Cybersecurity, Regulatory Intelligence, Software as a Medical Device and Data Integrity Failures

Feature articles throughout May examined global regulatory compliance and enforcement issues, including FDA’s review framework for medical devices, global cybersecurity compliance and a process for communicating with China's Center of Drug Evaluation (CDE) during drug development. Other articles explored Regenerative Medicine Advanced Therapy (RMAT) designations, changes in guidance documents, new legislation and helpful regulatory intelligence tools. Experts also provided examples of artificial intelligence and discussed the introduction of FDA’s Precertification pilot program.
 
Cybersecurity
 
Cybersecurity can be defined as a process for preventing unauthorized access, modification, misuse or denial of use, or the unauthorized use of information, stored, accessed or transferred from a medical device to an external recipient. Researchers have recently reported on a number of examples demonstrating how the security of medical devices have been compromised by cyberattacks. Clinical evaluation expert, Adina Bar, discusses “Global Medical Device Cybersecurity Compliance Requirements” to maintain global medical device cybersecurity. The author provides examples of recent cybersecurity breaches and also reviews efforts made by regulatory agencies in the US, Australia and China to be proactive in encouraging better cybersecurity, offering tools and tips to help a variety of healthcare organizations to achieve better cybersecurity.
 
Regulatory experts, Suzanne Schwartz and Michelle Jump, review past and current efforts to protect medical devices and other connected healthcare infrastructure from security breaches in “Protecting the Healthcare Infrastructure: Global Cybersecurity Compliance.” The authors cover recent regulatory efforts in Australia, Canada, China, Europe, Japan and the US aimed at enhancing cybersecurity and industry’s efforts in cybersecurity regulatory compliance to protect patients as well as healthcare infrastructure.
 
Regulatory Intelligence
 
If you thought 2017 had a lot of changes, 2018 was even busier and 2019 is shaping up to be another groundbreaking year for transformation. Global intelligence expert, Meredith Brown-Tuttle, has assembled the major changes during 2018 in “Regulatory Strategist Toolbox: 2018 FDA Regulatory Intelligence Briefing.” She provides resources for guidance documents drafted and finalized, new legislation, other areas of interest and regulatory intelligence tools.
 
Regulatory experts, William Sietsema and Janet Lynch Lambert, discuss the scope and purpose of the special designation for Regenerative Medicine Advanced Therapy (RMAT) created by the passage of the 21^st Century Cures Act. “Regulatory Intelligence: Update on Regenerative Medicine Advanced Therapies Designations” explains the expected benefits to be realized with an RMAT, such as keeping the US globally competitive in the field. The authors provide a tally of products receiving the special designation to date and a current count of products for which RMAT designation has been requested.
 
Software as a Medical Device
 
Artificial Intelligence (AI) is the science and engineering of creating an intelligent machine and can use various techniques to create intelligent behavior. FDA explains that AI algorithms are software that can learn from and act on data. FDA issued a statement on steps toward a new review framework specifically tailored to promote the development of medical devices using artificial intelligence algorithms. In addition, FDA released a discussion paper and request for feedback, Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD), as a first step toward developing a new approach to help innovators and developers bring artificial intelligence devices to market. In “FDA’s Steps Toward a new Review Framework for Medical Devices Using Artificial Intelligence Algorithms,” two legal regulatory experts, Alan Minsk and Genevieve Razick, provide a high-level overview of FDA’s proposed framework specifically tailored to promote the development of medical devices using artificial intelligence algorithms.
 
Because the regulatory system does not currently take into consideration software as a medical device using artificial intelligence and machine learning, FDA has initiated a conversation with SaMD stakeholders to develop an appropriate regulatory pathway to accommodate AI/ML SaMD continuous adaptation. Regulatory specialist, Michelle Rubin-Onur, summarizes the current and proposed regulatory landscape for SaMDs with artificial intelligence and machine learning capabilities. “Regulating Software as a Medical Device in the age of Artificial Intelligence” provides definitions for SaMD, categorization and testing features and how to approach and adjust regulatory pathways for SaMDs that “learn” by using real-world evidence to continuously adapt and improve and, therefore, may need to be re-submitted for a new premarket approval due to changes to the device via its adaptations. 
 
Digital health products often fall into a class of their own. FDA is proactively looking to redefine how to get an SaMD product to market. Scott Thiel and Jason Brooke address this controversial issue in “Will the FDA Precertification Pilot Program Work?” The legal experts discuss the new pilot from FDA that aims to make it easier for qualified companies to move software through premarket review, while better leveraging postmarket data collection and whether the program will work in practice.
 
Global Issues
 
African countries have fast-growing economies and in the last two decades, various multinational pharmaceutical companies have entered and established themselves in one or more emerging markets, including Brazil, China and India. In “The African Pharmaceutical and Medical Industry: Growth Factors,” regulatory expert Sofina Jain discusses some important aspects of this growing economy and how the local governments, as well as pharmaceutical companies can benefit from each other. While healthcare spending has gone down in developed countries, emerging economies have been fueling growth in the form of establishment of better infrastructure, improved health insurance and regulatory systems, support to local manufacturing, logistics, etc.
 
China’s national drug regulator, the National Medical Products Administration (NMPA, formerly CFDA), published a regulation on communication with Chinese Center for Drug Evaluation (CDE) on drug development in October 2018. Pharmaceutical science and technology expert, Yingying Liu, provides an English translation of CDE’s regulations for communication with CDE on meeting management practices. In Communication With the Chinese Center of Drug Evaluation (CDE) During Drug Development, the author describes standard procedures for requesting, preparing for, scheduling, conducting, rescheduling/cancelling and documenting meetings or other correspondence with the agency.
 
More than 90% of data integrity failures are considered to be unintentional with no apparent efforts to violate or falsify data. However, in the end, data integrity failures are caused by noncompliance. Pharmaceutical quality expert, Heloisa Mizrahy, discusses the importance of considering human factors when investigating data integrity failures in “Investigating Data Integrity Failures for Manufacturing Changes: Human Factors.” The author reviews the potential for human factors to cause data integrity failures, describes how people can discover solutions for preventing data integrity failures and recommends ways to reduce failures.
 
What’s Coming in June
 
Over time, regulatory frameworks have evolved to protect consumers and patients. An unprecedented progression of demographics—including an aging society, noncommunicable chronic diseases and transforming innovations in healthcare—pose challenges and provide potential opportunities. Action is needed to develop timely, appropriate and affordable healthcare solutions for patients and society. Policies and regulatory frameworks also must be fit-for-purpose to stimulate innovation. June’s theme will examine nutrition in health and disease management and explore the changing healthcare paradigms as food (health) and drug (disease) systems—once separate silos—move closer together, creating new opportunities and requiring traditional pharmaceutical and nutrition “models” to be revisited.
Q2 Regulatory Focus Article Series
 
Regulatory Focus has released its second article series in 2019 featuring global regulatory strategies and best practices. Stay tuned for more information on the 12 June “Ask Me Anything” session with an expert panel to discuss the series.
 
Contribute to Regulatory Focus
 
The Editorial Advisory Committee is looking for articles for monthly themes and quarterly topics. If you are interested in contributing, contact ghall@raps.org.