Clinical Trials for Medical Device Innovators Part I: Introduction and Designing Clinical Trials

The first, in a blog series about clinical trials for medical device innovators.

In 2017, Cook was approached to co-author the recently published book, “Medical Innovation Concept to Commercialization.”  William D. Voorhees III, Ph.D., Vice President and Chief Science Officer and Theodore Heise, Ph.D., RAC, Vice President Regulatory and Clinical Services, both of MED Institute, collaborated to write the chapter, “Clinical Trials for Medical Device Innovators.” Overall, the purpose of this book is to provide physician-inventors and entrepreneurs with a practical, step by step approach to move a novel concept from the back of a napkin to a tangible, commercially successful product.

Cook News August 2018 MED InstituteWilliam D. Voorhees III, left, and Theodore Heise, holding a copy of “Medical Innovation Concept to Commercialization”.

Dr. Voorhees earned his A.B. in Biology from Hamilton College and a Ph.D. from the Department of Veterinary Physiology & Pharmacology at Purdue University.  As a faculty member of the Hillenbrand Biomedical Engineering Center at Purdue, Bill conducted a wide variety of original research in applied physiology including CPR, transchest cardiac pacing, electroventilation, hyperthermia therapy for solid tumors, hypothermia to protect the myocardium during myocardial infarction, and respiratory function monitoring.  He has authored over 70 refereed scientific articles resulting from this research.  He also served as liaison with the R&D Department of Methodist Hospital of Indiana in Indianapolis.  Bill has been with MED Institute for 28 years, joining the newly formed Clinical Trials/New Product Approvals Group in September 1990.  He was named Vice President/Chief Science Officer in September 2001.  Bill also serves as the Director of Regulatory Affairs and Director of Scientific Communications.  He takes seriously his commitment to patients to ensure the quality and scientific integrity of the research conducted by MED Institute.

Dr. Heise has 25 years’ experience in regulatory affairs, currently serving as Vice President of Regulatory and Clinical Services at MED Institute.  In this capacity, Ted leads the company in designing scientifically robust regulatory and clinical study strategies for its clients: entrepreneurs, consultants and physicians bringing novel medical products through the complex steps of the development process. Graduating with a BS in chemistry from the University of Nebraska at Omaha, Ted went on to earn a Ph.D. in analytical chemistry from Iowa State University.   He has been a member of the Regulatory Affairs Professionals Society since 1993, and the American Chemical Society since 1988. Ted is a U.S. delegate to the technical committee for international consensus standards that governs biocompatibility testing and clinical investigations of medical devices, and serves as convener of its working group on chemical characterization. Ted is also active in developing processes to generate real world evidence for medical devices, representing Cook Medical on the corporate stakeholder board for the SVS/Vascular Quality Initiative and participating in projects within MDEpiNet and Harmonization by Doing.

In their chapter from the book, “Medical Innovation Concept to Commercialization,” presented here as a series of 5 blog posts, Bill and Ted share the wisdom they have gained from their 20 plus-year adventure designing, conducting, and analyzing clinical trials on novel medical devices.

Designing Clinical Trials

Perhaps the most exciting and rewarding time in the development of a new medical device is the first time one sees it work successfully in a patient, but the ensuing clinical trial can be the most exhausting, frustrating, expensive, and time-consuming part of the entire enterprise. So before rushing headlong into the unknown, consider the following: “Is it necessary for me to conduct a clinical trial of my new device?” The answer is “It depends.”

It depends on what you are trying to accomplish. Maybe you just want to show that your device works (i.e., the Proof of Concept). Perhaps you have reached a point at which no more can be learned without testing in humans, for example, pain relief cannot be studied on the bench at all and rarely well in animals. Your goal may be to demonstrate product effectiveness to investors and to raise additional funds. Maybe all you want is enough clinical data to improve your chances of selling the rights to the intellectual property. Perhaps you just want to enhance market awareness and exposure to the device (such as having a few key opinion leaders use it and write a paper), or maybe you want to take it all the way to regulatory approval with proof of safety and effectiveness, which is collected typically in what is called a pivotal study. Even if you want to own the regulatory approval of your device, keep in mind that a clinical study may not be needed if you can show that all relevant risks can be mitigated by bench and/or animal testing or with appropriate labeling. This is why a rigorous risk-analysis is imperative to your plan for development of the device.

