Blog Tag: FDA

U.S. FDA Approves Monkeypox Treatment Formulation

By Mark Rubinshtein

(May 25, 2022) SIGA Technologies Inc., a New York-based pharmaceutical company, has received approval from the U.S. Food and Drug Administration (FDA) for an intravenous formulation of TPOXX (tecovirimat) for the treatment of smallpox.  The U.S., Canada, and Europe have approved an oral formulation for treating smallpox, and Europe has also approved it for treating monkeypox and cowpox.  The newly approved intravenous formulation provides an option for patients who are unable to swallow.

The approval is welcome news as over 100 cases of monkeypox have been identified outside its endemic area.  Australia, Belgium, France, the U.K., Sweden, Italy, Spain, Portugal, Canada, and the United States have reported cases.  The World Health Organization (WHO) warns more cases are likely.

Monkeypox is endemic to Central and West Africa and belongs to a subset of the Poxviridae virus family, which includes smallpox and cowpox.  Monkeypox symptoms (fever, sweating, headaches, enlarged lymph nodes) are generally much milder than smallpox.  The infection generally spreads from animal to human.  However, it can also be transmitted between humans.  This can occur through contact with bodily fluids, lesions on the skin or on internal mucosal surfaces, such as in the mouth or throat, respiratory droplets, and contaminated objects.

TPOXX is the first antipoxviral drug approved in the United States.

SIGA is the Assignee of multiple patents relating to tecovirimat.  These include U.S. Pat. Nos. 8,124,643, 8,802,714, 9,862,683, 10,029,985, and 10,864,282.

FDA Draft Guidance for Fostering Medical Device Improvement Using the Voluntary Improvement Program

On May 5, 2022, the FDA’s Center for Devices and Radiological Health (CDRH) issued draft guidance regarding the FDA’s Voluntary Improvement Program (“VIP”). The draft guidance, Fostering Medical Device Improvement: FDA Activities and Engagement with the Voluntary Improvement Program, can be found here.  According to the FDA:

“The VIP is a voluntary program facilitated through the Medical Device Innovation Consortium (MDIC) that evaluates the capability and performance of a medical device manufacturer’s practices using third-party appraisals, and is intended to guide improvement to enhance the quality of devices.”

The VIP draft guidance, is an extension of the 2018 pilot program Case for Quality Voluntary Medical Device Manufacturing and Product Quality (“CfQ Pilot Program”). According to the FDA, the CfQ Pilot Program assessed the “capability and performance of key business processes using a series of integrated best practices detailed in the Information Systems Audit and Control Association (ISACA) Capability Maturity Model Integration (CMMI) system.” The results of the pilot program can be found here.  Participants in the CfQ Pilot Program reported that “the appraisal had a direct value to product quality and over 90% reported a positive experience with the appraisal.”

As described in the draft guidance, the goal of the VIP is to “elevate and enhance manufacturing practices and behaviors through which quality and safety of medical devices can be improved.” As indicated in its name, this program is voluntary. Through use of the program, third-party appraisers visit participants to evaluate their practices in order to identify strengths and areas for improvement.

According to the draft guidance, VIP offers various benefits and opportunities for those manufacturing sites who demonstrate sustained capability and performance. Examples of opportunities from the draft guidance include:

  • FDA Consideration in Risk-Based Inspection Planning
  • Utilization of a Modified Submission Format for Premarket Approval Application (PMA) and Humanitarian Device Exemption (HDE) 30-Day Change Notices for Modifications to Manufacturing Procedures or Methods of Manufacture
  • Utilization of a Modified Submission Format for PMA and HDE Manufacturing Site Change Supplements
  • Utilization of a Modified Submission Format for PMA or HDE – Manufacturing Modules

The VIP has various participation and enrollment criteria for manufacturing sites, which can be found here.

The FDA requests comments on the draft guidance by July 5, 2022.

FDA Publishes Draft Medical Device Cybersecurity Guidance Amidst Continued Cybersecurity Concerns

On April 08, 2022, the Food and Drug Administration (FDA) published a draft cybersecurity guidance document for medical devices, titled Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions. The draft guidance covers a wide range of issues, including cybersecurity device design, labeling, and documentation. The guidance is intended to provide medical device makers a road map on how to satisfy the FDA’s quality system and patient safety regulations and how to address cybersecurity considerations within their premarket submissions.

