FDA Friday - Device Evaluation Intern Program

Our #FDAFriday series has focused on some of the various roles at FDA from former FDA employees. Well, what if we told you FDA is looking to hire you!?

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In one of AcKnowledge RS’ first blog posts (woah, I just checked and that was almost 2 years ago!), I talked about how I got into Regulatory Affairs (RA). In that post I discussed some options and suggestions for people who might be trying to do the same. To recap, there are several different ways you can break into RA, namely by checking local and national resources, by taking regulatory courses offered online or at certain universities, and most importantly, networking! But FDA is taking it one step further and making it even easier to cut your teeth on one of the coolest career paths out there. 

Many device companies offer “hands-on” internships during the summer, which is a great opportunity for college students on summer break and recent graduates who are looking for some summer experience. The Office of Device Evaluation (ODE) at FDA just announced one such internship program. ODE, at the Center for Devices and Radiological Health (CDRH), is the part of the FDA that is responsible for the review and regulation of new medical devices before they are introduced into the marketplace. 

The Device Evaluation Intern Program is the internship program that allows college-aged students to receive some experience in the field, and is offered year-round. When it comes down to the end, the program settles on 4-5 selected interns to participate in the program. The FDA also has a program that is designed specifically and primarily for students and recent graduates, and is called the Federal Pathways Program. Any and all applicants are encouraged to apply through the usajobs website (see links below).

ODE describes the internship opportunity as follows:
“Our Intern Program can be a challenging and rewarding experience for individuals interested in pursuing careers in the fields of science, engineering, and/or medicine. You will be given the opportunity to test your educational interests in a practical work environment, gain entry level professional "real work" experience, work alongside some the Agency's top healthcare authorities, establish professional contacts and most importantly, have a learning experience of a lifetime.”

FDA writes that the duties and responsibilities of the intern include:

  • Obtain and review technical literature or data to determine the safety, efficacy, and degree of risk to the public health of medical devices;
  • Perform administrative duties associated with device submissions, write minutes of technical and administrative discussions held between division personnel, industry, and management;
  • Assist senior reviewers in obtaining and reviewing technical data and material related to medical device submissions (510(k)s, IDEs, and PMAs);
  • Perform literature searches for senior scientists and prepare summaries;
  • Assist in preparing correspondence regarding informal inquiries about various types of medical devices.

The intern will get opportunities to participate in meetings, lunch seminars, and intern get-togethers. What a great opportunity to work at FDA!

So, how do you apply to the program? Apply through the http://www.usajobs.gov/ website. Your application should include a cover letter with a summary of your interests in the medical device area. You can mention all the cool stuff about medical devices you’ve learned over here on the AcKnowledge RS blog!


Wednesday Wisdom: Breakthrough Devices Program

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#WednesdayWisdom here at the AcKnowledge RS blog space consists of changes in FDA regulations, updated guidance, new programs, and regulatory considerations that we find interesting. The regulatory world is constantly changing with new medical technology and different questions surrounding device safety and effectiveness. Let us know if you have any regulatory questions that you'd like addressed at info@acknowledge-rs.com.

Last week, we mentioned a program called the Breakthrough Devices Program in our blog post about a quick, non-invasive test that could help diagnose the degree of a brain injury. The post from Monday has generated many emails and questions regarding the Breakthrough Devices Program, and today, we are here to settle the seas and answer some questions in order to better educate our readers about what this program really is!

The Breakthrough Devices Program— established under the 21st Century Cures Act in 2016— is a program in which devices with innovative and breakthrough technologies for life-threatening and irreversibly debilitating diseases are approved. These devices that get approved through this program are great for two different reasons: they either offer solutions for diseases for which no approved or cleared treatments exist, or they provide significant advantages over treatments that are already pre-existing. The Breakthrough Devices Program is an expansion of the Expedited Access Pathways (EAP), a program for devices that are subject to Premarket Approval applications (PMAs), 510(k) premarket notifications, or De Novo designation. The Breakthrough Devices Program is intended to help patients get timely access to breakthrough technologies by reducing the time and money to develop and market these devices. In that sense, this program is intended to help both the patients and the device manufacturers. Just think of the program as a catalyst of sorts, or— in the most basic sense— like getting upgraded to business class on a long flight; the devices that get approved/cleared/granted through the program get extra attention and may receive a decision quickly in order to get them to the patients in a more timely matter.