Assume you have developed your device to the point that you have made prototypes that you have bench-tested adequately to satisfy yourself that they function as expected and they appear safe to use in humans. The “Grandmother Test” is a good benchmark; would you let your grandmother be treated with this device? Even if the answer is “Yes,” you probably need a clinical feasibility study first. Conducting a clinical feasibility study may also be a good first step when only formal testing in humans can provide the evidence that the device offers the expected benefit (Proof of Concept) or is required for making any final changes in design (e.g., to apply to specific human anatomy). Such data can simply be gathered no other way than to test in humans. Even if you know you will need a pivotal study for regulatory approval, it is likely that you will need initial information about how large a therapeutic effect the device will have before you can design a larger pivotal study to compare its results with state-of-the-art therapy (often a currently marketed device) in a statistically rigorous clinical study. A feasibility clinical study can be used to provide this crucial information.

If your interest lies only in developing the new device to the point that the concept (intellectual property) can be sold to another company to finalize its development and take it to commercialization, then conducting a clinical feasibility study may be adequate to provide the information that the company planning to purchase your device will need to decide to close the deal.

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Continue to follow our blog to view the upcoming Part II: Regulatory Considerations for Clinical Studies.

White Paper: Radial Force

Radial Force Testing
Radial force testing is used to determine the stiffness (hoop strength) of a medical device when placed under radial compressive forces, both loading and unloading. Devices that are commonly tested include balloons, stents, stent grafts, and feminine hygiene products, among other devices that are required to apply a chronic outward force. The importance of radial force testing in the medical device development process is perhaps best illustrated with an example. The following case study shows the importance of radial force in the functionality of a self-expandable stent.

Case Study: The Self-Expandable Stent
Accurate stent sizing is crucial. If a stent does not exert enough radial force to stay lodged in its desired position, it may migrate. Stent migration can cause a number of different problems, paravalvular leakage being one of them [1]. When paravalvular leakage occurs, blood flows through the stent and proceeds through cardiac tissue. Paravalvular leakage can cause heart failure, hemolytic anemia, and infectious endocarditis. [2]

Conversely, a stent that exerts too much force on its host vessel can cause vessel wall degeneration and damage. [1] Self-expandable stents, in particular, can be difficult to match to the proper vessel size. Self-expandable stents show a chronic outward radial force once they are deployed in the body. This can result in negative chronic recoil. Negative chronic recoil causes the vessel to expand outward, becoming larger than it naturally was. Other adverse reactions that may occur from improper stent sizing include: in-stent restenosis, thrombosis, and neo intimal proliferation.

Performing radial force testing on your device can help quantitatively characterize device functionality and performance, in turn allowing you to accurately assess the safety and effectiveness of your product.

Our Method
Our lab is ISO 17025 accredited in regards to radial force testing per ASTM 3067-14 and ISO 25539. Additionally, with over 30 years of experience developing test methods and evaluating a wide variety of medical devices, we have the ability to develop unique test methods tailored to your needs.

Radial ForceFigure 1. MSI RX550 Radial Force Tester at MED Institute.

Our Services
At MED Institute, we have the tools and experience to help with your radial force needs. Contact us so that we can help you make products and therapies that will improve patient outcomes.

If you have any questions or need any additional information, please contact:

Justin Metcalf, Director of Engineering Services


[1] M. S. Cabrera, C. W. Oomens and F. P. Baaijens, “Understanding the requirements of self-expandable stents for heart valve replacement: Radial force, hoop force and equilibrium,” Journal of the Mechanical Behavior of Biomedical Materials, vol. 68, pp. 252-264, 2017.
[2] D. Smolka and M. W. Wojakowski, “Paravalvular leak – important complication after implantation of prosthetic valve,” European Society of Cardiology, 8 November 2010. [Online]. Available: [Accessed 30 August 2017].

