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Five Steps to Obtaining FDA Clearance for your Medical Device

From Bench to Bedside: Five Steps to Obtaining FDA Clearance for your Medical Device

Process Overviewuntitled

The journey from product ideation and discovery to clinically utilized patient care device can be a daunting one. There are five important steps to marketing a new medical device with FDA clearance. We will attempt to streamline this process and make it more user friendly. It is crucial to be familiar with the governmental regulations at play here.

Is the product a medical device?

While this may sound like a simplistic question, it is important to make sure that your product meets the qualifications to be considered a medical device before embarking on the process of obtaining FDA clearance. A medical device is defined within the Food Drug & Cosmetic Act as

“…an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of it’s primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes.” [1]

Regulatory Controls

Medical devices marketed in the United States are subject to the regulatory controls in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the regulations in Title 21- Code of Federal Regulations (21 CFR) Parts 1-58, 800-1299. It is important to note that not all medical devices are created equal in the eyes of the government. Some will be subject to further regulations depending on how they are classified (ones that emit radiation for instance). Which brings us to our first step in bringing your device to market, finding the appropriate classification.

Device Classification

untitledStep I: Classify the Device

Under the Federal Food, Drug, and Cosmetic Act, all medical devices must be classified under one of three categories:

  1. Class I devices: This is the “low to moderate risk” category. These devices present a low risk of harm to the individual user and will fall under general regulatory controls. Many of these devices may even be exempt from parts of the regulatory process. Some examples of class I devices are bandages, compression stockings, manual blood pressure cuffs, and stethoscopes. These are non-invasive devices that don’t require special patient precautions prior to usage.
  2. Class II devices: This category is considered “moderate to high risk”. These devices are usually non-invasive but slightly more complicated in their usage and present a moderate risk to the patient.   Therefore, devices in this category must be subject to the special controls in addition to general governmental controls. Such devices require further monitoring and must meet performance standards for the patients. In addition, a Premarket Notification 501(k) must be filed for these products. A few examples include x-ray machines, infusion pumps, and electronic wheelchairs.
  3. Class III devices: This is considered the “high risk” category. Devices within this category are invasive, present a potential significant risk to the patient, or fill a highly important role in supporting the life of the patient. Therefore, they are subject to the strictest controls to ensure their safety and efficacy. They are often subject to premarket approval (PMA). Such devices include implantable defibrillators, pacemakers, artificial heart valves, and breast implants. [2]

Step II: Premarket submission

Depending on the device classification, a premarket submission may be required prior to marketing the new device. A few common types of premarket submissions are:

  1. Premarket Approval (PMA): This type of submission is the most rigorous type of application required by the FDA. This approval is required for many class III devices and is only granted when the FDA review finds sufficient scientific evidence that the device is both safe and effective. This type of approval generally requires randomized clinical trials or meta-analysis to establish a greater benefit vs. potential risk of use.
  2. Premarket Notification 510(k): in contrast to the FDA “approval” granted through the PMA process, a 510(k) is designed to obtain FDA “clearance” by proving that the device is substantially equivalent to a predicate device currently on the market.
  3. Humanitarian Device Exemption: This exemption is intended to provide incentive to companies who produce products that aid in the treatment of diseases that affect only a small portion of the population.
  4. Investigational Device Exemption: This allows a new device to be used in clinical studies.

Step III: Determine what kind of studies are needed to support your device

The requirements of your submission packet will entirely depend on which premarket submission category your device falls into. If your goal is to market a Class III device, you will likely be required to follow the PMA process of scientific and regulatory review. The FDA has established elevated general and special controls in order to appropriately evaluate a device that will be depended on to support or sustain human life, and which will carry a substantial risk of illness or injury. Companies who want to market a Class I, II, or III device that does not fall under PMA requirements, must then submit a 510(k).