The program is a non-User Fee (this means it’s free!), voluntary program in which the device sponsor can contact FDA during early phases of the device development to help with a device study plan. The Breakthrough Devices program helps sponsor with an interactive, priority review involving senior management and a case manager. The early interaction helps the sponsor develop an efficient study plan to evaluate devices with complex technologies.

For a device to be considered “breakthrough”, the following criteria should be met:

  1. It should provide a more effective treatment or diagnosis for a life-threatening or irreversibly debilitating human disease or conditions.

AND

The device should meet at least one of the following four conditions:

  1. It should represent a breakthrough technology;

  2. There should be no approved or cleared alternatives existing for the device;

  3. The device should offer advantages over existing devices including the potential to reduce or eliminate the need for hospitalization, improve patient’s quality of life, facilitate patients' ability to manage self-care or establish long-term clinical efficiencies; or

  4. The availability of which is in the best interest of patients.

Sponsors intending to use this program should submit a Pre-Submission for an EAP designation. Unless there is insufficient information, FDA grants EAP designation within 30 days of receipt of a request. The EAP designation, however, can be revoked if the device no longer meets the criteria outlined by the EAP guidance document or if any untrue or false documents were submitted in support of the request. Also, just because you think your device is breakthrough doesn't always make it so. Keep in mind that FDA might not agree with your request, though that shouldn't be a reason to despair! We hear this has happened to a few companies who intend to submit a traditional premarket notification. (Remember, the whole premise behind the 510(k) program is 'demonstrating substantial equivalence' to a device that's already on the market. This might be hard to reconcile with the criteria listed above.) 

FDA grants the EAP designation based on benefit-risk determinations. If the device provides considerable benefit to patients with a life-threatening disease when no alternative treatments are available, then FDA grants the EAP designation if adequate post market controls are in place.

Ever since the establishment of the program, 54 devices have been granted breakthrough status through the Breakthrough Devices Program. Many of these devices have progressed to become extremely effective mechanisms that are highly exalted. One such device that has attained much success is the Orion Cortical Visual Prosthesis System from Second Sight Medical Products Inc., a brain implant that is targeted towards blind people who have damage to their optic nerve. The device mimics light perception and transmits signals to an implant that is situated in the patient’s visual cortex, a truly remarkable development in the medical and optic world.  

Overall, the Breakthrough Devices Program, as developed by the FDA, promises to have the patient’s interest as the foremost concern, without compromising on the safety and effectiveness. While it might not be a good fit for all devices (i.e. if your device isn't breakthrough, or you're all ready to submit and the review of your request may delay your submission), we think this program is a potential win/win/win situation for FDA, industry, and patients!

Further Reading:

  1. Draft Guidance for Industry and FDA Staff

  2. Medical Device Monday from April 2, 2018

  3. Example of Data Development Plan

Med Device Monday: Diagnostic for Detection of Brain Trauma

 Image from thepinetree.net

Image from thepinetree.net

Every once in a while, a "breakthrough" medical device promises to address unmet medical needs through its innovative technology. Such devices are reviewed by the FDA under their Breakthrough Devices Program, which allows for expedited development and release of the devices into the market. One such promising in vitro diagnostic device is for detection of mild traumatic brain injury (mTBI)—commonly known as concussion. The Banyan BTI (Brain Trauma indicator) is a biomarker-based, in vitro diagnostic blood test developed by Banyan Biomarkers, Inc. That's right! A blood test for brain trauma. Truly, we are living in the future. 

Traumatic brain injury (TBI) is an injury to the brain following a violent blow to the head. Accidents, sport-related concussions, and falls can all cause TBI. In turn, TBI can be classified as either Mild and Severe. Mild TBI, or mTBI, causes loss of consciousness for less than 30 minutes, resulting in cognitive dysfunctions such as memory loss, attention deficits, and mood swings. It is often missed at the time of initial injury. Severe TBI, on the other hand, causes loss of consciousness for more than 30 minutes. This is due to penetrating skull injury which can result in severe cognitive impairment and even a comatose state for the patient. According to the Centers for Disease Control and Prevention (CDC), in 2013 TBI resulted in approximately 2.5 million emergency visits and 282,000 hospitalizations out of which 94.5 percent of TBIs are mTBIs or concussions.

Banyan BTI detects the presence of two brain-specific biomarkers—UCH-L1 (Ubiquitin Carboxy-terminal Hydrolase-L1) and GFAP (Glial Fibrillary Acidic Protein)—which are quickly released into the blood following a concussion. Measuring these protein levels within 12 hours of a head injury can help identify intracranial lesions following an incident.

