Med Device Monday: Hemospray from Cook Medical

This week, we are talking about Hemospray®, a device marketed by Cook Medical that has been developed for hemostasis of Non-Variceal gastrointestinal Bleeding (NVGIB). Quite the mouthful there, right? Let’s talk about what NVGIB is in order to better understand how the device works.

Non-Variceal Gastrointestinal Bleeding (NVGIB) is bleeding that develops in the upper gastrointestinal tract, stomach, or the proximal duodenum. The most common cause of the bleeding is a peptic ulcer caused by the gut bacteria Helicobacter pylori (H. pylori) infection. This type of infection is often associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin, and can be uncomfortable to live with.

H. pylori infections are most commonly treated with antibiotics, however, the more serious resulting NVGIB continues to be a medical emergency with a mortality rate of approximately 1–5% (Lanas et al., 2018). Recent advances in the prevention and management of NVGIB has resulted in decreased incidence (~67 per 100,000 individuals). However, treatment for NVGIB has not yet been perfected, with options such as endoscopic interventions and pump inhibitors being the current methods of treatment. Here is where Hemospray comes in.

https://www.cookmedical.com/newsroom/hemospray-to-us-physicians/

https://www.cookmedical.com/newsroom/hemospray-to-us-physicians/

Hemospray® is a single use device which achieves hemostasis using a proprietary mineral blend powder. This inorganic powder is metabolically inert and is not absorbed by the body; instead passing through the lower GI tract within 72 hours after application. According to the manufacturer, Hemospray® has advantages over traditional therapies as it is a non-thermal, non-traumatic, non-contact treatment. The device uses a catheter that is inserted through an endoscope to the site of the bleed. The catheter delivers the powder using a carbon dioxide-powered delivery system. When the powder contacts an active bleeding site, it absorbs water and forms a mechanical barrier by acting both cohesively and adhesively (as shown in step three and four of the image below). This barrier blocks further bleeding from occurring, and seals off the hemorrhage or bleeding site.

https://www.cookmedical.com/data/resources/ESC-D43196-EN-F_M3_1528401363290.pdf

https://www.cookmedical.com/data/resources/ESC-D43196-EN-F_M3_1528401363290.pdf

FDA reviewed data from clinical studies consisting of 228 patients with upper and lower GI bleeding, and supplemented this data with real world evidence from medical literature reports that included an additional 522 patients. The Hemospray device stopped GI bleeding in 95 percent of patients within five minutes of device usage. Re-bleeding was observed in only 20 percent of these patients between 72 hours and 30 days following device application. Hemospray is contraindicated for patients who have a gastrointestinal fistula or are at high risk for experiencing a gastrointestinal perforation .

An ease of use comparison study carried out on 79 patients showed that Hemospray® was comparable to or easier than other hemostasis treatment modalities. Hemostasis was achieved in less than 10 minutes in over 77% of cases and thought to save time in 59% of cases (Morris et al.,2014).

FDA reviewed the device under their de novo pathway and concluded that Hemospray® be classified as a Class II, moderate risk device. In addition to general controls that are applicable to a Class II device, these types of devices are also subject to the following special controls:

1. Biocompatibility testing of the patient-contacting components of the device

2. Sterility and pyrogenicity of patient-contacting components of the device the device

3. Shelf life

4. In vivo performance testing

5. Non-clinical performance testing

6. Labeling

We’re excited to see new device-based treatment options for diseases like NVGIB! We’re also excited to see FDA accept real world evidence in support of premarket submissions. There is a big effort at the agency on reducing burden, improving patient safety, and supporting new technologies like the Hemospray® device. Using real world evidence to bring products like this to market is one of the ways FDA continues its mission!

References:

1. Lanas A, Dumonceau JM, Hunt RH, Fujishiro M, Scheiman JM, Gralnek IM, Campbell HE, Rostom A, Villanueva C, Sung JJY. Nature Reviews Disease Primers. volume 4, Article number: 18020 (2018)

2. Morris AJ, Smith LA, Stanley A, et al. Hemospray for non-variceal upper gastrointestinal bleeding: Results of the Seal Dataset (survey to evaluate the application of Hemospray in the luminal tract). Journal of Clinical Gastroenterology. 2014 Nov; 48(10): E89-92.