Step IV: Submit your completed packet and interact with FDA during the review process

Once you have gathered the appropriate supportive information for your device, the completed packet can be submitted to the FDA along with any required fees. The submission packet will then undergo an administrative filing review during which FDA representatives will assess the submission for completeness. This evaluation is then followed by an interactive review, which requires close communication between FDA staff and the applicant.

Step V: Complete your registration and device listing with the FDA

The final step before commercial marketing is establishment registration and device listing. Any company that develops and markets medical devices must register annually with the FDA. Once a device is approved, it must be added to the FDA list of medical devices. These ultimate steps serve several purposes. They allow the FDA to monitor performance and usage of medical devices. More importantly, knowing where devices are developed can be vital information during national public health emergencies.

Final Thoughts…

Though the road from device development to FDA approval and commercial release may be complicated at times, it is important to be sure to follow FDA regulations precisely. Processing time can be minimized through close communication with FDA staff, and usage of the wealth of regulatory information presented on their website.

Helpful Links

FDA’s Center for Devices and Radiological Health (CDRH) web page:

Types of Communication During the Review of Medical Device Submissions – Guidance for Industry and Food and Drug Administration Staff


  1. FDA Overview of Medical Device Regulation.
  2. FDA Resource Guide, Learn if a Medical Device Has Been Cleared by FDA for Marketing ResourcesforYou/Consumers/ucm142523.htm

The IRB Fast Track: Exempt and Expedited IRB Review

How to take advantage of a simpler review process and begin your study earlier.

The average time from submission to approval for a newly submitted IRB application varies widely from institution to institution. It can also depend greatly on the type and complexity of the research being considered as well as the level of human subject involvement. There are three levels of review under the IRB guidelines: exempt research, expedited review, and full review. Average wait times can range from 2-3 weeks for an exempt study, 3-4 weeks for an expedited review, and 5+ weeks for a full review. Knowing whether your research qualifies for IRB exemption or the expedited review procedure can help new studies get going much sooner than they would otherwise be able to.

What qualifies as “exempt” research?

Though the name implies that research in this category does not need to go through any IRB review, the IRB committee must assess “exempt” research. In general, these studies involve the least possible risk to the participants and generally consist of studies evaluating already-existing data so long as patient identifiers are removed and anonymity of the subjects is protected. Under article 45 CFR 46.101(b) Categories of Exempt Human Subjects Research, there are 6 federally established categories of research that may qualify for IRB exemption.[1] A few examples are listed below:

  1. Research within established educational settings (i.e., schools, universities, and training facilities) involving instructional techniques, efficacy, curriculum changes, classroom management, etc.
  2. Research involving aptitude tests, public surveys, interviews, or observation of public behavior
  3. Research involving the collection of existing data such as medical records or pathological specimens
  4. Research involving public service programs
  5. Taste and food evaluation studies intending to test consumer acceptance of foods that meet FDA requirements for safety.

It is important to note that the Department of Health and Human Services has added a footnote to their policy regarding exempt research indicating that all research involving prisoners and some research involving children will not be considered “exempt” and must go through either the expedited or full review procedure.

What is the expedited IRB review process?

An expedited review is a procedure through which either the IRB chairperson or several experienced members may review eligible research without waiting for a formal meeting of the IRB. These committee members have all of the authorities of the full committee except disapproval of the application. A formal rejection of an IRB application may only be decided by a full committee meeting. Research eligible for expedited IRB review must meet at least one of two criteria:

  1. It must involve minimal risk to human participants. We will discuss what exactly qualifies as “minimal risk” in more detail in the next section
  2. It must involve minor changes in a previously approved study, during the period covered by the original approval.

How do I know if my study qualifies?