The FDA’s draft guidance was released shortly before a report underlining the cybersecurity security practice deficiencies of various medical device makers. On April 20, 2022, Cybellum – a company specializing in assessing product security – reported the results of its 2022 medical device cybersecurity survey in an article titled Medical Device Cybersecurity: Trends and Predictions. The survey found that, although 83% of the medical device companies surveyed saw device security as a competitive edge, 75% of respondents noted that they do not have a dedicated senior management who takes responsibility for device cybersecurity.

The Cybellum survey also revealed that only about a quarter of the medical device companies surveyed (27%) generate and maintain a Software Bill-of-Materials (SBoM) for their products. An SBoM is a formal record containing the details and supply chain relationships of various components used in building software. President Joe Biden previously highlighted the importance of an SBoM in his Executive Order on Improving the Nation’s Cybersecurity from May 2021. Moreover, the National Telecommunications and Information Administration published The Minimum Elements for an SBoM on July 21, 2021, in an effort to bring “transparency to the components and connections within and across supply chains.”

The FDA’s draft cybersecurity guidance document is available here and is available for stakeholder comments until July 7, 2022.

FDA Proposes Changes to Medical Device Quality Regulations

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.

FDA: Approval for Novel Medical Devices Remains a High Priority, Despite COVID-19

FDA: Approval for Novel Medical Devices Remains a High Priority, Despite COVID-19

According to the FDA’s Center for Devices and Radiological Health (CDRH) Annual Report, in addition to its significant efforts to fast track the approval of COVID-19 related devices, the CDRH has also maintained its high priority focus on supporting innovation of new medical devices in the United States.

As provided in the Report, according to CDRH Director Jeff Shuren, M.D., J.D., the FDA has now granted emergency use authorization (EUA) or full marketing authorization to over 2,000 medical devices intended to prevent, diagnose, or treat COVID-19 and more than half of CDRH’s workforce has been directly involved in the COVID-19 response.  The Report further states that the CDRH moved quickly with respect to COVID-19 treatment devices to ensure the availability of the wide range of related products shown below, including diagnostic tests, personal protective equipment (PPE), ventilators, and other critical devices and supplies for health care providers and patients.

As one example in the Report, CDRH authorized 15 additional over-the-counter (OTC) COVID-19 tests for at-home use during 2021.  According to CDRH Director Shuren, these were authorized in record times—in some cases in less than a week—highlighting CDRH’s devotion to providing a rapid response to the COVID-19 pandemic.

The report also states that CDRH’s pandemic-related efforts have not brought its other authorizations to a grinding halt, and that the CDRH also managed to clear or approve 13 devices with breakthrough designation and granted market authorization for 103 novel devices during 2021.  “One way that we are measuring the success of our efforts is through tracking the number of innovative medical technologies being brought to the U.S. first so that patients have access to the safest and most innovative devices available,” says Shuren.   “A decade ago, the U.S. was too often behind in this regard. But we are gratified to see our efforts have resulted in 103 novel devices receiving marketing authorization in 2021, despite the unprecedented demands of our pandemic response,” continues Shuren.  “Spurring innovation in developing safer, more effective devices is key to improving patient care and quality of life.”

Giving marketing authorization to 103 novel devices is touted by the Report as “an incredible achievement” in light of the increased demand on CDRH staff resulting from the COVID-19 pandemic.  “This highlights the commitment and dedication of CDRH staff to strengthen public health by bringing innovative devices to patients,” comments CDRH.

In the past ten years, according the Report, the CDRH has issued four times as many approvals, authorizations, and clearances of novel technologies as a result of the innovative policies and approaches developed and implemented by CDRH.  Novel technologies include those brought to market through the Premarket Approval, Humanitarian Device Exemption, and De Novo pathways, as well as a subset of those brought to market through Emergency Use Authorization (EUA), or the Breakthrough Devices Program.

The Breakthrough Devices Program is another program available for emerging companies that provides device manufacturers with an opportunity to engage directly with CDRH’s experts through several different program options to address topics as they arise during device development, evaluation, and premarket review. 

