Blog Tag: Food and Drug Administration
The U.S. Food and Drug Administration (FDA) published on February 23rd, 2022, a rule proposal to overhaul medical device quality control regulation. According to the FDA, the proposed rule change would “amend the device current good manufacturing practice requirements of the Quality System Regulation to align more closely with the international consensus standard for devices by converging with the quality management system requirements used by other jurisdictions.”
The proposed rule, titled Medical Devices; Quality System Regulation Amendments, would incorporate by reference International Organization for Standardization ISO 13485:2016, which is the international consensus standard for medical device manufacturers. The FDA claims that finalizing the proposed rule “will continue our efforts to align our regulatory framework with that used by other regulatory authorities to promote consistency in the regulation of devices and provide timelier introduction of safe, effective, high-quality devices for patients.” The FDA is also proposing to amend other aspects of its regulations to more closely align with the Food, Drug, and Cosmetics Act, as well as clarify good manufacturing practice requirements for co-packed and single-entity combination products.
Since early 2018, the FDA has said it is considering how to harmonize its regulatory requirements for medical device quality systems contained in 21 CFR part 820 with ISO 13485:2016, amid the international standard’s three-year transition period. This proposal would become effective one year from the publication date of February 23rd, 2022, and would result in the replacement of its current inspection approach for medical devices, the Quality System Inspection Technique (QSIT), with an inspection approach that will be consistent with the requirements of the Part 820 as finalized.
Beyond the harmonization with international standards, the FDA estimates that this rule change will save between $439 million to $533 million over the next 10 years. At the same time, it is expected that the expenditure for all companies to get up to speed with the proposed rule change will total $7.6 million.
The FDA had announced last week a March 2, 2022 meeting of the Device Good Manufacturing Practice Advisory Committee to “discuss and make recommendations on the current good manufacturing practice requirements for medical devices . . . to align more closely with an international consensus standard for medical devices used by other regulatory authorities.”
The text of the proposed rule change can be found here.
The United States Department of Justice announced that medical device company Affordable Healthcare Solutions, LLC has pleaded guilty to charges related to unapproved prescription hyaluronic acid medical devices, as reported by a press release dated September 28, 2021. The devices are “intended for the treatment of pain in osteoarthritis of the knee that must be injected by a doctor or other qualified health care professional.” The company was sentenced for “Receiving Adulterated Devices in Interstate Commerce and Delivery for Pay with Intent to Defraud or Mislead, in violation of 21 U.S.C. §§ 331(c) and 333(a)(2).”
21 U.S.C. § 331(c) prohibits “[t]he receipt in interstate commerce of any food, drug, device, tobacco product, or cosmetic that is adulterated or misbranded, and the delivery or proffered delivery thereof for pay or otherwise.” According to the facts admitted during the plea, special agents with the United States Food and Drug Administration (FDA) located and seized foreign-market Supartz, Euflexxa, Synvisc, Synvisc-One, and Orthovisc that were adulterated for lacking FDA approval for distribution and use in the United States.
According to the press release, a review of the devices seized from Affordable Healthcare Care Solutions confirmed various differences between the outer box and carton labels, patient information brochures, and instructions for use between the FDA-approved labeling for Supartz, Orthovisc, Synvisc, Synvisc-One, and Euflexxa versus the labeling included with the unapproved versions being distributed by Affordable Healthcare Solutions. While discussing the seizure, Special Agent in Charge, Justin C. Fielder, emphasized that the “FDA regulates the manufacturing and distribution of medical devices to help ensure the safety of American patients.”
As a result of the plea agreement, Affordable Healthcare Solutions pleaded guilty to a felony, was fined, and was ordered to forfeit $837,000 worth of devices seized by the special agents. Juan Antonio Gonzalez, Acting United States Attorney for the Southern District of Florida, announced the felony guilty plea and stated:
Medical device suppliers whose greed leads them to disregard FDA protocols and approval processes put the public in danger. . . . These are serious crimes and, in our district, companies that put profit over patient safety will be held accountable.
The U.S. Food and Drug Administration (FDA) announced an agreement with the U.S. Department of Homeland Security (DHS) to strengthen the partnership between the agencies and “stay a step ahead of constantly evolving medical device cybersecurity vulnerabilities.”
