Showing all posts written by Mark Davis
Mr. Davis earned his Bachelor of Science in Mechanical Engineering at Brigham Young University, where he competed in the international University Rover Challenge. After graduation, he worked as a regulatory compliance engineer at Novarad, a small medical device company.
Following his work as an engineer, Mr. Davis attended the University of Texas School of Law. At Texas, he was an officer in the Texas IP Law Society and served as an associate editor of the Texas Law Review. He also represented small business owners and nonprofit groups as a member of the Texas Clinical Law Programs.
He joined the firm in 2015. Click here to read full bio
Best Practices, LLC recently released a study that provides insights into the amount of resources pharmaceutical and medical device companies allocate to ensure their products meet quality and regulatory standards. The study includes aggregate and anonymized data from 31 large medical companies, including Fisher & Paykel Healthcare, ResMed, Smith & Nephew, and Medtronic, among others. The majority of the surveyed companies operate primarily in the medical device field, but the data also includes results from diagnostic and pharmaceutical companies.
According to Best Practices, the study benchmarks the amount resources spent on quality assurance systems, regulatory affairs, and post-market surveillance of products. One exemplary finding was that, for the average company, the resources expended on the combined quality and regulatory systems amounted to nearly 8% of all company FTEs (full-time employee equivalence). The report further observes that more resources should be spent on the quality assurance system as company revenues increase to maintain consistent quality practices during expansion of operations.
Other sections of the report include data and analysis regarding the particulars of quality assurance systems including the number of CAPAs, NCEs, field actions, change requests, and FDA warning letters reported by individual companies. The study also includes data on the volume and duration of complaints received through post-market surveillance and benchmarks the amount of employee time spent addressing theses complaints.
The complete study is available for purchase through Best Practices, LLC.
The FDA recently announced its approval of GW Pharmaceutical’s Epidiolex drug, described as the first ever plant-derived cannabinoid medicine in the United States. The announcement notes that Epidiolex contains a highly purified form of cannabidiol (CBD), one of many cannabinoids derived from cannabis plants. CBD, however, lacks the psychoactive properties of its more famous cousin, tetrahydrocannabinol (THC). The FDA approved the use of Epidiolex for the treatment of seizures associated with several rare forms of epilepsy in patients 2 years and older.
According to public databases, GW Pharmaceuticals is the listed assignee of seven issued patents for methods of treating various epileptic and other medical conditions using CBD, as well published filings in Europe, Canada, Japan, and the United Kingdom.
Although CBD is an active ingredient of an FDA approved drug, CBD is still considered a Schedule 1 controlled substance under the federal Controlled Substances Act and cannot yet be placed for sale on the market. As a part of its approval of Epidiolex, the FDA has sent a recommendation to the Drug Enforcement Agency to reschedule CBD to a less-controlled schedule. The DEA must act on this recommendation within 90 days of the original approval, although the DEA is not under any obligation to reschedule marijuana or any of its components, including CBD. Nevertheless, observers have noted that the FDA’s approval of a CBD-based drug is at odds with the requirement that a Schedule 1 substance have “no currently accepted medical use in treatment.”
In a press release issued the same day as the approval of Epidiolex, the FDA Commissioner Scott Gottlieb, M.D. stressed that the approval was not a recognition of cannabis or any of its components as medicines. The press release notes that approval of Epidiolex was based on controlled clinical trials evaluating a highly purified form of CBD for treatment of specific conditions, manufacturing under consistent quality controls, and the creation of a reliable dosage form. Nevertheless, the Commissioner encouraged continued clinical research into cannabis related drugs and noted programs and guidances intended to facilitate and expedite development and review of drugs to address unmet medical needs.
Cyberdyne, Inc. recently announced FDA marketing approval for its Medical HAL [Hybrid Assistive Limb] therapeutic device and services. Cyberdyne describes itself as a Japanese company founded by Professor Yoshiyuki Sankai of the University of Tsukub and is traded publicly on the Tokyo Stock Exchange. The press release notes that Medical HAL has received previous marketing approval in Japan and the European Union.