The following research categories may qualify for an expedited review (adapted from the Office of Human Research Protection, Article 45 CFR 46.110 Categories of Research That May Be Reviewed through an Expedited Review Procedure)[2]

    1. Clinical studies of drugs
      1. If they do not require a new drug application
    2. Studies of medical devices
      1. If they do not require an investigational device exemption, or
      2. The device has already been cleared for marketing and is being used in accordance with its approved labeling
    3. Collection and examination of blood samples
      1. If obtained through less invasive finger stick or venipuncture from healthy, non-pregnant adults weighing at least 110 pounds. In addition, there are limitations to the frequency with which blood may be drawn.
      2. Other adults and children with consideration to age, weight, and overall health of the subjects with blood draw frequency limitations.
    4. Noninvasive collection of biological specimens for research purposes
      1. This category includes specimens drawn in a non-invasive/non-disfiguring manner such as nail clippings, hair, sweat, saliva, mucosal cells, and sputum
      2. Other specimens taken during routine medical procedures such as teeth extracted by a dentist for medically necessary purposes and amniotic fluid sampled at the time of membrane rupture by a physician.
    5. Noninvasive collection of data drawn through means commonly used in clinical practice such as:
      1. Measurement of weight or sensory acuity
      2. Magnetic resonance imaging, electrocardiography, echocardiography, ultrasound, etc.
      3. Muscular strength testing
      4. Moderate, age/health-appropriate exercise, flexibility testing

Note: If data collection involves a medical device (i.e., test muscular strength) it must be previously approved for marketing. In addition, if the study intention is to investigate the safety and efficacy of the device it is typically not eligible for expedited review and will be deferred to a full committee review.

    1. Collection of voice, digital, video, or image recordings
    2. Research regarding individual characteristics or behavior such as:
      1. Perception
      2. Cognition
      3. Motivation
      4. Identity
      5. Language
      6. Social behavior
    3. Continuing review of previously approved research that meets at least one of the following:
      1. The study is no longer accepting new research subjects
      2. The currently enrolled subjects have completed all research-related tasks
      3. The research remains active only for long term follow up
      4. The remaining research activities consist only of data analysis
      5. The study does not fall into any of the above categories, but the IRB has documented that it involves no more than minimal risk to subjects

What types of research studies DO NOT qualify for expedited review?

The expedited review process may not be used in situations where identification of the subjects or their responses would place them at risk of criminal or civil liability. In addition, studies in which the subjects’ responses may be damaging to them financially or in terms of their employability or reputation. Furthermore, any classified research involving human participants is not eligible for the expedited review process.

Where can I find more information about IRB review categories and regulations?

A helpful visual decision chart may be found at:

The applicability requirements are listed in more detail at:


    1. Federal Article 45 CFR 46.101(b) Categories of Exempt Human Subjects Research,
    2. U.S. Department of Health and Human Services, Office for Human Research Protections Expedited Review Categories,

Proof of Concept Studies: 5 reasons to perform one before launching a large-scale research study

The topic of pilot studies or proof of concept studies is rarely taught in healthcare education. In addition, they tend to be largely overlooked by the scientific community. Yet, they can be quite important from the point of view of a healthcare startup looking to introduce a new product to the market in terms of saving wasted time and money on larger studies in the long run. In this report, we will attempt to define this process, offer 5 important reasons to invest in a pilot study as a way of revealing problems that may arise during a full-scale study, and how to use it to direct a larger pre-market study.

What is a pilot study?

In the healthcare field, a proof of concept study, or pilot study, is an exploratory test or preliminary trial intended to guide further development of a drug, device, or product. It is designed to occur before a large scale study in order to assist in the preparation of a more comprehensive examination. Think of it as a practice run where the researchers are able to test their methods and study design ahead of time and make necessarily changes before embarking on a more extensive study.

The elements most commonly examined during a preliminary study include: the procedures involved, tools/instruments, recruitment rate, and estimated sample size required for statistical power in a full-scale study. In order to optimize this process and reduce cost and time to reach market for new devices, the purpose of the pilot study must be clear and established from the outset.

Why conduct a pilot study?

