Cell Therapy: Types, Regulation, and Clinical Benefits

Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non–stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review article, we delineate the vast types of cell therapy, including stem cell-based and non–stem cell-based cell therapies, and create the first-in-literature compilation of the different “multicellular” therapies used in clinical settings. Besides providing the nuts and bolts of FDA policies regulating their use, we discuss the benefits of cell therapies reported in 3 therapeutic areas—regenerative medicine, immune diseases, and cancer. Finally, we contemplate the recent attention shift toward combined therapy approaches, highlighting the factors that render multicellular therapies a more attractive option than their unicellular counterparts.

Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin Delivery

Objective. The objective of this article is to provide a high-profile review and discussion on the study design and statistical analysis of pivotal clinical trials conducted to demonstrate the safety and effectiveness of closed-loop investigational artificial pancreas device systems (APDSs) in premarket approval applications. Methods. The United States Food and Drug Administration (FDA) guidance on the content of investigational device exemption and premarket approval applications for APDSs is reviewed with special emphasis on study design and statistical analysis of the pivotal clinical trials. The two pivotal studies for the MiniMed 670G hybrid closed-loop system by Medtronic in their premarket approval application are summarized and discussed. Results. The United States FDA established detailed recommendations on the study design and statistical analysis of pivotal clinical trials for the industry that seek market investigational APDSs and for FDA scientific reviewers that regulate the device applications. The recommendations cover specifics regarding patient population, clinical endpoints, and strategies for data analysis. However, the two pivotal studies that demonstrated the effectiveness of the FDA-approved MiniMed 670G hybrid closed-loop system were not typical randomized controlled trials as per FDA recommendations. Conclusion. The development and regulation of investigational APDSs require careful and sophisticated clinical study designs and data analysis in premarket approval applications. The regulatory evaluation process of the APDSs is rather complicated since the devices consist of multiple components that collaboratively function to mimic human pancreases.

RESEARCH: Evaluation of Orthopedic Hip Device Recalls by the FDA from 2007 to 2017

Background: Medical device recalls have increased in the previous two decades. Orthopedic devices are estimated to constitute 12% of all medical devices recalled. Medical devices enter the market via the Food and Drug Administration's (FDA's) premarket approval (PMA) or 510(k) pathways. This article evaluates orthopedic hip device recalls between Jan. 1, 2007, and Dec. 31, 2017. We hypothesized that the 510(k) approval process would have substantially higher recall rates for defective devices. Methods: The FDA's device recall database was queried for all orthopedic hip devices from Jan. 1, 2007, to Dec. 31, 2017. Each recall included product description, recall number, device class, date of recall posting, date of recall termination, manufacturer, FDA-determined cause for recall, number of recalled units, distribution, product classification, and method of approval [510(k), PMA, or unspecified]. Results: In total, 774 orthopedic hip devices were recalled between Jan. 1, 2007, and Dec. 31, 2017. The 510(k) approval process constituted 85% of hip device recalls. The most common FDA-determined cause of hip device recalls was device design, which constituted 37% of 510(k)-approved device recalls but only 6% of PMA-approved device recalls. The most recalled hip devices were hip prostheses. Orthopedic hip device recalls have shown a decrease of about 10 recalls per year during the 11-year period of analysis. Conclusion: Devices approved through the 510(k) process, compared with the PMA process, were more likely to be recalled for design defects. Although device design is the most common reason for device recall, many recalls are due to suboptimally standardized processes (e.g., packaging, process controls, device labeling). Overall, orthopedic hip device recalls decreased during the period of analysis (2007–17).

The state of artificial intelligence-based FDA-approved medical devices and algorithms: an online database

At the beginning of the artificial intelligence (AI)/machine learning (ML) era, the expectations are high, and experts foresee that AI/ML shows potential for diagnosing, managing and treating a wide variety of medical conditions. However, the obstacles for implementation of AI/ML in daily clinical practice are numerous, especially regarding the regulation of these technologies. Therefore, we provide an insight into the currently available AI/ML-based medical devices and algorithms that have been approved by the US Food & Drugs Administration (FDA). We aimed to raise awareness of the importance of regulatory bodies, clearly stating whether a medical device is AI/ML based or not. Cross-checking and validating all approvals, we identified 64 AI/ML based, FDA approved medical devices and algorithms. Out of those, only 29 (45%) mentioned any AI/ML-related expressions in the official FDA announcement. The majority (85.9%) was approved by the FDA with a 510(k) clearance, while 8 (12.5%) received de novo pathway clearance and one (1.6%) premarket approval (PMA) clearance. Most of these technologies, notably 30 (46.9%), 16 (25.0%), and 10 (15.6%) were developed for the fields of Radiology, Cardiology and Internal Medicine/General Practice respectively. We have launched the first comprehensive and open access database of strictly AI/ML-based medical technologies that have been approved by the FDA. The database will be constantly updated.

The state of artificial intelligence-based FDA-approved medical devices and algorithms: An online database (Preprint)

BACKGROUND At the beginning of the artificial intelligence (A.I.) era, the expectations are high, and experts foresee that A.I. shows potential for diagnosing, managing and treating a wide variety of medical conditions. However, the obstacles for implementation of A.I. in daily clinical practice are numerous, especially regarding the regulation of these technologies. OBJECTIVE Therefore, we provide an insight into the currently available A.I.-based medical devices and algorithms that have been approved by the U.S. Food & Drugs Administration (FDA). We aimed to raise awareness about the importance of regulatory bodies, clearly stating whether a medical device is A.I.-based or not. METHODS Cross-checking and validating all approvals, we identified 64 A.I.-based, FDA approved medical devices and algorithms. Out of those, only 29 (45%) mentioned any A.I.-related expressions in the official FDA announcement. RESULTS The majority (85.9%) was approved by the FDA with a 510(k) clearance, while 8 (12.5%) received de novo pathway clearance and one (1.6%) premarket approval (PMA) clearance. Most of these technologies, notably 30 (46.9%), 16 (25.0%) and 10 (15.6%) were developed for the fields of Radiology, Cardiology and Internal Medicine / General Practice respectively. CONCLUSIONS We launched the first comprehensive and open access database of strictly A.I.-based medical technologies that have been approved by the FDA. The database will be constantly updated.