In the press release, Cyberdyne explained that Medical HAL “is considered to be an innovative cybernic treatment device that attends to actually improve and regenerate the function of the patient’s own brain-nerve-physical systems, instead of an orthosis that physically supports the patient to walk or a robot that repeatedly performs specific movements for its patients.” The press release further describes Medical HAL as designed as an exoskeletal aid that attaches to a patient’s limb to assist their movement. Rather than providing movement to the limb through preprogramed algorithms or artificial intelligence, Medical HAL is controlled through nerve signals received with bioelectric sensors attached to the patient’s body. These bioelectric sensors attach at various places on the body, including the lower spine, legs, and arms. The sensors are designed to sense specific nerve signals sent from the patient’s brain to muscles in the limb. These signals can then be translated into specific motions in the exoskeletal aid that assist natural movement of the limb.
Current testing and research is being conducted that uses Medical HAL as an aid for retraining patients with severe nerve damage through physical therapy. According to the press release, retrained nerves and limbs can function similarly to the way they functioned before nerve damage. One example of a positive patient outcome relates to a patient who injured his spine and lower back, leaving one leg paralyzed. After treatment and training for several months with the Medical HAL device, he was able to improve control over that leg and eventually walk with the aid of a walker.
According to public USPTO databases, patents and publications listing Cyberdyne as the assignee include the following: “Wearing-Type Movement Assistance Device,” “Electrodes For Biopotential Measurement, Biopotential Measuring Apparatus, And Biopotential Measuring Method,” and “Ambulation Training Device And Ambulation Training System.”
The FDA recently issued a draft guidance document intended to “to ensure that least burdensome principles are implemented for all device-related applications and interactions with FDA.” The FDA provides this draft guidance following a December 2017 Government Accountability Office (GAO) report assessing the FDA’s application of the “least burdensome” approach to regulation.
The least burdensome mandate for medical devices has been a part of the FDA’s governing law since Congress’ passage of the FDA Modernization Act of 1997. Its intent is to eliminate unnecessary delays for approving new devices, while still maintaining the statutory requirements for approval. The GAO report found that, between 2013 and 2016, device sponsors had appealed FDA staff decisions to agency management a total of 63 times. Of these 63 appeals, 33 raised issues related to the FDA’s application of the least burdensome approach, and the FDA at least partially agreed in 11 of these cases. The GAO report further notes that the FDA has not evaluated its compliance with the least burdensome mandate and suggests the development of performance metrics to meet this end.
FDA Commissioner Scott Gottlieb states that he is “fully committed” to implementing the least burdensome mandate. The draft guidance defines least burdensome to be the “minimum amount of information necessary to adequately address a regulatory question or issue through the most efficient manner at the right time.” The guiding principles espoused in the draft guidance include the FDA’s intent to require the “minimum information necessary to adequately address the regulatory question or issue at hand,” a call for industry sponsors to submit “well-organized, clear, and concise information” for the FDA to review, and the FDA’s commitment to apply regulatory approaches that “fit the technology, taking into account its unique innovation cycles, evidence generation needs, and timely patient access.”
The draft guidance also provides examples of how the least burdensome approach can be applied. For example, it suggests that:
- Computer modeling and simulations “should be used to support medical device safety and effectiveness as alternatives to traditional benchtop or animal performance testing in appropriate circumstances.”
- “Alternative approaches should be considered, when appropriate, to optimize the time and resources of FDA and industry. Both FDA and industry should understand that there are often
multiple ways to satisfactorily address a particular regulatory issue. The resolution of the regulatory issue should be based on a discussion about which method is least burdensome, while still satisfactorily addressing the regulatory issue.”
- “Bench performance testing should be considered to address preclinical or clinical endpoints,
when appropriate. This may include bench models for anatomy, such as evaluating tortuous
paths for catheters used across many clinical applications.”
Kalytera Therapeutics, clinical-stage pharmaceutical company, recently announced plans for clinical trials focused on the treatment of Graft versus Host Disease using Cannabidiol (CBD), a compound found in cannabis. This development highlights the expanse of continued research—and potential—of CBD-based medicines and methods of treatments being pursued by companies globally.