Medtronic’s Intellis and Vanta Neurostimulators Receive FDA Approval for DPN

Medtronic’s Intellis and Vanta Neurostimulators Receive FDA Approval for DPN

Medtronic  announced that its Intellis™ neurostimulator and the Vanta™ neurostimulator have both received approval from the U.S. Food and Drug Administration (FDA) for the treatment of chronic pain associated with diabetic peripheral neuropathy (DPN), in a January 24, 2022 press release. The approval grants patients suffering from DPN access to both products within Medtronic’s spinal cord stimulation (SCS) portfolio.  The IntellisTM neurostimulator is rechargeable whereas the VantaTM neurostimulator is recharge-free .

DPN, also referred to also as painful diabetic neuropathy (PDN), is a neurological disorder that impacts about 30% of individuals with diabetes, according to the press release. DPN occurs when high blood sugar levels damage nerves causing numbness, burning, or stabbing pain. Charlie Covert, a Medtronic vice president and general manager, views the new approvals as another example of Medtronic’s expertise:

DPN is a significant challenge for patients with diabetes, leading to disability and a diminished quality of life . . . This new indication enables us to apply Medtronic’s more than 40 years of proven SCS experience, as well as the company’s deep diabetes expertise, to deliver better care to even greater numbers of diabetes patients

According to the press release, Medtronic estimates that the US market revenue for SCS treatment of chronic pain associated with DPN is approximately $70 million and expects market revenue to grow to $300 million by fiscal year 2026.

With the new approval, Medtronic’s IntellisTM and VantaTM neurostimulator products now join Nevro’s HFXTM for PDN as the only SCS devices with FDA approval for treatment of DPN/PDN. Nevro’s Chairman, CEO, and President, D. Keith Grossman, responded to the FDA’s approval of the IntellisTM and VantaTM neurostimulators in a press release, stating:

PDN represents a very large potential market, and having another competitor validate this large opportunity speaks to its attractiveness.

Nevro announced the FDA’s approval of its HFXTM on July 19, 2021.

Two Drugs Recalled Due to Manufacturing Issues

By Mark Rubinshtein

(December 13, 2021) Two pharmaceutical companies have issued recalls in December due to manufacturing issues that may impact the safety and quality of their drug products.

Edge Pharma issued a voluntary recall for all drug products produced in its FDA-registered 503B outsourcing facility in Colchester, VT.  Edge stated that products were removed as a result of “process issues” that may have impacted the sterility of its drug products.  The recall includes a wide variety of sterile products.  These include lidocaine, vancomycin, norepinephrine, and methotrexate, as well as a number of non-sterile products.  The use of non-sterile drug products that are intended to be sterile may result in serious, possibly fatal, infections.

Also this month, Teligent, Inc. issued a voluntary worldwide recall on two lots of their topical lidocaine solution due to superpotency.  The two lots had been distributed throughout the United States.  Superpotent lidocaine can be dangerous to patients and has the potential to cause systemic toxicity leading to hypotension, brachycardia, and possible cardiovascular collapse. In October, the New Jersey company issued a similar recall in connection with five lots of topical lidocaine solution.

Fortunately, no adverse events related to the December recalls by either Edge or Teligent have been reported.

FDA Breakthrough Device Designation for Biology-Guided Radiotherapy (“BgRT”) Device

On December 1, 2021, RefleXion Medical, Inc. (“RefleXion”), announced that the U.S. Food and Drug Administration (“FDA”) has granted the company breakthrough device designation for its biology-guided radiotherapy (“BgRT”) for lung tumors.

The FDA breakthrough devices program:

is a voluntary program for certain medical devices and device-led combination products that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.  The goal of the Breakthrough Devices Program is to provide patients and health care providers with timely access to these medical devices by speeding up their development, assessment, and review, while preserving the statutory standards for premarket approval, 510(k) clearance, and De Novo marketing authorization, consistent with the Agency’s mission to protect and promote public health.

Further details regarding the breakthrough devices program can be found here and here.

According to RefleXion, “the breakthrough potential of BgRT lies in its ability to detect and then immediately treat moving tumors.  It is the first and only technology to use injected radiotracers to produce active signals, called emissions, from each tumor to guide treatment delivery” and “aims to remove the uncertainty of guiding radiation delivery using images taken days before treatment.” Many patients with stage four cancer cannot use current forms of radiotherapy because existing technology is unable to efficiently track and treat multiple tumors.  “The unmet need in lung cancer is staggering,” said Todd Powell, president and CEO of RefleXion.  According to Cancer.Org, “[l]ung cancer is the most common cause of cancer-related death,” accounting for 25% of all cancer deaths in the United States.