The agreement formalizes a long-standing relationship by developing a new framework for greater coordination and cooperation. As part of the new framework, specific responsibilities have been assigned to the FDA and the National Protection and Programs Directorate (NPPD), a component of the DHS. The following table provides a breakdown of the responsibilities outlined in the agreement:
|FDA Responsibilities||NPPD Responsibilities|
|1. Coordinate and participate in regular, ad hoc, and emergency coordination calls to enhance mutual awareness of vulnerabilities and threats||1. Serve as central medical device vulnerability coordination center|
|2. Provide NPPD with draft public releases to facilitate coordination of messaging||2. Participate in regular, ad hoc, and emergency coordination calls with FDA to enhance mutual awareness of vulnerabilities and threats|
|3. Comment in a timely manner on NPPD draft advisories and alerts||3. Confer with entities providing sensitive information prior to sharing any CCI, trade secret, or PCII-protected vulnerability or product information with the FDA|
|4. Assess the risk to health and patient harm when potential impact is disputed||4. Coordinate with FDA on the content of alerts and advisories to be published by DHS|
|5. Submit requests to NPPD for independent third-party technical assistance to analyze and test medical systems||5. Maintain technical capabilities to support requests for independent third-party analysis regarding the impact of vulnerabilities|
|6. Share non-trade secret information to resolve disputes of risk, impacts, and communication||6. Publish healthcare and public health related alerts and advisories|
In summary, the DHS will serve as the central coordination center and interface with appropriate stakeholders, and the FDA will provide technical and clinical expertise regarding medical devices.
FDA Commissioner Scott Gottlieb, M.D., during his discussion of the new agreement, addressed the FDA’s continued commitment to confront cybersecurity risk, while also recognizing the need for increased coordination between government agencies:
The FDA has been proactive in developing a robust program to address medical device cybersecurity concerns . . . But we also know that securing medical devices from cybersecurity threats cannot be achieved by one government agency alone. Every stakeholder has a unique role to play in addressing these modern challenges. That’s why this announcement is so important.
This agreement is not the first time a government agency has reached out to the FDA in an effort to strengthen medical device cybersecurity. As previously reported on the KnobbeMedical blog, the U.S. Department of Health & Human Services (HHS) Office of the Inspector General recommended earlier this year that the FDA include cybersecurity review as a greater part of the premarket review process for medical devices (e.g., through the inclusion of a Refuse-To-Accept checklists). This new FDA-DHS agreement is another example of continuing attempts to address ongoing medical device cybersecurity risks.
On May 30, 2018, the U.S. Food and Drug Administration launched an innovation challenge as a way to combat the fight against opioid addiction. The challenge was issued to “spur the development of medical devices, including digital health technologies and diagnostic tests that could provide novel solutions to detecting, treating and preventing addiction, addressing diversion and treating pain.”
FDA Commissioner Scott Gottlieb stated that “[m]edical devices, including digital health devices like mobile medical apps, have the potential to play a unique and important role in tackling the opioid crisis.” Medical devices can be used to address opioid addiction by, for example, effectively addressing local pain syndromes in order to supplant the use of systemic opioids and reduce the use of opioids. “New digital technology products and diagnostic tests could help in the opioid addiction fight by detecting, treating, and preventing addiction; addressing diversion of the opioid supply chain to illicit use; and treating pain,” the FDA said.
According to Bloomberg, “accepted companies will get to work more closely with the FDA’s review offices than usual to help get their products approved. Products that qualify as breakthrough devices under food and drug law will receive that designation without the sponsor needing to submit an application, the agency said. A breakthrough device designation can reduce the time and cost to get a product to market that addresses life-threatening or irreversibly debilitating diseases.”
The innovation challenge is open to any product in any stage of development. The challenge also is open to developers of currently marketed devices who can show that their devices have an improved benefit-risk profile compared to opioid use in pain management. The FDA anticipates “that applicants will eventually submit one or more formal applications to the FDA, such as an investigational device exemption, De Novo, premarket clearance (510(k)) or premarket approval application.”
This innovation challenge is part of the FDA’s plan to aid in the opioid crisis and supports several overarching goals of the U.S. Department of Health and Human Services’ Five-Point Strategy to Combat the Opioid Crisis. On April 20, 2018, the agency also released the first of two new draft guidances intended to aid industry in developing new medications for use in medication-assisted treatment (MAT) for opioid dependence.
More than two and a half years after the China Food and Drug Administration (CFDA) formally approved its first three-dimensional (3D) printed medical device for mass production, a hip implant co-developed by Peking University’s Third Hospital and AK Medical, the agency has issued a draft guidance on the regulatory requirements for approval of 3D printed devices. The new guidance, titled “Guidelines for the Technical Review of Custom Additive Manufacturing Medical Device Registration,” proposes that “[t]he process of production and verification of custom-built additive-produced medical devices should, in particular, control the testing of printing equipment, processes, post-processing, raw materials and final products, as well as cleaning, packaging and sterilization.”
Although the CFDA is open to consultation on the guidance until March 30, the existing draft would require 3D device applicants to provide at least (1) a product name according to its scope and design for classification and standardization purposes; (2) a description of the product including the chemical composition of each component; (3) clinically relevant model specifications; (4) the scope of the application and contraindications; (5) the product’s research and development background with a comparison to similar products; and (6) research data on product performance with supplementary material characterization.