Cannabis is a flowering plant that has long been recognized for its uses in fiber production and hemp oils, recreation, and medical applications. According to Project CBD, CBD is one of a diverse class of chemicals called cannabinoids found in the cannabis plant. CBD was first identified in the early 1940s , but more than 20 years would pass before researchers identified the more famous cannabinoid, tetrahydrocannabinol (THC). Likely because of its psychoactive effects, THC would go on to dominate research studies of cannabis. However, the classification of marijuana as Schedule I substances under the Controlled Substances Act of 1970, federally sponsored medical research into CBD and its effect dwindled.
Both CBD and THC interact with the human body through the CB1 receptor of the endocannabinoid system, a system of receptors found in the central and peripheral nervous systems and many other organs of the body. The endocannabinoid system is involved in the regulation of, for example, appetite, pain, mood, and memory. By binding more weakly with the CB1 receptor than THC, CBD invokes a different response within the endocannabinoid system. Unlike THC, CBD tends not to cause psychoactive effects. Instead, as a growing body of research suggests, CBD plays a role in moderating the effects of THC and reducing inflammation, nausea and pain. Multiple studies suggest that CBD has therapeutic applications for a wide variety of conditions, and companies across the world are researching medical treatment for specific maladies. A few notable projects evaluating potential uses for CBD include:
- GW Pharmaceuticals has commenced FDA-authorized clinical trials for Epidiolex®, a CBD-based drug for treating a rare genetic epileptic encephalopathy called Dravet syndrome. GW reports to have fourteen distinct patent families with claims directed to treatment of epilepsy. Other GW patent filings for CBD include treatments for constipation and cancer.
- Zynerba Pharmaceuticals is developing a synthetic CBD-based gel that is absorbed through the skin and aimed at treating adult epilepsy, osteoarthritis, and fragile-X syndrome. Zynerba has patents directed to transdermal CBD compositions and other CBD delivery systems.
- Insys Therapeutics, Inc. is in Stage 2 clinical trials for a CBD-based drug to treat severe pediatric epilepsy and applications directed to stable formulations of CBD for oral administration.
- Kannalife Sciences Inc. licenses a U.S. government-owned patent for cannabidiol-based drugs for the treatment of diseases caused by oxidative stress. Kannalife is developing CBD-based drugs for the treatment of Hepatic Encephalopathy and Chronic Traumatic Encephalopathy, a type of brain damage.
- Kalytera reports to have filed composition and method-of-use patents on its CBD treatments.
The science of CBD medicine is still being developed. To date, no CBD-based drug has received FDA approval. According to the DEA, CBD is still considered a Schedule I Controlled Substance by the Drug Enforcement Agency (DEA).
According to press releases, INC Research Holdings, Inc. has agreed to merge with inVentiv Health, creating a combined company having an enterprise value of approximately $7.4 billion. The press release further notes that the combined company will be the second largest biopharmaceutical outsourcing provider, one of the top 3 contract research organizations and the largest contract commercial organization by net revenue.
In other news, INC Research was recently recognized for its cybersecurity awareness training at the 5th annual CSO50 Conference + Awards event held on May 1–3. The CSO50 recognizes 50 organizations for security projects that demonstrate “outstanding business value and thought leadership” and are selected through a nomination and review process each year by a team of security experts and academics. CSO is an online publisher focusing on information security, physical security, business continuity, identity and access management, and loss prevention.
According to its website, INC Research is a contract research organization that provides clinical development services to the pharmaceutical, biotechnology, and medical device industries. With more than 6,000 employees across 110 countries, over 100 client audits a year, and access to sensitive medical information by most employees, INC Research was tasked with providing adequate and efficient cybersecurity training—in addition to many other internal training programs.
The award-winning program it developed was said to save over 3,500 hours of disruptive training time. According to news sources, INC Research’s security program focused on frequency of training communications, as opposed to a single one-hour yearly session. Its program used two 15-minutes trainings per year, quarterly two-minute training videos and regular contacts with employees using the company’s intranet and email systems to reinforce cybersecurity principles.
Other honorees included AstraZeneca, Beebe Healthcare, Celgene Corporation, the FDA, and Health Management Systems.