The current mode for detecting brain tissue damage is to use a neurological scale, called the 15-point Glasgow Coma Scale, followed by a computed tomography or CT scan of the head. The current methodology is defective in the sense that over 90% of patients with mild TBI have a negative CT scan. Moreover, the CT scan has the disadvantage of considerable radiation exposure to patients. Availability of a blood test for mTBI/concussion will likely reduce the amount of CT scans done—saving essential dollars for our health care system.

According to a multi-center, clinical study of 1,947 individual blood samples from adults with suspected mTBI or concussion, and compared with CT scan results, Banyan BTI was able to predict the presence of intracranial lesions with an accuracy of 97.5 percent. Banyan BTI was cleared by FDA via the de novo pathway, and it promises to be the first objective blood test that will help clinicians rule out the need for unnecessary CT scans in persons with mTBI.

These are exactly the types of breakthrough devices that FDA seeks to get to market: it's less invasive and risky for patients, and provides quick results at a lower cost. What's not to like? 

 

Further Reading:

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm596531.htm

https://www.banyanbio.com/about-biomarkers.html

Med Device Monday: Guided CPR Device

Most of us have probably been through a cardiopulmonary resuscitation (CPR!) training course, or at least have a passing familiarity with what CPR entails. Chest compressions, mouth-to-mouth, keeping up certain counts and rhythms: if you haven't been trained or had to do it yourself, then it's likely you at least know about it from movies and TV. Indeed, a quick YouTube search shows up dozens of clips and montages of CPR being done on screens big and small. Although, maybe be wary if you're trying to learn CPR at a paper company in Scranton, PA:

Performing CPR on someone, particularly if you're not a professional, can be a scary proposition. Especially if it's the first time you've had to do it, your training wasn't recent or hasn't been practiced very much, and/or it's someone you love. It's easy for all that training to go out the window in a moment of crisis. Imagine how it would be made easier if there were a device guiding you? Well now there is...although it's only for professionals. It's still pretty exciting!

When a person experiences sudden cardiac arrest, defibrillation and CPR are the two of the most critical components of the first line of treatment. Zoll® is marketing a new line of professional defibrillators—X Series®, R Series®, AED Pro®, and AED 3 BLS®—to help make delivering this time-dependent treatment as quickly and effectively as possible. In addition to delivering lifesaving electrical shocks, this line of defibrillators also provide realtime CPR help, giving the person administering CPR live feedback on the depth and rate of chest compressions—thus allowing any changes to be made to help provide the most effective treatment. While these devices are only to be used by medical professionals, it's not hard for the rest of us to imagine how very useful they could be. 

 Photo from fda.gov.

Photo from fda.gov.

These devices from ZOLL have the ability to monitor: electrical activity of the heart via electrocardiogram (ECG) and 12-lead ECG analysis; effectiveness of the CPR; temporary cardiac pacing (external transcutaneous pacing); blood pressure, without puncturing the skin (non-invasive blood pressure monitoring); amount of oxygen in the blood (SpO2); number of breaths a patient takes per minute (respiration monitoring); carbon dioxide (CO2) levels; blood pressure.

So, how does it work? Per FDA, "The ZOLL® X Series®, R Series®, AED Pro®, and AED 3 BLS® devices use two multifunction defibrillation electrodes to acquire a patient's electrocardiogram (ECG). If this device detects an abnormal heartbeat, it may advise the user that a high-energy shock is necessary. The user interface will provide voice instructions to guide the user through the rescue process including cardiopulmonary resuscitation (CPR). The device will provide an audible rhythmic beeping sound to help the user deliver the correct rate of compressions while giving CPR. If a defibrillation shock is required, the device will prompt the user to deliver an electrical shock, through the electrodes."

When the unit detects a shockable rhythm, it charges and issues the warning "PRESS FLASHING SHOCK BUTTON". The rescuer presses the Shock Button to deliver the shock. The rescuer will then be prompted to perform CPR for a period of 2 minutes, after which the unit automatically initiates a new ECG analysis.

As previously stated, the ZOLL® X Series®, R Series®, AED Pro®, and AED 3 BLS® devices should be used only by trained medical personnel to treat both adult and pediatric patients with sudden cardiac arrest or who are unconscious, not breathing, and without a pulse. While most of us 'medical civilians' will still have to rely on our CPR classes and proper training to deliver CPR in an emergency, this is pretty impressive stuff. We've said it here before, but sometimes technology is most interesting when it makes an existing staple of healthcare even better. 