This development is in line with increased attention to 3D printing technology by regulatory authorities worldwide. In December 2017, the U.S. Food and Drug Administration (FDA) published its guidance titled “Technical Considerations for Additive Manufactured Medical Devices,” which provided the agency’s initial thoughts on 3D printing, including important considerations for design, manufacturing, device testing, and premarket approval. This initial non-binding document was published as “a type of guidance that serves as a mechanism by which the Agency can share initial thoughts regarding emerging technologies that are likely to be of public health importance,” and identified the significant issues that the FDA was likely to emphasize in future regulations. Similarly, Australia’s Therapeutic Goods Administration (TGA) opened consultation on the topic in November 2017.
The U.S. Food and Drug Administration (FDA) recently authorized 23andMe to market its Personal Genome Service Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants). According to an FDA news release, the approved test is the first direct-to-consumer test to report on three specific BRCA1 and BRCA2 breast cancer gene mutations.
According to the news release, BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. Mutations of these genes may interfere with the production or functioning of the proteins and are linked to an increased risk of female breast and ovarian cancers. About 12% of women in the U.S. population will develop breast cancer sometime during their lives. However, according to the National Cancer Institute, a recent large study estimated that about 72% of women who inherit a harmful BRCA1 mutation will develop breast cancer by the age of 80. Similarly, about 69% of women who inherit a harmful BRCA2 mutation will develop breast cancer by age 80. Because mutations of the BRCA1 and BRCA2 genes may be passed down to future generations, genetic testing for breast cancer risk has become more common.
23andMe offers genetic testing directly to consumers. Traditionally, genetic testing was only available through healthcare providers: an individual would request tests from a healthcare provider, the healthcare provider would order tests from a laboratory, collect and send the samples, and interpret the test results before passing them onto the individual. In contrast, direct-to-consumer genetic testing allows consumers to order and perform genetic tests without needing to interact with a healthcare professional. 23andMe has previously offered direct-to-consumer tests for the purposes of discovering an individual’s ancestry. However, this new FDA approval indicates expansion of genetic testing services to other applications.
Although the FDA approval of 23andMe’s test is positive, the FDA expressly noted certain caveats regarding the test. Specifically, the FDA clarified that the test only detects three out of more than 1,000 known BRCA mutations and that only a small percentage of Americans carry one of the three mutations. A negative result therefore does not rule out the possibility that an individual carries other BRCA mutations that increase cancer risk. Additionally, the FDA is establishing criteria, called special controls, which set forth the agency’s expectations in assuring the test’s accuracy and performance. Though this test may be a precursor for exciting possibilities on the horizon, the FDA warned that this limited test should not completely replace consultations with a health care professional.
The U.S. Food and Drug Administration (FDA) Commissioner Scott Gottlieb recently announced that the agency plans to publish a draft guidance outlining a voluntary alternative pathway for new, moderate-risk devices for use in patient care.
According to Commissioner Gottlieb, the FDA regulatory processes for medical devices have remained relatively unchanged for over 40 years. Under a commonly used clearance pathway, device manufacturers are required to submit a Premarket Notification, known as a 510(k). The 510(k) constitutes a premarketing submission demonstrating substantial equivalence of a new device to a similar, legally marketed “predicate” device. The FDA explains that the submission allows the FDA to determine whether the device is as safe and effective as an equivalent device already placed into one of the three FDA classification categories.
However, Commissioner Gottlieb believes that “there are an increasing number of cases where this basic framework isn’t well-suited to reflect the innovation that we see today in certain technologies, and how we must evaluate those technologies.” Similarly, he states that the current 510(k) requirements fail “to realize the full potential of the FDA’s consensus standards program, which was established through the Food and Drug Administration Modernization Act of 1997, and will be refined and expanded as a result of provisions in the 21st Century Cures Act of 2016.” To address these shortcomings, the FDA plans to offer an alternative pathway for demonstrating substantial equivalence in a 510(k) submission.
Under the new pathway, Commissioner Gottlieb states that manufacturers could obtain clearance without direct comparison testing to a predicate device. Instead, substantial equivalence could be established by meeting objective safety and performance criteria, including FDA-recognized standards, FDA-developed guidance documents, or a combination of the two. The pathway would only be available for pre-specified categories of mature devices – those for which safety and performance criteria that meet or exceed the performance of existing, legally marketed devices can be identified.
Commissioner Gottlieb believes that this alternative pathway:
[H]olds tremendous promise to further streamline device review for sponsors and FDA and allow new innovations to get to patients more quickly; to allow more advanced technologies to be efficiently incorporated into new devices; and to foster greater confidence in the FDA’s ability to efficiently evaluate safety and benefits of technologies cleared under this pathway – all while maintaining the same gold standard that we apply to existing review processes.
The FDA will release its draft guidance on the new 510(K) pathway in the first quarter of 2018.
