WEPs) are organizations that conduct outdoor programs in wilderness or comparable lands for purposes of personal growth, therapy, rehabilitation, education, or leadership/organizational development. More than 700 potential WEPs were identified through search of multiple sources and then surveyed, with promotional materials and response forms received from 70 percent of them. From these data WEPs are characterized as to the number of trips offered per year, number of clientele served, kind of areas used, a typology to categorize how they used the wilderness was developed — whether as a teacher or as a classroom, and a directory of WEPs was compiled. Dynamics of the WEP industry are inferred from these data, other studies, and the literature.

Pinellas County Resource Recovery Facility Capital Replacement Project: One Year of Improved MSW Throughput and Electrical Generation

2005 ◽  
Author(s):  
Thomas M. White ◽  
Donald J. Castro ◽  
Robert Hauser
Keyword(s):  
United States ◽  
Resource Recovery ◽  
The United States ◽  
Waste To Energy ◽  
Class Iii ◽  
Pinellas County ◽  
Energy Plant ◽  
One Year ◽  
Electrical Generation ◽  
Capital Replacement

In May of 2003, the 3,150 TPD Pinellas County Resource Recovery Facility (PCRRF), the largest waste-to-energy plant in the United States, reached its 20-year milestone. The PCRRF is located in St. Petersburg, Florida, on a 705 acre (1.1 square mile) site owned by Pinellas County and known as “Bridgeway Acres”. The PCRRF has been owned by Pinellas County, operated by Wheelabrator Pinellas, Inc. (WPI) and monitored by HDR Engineering, Inc. since its inception. In addition to the PCRRF, the County operates both Class I and Class III landfills on the site.

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