As RefleXion explains, the use of PET emissions in BgRT to guide treatment makes the “cancer itself act as a fast, biological fiducial continuously signaling its locations even during motion.”  As the PET tracer collects in the tumor, “a series of positron annihilation events occur resulting in the emission of two photons almost 180 degrees to each other.”  The detector in the RefleXion X1 device finds these emissions and outputs images in real time.  A video of RefleXion’s X1 Machine (shown below), used for BgRT, can be seen here.

 

FDA Issues Draft Guidance for Software Contained in Medical Devices

On November 3, 2021 the FDA issued draft guidance titled “Content of Premarket Submissions for Device Software Functions.” The final version will eventually replace the FDA’s “Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices,” originally released in May 2005.

In a press release Bakul Patel, director of the FDA’s Digital Health center, stated:

 “As technology continues to advance all facets of health care, software has become an important part of many products and is integrated widely into medical devices. The FDA recognizes this evolving landscape and seeks to provide our latest thinking on regulatory considerations for device software functions that is aligned with current standards and best practices.”

The draft guidance pertains to software in a medical device (“SiMD”) and software as a medical device (“SaMD”). The Regulatory Affairs Professional Society (RAPS) describes SiMD as “software that is a part of a medical device or controls it” and SaMD as “software that meets the definition of a device but is not part of the overall device’s hardware.” According to the FDA, both SiMD and SaMD are “device software functions.”

The draft guidance is intended to cover: firmware and other means for software-based control of medical devices, stand-alone software applications, software intended to be operated on general-purpose computing platforms, dedicated hardware/software medical devices, and accessories to medical devices when those accessories contain or are composed of the software.

Portions of the draft guidance to consider include the software device documentation and software risk management requirements. Software may require a basic or enhanced level of documentation, depending on risk to a patient, user, other individual, or environment.  A risk assessment and risk management plan may be required.

The draft guidance can be found here.

Alpha Tau Receives FDA Breakthrough Device Designation for Alpha DaRT Treatment of GBM

Alpha Tau Medical Ltd. (“Alpha Tau”) is a medical technology start-up focused on the research, development, and commercialization of its Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) treatment for solid cancerous tumors.  On October 8, 2021, Alpha Tau announced that it received FDA Breakthrough Device Designation for using Alpha DaRT to treat recurrent glioblastoma multiforme (GBM).  GBM is an aggressive, often incurable form of cancer responsible for malignant brain tumors.

According to the FDA, the goal of its Breakthrough Devices Program is to “provide patients and health care providers with timely access to [] medical devices by speeding up their development, assessment, and review.”

In a press release, Alpha Tau CEO Uzi Sofer stated:

“As GBM is such a terrible disease, it is critical that we find new solutions for these patients, and we are thrilled that receipt of the FDA’s Breakthrough Device Designation will allow us to expedite our clinical collaborations with leading cancer centers in the U.S. and across the world, and to bring new hope for GBM patients.  I am very proud of our team and our collaborators who have worked hard to extend the use of Alpha DaRT to GBM and have already accomplished so many amazing things.  This is fantastic news for Alpha Tau and fantastic news for so many GBM patients around the world.”

Alpha DaRT works by first inserting a “seed” into a cancerous tumor.  The seed then releases high-energy alpha particles that destroy the tumor while sparing the healthy tissue around it.

This is the second FDA Breakthrough Device Designation Alpha Tau has received.  In June 2021, Alpha Tau announced the FDA’s designation of Alpha DaRT for treating squamous cell carcinoma, a type of skin cancer.

Medical Device Company Pleads Guilty to Dealing in Non-FDA Approved Devices

Medical Device Company Pleads Guilty to Dealing in Non-FDA Approved Devices

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.

FDA Taking Steps to Prevent Future Medical Device Shortages

According to the FDA, the medical device industry experienced significant supply chain disruptions during the COVID-19 pandemic.  Such disruptions caused shortages of PPE, ventilators, diagnostic testing, and other medical devices.  As Janet Woodcock, M.D., the Acting Commissioner of Food and Drugs, acknowledges in her July 21, 2021 statement:

“the pandemic has exposed great weaknesses in the medical device supply chain and its dependence on foreign medical devices.”