According to IlluminOss Medical, Inc.’s recent press release, the company has successfully obtained the first-ever de novo clearance from the FDA’s Orthopedic Branch for its minimally invasive bone stabilizaion system (the “IlluminOss System”). According to the FDA, the de novo clearance is reserved for new, novel devices whose type has not been previously classified.
IlluminOss, a privately held commercial-stage medical device company based in East Providence, Rhode Island, describes itself as being involved in the development and commercialization of minimally invasive fracture fixation techniques. The company explains that the newly-approved IlluminOss Bone Stabilization System is used for the treatment of impending and actual pathological fractures of the humerus, radius, and ulna resulting from metastatic bone disease.
Traditional bone stabilization procedures utilizing invasive techniques and intramedullary rods can risk causing extensive soft tissue damage and reduced patient mobility. Moreover, the metal plates and rods may increase patients’ risk of cortical porosis, delayed bridging, and refractures upon removal. Regarding its IlluminOss System, IlluminOss states:
The IlluminOss System was developed with an aim to provide improved patient experiences and outcomes when treating pathologic fractures. There is a critical need to make less invasive orthopedic fracture repair options available to an aging and underserved market segment.
In contrast to traditional fixation techniques, the IlluminOss explains that its System uses a small-diameter PET balloon and visible light fiber, each of which may be threaded through a 4.5 mm pathway into the medullary canal through a small incision in the patient’s skin. Once inserted, the PET balloon is filled with a photoactive liquid monomer, causing the balloon to expand and conform to the specific shape of the patient’s bone. With the liquid-filled balloon in place, the photoactive monomer is polymerized utilizing the visible light fiber, resulting in a hardened implant which conforms to the patient’s specific bone structure within 90 seconds. The hardened implant stabilizes the fracture by providing both longitudinal and rotational stability across the length of the implant.
The IlluminOss System has been available internationally since 2010. IlluminOss reports success in international markets: surgeons have reported smaller incisions, shorter procedure times, and a faster return to the patient’s daily living activities. Reduced complication rates, and shorter hospital stays have also been observed.
With marketing clearance in hand, IlluminOss plans to initiate U.S. commercialization efforts in the second quarter of 2018.
Globus Medical announced early today that the Excelsius GPSTM surgical platform has received 510(k) clearance from the U.S. Food and Drug Administration (FDA), as reported by a press release dated August 17, 2017.
Globus Medical, which describes itself as a musculoskeletal implant manufacturer, acquired the robotics developer Excelsius Surgical and its robotic guidance device Excelsius GPSTM three years ago according to press releases. The Excelsius GPSTM platform is said to function as a robot-assisted surgery guidance system “designed to minimize radiation exposure, streamline workflow, and reproducibly assist in implant placement,” according to the press release. Globus Medical further describes the platform as being compatible for use with pre-operative CT, intra-operative CT, and fluoroscopic imaging modalities.
The FDA’s decision is stated to allow the platform for use within minimally invasive and open orthopedic and neurosurgical procedures, including screw placement applications in spine and orthopedic surgery. This announcement also follows Globus Medical’s earlier news release announcing that the Excelsius GBSTM system received CE mark approval in the European Union.
Norbert Johnson, Vice President of Robotics, Imaging, & Navigation at Globus Medical, views these results as an example of Globus Medical’s developmental capabilities:
We believe the Excelsius GPS™ System will advance patient care and provide tangible benefits for surgeons and hospitals in terms of time, accuracy and reduced radiation exposure through the application of robotic and navigation technology in spine and orthopedic surgery.
The Excelsius GPSTM received FDA 510(k) clearance after Globus Medical re-filed its 510(k) bid following an FDA decision that Globus Medical’s initial bid had not “sufficiently addressed the FDA’s questions,” according to Mass Device.
The U.S. House of Representatives recently passed the FDA Reauthorization Act of 2017. This bill seeks to change the requirement for companies to report medical device malfunctions to the FDA. Previously, companies had to submit a report within 30 days of a problem. Under the current version of the Reauthorization Act, companies will be able to submit reports once every three months instead. Additionally, these reports will be able to “summarize previously reported product malfunctions, rather than filing detailed reports on each case” as reported by the StarTribune. However, this does not affect the 30-day reporting requirement for medical device companies to report “adverse events” or anything that result in actual injury to consumers.
This measure is part of a piece of legislation that must be renewed every five years and which sets the fees that device makers pay the FDA to review their products. The goal of the agreement from the device maker’s perspective is to reduce the time it takes for the FDA to review products and get them to market. According to the New York Times, this bill “compels the F.D.A. to speed medical devices onto the market — and into patients — faster than ever.” But this may not be in patients’ best interest, because medical device malfunctions are already “vastly underreported” as acknowledged by the FDA.
