FDA Friday

FDA Friday - Dulciana Chan, M.S.E.

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.


A common mistake that manufacturers make in their Investigational Device Exemption (IDE) submissions is not having a plan to deal with missing data. It is important to have a plan upfront so that the data from all patients can be used.
— Dulciana Chan, M.S.E.
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Dulciana Chan received her B.S. in Biomedical Engineering from Johns Hopkins University in 2002, and her M.S.E. in Bioengineering from the University of Maryland in 2010. Directly following her undergraduate degree, Dulciana began her FDA career as a research associate in the Center for Devices and Radiological Health (CDRH), Office of Science and Engineering Laboratories (OSEL). A year later, she became a Biomedical Engineer at FDA, and for 14 years operated in various branches of the administration, including as a scientific reviewer and policy analyst in the Office of Device Evaluation (ODE), and as an OSEL principal investigator.

While working at FDA, Dulciana received numerous honors and awards, including the 2014 CDRH Honor Award and the 2014 FDA Scientific Achievement Award for Excellence in Analytical Science. Dulciana has extensive experience in the areas of electromagnetic compatibility (EMC) testing and electrical safety, and is an asset to Acknowledge Regulatory Strategies, where she is a Senior Regulatory Specialist.


Tell us a little bit about your time at FDA.

I started at the FDA as a research associate in the Center for Devices and Radiological Health (CDRH) in the Office of Science and Engineering Laboratories (OSEL). I worked on several research projects and gained skills including computational modeling and electromagnetic compatibility. One of my main projects focused on optical recording of cardiac myocyte monolayers to study cardiac arrhythmias. After my first year at FDA, I also became a scientific lead reviewer in the Office of Device Evaluation (ODE). Fortunately, I was able to continue performing research in OSEL while doing premarket reviews for devices in ODE for the next 14 years.

Can you tell us a little more about your research in the Office of Science and Engineering Laboratories (OSEL)?

The lab I was in began to use pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias. It was part of a larger program to predict drug proarrhythmic risk in cells prior to the clinical studies that are required for new drugs. This research was very rewarding in clinical relevance and scope.

You also worked as IDE staff while you were at FDA. What was one of the common mistakes you saw companies make when submitting their clinical study to FDA?

A common mistake that manufacturers make in their Investigational Device Exemption (IDE) submissions is not having a plan to deal with missing data. It is important to have a plan upfront so that the data from all patients can be used. The reality is that there will be missing data, whether from a patient missing a follow-up or a missing test or outcome. However, with preplanning, the data can still be interpreted correctly.

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

One of the benefits of working with a review team is being able to access the knowledge of an expert. Often there may be an aspect about a device that you only have high level knowledge about. The review team can quickly explain the technicalities to you in a meaningful way. Their expertise might also help in identifying potential problems.

What past experience or trait do you think helped you be a successful reviewer/during your tenure at FDA?

I think being a lifelong learner helped me be a successful reviewer. Some might see the process of reviewing medical devices as repetitive. However, I found that each product provided a unique learning experience due to the many types of devices, regulation pathways, and emerging public health issues to learn about. There were endless ways to learn new things at the FDA.

What were your favorite FDA submissions to work on and why?

My favorite FDA submissions were IDEs because I learned about the details of a clinical study and about an emerging technology or trend. It was also nice to ensure that all the aspects necessary for a successful clinical study were planned out. Although there was pre-clinical work performed before an IDE submission, it was interesting to see a device at the beginning of its regulatory path.

What's something that you learned from FDA that helped you in your current position?

Working at FDA helped me learn team communication and managing expectations. Everyone’s time is valuable and it is important to make the most of team meetings. When leading a team, I aim to let each member of the team know the goal, their responsibility, and potential outcomes.

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

Many times, companies are not sure what to submit to the FDA so they submit everything (test report and data), which can be overwhelming to an FDA reviewer. I think my regulatory experience can help companies determine what to submit so that they clearly show they meet all FDA requirements.


More about Dulciana Chan, M.S.E.

For more information about Dulciana, please visit her LinkedIn page.

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
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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.

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

FDA Friday: Updates to our Previous De Novo Pathway Blog

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A little over two years ago, in one of our earlier blog posts, we discussed the de novo pathway. Since then, while the fundamentals of the program have remained the same, several changes have occurred to this pathway in terms of user fees and review time. We’d like to bring you up to speed on some of the changes in this blog post.

Briefly, the de novo pathway (as mentioned in our previous blog post) is an alternate pathway added through the Food and Drug Administration Modernization Act of 1997 (FDAMA). This pathway was added in order to classify novel, low- to moderate-risk Class I and Class II medical devices that did not have an acceptable predicate device (in order to establish substantial equivalence via the 510(k) pathway), and had not already been classified as Class III (“high-risk” devices).