Woodcock also explains the steps being taken by the FDA to avoid such shortages in the future.  One step includes a request for $21.6 million to fund a new Resilient Supply Chain and Shortages Prevention Program (RSCSPP).  This funding request is part of the FDA’s request for $97 million to support its core safety programs.  Woodcock explains “the funding will provide, for the first time, resources to establish a permanent program for U.S. supply chain resilience for medical devices.”  RSCSPP’s goal is to prevent and mitigate the supply chain issues like those experienced during the pandemic while reducing dependence on foreign medical devices.

Additionally, the FDA is looking to expand its authority to prevent future shortages.  The FDA seeks broader authority “to obtain supply disruption notifications for critical devices.”  Broader authority has also been requested to require manufacturers to develop and share risk management plans.  The FDA plans to work with Congress to ensure the FDA has the resources and authority needed to advance these initiatives.

Trademarks Require “Use in Commerce” – But What If You Need Regulatory Approval Before Selling Your Medical Device?

The U.S. Patent and Trademark Office (USPTO) allows for a trademark application to be filed on an “Intent to Use” basis to establish a priority date before the mark is actually “used in commerce.” However, such use in commerce must happen before the trademark application will register with the USPTO. If your company markets medical devices or related goods that require regulatory approval, the use in commerce requirement presents unique issues.

Typically, use in commerce is established when the goods affiliated with the trademark application are shipped between two states or to a foreign country, and with a label or packaging showing the trademark on the goods. For most industries, use of a trademark “in preparation” of sales will not suffice to satisfy the use in commerce requirement. Additionally, a trademark owner is only given three years to use the mark in commerce and provide evidence of such use after the USPTO determines the application is otherwise ready for registration. If the owner does not submit proof that it has used the mark by the deadline, the application is deemed abandoned. Three years seems like ample time for many trademark owners, but anyone who has needed regulatory approval for a product knows the process can stretch well beyond these three years. How does one deal with this conundrum?

You may think that you should wait to file your trademark application so that you don’t run out the three-year clock. But this may allow competitors to swoop in and file intervening trademark applications. If the USPTO believes your mark is confusingly similar to the mark in a competitors’ prior application or registration, it could prevent you from being able to register your mark.

With few exceptions, the best strategy is to file your trademark application as soon as possible. Fortunately, the law provides an accommodation for trademark registrants with goods and services that require regulatory approval. Legislators recognized the fact that “commerce” varies in different industries. For instance, while some companies can sell products as soon as they are ready for market, others must undergo testing to get a stamp of approval prior to marketing or selling their products. This latter group typically includes medical device companies. These and other devices may require pre-market approval (PMA) or a 510(k) clearance from the U.S. Food and Drug Administration (FDA), which can take many years.

Lawmakers revised the definition of “use in commerce” to state that such requirement:

be interpreted to mean commercial use which is typical in a particular industry. Additionally, the definition should be interpreted with flexibility so as to encompass various genuine, but less traditional, trademark uses, such as those made in test markets, infrequent sales of large or expensive items, or ongoing shipments of a new drug to clinical investigators by a company awaiting FDA approval (Senate Judiciary Committee Report on S. 1883, S. Rep. No. 100-515, p. 44-45 (Sept. 15, 1988))

This expanded meaning of “use in commerce” has been generally adopted by the USPTO and the courts.

FDA Issues Guidance on “Abbreviated” and “Special” 510(k) Pathways

The U.S. Food and Drug Administration (FDA) has issued two new guidance documents related respectively to an “abbreviated” and a “special” approach to the typical 510(K) process for medical devices.

The FDA describes the usual 510(K) process as “a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device…that is not subject to premarket approval.”  According to the FDA, “Each person who wants to market in the U.S., a Class I, II, and III device intended for human use, for which a Premarket Approval application (PMA) is not required, must submit a 510(k) to FDA unless the device is exempt from 510(k) requirements of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) .”

Now, two recent guidance documents issued by the FDA allow for altered 510(K) approaches for certain medical devices.  The first guidance, issued September 13, 2019, is for a “Special 510(K) Program.”  The FDA describes this program as “an optional pathway for certain well-defined device modifications where a manufacturer modifies its own legally marketed device, and design control procedures produce reliable results that can form, in addition to other 510(k) content requirements, the basis for substantial equivalence (SE).”  The guidance is intended to clarify “the types of technological changes appropriate for review as Special 510(k)s.”  The new guidance also supersedes prior FDA guidance from 1998 regarding Special 510(k) policy in “The New 510(k) Paradigm: Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications.”