StarTribune reports that proponents of the change say that it would “simplify the needlessly repetitive process of reporting known product problems.” Minneapolis-based med-tech regulatory attorney Mark DuVal said that “A lot of MDRs (Medical Device Reports) are really boilerplate and repetitive,” and that “[i]t would be nice to be able bundle them.” According to the StarTribune, DuVal thinks that the current system of reporting MDR’s creates a lot of work for companies while doing little to inform doctors about issues that are known. Janet Trunzo, a senior executive vice president with the lobbying group AdvaMed, said in a statement that the reporting provision “will allow the agency to better focus its resources on more serious reportable events.” According to Trunzo, the quarterly summary reporting only applies to well-understood and familiar malfunction incidents. Medical device companies would still be required to file an individual report on any malfunction incident that had not been previously reported.
According to the New York Times, critics of the change do not think relaxing the rules is proper when so much already goes unreported. Jack Mitchell, director of health policy for the National Center for Health Research, said that “[p]ost-market surveillance of medical devices continues to be dangerously slow and clearly inadequate to protect patients from risky devices.” Mitchell thinks that loosening up the reporting rules will “exacerbate the tendency to underreport.” Ms. Tomes, who is now the chief executive of Device Events, which mines FDA’s device data to find signals of problems, also does not think this loosening of the reporting rules is in the public’s best interest. Ms. Tomes pointed out that last year, many reports about battery depletion of cardiac defibrillators were reported as “malfunctions.”
Boston Scientific recently announced that it is launching a worldwide study for its EMBLEM™ MRI Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) device. According to the press release, a multicenter trail of the device will focus on a group of patients who are above 65 years old with a history of prior heart attack, diabetes, and moderately reduced left ventricular ejection fraction, considered to be at higher risk of sudden cardiac arrest but unsuitable for implantable cardiac defibrillators. The study, according to Boston Scientific, is designed to evaluate whether the company’s EMBLEM MRI S-ICD System improves the survival rate in the target group of patients in comparison to patients continuing with their present treatment. Boston Scientific indicates that it is also seeking parallel approvals for a new indication from the FDA and the Center for Medicare & Medicaid Services for use of the device in treating the target group of patients.
Commenting on the study, Senior VP and Chief Medical Officer of Global Health Policy and Rhythm Management Dr. Kenneth Stein, stated:
“In addition to the knowledge we hope to gain from this population of patients with diabetes, we are excited for the opportunity to improve the broad applicability of the [multicenter] trial results by increasing the enrollment of women in this study. Moreover, the trial emphasizes our continued commitment to expanding access to all patients who may benefit from this proven technology.”
Dr. Valentina Kutyifa, principal investigator and research assistant professor of cardiology at the University of Rochester Medical Center, also stated:
“Our hypothesis is that the S-ICD device may reduce all-cause mortality in this high-risk cohort of cardiac patients with diabetes. The value of eliminating unnecessary patient complications by implanting a defibrillator which does not require intracardiac leads was an important factor in our decision to utilize the S-ICD device when designing this trial.”
Boston Scientific previously reported acquiring the S-ICD technology from Cameron Health in 2012.
The FDA‘s planned National Evaluation System for Health Technology (NEST) will focus on new forms of clinical data, data sharing, and advanced analytics as the keys to optimizing the medical device ecosystem, says a new report issued by the NEST Planning Board. The Planning Board was convened by the FDA and the Duke-Margolis Center for Health Policy in order to outline the initial priorities for NEST.
The FDA plans for NEST to be the national evaluation system for medical devices and is aiming to evaluate evidence from the entire life-cycle of medical device products in order to more effectively monitor medical device safety and efficacy.
In July, FDA Commissioner Dr. Robert Califf and Dr. Jeffrey Shuren, director of the FDA’s Center for Devices & Radiological Health (CDRH) stated that this system for evaluating health technology:
could quickly identify problematic devices, accurately and transparently characterize and disseminate information about device performance in clinical practice, and efficiently generate data to support premarket clearance or approval of new devices and new uses of currently marketed devices.
The Planning Board’s report explains that new standards for sharing medical data between multiple entities will be the focus of a planned NEST Coordinating Center. The proposed Coordinating Center will work to develop a network of experts which will aid NEST in collecting and evaluation clinical data, as well as data received directly from patients. According to the report, the Coordinating Center will foster the development of a NEST clearinghouse of analytical tools, methods, and standards for using linked real-world data collected through clinical and administrative workflows as well as from patients themselves to evaluate devices.
Security firm InfoArmor published a report in late July 2016 stating that a group of attackers infiltrated American health care institutions, stole at least 600,000 patient records and attempted to sell more than 3 terabytes of that associated data. In an interview with eWeek, chief intelligence officer Andrew Komarov noted that the hackers he investigated were able to compromise different health care institutions such as private clinics, vendors of medical equipment, and suppliers. Once inside the compromised systems, the hackers were able to take personally identifiable information and medical data, including imaging data (as shown to the right).
Komarov’s research should come as no surprise in view of a report issued by the Brookings Institute in May 2016 reporting that 23% of all data breaches occur in the healthcare industry. In fact, nearly 90% of healthcare organizations had some sort of data breach between 2013 and 2015, costing the healthcare industry nearly $6.2 billion.