How Mobile Health Technology can Lead to Clinical Trial Success


Mobile Health Technology (mHealth) is a general term for the use of mobile phones or other communication devices in medical care. The use of mHealth has received significant attention recently, with good reason. mHealth is making a strong case for its ability to improve clinical trial management and participant engagement. For a technology to be effective in this area, it must provide necessary features and benefits and fit effortlessly into the patient’s daily schedule.

mHealth may help to improve data quality and participant trial adherence. Sponsors/CROs can equip participants with mobile devices and tablets to capture health data from home. Participants can complete diaries and surveys on mobile applications (apps) and submit the information from home versus onsite at the research center. Such convenience increases the likelihood of patients’ full participation in the trial and decreases the likelihood of noncompliances in the participants’ performance. Data can be captured real-time using mHealth which generally improves data fidelity. Timely data capture also allows for prompt identification of participant noncompliance. Action can then be taken to swiftly address any issues and ensure participant compliance going forward—correcting potential problems before they become widespread.  Some apps are developed to assist sponsors/CROs with patient recruitment for clinical trials. For example, Novartis Oncology developed a mobile app, Clinical Trial Seek, where patients and physicians can look for trial information.

In addition to more effectively and conveniently capturing trial data, mHealth may also increase participant engagement in a trial by making it easier to communicate information. If a participant has a trial-related question, it may be possible to check the mobile app and get the answer when needed, either through documentation available on the app or by direct communication with trial staff. Additionally, using mHealth, trial protocols can be set up with flexible schedules that can be fixed, randomized, or event-triggered. Schedules can be set up for daily, weekly, or monthly events and could even be customized with personalized instructions for an individual participant. Educational programs with web-based content can be scheduled on mobile apps to provide the latest information to participants in the trial. Solid participant engagement is key to minimizing the incidence of noncompliance with the trial protocol. mHealth could also increase the reach of certain trials by encouraging patients to participate from a greater distance, as burdensome patient travel requirements of trials are reduced.

As mentioned above, mHealth has a number of potential uses in the clinical research space, and could help make your trial more participant-centric. It could also provide solutions to two of the biggest challenges: participant recruitment and continued participant engagement. Although these technologies may not be appropriate for every trial, they should be considered in trial design as a tool to help optimize chances for success and participants’ best interests.  Despite the expected benefits of using mHealth in clinical trials, the regulatory status with the FDA is not yet entirely clear. Evolving acceptance by regulators will help drive implementation of mHealth in clinical research.

MED Institute has decades of experience in designing and executing clinical trials, and would be pleased to discuss with you how we can help you achieve success in your clinical trial objectives.

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How wearable technology is optimizing the clinical research industry

wearables IIThe second, in a blog series about how advances in technology are impacting clinical trials. Read part I, here

Increasingly popular wearable technology has the potential to profoundly affect the possibilities for clinical research. Initially, some wearable devices, such as wristbands and smart watches, targeted consumers wanting to track their health and fitness level. Wearables allowed collection of data on a 24/7 basis as people went through daily routine activities. More recently, wearable devices are being designed and developed for use in clinical trials, with a real possibility of transforming the clinical research industry. Wearable devices are currently gaining huge popularity, with many technology companies developing wearables for entry into the clinical research space. These devices offer a vital opportunity to collect real-time data, to better understand patients’ needs, and to improve patients’ experience throughout participation in the clinical trial.

The most common use of wearable devices in clinical trials is to collect continuous real-time data from the participants. These devices can measure heart rate, gait, velocity, step count, sleep pattern, blood pressure, temperature and other parameters. Some more sophisticated devices are capable of measuring lung function and generating electrocardiograms. Non-invasive glucose monitoring is currently a target technology, and several companies are developing prototypes.  Some wearable devices can be paired with mobile applications to measure indicators such as tremor, balance, posture, and memory characteristics. This function can be of great importance in clinical trials of certain patient groups, such as those with Parkinson’s disease. The contemporaneous nature of data recording and the opportunity for more frequent measurement could reveal patterns for physiological changes, which would help determine the effect of a participant’s activity level on drug/device success.

Wearable devices may also make possible the remote monitoring of participants for adverse events (AE), which would certainly improve compliance with AE reporting. Wearables can continuously monitor participants’ vital signs, social interactions, sleep patterns, motor activity, and other markers of health. These physiological and behavioral changes that may indicate adverse events could provide robust, timely, and unbiased data for monitoring a participant’s status in a clinical trial. Wearable technology may be deployed within a wireless body area network (WBAN). WBAN devices can be implanted inside the body or attached to the exterior of the body. These devices include a number of wirelessly connected physiological sensors to help gather required data for a trial to monitor participant’s safety.