This MDDI article purports to offer a “handy checklist” to determine “if changes made to your medical device can be reviewed under the [Special 510(K)] program.”  Some of the questions listed on the article’s checklist include the following:

  • Is it a change to the manufacturer’s own device?
  • Are performance data needed to evaluate the change?
  • Is there a well-established method to evaluate the change?
  • Can the data be reviewed in a summary or risk analysis format?

The second FDA guidance, also issued September 13, 2019, is for the “Abbreviated 510(K) Program.”  The FDA describes the program as “an optional approach that may be used to demonstrate substantial equivalence in premarket notifications (510(k)s)” and that “uses guidance documents, special controls, and/or voluntary consensus standards to facilitate FDA’s premarket review of 510(k) submissions.”   The guidance is “intended to facilitate 510(k) submission preparation by manufacturers and review by FDA.”

A copy of the guidance for the Special 510(K) Program can be found here, and a copy of the guidance for the Abbreviated 510(K) Program can be found here.   The FDA currently states that comments on either guidance may be submitted at any time.  Public comments on the guidance for the Special 510(K) Program may be submitted here and for the Abbreviated 510(K) Program here.

FDA Plans Overhaul of 510(k) Clearance Program

Recently, the U.S. Food & Drug Administration (FDA) announced plans to modernize FDA’s 510(k) clearance pathway, which was adopted more than 40 years ago.  The FDA stated that the plans are aimed at continuing to ensure that new and existing devices meet their standard for safety and effectiveness as technology rapidly advances. 

The FDA announcement reflects its focus on innovation by driving innovators toward reliance on more modern predicate devices.  Under the current framework, medical device manufacturers are required to submit a premarket notification to demonstrate that the low- to moderate-risk device to be marketed is safe and effective by proving substantial equivalence to a legally marketed device (“predicate device”) that is not subject to Premarket Approval.  According to the announcement, nearly 20 percent of current 510(k)s are cleared based on a predicate that’s more than 10 years old, contrary to the Agency’s belief that newer devices should be compared to the benefits and risks of more modern technology.

The Agency announced that it is considering, in the next few months, publishing on CDRH’s website those devices that have been cleared on the basis of demonstrated substantial equivalence of predicate devices that are more than 10 years old. The Agency also said that they are developing proposals to potentially subset certain older predicates and promote the use of more modern predicates.  Following up on the announcement, FDA Commissioner Scott Gottlieb, M.D., stated,

As devices become increasingly complex, it’s important that they meet the latest standards for cybersecurity, interoperability, biocompatibility and usability engineering.  The FDA has recently advanced policies on these issues, and we know that older predicates often don’t meet our more recent expectations.

Even though the announcement lacks details on these proposals, according to the announcement, in early 2019, the FDA intends to finalize guidance establishing an alternative 510(k)  pathway that allows manufacturers of certain well understood device types to rely on objective safety and performance criteria to demonstrate substantial equivalence as a way to make it more efficient to adopt modern criteria as the basis for the predicates that are used to support new products. 

 

FDA Approves Marketing of Self-Fitting Hearing Aid

The U.S. Food and Drug Administration recently announced approval for Bose to market their Bose Hearing Aid.  According to the press release, the Bose Hearing Aid, which was approved through the FDA’s De Novo premarket review pathway, is the first approved hearing aid that can be self-fit and adjusted by a user.

Malvina Eydelman, M.D., the Director of the Division of Ophthalmic, and Ear, Nose, and Throat Devices at the FDA’s Center for Devices and Radiologic Health commented:

“Today’s marketing authorization provides certain patients with access to a new hearing aid that provides them with direct control over the fit and functionality of the device. The FDA is committed to ensuring that individuals with hearing loss have options for taking an active role in their health care.”

According to the press release, clinical studies found the self-fitting Bose Hearing Aid to yield comparable outcomes relative to those found using a professional fitting.   The press release also reported that users generally preferred self-adjusted settings over those selected by a professional.

In a statement made to TechCrunch, Joanne Berhiaume, a spokesperson for Bose, stated:

“Now, the De Novo grant by the FDA validates that Bose technologies can be applied to help people with mild to moderate hearing impairment take control of their hearing. We look forward to bringing affordable, accessible and great sounding solutions to the millions of people who could benefit from hearing aids but don’t use them.”