There are still two routes for a de novo classification:

1.       Submitting a de novo request to the FDA after an NSE determination in response to a 510(k) submission.

or,

2.        If there is no legally marketed device upon which to base a determination of substantial equivalence, the sponsor may submit a de novo request without first submitting a 510(k) and receiving an NSE determination.

 

Such devices cleared through the de novo pathway may be used as predicates for future 510(k) submissions. Though not required, FDA strongly recommends a Pre-Submission in order to obtain early feedback from FDA, saving the submitting company both time and money. A Pre-Submission will not only help sponsors obtain feedback on whether a device may be eligible for the  de novo classification process, but also feedback on any on non-clinical and/or clinical data that will likely be necessary to support the de novo request.

In terms of the submittal, the de novo application should be submitted as an e-copy to the appropriate Document Control Center in CDRH or CBER. FDA’s goal is make a decision on the de novo request in 150 days. Since 2010, FDA has been releasing summaries of the devices cleared through the de novo process which will help sponsors that may wish to use the device as a predicate for future 510(k) submissions. Starting on October 1, 2017, changes were made to the user fees that are as follows: FDA now charges a fee for review of the de novo application unless you qualify for one of the exceptions:

1.        The device being submitted is a device intended solely for a pediatric population

or,

2.       Any application from a state or federal government entity

 

In 2017, FDA also released guidance documents on the de novo Classification Process and User Fees and Refunds for de novo Classification Requests.  De novo may be a faster pathway for you to get your novel, low- to moderate- risk devices to the market. Ask your regulatory consultant if a de novo is right for you!

 

Additional Reading (Guidance Documents):

1.        Our Previous Blog about De Novos

2.        De Novo Classification Process

3.       User Fees and Refunds for De Novo Classification Requests

4.       FDA and Industry Actions on De Novo Classification Requests: Effect on FDA Review Clock and Goals

5.       Acceptance Review for De Novo Classification Requests

FDA Friday: FDA's Looking for Sites to Participate in their Experiential Learning Program

Calling all medical device companies, academics, contract manufacturers, incubators, tech accelerators, health insurers, third party test labs, and healthcare facilities! FDA wants to come visit YOU! 
[And not to worry, they won't throw in a free "inspection" while they're there.]

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The Center for Devices and Radiological Health (CDRH) is offering an innovative learning opportunity for new and experienced FDA review staff. The Experiential Learning Program (ELP) is intended to provide a formal training mechanism for regulatory review staff to visit research, clinical, manufacturing, and healthcare facilities to observe how medical devices are designed, developed, and utilized. The ELP is intended to provide CDRH staff with an opportunity to understand the policies, laboratory and manufacturing practices, and the challenges addressing patient perspective/input, quality system management, and other challenges that impact the device development life cycle.

It's always exciting for FDA reviewers to leave their offices in Silver Spring to go out and see what you're doing! This program is a collaborative effort to enhance communication and facilitate the premarket review process. As mentioned earlier, these visits are not intended for FDA to inspect, assess, judge, or perform a regulatory function (e.g., compliance inspection), but rather, they are an opportunity to provide CDRH review staff a better understanding of the products they review, how they are developed, the voice of the patient, challenges related to quality systems development and management in the product life cycle, and how medical devices fit into the larger healthcare system. And hey, maybe it'll help some people in industry realize that FDA is made up of real flesh-and-blood humans too! We all move forward when we can learn from each other. 


Areas of Interest
Areas of Interest for visits are identified by managers at CDRH and are listed on the FDA website (see link below). The Areas of Interest will be updated quarterly, and assigned a one month submission window time-frame. If you're interested in ELP participation, you should preview the identified Areas of Interest by viewing the list. Once an Area of Interest has been determined, the Sample Site Visit Request and the Sample Site Visit Agenda templates can be utilized to make a request for participation. Currently, FDA has listed biocompatibility, combination products, clinical trials/research, device development/manufacturing/demos, digital health/software, innovation/health technology assessment, in vitro diagnostics, standards conformity testing, and quality management systems as Q1's Areas of Interest. 


Application Process Summary
Any stakeholders interested in placing a proposal in the program may submit a proposal to the program using following the steps:

  • Review the table of Training Needs displaying CDRH identified Areas of Interest.
  • Determine which Area of Interest your site would like to provide training for during a visit to your location. Each visit may last 1 or more days.
  • Utilize the Site Visit Sample Request and the Site Visit Agenda Templates to fill out your proposal for submission.
  • Complete all fields in the Site Visit Sample by first listing the Area of Interest along with its Identifier Code.
  • Proposals must be submitted to ELP Program Management within the specified dates (8/24/2018 – 9/26/2018 12:00 pm EST) in order to be considered eligible for that relevant training cycle. Proposal may be emailed to elp@fda.hhs.gov.

Further Reading:

  1. ELP Website

  2. Areas of Interest