The possibilities of collecting real-time, highly objective time-marked data are exciting.  The future of wearable devices will not be limited to wristbands and smart watches.  Smart fabrics, ingestible sensors, and even smart lenses will be available soon for use in clinical trials. The use of these wearables will help to reduce the overall costs of running a trial by reducing the number of patient visits to the clinic and may improve participant compliance and retention.

A word of caution: despite the expected benefits of using wearable technology in clinical trials, the regulatory status with the FDA is not yet entirely clear. In addition, there will be a need for the data collected through these devices to be adequately validated for use. Evolving acceptance by regulators will help drive implementation of wearable technology in clinical research.

We would love to hear from you! What are your thoughts on wearable technology in the clinical research industry?

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How are technological innovations affecting the clinical research process & likelihood of trial success?

Technology Clinical 2The first in a series of blogs about how advances in technology are impacting clinical trials.

New technologies are revolutionizing all industries, including health care and drug/device research. Technological innovations provide the potential to improve clinical trial efficiency and data accuracy by reducing patient burden and improving trial management. From wearable devices and smartphone apps for data collection to applications for trial management, the options to use technology in a clinical trial seem limitless. Technology’s rapid growth is challenging our traditional methods of running clinical trials by continually raising participants’ expectations, while also providing great opportunities for optimizing clinical trial management, patient recruitment and data collection.

Specifically, one of the most difficult things to accomplish in clinical trials is efficient patient recruitment. Recruitment failure has several consequences, including lack of usable findings from a trial, trial discontinuation, and financial loss. Successful patient recruitment and retention are common challenges that clinical trials face, but new technologies and platforms such as mobile applications are emerging to overcome this hurdle. These new technologies help keep investigators aware of the open clinical trials and communicate information efficiently across multiple locations in a large geographic area. There are many healthcare applications for mobile devices that help provide information to patients about their health.  These platforms have a large database of patients that may help the investigators and sponsors detect types of patients eligible for participation in a specific trial without disclosing any personal information. The technology platform then delivers personalized communications to the eligible patients to inform them of the clinical trial. In addition to identifying more potential trial participants than ever before, this approach simplifies for trial site staff the recruitment of patients by reducing administrative burden.

Another example of a quantum leap in clinical trial management enabled by technology is the advent of electronic data capture (EDC) systems. The change from paper-based data collection to EDC systems has revolutionized the process—making it possible to collate and analyze data from any location as soon as it is collected. This has also helped optimize patient safety by reducing data collection errors prior to the data review process. EDC systems can include clinical trial management system (CTMS) functionality, which can assist the user in tracking all essential trial documents and providing a snapshot of progress of a clinical trial.

In yet another advance, sensors and mobile technologies may be linked to the EDC system, making it possible to electronically collect patient-generated and patient-reported data which can then be automatically uploaded directly to the EDC system database. One of the most exciting capabilities of mobile technology is its real-time data collection feature. These features make data collection from everyday activities more accurate by collecting only the required clinical trial data in real-time. These capabilities can also lead to a decrease in clinic visits or follow-up phone calls for patients, making it easier and more cost-effective for patients to participate in a clinical trial.

Blockchain technology may provide another future key opportunity for sponsors to use in clinical trials. Blockchain is an electronic ledger that can be openly shared among users that creates an unchangeable record, each one linked to another with a time stamp. The use of this technology could potentially make it easier to securely store and share data. However, in the immediate future, a more realistic goal might be to use this technology to address issues around data integrity, reproducibility and transparency. For example, blockchain technology could support a robust process for collection of consents based on protocol revisions, storing and tracking the consent in a secure, traceable manner, and enabling highly reliable sharing of this information in real-time.

Another example of the Blockchain technology is the use of Smart Contracts to help effect transparent control over clinical trial activities occurring in the correct sequence.