FDA & DHS Coordinate Efforts to Address Cybersecurity

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.

FDA Expresses Priorities for Clinical Trial Efficiency, Artificial Intelligence

The FDA has announced new goals to help modernize its procedures and respond to new technologies.  In a blog post by FDA Commissioner Scott Gottlieb, M.D., the agency expressed new priorities to help modernize clinical trials for medical devices and develop standards for new technologies like artificial intelligence.

According to Gottlieb, clinical trials “are becoming more costly and complex to administer” while “new technologies and sources of data and analysis make better approaches possible.”  In order to take advantage of these better approaches, Gottlieb pointed to the FDA’s Breakthrough Devices Draft Guidance, which proposes streamlined procedures to develop flexible clinical trial designs for important medical devices.  This will allow the FDA to “evaluate . . . innovative devices more efficiently.”  Six breakthrough devices have already been cleared using this program.

Additionally, Gottlieb discussed the FDA’s new goal of enabling the use of “real-world evidence” to support decisions to approve devices.  According to Gottlieb, “[r]eal world evidence can help answer questions that are relevant to broader patient populations or treatment settings where information may not be captured through traditional clinical trials.”  The FDA is helping to design several proof-of-concept trials that utilize real-world evidence.

Finally, Gottlieb discussed the FDA’s role in dealing with new and emerging technologies.  In particular, Gottlieb discussed artificial intelligence, which “holds enormous promise for the future of medicine.”  Medical artificial intelligence models are currently in development and the FDA recently approved an AI algorithm for detection and treatment of distal radius fractures.  According to Gottlieb, the FDA is exploring ways to handle and evaluate the kinds of data that are relevant to AI performance and safety, hoping to “enable a transparent benchmarking system for AI algorithm’s performance.”

Gottlieb concludes that the FDA has “undertaken a comprehensive effort to make sure that our organization and policies are as modern as the technologies we’re being asked to evaluate, and that we’re able to efficiently advance safe, effective new innovations.”

BrainsWay Deep TMS System Receives FDA Clearance for OCD Treatment

Israel-based BrainsWay recently announced the de novo FDA clearance of its Deep Transcranial Magnetic Stimulation (TMS) system for treatment of obsessive compulsive disorder (OCD).

According to the press release, the BrainsWay Deep TMS system was previously cleared for treatment-resistant major depressive disorder in 2013, and this month’s de novo clearance is the second indication granted for the device, and marks the first clearance of a non-invasive device for treatment of OCD.  The BrainsWay press release further notes that the Deep TMS system’s H7-coil targets the anterior cingulate cortex, which is known to play a role in the pathophysiology of OCD.  BrainsWay stated that Deep TMS treatment, which uses changing magnetic fields to stimulate nerve cells in the brain, is non-invasive and has been shown to be safe and well-tolerated by patients.

BrainsWay plans to offer its OCD treatment both in new installations and as an upgrade to its existing systems.  Addressing the broad future applicability of the Deep TMS system, BrainsWay president and CEO Yaacov Michlin said:

This clearance further establishes Deep TMS as a platform technology that will provide treatments for additional psychiatric indications, subject to successful completion of our currently ongoing multi center studies and regulatory approvals.

FDA Approves First Generic Epinephrine Autoinjectors

FDA Approves First Generic Epinephrine Autoinjectors

The United States Food and Drug Administration recently announced approval for Teva Pharmaceuticals to market generic epinephrine autoinjectors.  According to the press release, Teva’s autoinjectors are the first generic versions of Mylan’s EpiPen® and EpiPen Jr ® to receive FDA approval.

Food Allergy & Research reports that as many as 15 million people in the U.S. have food allergies, which results in about 200,000 needing emergency medical care per year.  Commenting on the approval, U.S. FDA Commissioner Scott Gottlieb stated:

This approval means patients living with severe allergies who require constant access to life-saving epinephrine should have a lower-cost option, as well as another approved product to help protect against potential drug shortages.

Analyst reports indicate wholesalers are not expecting to receive the generic epinephrine autoinjectors from Teva for several months.  A Teva spokesperson commented that the company “is applying its full resources to this important launch in the coming months and is eager to being supplying the market.”  Currently, Mylan’s EpiPen® 0.3 mg autoinjector 2-pack sells for about $697 at HealthWarehouse.com.  Teva has not yet indicated the price of its generic autoinjector.