Additional Resources:

1. FDA Press Release

2. FDA Decision Summary

3. FDA Reclassification Order

4. Hemospray Animation

5. Cook Medical Website

FDA Friday - Srinidhi Nagaraja, PhD

This #FDAFriday series consists of mini-interviews with former FDA regulators. Our goals are twofold: (1) help students and professionals interested in Regulatory Affairs see what career paths are possible, and (2) talk about some of the various roles at FDA to demonstrate the diversity of responsibilities at the Agency. If you are a former FDA employee and would like to participate, please email us at info@acknowledge-rs.com.


While working on a premarket approval (PMA) submission, I always enjoyed the diversity in skills and expertise within the team. It was a great opportunity to listen to and learn from medical officers, toxicologists, and veterinarians, and better understand their perspective of the risks and benefits of a particular device.
— Srinidhi Nagaraja, PhD
Nagaraja - head shot.BW.JPG

Dr. Nagaraja received his Doctorate and Master of Science degrees in Mechanical Engineering from the Georgia Institute of Technology, following a Bachelor of Science degree in Mechanical Engineering from the University of Michigan. In his role at FDA, Srinidhi acted as a senior consultant for mechanical safety of premarket medical device submissions, including IDE, PMA and 510(k) applications. He also analyzed post market mechanical failures, with expertise in cardiovascular and orthopedic devices. Concurrent with his time at FDA, Srinidhi was an affiliate faculty member at the University of Maryland, and developed an active research program improving assessment and studying the integrity of cardiovascular and spinal devices.


Tell us a little bit about your time at FDA.

I spent 10 years at the FDA’s Office of Science and Engineering Laboratories (OSEL) in the Center for Devices and Radiological Health (CDRH). Not many in industry are aware that CDRH has facilities to perform device research and testing. During my time at FDA, my responsibilities spanned both the regulatory and science based mission of CDRH. For example, I was a technical consultant to the review teams in the Office of Device Evaluation (ODE) for various regulatory submissions. My area of expertise was mechanical safety and performance of medical devices. In particular, I was involved in evaluating the durability, corrosion resistance, and mechanics of various medical devices. I was also a principal investigator for research studies focused in areas such as spinal biomechanics, nitinol durability, and corrosion susceptibility of implants. These studies were performed to help ensure that CDRH was ready to evaluate emerging and innovative medical technologies. In addition, the research aided in the development of appropriate testing standards (e.g. ASTM or ISO standards) or acceptance criteria for use by the medical device community during design verification activities.

How did your research in OSEL inform your work as a reviewer?

One example of how my research informed regulatory review was a study to better understand in vivo corrosion resistance of nitinol implants. This was an important topic within the implant community as there was considerable debate regarding suitable acceptance criteria during an FDA workshop that I co-organized in 2012. We conducted an animal study to address the issues raised and provide scientific data to help determine acceptable limits for the corrosion of implants. The papers published on this topic have helped clients I work with in my current position as part of design verification testing activities, and also have been referenced by FDA during regulatory review.

What was your favorite thing about working with a review team on a premarket notification or approval submission?

While working on a premarket approval (PMA) submission, I always enjoyed the diversity in skills and expertise within the team. It was a great opportunity to listen to and learn from medical officers, toxicologists, and veterinarians, and better understand their perspective of the risks and benefits of a particular device. I also was fortunate to work on PMAs in many different product areas, especially in those where the use of nitinol was increasing. This really made the day-to-day work fun, as I needed to think critically about how to apply mechanics principals to various significant risk devices.

While at FDA, you were also affiliate faculty at the University of Maryland. How did you swing that sweet gig? What was it like having that joint appointment?

It was great having a faculty appointment at the University of Maryland while at FDA. The connection was beneficial for both FDA and the university’s Bioengineering Department. As a result of the joint appointment, I was able to advise PhD candidates and participate in seminars and collaborate on research studies at the university. My dual position also created opportunities for University of Maryland students to gain experiences in regulatory science and device approval process as FDA interns. Overall it was a wonderful experience, and allowed me to mentor undergraduates and graduate students pursuing biomedical engineering degrees.

What are you up to these days?

I left FDA over a year ago and started at G. Rau Inc., which is an independent medical device testing laboratory in the Bay Area. Our company provides standard and custom mechanical testing (e.g., durability, corrosion) and technical consulting to medical device companies. My role at G. Rau Inc. is to support device companies seeking approval/clearance of their device. In particular, we help establish testing strategies, conduct testing to characterize device safety and performance, and address FDA deficiencies during the approval/clearance process.