In conclusion, the adoption of technology in clinical trials is on the rise. As more experience in the use of these technologies is accumulated, it will become increasingly clear how their use can significantly improve clinical trial outcomes.  In addition, the technologies will become less burdensome and will likely be widely adopted as clear improvements.

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Continue to follow our blog to view the upcoming posts in the technology series.

6 things sponsors or CROs can do to help sites be more efficient in clinical studies.


Successful execution of a clinical trial depends upon excellent working relationships between clinical research sites and sponsors. However, the rapport between sponsors and sites can sometimes become strained due to challenges in communicating effectively. With both parties working on numerous studies simultaneously, it can be difficult to address each other’s concerns in a timely manner.

To address this issue, it is important that both sites and sponsors (or their expert CRO delegates) actively maintain an open line of communication, and collaborate to eliminate miscommunication and obtain the best outcome possible for all involved, especially the patients being served.

Here are some useful tips for sponsors to consider when planning and conducting a clinical trial:

1. Ask your sites to explain barriers to estimating accurate potential trial enrollment rates

When it comes to filling out site assessment questionnaires, sites can provide a lot of valuable information beyond just a projected number of patients they can enroll in a week or a month. They can help identify potential barriers to achieving the desired enrollment rate.  Knowing this information, sponsors may be able to work proactively with their sites to eliminate these potential barriers.  There are many important factors that may affect patient enrollment and sites can provide the practical input needed to optimize patient recruitment and enrollment.

2.  Share enrollment updates with the study sites throughout the study and a summary at trial closure

During the enrollment phase of a trial, it is useful to share periodic enrollment updates with the sites.  The regular communication keeps them engaged with the trial, and it gives them some perspective as to how they are performing compared with the other trial sites.  Many times this will spur a friendly competition to try to be the trial’s top enroller (particularly since the various investigators are often colleagues who know each other personally).

At trial closure, the information tracked by the sponsor throughout the study must be analyzed and shared with all of the sites to compare realities with predictions. Sites can learn from past performance data, and use the information when considering future trials. This can help sponsors design future trials and plan recruitment strategies.

3. Avoid collection of redundant information from prior projects

Sponsors can use data collected from sites for previous projects, and evaluate site capabilities from this history, to reduce or eliminate the need for the sites to complete questionnaires when being considered for a trial. This will enable sites to use the saved time for more robust study start-up efforts and plan to increase study success.

4. Consider inputs from sites for better trial design

One of the best paths to study success is to involve trial sites before the protocol is finalized. If sites have a chance to evaluate the draft inclusion/exclusion criteria and data collection methods and time points, they can determine how difficult it would be for the site staff to implement the trial as designed. These inputs can provide improvements in accuracy of anticipated patient costs and trial timelines. Additionally, these inputs can prevent last minute surprises and challenges during trial progress.

5. Let sites know why they were not selected for the trial

It is important to provide sites with feedback when they are not chosen to participate in a trial. Sites typically don’t receive detailed information from the trial sponsor, just a rejection notification. Sponsors should provide sites with reasons for not being selected to help them improve and to build a good relationship for the long-term. Obviously this will not benefit the current trial, but it may give the site justification to address some of the shortcomings in its preparedness to conduct clinical trials or give the site insight needed to better target trials suited to its strengths.  This will lead to increased success in future trials, perhaps even one of yours.

6. Provide access to database systems for operational needs

Most sites don’t have enough funds to purchase database management systems like Clinical Trial Management Systems (CTMS). Sponsors realize the importance of data management systems and can consider providing sites access to CTMS systems to track their progress and simplify their operational and reporting needs. This can save staff time, and enhance accuracy and consistency of data.

Early planning and consistent communication with clinical sites can help move your trial along more efficiently. If you have any questions, or if you would like to discuss this topic in more detail, please email

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IHIF Annual Gala Dinner

On September 13th, MED had the opportunity to be a sponsor at the 2017 IHIF Annual Gala Dinner. The IHIF is an outstanding organization that works to connect key stakeholders to enhance business networks advocate for member interests, develop workforce skills, and provide strategic vision in the interest of growing the state’s health industry economy and reputation. The Annual Gala Dinner was held at the beautiful Alexander, A Dolce Property in Indianapolis, IN. The evening started with a general reception in the Gallery and special VIP Event with the keynote speaker. The meeting included an IHIF organizational and industry update, presentation of the Legislator of the Year award, and focused on Alzheimer’s disease. The feature on Alzheimer’s was made possible through a partnership between IHIF and the Alzheimer’s Association, Greater Indiana Chapter.