Forward Pharma A/S (“Forward”) recently announced that a necessary super majority of its shareholders have approved a settlement of various patent disputes with two wholly-owned subsidiaries of Biogen Inc. (“Biogen”) in which Forward will receive USD $1.25 billion cash from Biogen. 77% of the voting shareholders voted in favor of accepting the settlement agreement.
Founded in 2005, Forward, a Danish biopharmaceutical company, develops pharmaceutical treatments for patients with neurological conditions such as multiple sclerosis. The company reports that it is currently conducting Phase 1 clinical trials for its formulation of dimethyl fumarate (DMF).
Boston, Massachusetts-based Biogen, founded in 1978, is also a biopharmaceutical company specializing in treatments for multiple sclerosis and other neurological conditions and rare genetic disorders. Biogen developed and now markets an oral multiple sclerosis medication (a DMF therapy) under the trade name TECFIDERA™ for which FDA approval was obtained in early 2013.
Forward and Biogen have been engaged in patent disputes before tribunals in the US and Europe since at least 2014. As exemplified by its suit for patent infringement brought in Germany, Forward alleges that Biogen infringes certain of Forward’s patents relating to oral DMF therapies for the treatment of multiple sclerosis. Forward has also brought an interference proceeding (seeking priority over Biogen’s patent to DMF therapy) in the U.S. Patent and Trademark Office (“USPTO”), and multiple opposition proceedings in the European Patent Office (“EPO”). Under the terms of the settlement agreement, one of the EPO oppositions and the patent infringement suit will be terminated, but the USPTO interference proceeding and the other EPO opposition will be allowed to continue to a final determination of patentability (appeals included).
In addition to the up-front cash payment it agreed to pay Forward, Biogen will pay royalties (10–20%) on U.S. and non-U.S. sales of its orally administered DMF products, but only if Forward successfully obtains patent rights covering those treatment methods as a result of the USPTO and EPO proceedings referenced above.
The third annual Security of Things® Forum (SECOT) in Cambridge, Massachusetts fostered discussion on a variety of cyber-security related topics ranging from a standards-based approach to security connected devices to connected healthcare platforms. Even the Department of Homeland Security weighed in on its own efforts to influence the next generation of connected networked devices by developing strategic principles for developers to consider when addressing the Internet of Things.
Keynote speaker Dr. Kevin Fu of the University of Michigan spoke specifically about both the benefits and security problems in networked medical devices. Dr. Fu noted that pacemakers, for example, require direct contact from a sterile needle to adjust or maintain them, which creates an infection risk; and thus a wirelessly controlled pacemaker therefore can offer both the benefits of easier access and control, but also the security risk of being accessible—and therefore hackable—via a network. Moreover, a password protected pacemaker cannot simply lock out the user or attending physician because they fumbled the password at a critical moment.
While cyber-security for medical devices is a complex problem, especially in view of the aging infrastructure of most healthcare systems, Dr. Fu concludes that overall “patients prescribed an implant are far safer with those devices than without” despite even “major security problems.” In fact, he believes that most security flaws can be addressed by practicing basic security hygiene, addressing the “low lying fruit” and designing critical systems to “fail gracefully” by localizing breaches.
A second session of the SECOT Forum occurred on October 27, 2016 in Washington, DC. Speakers included: Suzanne Schwartz, FDA Director of Emergency Preparedness/Operations and Medical Countermeasures; Beau Woods, Deputy Director of the Cyber Statecraft Initiative in the Brent Scowcroft Center on International Security; and keynote speaker Ralph Langer, Managing Principal of Langer Communications.
IBM’s Watson for Genomics and the U.S. Department of Veterans Affairs (VA) just announced a public-private research partnership to study genomics and provide tailored medical solutions to patients. This partnership is poised to expand the benefits of precision medicine to 10,000 American veterans with cancer over the next two years.
Genomics is subset of genetics dedicated to sequencing and analyzing the complete DNA content of a single cell, including each of its constituent genes. One of the goals of this approach is to better understand how both diseases and medicines are affected by a unique genomic sequence. This understanding can be leveraged into tailored medical treatments determined by a patient’s DNA.
Advances in DNA sequencing technology means that the availability of data for conducting genomics research is at an all-time high. However, without a way to process that data efficiently and analyze it relative to actual diseases, available drugs, and the most current research, practical progress toward clinical benefit may be challenging. At large medical institutions such as the VA, the sheer volume of data produced could be overwhelming to researchers and caregivers.