 

Further Reading:

FDA announcement of recent approval

ZOLL Premarket Approval (PMA)

Zoll FDA approval letter

 

 

 

Med Device Monday: Implantable Continuous Pump for Remodulin

Imagine you have a condition where your body doesn't produce enough of the chemical that keeps your blood vessels open and clear, instead allowing them to thicken. This of course impacts the amount and flow of oxygen you're getting and thus affects your heart and lungs. Imagine that there is, fortunately, a treatment for this. But treatment requires regular visits to medical professionals for IV drips or shots, to keep your body functioning and battling this condition. You go because these visits are helping keep you alive. But what if you could just have the whole system implanted and skip most of those visits, constant monitoring, frequent skin punctures, and some of the possible side effects? Well, now you can. 

Pulmonary arterial hypertension (PAH) is a progressive disease where they body doesn't make enough prostacyclin, which allows the pulmonary system to function properly. Remodulin (treprostinil) is a drug that can treat this condition, but which needs to be regularly administered. A new system recently approved by FDA allows the whole thing to be implanted and doses administered automatically via an IV catheter, thus improving quality of life: the Implantable System for Remodulin is a fully implantable system designed to deliver Remodulin® (treprostinil) injection intravenously for the treatment of patients with pulmonary arterial hypertension (PAH). 

Remodulin is stored in the pump reservoir and, per a programmed prescription, moves through the pump tubing, the catheter port, and the catheter to the intravascular delivery site. The programmer is a handheld device that is used to review and program pump parameters using telemetry, a radio frequency (RF) communication. The physician or healthcare provider usually calibrates this at a first visit. Subsequent visits are of course required, but the level of maintenance versus routine IV drips or injections is considerably less.

 Image from medgadget.com.

Image from medgadget.com.

The American College of Cardiology sums it up well: "The most notable benefit of the implantable system is that it significantly reduces the rate of BSIs [blood stream infections] and site infections versus that associated with external IV systems. It also eliminates chronic treprostinil-induced infusion site pain associated with SC administration. By reducing the rate of catheter-related complications and pump user errors that cause drug interruptions or overdose, it improves the consistency of therapy. Finally, it improves patient's quality of life by eliminating the daily burden of system management, and reducing restrictions and fear during normal activities of daily life. The majority (93%) of patients rate the implantable system as "very good" or "excellent"."

The Implantable System for Remodulin, which is marketed by Medtronic, is made up of 3 parts:

·      The pump (Medtronic SynchroMed II 8637P Programmable Pump)

·      The catheter (Medtronic 8201 Implantable Intravascular Catheter)

·      The programmer (Medtronic N’Vision 8840 Clinician Programmer with 8870 Application Card)

The pump is implanted by the surgeon in the subcutaneous pocket using an incision in the lower abdomen. The intravascular catheter is connected to the pump and inserted through a vein at the superior caval-atrial junction which is the junction between the superior vena cava and the right atrium of heart. The pump reservoir remains permanently implanted and the health care provider uses a needle and syringe refill kit to refill the pump with Remodulin by a percutaneous procedure. 

 Image from medgadget.com.

Image from medgadget.com.

This medical device does come with some parameters. Restrictions for The Implantable System for Remodulin should not be used in the following patients, including NYHA Class IV heart failure patients; patients who cannot tolerate a sudden cessation of Remodulin therapy; patients with a known or suspected infection, bacteremia, or sepsis requiring antibiotics; patients with vasculature that is inadequate for an 8 French introducer or catheter advancement without stylet guidance; patients implanted with leads or catheters (active or abandoned) in the superior vena cava that cannot be removed prior to or at system implant; patients whose body size is not sufficient to accept pump bulk and weight; patients with skin or soft tissue that would heal poorly, increase susceptibility to infections, or is unacceptable for implant of this system; patients for which a health care provider cannot implant the pump 2.5 cm or less from the surface of the skin.

It's interesting and exciting to see how medical devices can make for new versions of existing successful therapies. This implantable system is a great example of how quality of life can be improved via medical device technology without having to reinvent the proverbial wheel.

 

Further reading:

Remodulin Implantable FDA Approval

Remodulin Implantable FDA Approval Letter

Remodulin website