Dr. Bruce Lamb, Director, Stark Neuroscience Research Institute with Indiana University School of Medicine presented “Alzheimer’s Research in Indiana”. Dr. Lamb’s presentation covered the disease state, current treatment modalities, difficulties studying the disease, recent advancements, and increased funding that is becoming available. Dr. Lamb’s research has focused on the basic disease mechanisms of Alzheimer’s disease and has shed light on how complex mechanisms associated with Alzheimer’s have hindered efforts to find effective treatments in clinical trials.

IHIF-Image.jpg2Pictured from left to right: Dan Peterson, Vice President Industry & Government Affairs at Cook Medical, Justin Renfrow, Contracts Director at MED Institute, Matthew Waninger, President at MED Institute, and Brooke Corcoran, Marketing Specialist at MED Institute.

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5 Tips for Medical Device Sponsors for Running a Successful Clinical Trial

5 tips2

Everyone is demanding more clinical evidence from medical device companies these days. FDA wants to see more clinical data before and after granting approval for marketing devices. Hospitals and physicians are asking for more of it when making purchasing decisions. This pressure is forcing medical device companies to collect more clinical data on their devices than ever before, and they primarily are responding by running more clinical trials to distinguish their products from competitors. However, most medical device companies lack internal resources and capability to run a complete clinical trial operation in-house. This is mostly true for small and start-up companies, which have little to no experience in running a clinical trial. As a result, we are observing a consistent rise in the outsourcing of clinical services to contract research organizations (CROs). Selecting the right CRO to manage a clinical trial can be a critical decision in a company’s successful outcome. Here are the five tips for medical device companies or sponsors to consider when subcontracting clinical trials to a CRO:

  1. Selecting a CRO with medical device expertise

Most CROs are focused on running pharmaceutical trials and lack sufficient medical device trial experience. When CROs give you a presentation and start talking about 1572s and Phase II/III studies, you know they have not conducted trials on medical devices. The basics of running pharma and medical device trials are the same, but there are some significant differences that cannot be overlooked. The ideal CRO for your trial will have demonstrated success running clinical studies in your product’s therapeutic area.

  1. Creating an internal clinical research team

Outsourcing doesn’t mean completely turning over the reins to your CRO. Nobody knows your product better than you do, and the CRO is going to need your guidance, feedback and support based on your expertise. Hence, it is important for a sponsor to form at least a one-member team who will be committed to this job. This person or team will be fully involved in the process, and ultimately be responsible for project outcomes.

  1. Engaging vendors early in the process

Sponsors need to initiate communication with prospective vendors as early as possible in the start-up process. This benefits sponsors by connecting with all clinical teams and laying the groundwork for future interactions. Having several meetings with the sponsor and outsourced staff prior to start-up can keep all parties apprised of trial protocols and progress.

  1. Having effective risk management processes

In reality, all projects have a mix of risks, problems and uncertainties. Hence, sponsors must not expect all the plans and schedules that are developed will happen exactly as planned. Sponsors must set more realistic timeline targets. Feasibility assessments are done in an effort to de-risk the study, although it may or may not reduce the uncertainty. Sponsors must create action plans and allocate funds to enable them. Risk management greatly improves the predictability of project outcome in terms of time and cost.

  1. Having full transparency for collaborative partnership

Sponsors should be open with a CRO about what exactly they need from the agreement, what they can afford, and the project scope. This will help them work with CROs in true partnership. Sponsors and CROs need single-view analytics and ability to collaborate through data-driven tasks and workflows. The advantages of building a collaborative relationship with your CRO can be significant.

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Is the Pre-Submission process worth the time and effort?

The last in a series of blogs about informal, pre-submission contact with FDA.  Visit our website for the previous six.