According to a report done by Bloomberg BNA, while a number of legal mandates exist (e.g. the Health Insurance Portability and Accountability Act (HIPAA), the Health Information Technology Certification Program, and the Food and Drug Administration’s (FDA) premarket review), the existing guidelines are limited. Furthermore, medical devices face certain unique cybersecurity pitfalls. For example, while HIPAA applies to protect health information regardless of where it’s stored, protected health information that exists on disposed of or nonfunctional medical devices can be overlooked.
Connected medical devices (i.e., medical devices that can transmit information through the internet or a networked system) also pose unexpected risks and challenges. For example, the ability for hackers to remotely access connected medical devices can hypothetically result in significant threats to patient health and safety. A 2012 episode of the television show Homeland featured a character hacking into and manipulating the pacemaker of the fictional vice president. While such situations seem far-fetched, in an interview on “60 Minutes,” it was revealed that Vice President Dick Cheney’s doctor had actually disabled the wireless functionality of his heart implant, fearing that it might be hacked in an assassination attempt.
While such fears may seem fueled by paranoia, recent studies have shown that such security threats may be a real concern. Bloomberg Businessweek reported in November 2015 that the Mayo Clinic engaged a number of high-profile “white hat” hackers to conduct a study of cybersecurity vulnerabilities in their medical devices. These “white hat” hackers worked on a number of different medical devices, including things such as cardiac monitors, infusion pumps, and hospital beds. In one alarming example, one hacker was able to gain control of an infusion pump – the Hospira Symbiq Infusion System – and was able to remotely cause it to deliver a potentially lethal dose of medication. Shortly thereafter, the FDA issued a safety notice recommending a recall and the stopped usage of the aforementioned pump.
With increasing concerns about cybersecurity, as discussed on this blog previously, the FDA is currently seeking comment on proposed guidelines that outline when software changes to medical devices would require manufacturers to submit a premarket notification.
The FDA has just released draft guidance for unique device identifiers (UDIs) tracking medical devices from their manufacturers to the end users. Specifically, the FDA is providing guidance to device the content and form of UDIs that was lacking (or at least unclear) in the original FDA UDI rule which was published on September 24, 2013.
UDI laws are currently listed under 21 CFR 801.20, and every medical device in commercial distribution is required to have a UDI, unless an exception or alternative applies (for example if the UDI is not technologically feasible). They must be given by an official UDI Issuing Agency that is in line with international standards for medical devices.
The UDI rule began applying to Class III devices in 2014 and implantable, life-supporting and life-sustaining devices in 2015. Class II devices will be in compliance this year, and Class I and non-classified devices will need to have them in 2018.
In this updated draft guidance, the FDA has clarified what forms that the UDI are required to be on medical device packaging. Specifically, the guidelines clarify that the UDIs must be present in two forms on the label and device packing: 1) “easily readable plain-text” and 2) automatic identification and data capture (AIDC) technology. The UDI then must be submitted to the Global UDI Database.
The guidelines provided further information on a number of other topics as well. For example, the guidelines clarified the AIDC technology should be read by a barcode scanner or similar technology, and the UDI may be split into multiple segments on medical device packaging. Moreover, multiple types of AIDC technology can be used on a device label, both representing the same UDI. However, if the UDI is not visible to the human eye, the packaging must disclose that there is the presence of AIDC technology.
The guidance further discussed the specific content of the UDIs, including device and product identifiers as well as data delimiters, and the particular ordering of such information on the packaging.
The FDA providing guidance to the UDI Rule is not uncommon, as a number of other guidances have been issued, such as the guidance issued on June 27, 2014 regarding the Global Unique Device Identification Database and the general guidance issued on August 20, 2014. As this is a complex and important issue, the FDA contains FAQ pages for any questions medical device manufactures may have.
The draft comments will be open for comment for 60 days, and both written and electronic comments are accepted.
On June 10, 2016, the U.S. Food and Drug Administration (FDA) issued a draft guidance advising manufacturers on appropriate and responsible dissemination of patient-specific information from medical devices.
The draft guidance defines patient-specific information as “any information unique to an individual patient or unique to that patient’s treatment or diagnosis that, consistent with the intended use of a medical device, may be recorded, stored, processed, retrieved, and/or derived from that medical device.” According to the guideline, patient-specific information include recorded patient data, device usage/output statistics (e.g., pulse oximetry data, heart electrical activity, and rhythms as monitored by a pacemaker), healthcare provider inputs, incidence of alarms, and/or records of device malfunctions or failures. Patients may contact their healthcare providers or manufacturers to obtain access to patient-specific information.