How does your current role incorporate or benefit from your regulatory experience?

I think there is a direct benefit to having regulatory experience. I apply my previous FDA regulatory and research experiences to help device companies with design verification testing and other scientific matters in order to demonstrate the mechanical safety and performance of their device. For example, my reviews of devices at FDA were focused on analyzing testing plans, reviewing mechanical test reports, and providing technical recommendations to device companies. Now, I use those experiences to help companies outline an approach to successfully establish safety and performance of their device.

What do you think is a common misconception about your current company?

One misconception is that our company provides testing and technical consulting solely for nitinol-based products. However, our testing capabilities and expertise are fairly broad, allowing for testing of devices manufactured from other materials (e.g. titanium spinal components).


More about Srinidhi Nagaraja, PhD

For more information about Srinidhi, please visit his LinkedIn page, and for more information on G. Rau Inc., please feel free to contact Dr. Nagaraja by email <srinidhi.nagaraja@g-rau.com> or click here.

Med Device Monday: The Fluobeam 800 and the PTeye System for Parathyroid Tissue Detection

Hi AcKnowledge RS Blog Followers!  We took a short hiatus in December as it was a hectic month submission-wise AND we’ve been working on a really exciting project that we’ll announce later this month. Also, everyone in the office took a little well-deserved vacation time to visit at least one of the following places: Hawaii, Disneyland, Paris, Universal Studios, Palm Springs and Florida. Now we’re back and ready to do what we love most: talk about medical devices!

 

In this week’s Medical Device Monday blog, we are discussing two devices that provide real-time identification of the parathyroid tissue during surgery. The devices— Fluobeam 800 Clinic Imaging Device (Fluobeam®) marketed by Fluoptics, and Parathyroid Detection PTeye System marketed by AiBiomed— were granted by the FDA recently under the De Novo review pathway.

Image from Fluoptics.com

Image from Fluoptics.com

Parathyroid Glands

Everyone has (or at least is supposed to be born with) four parathyroid glands. These pea-sized glands are located on the back of the thyroid gland at the base of the neck. Parathyroid glands produce the parathyroid hormone which, along with calcitonin (secreted by the thyroid gland), regulates the amount of calcium in the blood and within the bones. As you can imagine, this calcium regulation is essential for proper functioning of both our muscular system and our nervous system. The overproduction of the parathyroid hormone results in primary hyperparathyroidism, whereas an underactive parathyroid gland results in hypothyroidism.

Hyperparathyroidism can lead to hypercalcemia, or high levels of calcium in the blood. In turn, hypercalcemia can lead to a variety of problems in the body, such as fragile bones, abdominal pain, kidney stones, and excessive urination. In the United States, about 100,000 people are diagnosed with primary hyperparathyroidism annually1. People between age 50 and 60 are most commonly affected, with women being three times more affected than men2. Hypothyroidism, on the other hand, can cause health problems like joint pain, heart disease, and obesity, and can be characterized by dry skin, muscle weakness, sensitivity to the cold, along with other symptoms.

Surgery to remove the parathyroid tissue is the most common treatment for hyperparathyroidism. Parathyroid tissue can be visually difficult to locate as they can sometimes be indistinguishable from neighboring tissues. According to Binita Ashar, M.D., director of the Division of Surgical Devices in the FDA’s Center for Devices and Radiological Health, “Real-time identification of parathyroid tissue during surgery can provide surgeons with valuable information to help preserve healthy tissue or to remove diseased tissue.”

Unfortunately, the parathyroid is not naturally bright purple like this image depicts.

Unfortunately, the parathyroid is not naturally bright purple like this image depicts.

The Fluobeam 800 Clinic Imaging Device

Fluobeam® is an integrated fluorescence imaging device with a Class 1 laser as the excitation light source, and a near-infrared-sensitive camera. When exposed to the laser light, the parathyroid glands emit auto fluorescence in the near infrared without a need for any dye injection.

Parathyroid Detection PTeye System

The Parathyroid Detection PTeye System uses a probe that emits fluorescent light. Tissue detection is based on how the parathyroid tissue reacts to the fluorescent light. When parathyroid tissue is detected, the system provides an audio and visual display to indicate its presence.