The partnership between IBM’s Watson for Genomics and the VA aims to overcome these obstacles in the field of oncology. According to the press release, researchers at the VA will feed genomic data into Watson and Watson will generate a report that “identifies the likely cancer-causing mutations and possible treatment options to target those specific mutations through a comprehensive review of existing medical literature.” This approach will make critical information available to healthcare providers and help them create tailored medical treatments that target specific cancer-causing genetic mutations.
According to Dr. David J. Shulkin, Department of Veterans Affairs Under Secretary for Health, “[w]ith the help of Watson’s cognitive computing power, VA plans to bring precision treatment options to almost 30 times more patients than could be previously served.”
On January 26, 2016, the FDA offered for public comment its draft guidance on medical devices and interoperability, Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices—Draft Guidance for Industry and Food and Drug Administration Staff. The guidance defines interoperability as the interconnectedness of two or more different devices or systems that allow for “the availability and sharing of information . . . even when products from different manufacturers are used.” It specifically does not limit interoperability to “unidirectional patient data” and instead expands that to include “more complex interactions, such as exerting command and control over a medical device.” It suggests this can be accomplished through “use of standardized architectures and communication protocols” and specifying “non-standard interface requirements and characteristics” through public labeling.
The FDA’s intent in offering the guidelines is to encourage interoperability of medical devices and to improve patient care and efficiency while taking into account safety and security. It highlights three major design considerations for medical device manufacturers to consider as an industry: 1) designing systems with interoperability as an objective; 2) conducting appropriate performance testing and risk management activities; and 3) specifying the functional, performance, and interface characteristics in a public manner such as labeling.
While the guidance is still in draft form and would not be legally binding even after it becomes final, industry reception appears mixed. Some industry commentators have praised the guidance for dealing with devices that actually use shared data automatically for medical purposes and find the FDA’s approach encouraging. Others see the guidance as counterproductive because it places another pseudo-regulatory burden on device manufacturers in the form of additional performance testing and risk management activities.
“There is no such thing as a threat-proof medical device.”
Suzanne Schwartz, M.D., MBA, director of emergency preparedness and medical countermeasures at the FDA’s Center for Devices and Radiological Health.
Two months after finalizing its first guidance on cybersecurity, the FDA has announced a public workshop entitled “Moving Forward: Collaborative Approaches to Medical Device Cybersecurity” to continue to address a growing safety consideration.
Since 2013, the FDA and other organizations have taken increased steps to address cybersecurity in the medical device industry. In summer 2015, the FDA issued its first cybersecurity alert for a network enabled computerized pump designed for general infusion therapy. Both the manufacturer and an independent researcher confirmed that the pump was vulnerable to access by an unauthorized remote user through the networked hospital information system. The unauthorized user could then modify the dosage the pump delivers to a patient. While no actual incidents were reported, both the manufacturer and the FDA recommended all hospitals immediately transition to other devices or at least disconnect the pump from the network and run offline as a temporary solution.
Other past efforts by the FDA to address cybersecurity include the white paper Content of Premarket Submissions for Management of Cybersecurity in Medical Devices, Guidance to Industry: Cybersecurity for Networked Medical Devices Containing Off-the-Shelf (OTS) Software, and a 2014 public workshop to seek further input from the public health sector on medical device and general health care cybersecurity.
The stated purposes of the January 2016 workshop are multifaceted and designed to take a comprehensive look at the state of the medical device cybersecurity. The purposes include: highlighting past collaborative efforts between agencies, increasing awareness of models for benchmarking organizational cybersecurity status, reviewing standards and tools in development to address cybersecurity risk, and discussing unresolved gaps and challenges in advancing medical device cybersecurity.
The workshop will also bring together a diverse set of stakeholders including the National Health Information Sharing Analysis Center (NH-ISAC), the Department of Health and Human Services and the Department of Homeland Security.
The workshop is planned for January 20-21, 2016, from 9:00 am – 5:30 pm at the FDA White Oak Campus in Silver Spring, Maryland. Registration is free and the meeting will also be webcast.