According to the draft guideline, manufacturers may share patient-specific information with a patient at the patient’s request without obtaining additional premarket review. The Health Insurance Portability and Accountability Act (HIPAA) and the associated HIPAA Privacy Rule intend to prevent manufacturers from sharing individually identifiable health information with covered entities (e.g., health plans, healthcare clearinghouses, and healthcare providers that electronically transmit health information) without the patient’s consent. However, the draft guideline opines that HIPAA and the HIPAA Privacy Rule are not intended to prevent a medical device manufacturer from sharing patient-specific information with the affected patient.
1. Considerations When Sharing Patient-Specific Information
In the draft guideline, FDA recommends that device manufacturers should take certain considerations into account when sharing patient-specific information. These considerations relate to the content of information provided, the context in which patient information from medical devices should be understood, and the need for access to additional, follow-up information from the manufacturer or a healthcare provider.
FDA recommends that a manufacturer take appropriate measures 1) to ensure that the information provided is interpretable and useful to the patient and 2) to prevent the disclosure of confusing or unclear information that could be misinterpreted. For example, the manufacturer may provide supplementary instructions, materials, or references to aid patient understanding. Patient-specific information provided to patients should be comprehensive and contemporary.
When providing patient-specific information to the affected patient, it may be appropriate for the device manufacturer to include relevant context in order to avoid circumstances where this information may be misinterpreted, thus leading to incorrect or invalid conclusions. Informing patients about how parameters were measured and recorded by the medical device is a good example of providing relevant context.
- Access to follow-up information
Manufacturers should consider what, if any, information they should include about whom to contact for follow-up information. The FDA recommends, at a minimum, that such manufacturers advise patients to contact their healthcare providers if the patients have any questions about their patient-specific information. Moreover, FDA suggests that manufacturers provide their contact information to answer questions from patients about the device at issue.
Comments and suggestions for the draft guideline are open for 60 days from its publication.
2. Implications on the Medical Device Industry
FDA opined in its draft guidance that device manufacturers’ disclosure of patient-specific information with the affected patient would be subject neither to additional premarket review by FDA nor to the HIPPA and the associated Privacy Rule.
On June 14, 2016, the U.S. Food and Drug Administration approved AspireAssist, an obesity treatment device that uses a surgically-placed tube to drain a portion of the stomach contents after every meal. According to a press release by the manufacturer Aspire Bariatrics, the AspireAssist System is an endoscopic alternative to weight loss surgery for people with moderate to severe obesity and is indicated for adults with a BMI of 35 to 55 who have not succeeded with more conservative therapies.
The FDA news release summarized the procedure of installing and using AspireAssist as follows:
To place the [AspireAssist] device, surgeons insert a tube in the stomach with an endoscope via a small incision in the abdomen. A disk-shaped port valve that lies outside the body, flush against the skin of the abdomen, is connected to the tube and remains in place. Approximately 20 to 30 minutes after meal consumption, the patient attaches the device’s external connector and tubing to the port valve, opens the valve and drains the contents. Once opened, it takes approximately five to 10 minutes to drain food matter through the tube and into the toilet. The device removes approximately 30 percent of the calories consumed.
According to the FDA news release, the FDA reviewed results from a clinical trial of 111 patients treated with AspireAssist and appropriate lifestyle therapy and 60 control patients who received only the lifestyle therapy. The lifestyle therapy included nutrition and exercise counseling. After one year, patients who used AspireAssist lost an average of 12.1 percent of their body weight compared to 3.6 percent for the control patients. Clinical trial results also suggested that both patient groups had small improvements in conditions often associated with obesity, such as diabetes, hypertension and quality of life.
A youtube video on the AspireAssist System published by Aspire Bariatrics is attached below:
A new blog post by The Food and Drug Administration (FDA) published earlier this month provides an update regarding the implementation of the year-old Expedited Access Pathway (EAP) program, which was created in April 2015 by the FDA’s Center for Devices and Radiological Health (CDRH).
The EAP’s goal is to help new breakthrough technologies undergo pre-market evaluation more quickly than traditional regulatory pathways, as previously reported on the KnobbeMedical blog. While the products in the EAP program are still required to undergo the costly and time-consuming premarket approval processes, this voluntary program potentially provides more options to patients afflicted with life-threatening or irreversibly debilitating diseases.
According to the recent update, the FDA has granted EAP designation to 17 of 29 requests made for the program, and decisions were typically made within 30 days. Once a device has been accepted into the EAP, the FDA “maintains a high level of interaction with sponsors and provides advice on efficient device development.”
The accepted requests have encompassed a spectrum of technologies including devices relating to the heart, brain, or kidneys. Additionally, the device manufacturers involved in the program have included both small start-up companies and large corporations.
In the past year, the FDA has also observed particular entities that may especially benefit from the EAP:
As the program has grown the past year, we’ve learned that companies who benefit most from this program are those that have a preliminary proof of principle for how their device works, but haven’t undertaken formal studies to support future submissions to FDA. For these companies, discussing their Data Development Plan with the FDA and agreeing on a roadmap to their marketing application and beyond is an important part of a successful review.