Both of these devices are intended to assist (not replace) visual assessment by the surgeons in identifying the parathyroid tissue. FDA reviewed both of these devices and concluded that they should be classified as Class II devices, which, along with general controls, are subject to the following special controls:

1.       In vivo testing to show that the device can detect auto fluorescent signals from tissues

2.       Biocompatibility testing of the patient-contacting components of the device

3.       Testing to demonstrate the electromagnetic compatibility and electrical, mechanical and thermal safety of the device

4.       Software verification, validation, and hazard analysis

5.       Sterility testing of patient-contacting components of the device

6.       Performance testing to demonstrate laser and light safety for eye, tissue and skin

7.       Appropriate Labeling

Both of these de novo devices have undergone clinical testing to demonstrate their accuracy in locating parathyroid tissue during surgery. Removing the parathyroid and not surrounding tissue, or preserving the parathyroid when it’s meant to remain where it belongs, is important for doctors and their patients undergoing surgery. Using these tools to improve patient outcome during surgeries is a win-win in our opinion. We’re excited to see what other interesting technology comes to the US market in 2019!  Happy New Year!

 

 

Additional Reading:

1.       FDA Press Release

2.       https://fluoptics.com/en/fluobeam/

3.       Fluobeam Classification Order

4.       Parathyroid Detection PTeye System Classification Order

References:

1.        Bilezikian JP. Primary hyperparathyroidism. In: DeGroot LJ, ed.; Arnold A, section editor. Diseases of Bone and Mineral Metabolism. www.endotext.org  website. South Dartmouth, MA: MDTEXT.COM, Inc. Accessed February 22, 2012

2.       Silverberg SJ and Bilezikian JP. Primary hyperparathyroidism. In: Jameson JL and DeGroot LJ, senior eds. Endocrinology: Adult and Pediatric. 6th ed. (online version). Philadelphia: Saunders; 2010.

Med Device Monday: Reclassification of the Female Condom

Last week we discussed the two different ways for a medical device to be reclassified at FDA. This week we’re going to dive in and give you an example of a recent medical device that underwent reclassification.

Image from https://www.rutgers.international/news-opinion/news-archive/international-women%E2%80%99s-day-time-female-condoms

Image from https://www.rutgers.international/news-opinion/news-archive/international-women%E2%80%99s-day-time-female-condoms

On September 26th, FDA published a final order titled “Obstetrical and Gynecological Devices; Reclassification of Single-Use Female Condom, To Be Renamed Single-Use Internal Condom.” As you can tell by the name of the order, the device has been renamed from a “single-use female condom” to a “single-use internal condom,” effective October 29, 2018. In addition to the renaming of the device— which was done to differentiate it from the single-use internal condom— another change has been made to the device; it has been changed from a class III device to a class II device. This classification and name change comes as a result of newly evaluated information that was not available at the time of the original device’s premarket approval, as well as comments from the public that were received in response to FDA’s proposal to reclassify that came in December 4th, 2017. There were a total of 78 public comments in response to the proposed order from December 2017. The majority of these comments were in support of the reclassification of the device, as well as the name change and the effort to increase patient access to single-use internal condoms.

As previously stated, the device was originally classified as a class III device. Devices that weren’t in commercial distribution before May 28, 1976 were automatically classified as a class III device without any FDA rulemaking, and are traditionally called postamendment devices. Those devices maintain that classification until the device is reclassified. One of the ways this reclassification can occur is if the FDA issues an order that finds the device to be substantially equivalent to a predicate device that does not require premarket approval. FDA can reclassify devices on their own initiative, or in response to petition from manufacturer or importer of the device. FDA relies on valid scientific evidence in the classification process to determine the level of regulation for devices.

The final order highlights that when used correctly, the single-use internal condom is the only female-controlled method that is intended to prevent both pregnancy and the transmission of sexually transmitted infections (STIs). By finalizing this reclassification, the FDA minimizes the regulatory burden on industry, since single-use internal condoms will no longer require premarket approval (PMA). Instead, these devices will require a less burdensome 510(k) prior to marketing.

FDA is making the two modifications to the identification for single-use internal condoms by confirming that they’re over-the-counter devices, and that the device is intended to “prevent the transmission of sexually transmitted infections,” not “prevent sexually transmitted infections.”