A pilot study can be a valuable way to detect any weaknesses in study design and refine the study processes before continuing forward with a larger, more expensive study. Here are five important reasons to include a pilot study in your research plan: [1]

1. To refine your study process:

A proof of concept study can examine the process in question in order to determine the feasibility of the study’s methods and process before continuing with a large-scale study. It is crucial to determine the necessary sample size prior to beginning a study. Failure to recruit sufficient numbers in a trial will reduce the statistical power, and one of the main reasons for abandoning trials early.[2]
Other aspects of a study’s process that may be tested during a pilot study include:

  • Estimate of recruitment, retention, and refusal rates
  • Estimate sample size
  • Test randomization and blinding procedures
  • Determine eligibility criteria
  • Examining data collection tools such as participant surveys to assess whether they are effective in gathering participant responses.

2. To determine what resources your study will require in order to proceed in an efficient manner and to give you meaningful results.

Resource studies include the time and budget concerns that may arise during a larger study. For example:

  • Time for participants to fill out and submit any required forms
  • Investigators availability and schedule requirements
  • Whether the study site can accommodate the flow of participants
  • How long the study will take for each person to complete
  • Is the proper equipment available and in good working order?
  • How to manage technical glitches, equipment failure/maintenance
  • Time and money required for follow-up calls, mailing surveys, etc.

3. To be prepared for any management concerns.

This area deals with the potential personnel and data management issues such as:

  • What are our personnel needs?
  • How will the data be collected?
  • Where will the data be stored?
  • What are our proposed data analysis techniques?

4.To address crucial scientific questions that must be addressed:

Before proceeding with a study involving a medical device or new drug, several scientific or drug safety questions must be addressed:

  • Is the proposed intervention safe?
  • If a drug is being studied, what is the safe dosage?
  • What are potential side effects?
  • What is the expected treatment effect?

5. To convince potential investors or funding bodies that a large-scale study is worth supporting.

A properly executed pilot study can be invaluable in terms of demonstrating the potential of a medical device or drug and earning the required funding for further study.

What can I expect from the results of a pilot study?

The conclusion reached at the end of a pilot study is typically one of the following:

  • Stop- the main study will not be feasible
  • Continue with the main study, but modify the protocol
  • Continue with the main study as is, with close monitoring for necessary changes
  • Continue with the main study as is- the pilot study is determined that it is likely to succeed

What are potential pitfalls and limitations of a pilot study?

Several researchers have attempted to take a closer look at pilot studies in order to gather information on their common features and to gain insight into their potential limitations.

Statistical Power

Keep in mind the statistical power of a pilot study: A successful pilot study does not assure success on a larger scale simply because a pilot study is relatively small and cannot have the statistical power to guarantee success. However, a well-designed pilot study can make a significant difference in increasing the chance of success in a full-scale examination. Main investigators must keep in mind that the main function of the pilot study is not to make a determination of statistical significance, but instead to examine the feasibility of their study.

Data Contamination

Data contamination can occur when pilot study data is combined with the main results or when the same study participants are used in the pilot study then new data obtain from them for the main study. However, the data may be pooled if the methodology and sampling frame remain the same[1].

Final thoughts

A pilot study can be an excellent opportunity to examine the feasibility of a large-scale study and address many weaknesses in the study design before embarking on an expensive full-scale study. In order to optimize the pilot study design, researchers recommend having clear feasibility objectives from the beginning, solid analytic plans, and well-established criteria for success of feasibility. Overall, it is important to keep in mind that the main function of a pilot study should not be to test a critical hypothesis, but rather to optimize the design of subsequent pivotal trials.


  1. Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, Robson R, Thabane M, Goldsmith CH: A tutorial on pilot studies: The what, why and How. BMC Medical Research Methodology. 2010, 10: 1-10.1186/1471-2288-10-1.
  2. Ross S., Grant A., Counsell C., Gillespie W., Russell I. & Prescott R. (1999) Barriers to participation in randomized controlled trials: a systematic review. Journal of Clinical Epidemiology 52, 1143–1156.

Navigating the IRB Process

The IRB (Institutional Review Board) process is the critical oversight and approval foundation when embarking upon a research study. This article presents the most important things to know about the IRB application process before moving forward and offers some tips for expediting the process. Continue Reading…