Med_D6A1047The Pre-Sub process can be time-consuming (Pre-Sub; see FDA guidance here). You may wonder if it’s worth it. We discussed some of the reasons for having a Pre-Sub (or not having one) in a previous post, but let’s look at those again:

  • Is the device new (to you) or FDA?
  • How well do guidance documents, recognized consensus standards, or 510(k)/PMA summaries apply?
  • Where are you in the development cycle?
  • How expensive is it to be wrong?

Those are the “hard” questions to ask before you decide, but there are a few more “soft” reasons for asking for a Pre-Sub:

  • It is a valuable opportunity to make a good first impression.
  • It is a great way to sort out major issues in a non-adversarial manner.
  • It is a great way to educate FDA on your new device, technology, or test.

This last one is especially important. You may have 100% confidence in your development program. But if FDA has never seen this type of device before, it is helpful if they are exposed to it proactively. The back-and-forth of the Pre-Sub program gives you time to explain your device before your formal submission, when table upon table of data arrive at their doorstep unannounced.

MED believes it is important to integrate your engineering and regulatory strategies from the very beginning of the medical device development process, if possible, or at least as early in the process as you can. The Pre-Submission (Pre-Sub) process is a perfect opportunity to present both your engineering strategy and your regulatory strategy to FDA early in the process and ensure that everyone is in agreement.

We all have the same goal: to help patients by providing innovative and safe medical devices. Keeping this common goal in mind during our interactions will help us to focus on the supporting data and risk mitigation tools that support that goal. We can also develop trust and foster meaningful relationships with the agency in the process.

To have a more thorough discussion or to answer any questions you may have regarding the Pre-Sub process or tips on how to effectively communicate with FDA, please contact MED Institute via our website at

What happens once I submit a Pre-Submission? (Part 3: After the meeting)

The sixth in a series of blogs about informal, pre-submission contact with FDA. See here, here, here, here, and here for the previous five.

MED Inst, Med,  regulatory science, regulatory dataYou have sent FDA a Pre-Submission (Pre-Sub; see FDA guidance here) to get answers to questions you want to know well before your formal submission (e.g., an IDE or 510(k)). You have received comments from FDA, and met with them to discuss them. What’s next?

Minutes: Within 15 calendar days of the teleconference or in-person meeting, you will draft meeting minutes and submit them to FDA. FDA will review and edit the meeting minutes, if necessary, within 30 days of receipt. The final version will become the final record of the meeting or teleconference 15 calendar days after you receive FDA’s edits. If you disagree with FDA’s edits, you can submit an amendment and FDA will discuss them with you.

Don’t try to capture everything that was said, just important agreements (or disagreements) and action items. The process may seem tedious, but it is often a good opportunity to get further clarification on FDA’s thinking and to clear up any misunderstanding.

Issues needing further discussion: As mentioned in a previous post, you only have 60 minutes, so you may not have time to discuss some of the lesser points of disagreement. Many of these can be handled with supplements to the original Pre-Sub. Talk to your lead reviewer about how to structure the discussion.

FDA’s commitment: In the Pre-Sub guidance, FDA has committed to standing by their feedback, with the following conditions: information in the formal submission is consistent with the Pre-Sub interaction, the data in the subsequent submission do not raise new important issues, and no material issues have arisen since the time of their feedback, e.g., new scientific findings about risks.

It is not unreasonable to be wary of this commitment, especially the caveat about “new scientific findings”. If there is a long gap between the meeting and the final submission, consider whether you will need to double-back with FDA.

Future submissions: All of your work will go to waste if you don’t remind FDA what was agreed upon when your formal submission (e.g., IDE, 510(k), PMA) is submitted. Those formal submissions should include a copy your questions, FDA’s comments, the meeting minutes, detailed responses to each of FDA’s comments, and cross-reference to the same information in the main body of the submission.

For instance, suppose your Pre-Sub asked a question about the types of bench tests to be conducted. FDA responded that they agreed to the test matrix, but they wanted you to do two more tests. The meeting minutes reflect that you agreed to the first additional test, but not the second one. In this case, the appendix to the formal submission should include your original question, a clear statement that FDA agreed to it with reservations, and (1) a reference to the location of the agreed-upon tests in the main body, and (2) a well-supported justification about why the remaining test was unnecessary.

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Next time: Is the Pre-Sub Process worth the time and effort?