The single-use internal condoms have been reclassified to class II with special controls under 21 CFR part 884 for obstetrical and gynecological devices.The special controls established for this device are clinical performance testing, viral penetration testing, nonclinical performance testing, biocompatibility analysis, shelf-life and packaging testing, and labeling. Each of these special controls contains further details and requirements. For example, the clinical performance testing must include the rate of clinical failure, rate of individual failure modes, and the cumulative pregnancy rate when using the device based on a contraceptive effectiveness study. Viral penetration testing is required to demonstrate that the device is an effective barrier to STI’s, and the shelf-life and packaging testing is necessary to demonstrate that the device maintains the performance characteristics and integrity for the duration of the shelf-life. In addition, the nonclinical testing must include both mechanical testing and compatibility testing. That’s a lot, right? But it’s all for a good reason! Reviewers need to make sure that the reclassification is valid, and is being reclassified into the right class.

This is a good example on how FDA reevaluates medical devices as better understand the device’s benefits and risks. For more information on how FDA reclassifies devices, check out our FDAFriday blog post where we discuss “Reclassification.”

Additional Reading:

1.    Federal Register Female Condom Information

2.    Reclassification Information

3. Reasons to Use the Female Condom (opinion)

FDA Friday: Reclassification

The longer you know someone, the more you learn about them. Well, the same goes for medical devices! As knowledge about a medical device increases, we inevitably have a better understanding on its benefits and risks. As our understanding of a device evolves over time, it is possible that the classification of the device might need a little update. There are two different ways for a medical device to be reclassified at FDA, both of which we review below.

First, there is a way for a medical device to be reclassified as described in the Food, Drug and Cosmetic Act (the Act). Under Section 513(e) of the Act, FDA may reclassify a device based on new information, whether it is discovered on their own, or in response to a petition from an interested person. In this case, “new information” is defined as publicly available, valid scientific evidence. If FDA or a petitioner proposes that a device be reclassified to a lower class (say from the higher risk Class III to a moderate risk Class II), sufficient and valid scientific evidence must be provided in order to support the determination. In July of 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) was created, which changed the reclassification process to an administrative order process instead of rulemaking. According to FDA’s website that discusses reclassification, in order to reclassify a device under this section of the FD&C Act, FDA must do the following before making the reclassification final:

§  Publish a proposed order in the Federal Register that includes proposed reclassification and summary of the scientific evidence supporting the reclassification

§  Have a panel meeting for the device classification before or after the proposed order has been published

§  Take comments from the public docket into account

Image from https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHTransparency/ucm378724.htm

Image from https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHTransparency/ucm378724.htm

There are also additional rules and guidelines that apply depending on the original class level, and the new class level for a device. For example, for devices being reclassified from Class II to Class III, the scientific evidence must indicate that the general and special controls are insufficient to provide reasonable assurance of safety and effectiveness. Conversely, if a device is being reclassified from Class III to Class II, the scientific evidence must show the opposite; that the general and special controls are sufficient to provide reasonable safety and effectiveness. Lastly, if a device is being reclassified to Class I from either Class III or Class II, the scientific evidence must show that the general controls alone are sufficient to provide reasonable assurance of safety and effectiveness.

 

The other route for devices reclassification is described in Section 513(f)(3) of the FD&C Act. This originates from the understanding that any device not available before the Medical Device Amendments in 1976 was automatically classified as Class III. This classification was determined regardless of any risk the device posed, and without undergoing any FDA rulemaking processes. These medical devices are more commonly known as postamendment devices. Unlike the process above, these devices may only be considered for reclassification if the initiative comes from FDA or a petition from a manufacturer or importer. Similar to the 513(e) process discussed in the previous paragraph, reclassification of a device can only be made when sufficient regulatory controls can provide reasonable assurance of safety and effectiveness. A device reclassification panel may also be called, should FDA receive a petition requesting reclassification. After all information has been considered, FDA will determine whether the reclassification petition is approved or denied. Following approval, the order describes both the reason for reclassification, as well as any of the device’s risks to patient health.

 

By the way, if you’re wondering where the whole de novo process fit here, you should check our previous blogs here along with the update here. Keep in mind, a de novo request (per 513(f)(2) of the FD&C Act) is a file where a submitter can request a new classification altogether. Therefore, we don’t really consider it a ‘reclassification’ per the definition of our subject in this blog.

 

To see a full list of medical devices that have been reclassified since 2013, visit this link. If you’re wondering why the list only goes back five years, it’s because it wasn’t until FDASIA was enforced in 2012 that FDA was required to annually post the devices reclassified in the year prior.

 

Additional Reading:

  1. Overview of Medical Device Classification and Reclassification

  2. Classify your Medical Device