During these reviews, the FDA has stated that they carefully balance the potential risks and benefits of the new device against the risks of delaying a new therapy to patients. A decision may then be made by the FDA to accept more initial uncertainty for devices in the EAP program so that important technology can reach patients sooner. Once that device is on the market, the FDA and the program participant continue to collect additional data to address any potential uncertainty regarding the device’s safety and effectiveness.
As the EAP enters its second year, its successes will continue to be evaluated.
The Food and Drug Administration has proposed a new policy for earlier public notification of medical device safety issues. These notifications will be in addition to the recall notices, safety communications, and press releases the FDA already puts out.
In the proposed guidance, which is not yet final, the FDA notes the “need to notify the public about emerging signals that the Agency is monitoring or analyzing, even when the information has not been fully analyzed, validated, or confirmed, and for which the Agency does not yet have specific recommendations.” However, the FDA notes that “[p]osting this information does not mean that FDA has concluded there is a causal relationship between the medical device and the emerging signal. Nor does it mean that the FDA is advising patients or health care professionals to discontinue or modify use of these products.”
Examples of emerging signals given in the guidance include: “a newly recognized type of adverse event associated with a medical device, an increase in the severity or frequency of reporting of a known event, new product-product interactions, device malfunctions or patient injuries potentially related to improper device use or design, or a reduction in benefit to the patient.”
In the guidance, the FDA notes that a decision to issue a public communication about an emerging signal should only come when:
- the information represents a new, potentially causal association, or a new aspect of a known association (e.g., increased rate or severity of even or reduced benefit), between a medical device and one or more adverse events or clinical outcomes;
- the available information is reliable and supported by sufficient strength of evidence; and
- the information could have important clinical implications for patient management decisions and/or could it significantly alter the known benefit-risk profile of the device.
The guidance outlines that once an emerging signal is communicated, updates to the communication should be posted to the FDA website at least twice per year until a more formal and finalized communication is issued.
FDA Approves Expanded Use of Medtronic’s CoreValve System; Also Receives Regulatory Approval in Japan
This week the U.S. Food and Drug Administration announced its approval of Medtronic’s CoreValve system for “valve-in-valve” (VIV) replacement. According to the FDA press release, this represents the first transcatheter aortic valve replacement device approved for use in replacing a previously implanted artificial valve. The press release explained the need for replacing artificial valves over time:
Some patients whose own aortic valve failed to work properly in the past undergo open-heart surgery to replace the faulty valve with an artificial heart valve. Over time, artificial valves that are made of animal tissue wear out—becoming narrowed, leaky or both—and may need to be replaced again.
The press release notes that prior to this approval, the only option for patients needing to replace an artificial aortic valve was open heart surgery; however, some such patients may not be qualified candidates for open heart surgery. The press release also stated that the CoreValve system can now provide a less invasive alternative for replacing artificial valves, thereby opening the option of subsequent valve replacements to a new category of patients. Medtronic provided data on the CoreValve Expanded Use Study Failed Bioprosthetic Surgical Valve on its website.
According to press releases, the CoreValve system also just received regulatory approval in Japan, in addition to previous regulatory approval in the U.S. and Europe.
St. Paul, MN-based EnteroMedics Inc. recently announced that the Food and Drug Administration (FDA) approved the use of its VBLOC vagal blocking therapy, delivered via its Maestro system. The system is indicated for treatment of obese adults having a Body Mass Index (BMI) of at least 40 to 45 (units of Kilogram per Meter squared), or a BMI of at least 35 to 39.9 with a related health condition such as high blood pressure or high cholesterol levels, and who have already tried to lose weight in a supervised weight management program within the past five years. A news release by the FDA further noted that the Maestro System is the first obesity treatment device to be approved by the FDA since 2007.
According to the Wall Street Journal, the Maestro system disrupts signals between the stomach and brain by blocking electrical signals in the abdominal vagus nerve through the use of high-frequency electrical pulses. The FDA reported that the Maestro System was evaluated in a 233-patient clinical study where the experimental group lost about 8.5% more of its excess weight than the control group in a 12 month period. The FDA further reported that about half (52.5%) of patients in the experimental group lost at least 20% of their excess weight, and 38.3% of the experimental group lost at least 25%. According to NBCnews, as part of the approval process, EnteroMedics must conduct a five year post approval study following at least 100 patients to collect additional safety and effectiveness data.
According to its website:
EnteroMedics® is committed to the delivery of safe, effective and sustainable therapies that address the growing global health crises associated with the increased prevalence of obesity and metabolic diseases, including diabetes and hypertension. EnteroMedics is rapidly advancing its novel technology, VBLOC® vagal blocking therapy delivered via the Maestro® Rechargeable System, to broadly benefit patients, health care providers and stakeholders around the world.