Author Archives: sak7558

Real-World Evidence for Medical Device Regulatory Decision-Making

As health data continues to become increasingly available, opportunities are arising for the use of data to support medical device decision making. FDA has recognized this and is creating new paradigms to use real-world data (RWD) to support regulatory decision-making for medical devices.

RWD sources such as registries, EHRs, and administrative healthcare claims databases provide information relating to patients’ health status and/or the delivery of health care that is routinely collected. RWD may be used as real-world evidence (RWE) to support a variety of FDA decisions. Examples of uses include post-market studies, expanding indications, control groups, supplementary data, and objective performance criteria and performance goals.

The key to using RWD, which may become RWE, is to ensure the reliability of the data. FDA suggests two aspects to consider: data accrual methods and data quality control assurance. FDA will consider the reliability of the data before using it to inform decisions.

To learn more, feel free to read the FDA guidance document: Use of Real-World Evidence to Support Regulatory Decision-Making for Medical devices. Or feel free to contact one of our knowledgeable consultants at KAS.

Medical Device Regulation Book Suggestions: What Every Entrepreneur Should Know

Over the years, we have worked with many small companies who are interested in developing medical devices. Eventually, these companies encounter the regulatory paradigm established by the Food Drug and Cosmetic Act and/or the Medical Device Directive. Hopefully a first encounter with these regulations is part of a business plan, but sometimes this is not the case. We have seen regulatory issues present themselves at unfortunate times, for example while seeking venture capital funding. Sometimes a company is caught off guard after receiving an FDA Warning Letter, informing a company it is unknowingly marketing a medical device.

An in-depth understanding of medical device regulations is not necessary; however, a basic understanding is critical if you work in the industry. Here are a few book suggestions for any medical device professional, all of which provide indispensable knowledge for an entrepreneur.

Although slightly outdated and concerning a broader array of business topics than medical device regulations, The Entrepreneur’s Guide to a Biotech Start Up is an excellent resource for entrepreneurs and medical device professionals. The book’s chapters on “Device, Diagnostic & Instrument Models,” and “Medical Device Approval” provide a wealth of information that is presented in a clear and concise manner. The author, Dr. Peter Kolchinsky, also recommends a few resources under “Recommended Reading” which are also worth checking out. The best part about this book is that it is free!

Dr. Christopher Joseph Devine has published a handful of books that he brands “Devine Guidance.” These books are extremely helpful for understanding the basics of the Medical Device Directive and FDA’s CFR Part 820 (Quality System Regulations). Warning: the author’s use of third person and lame jokes can be annoying; however, his explanations are invaluable. If you need a crash course in Quality System Regulations, Dr. Devine’s books are for you.

Design Controls are critical for a small company to understand. Marie B. Teixeira published an excellent and practical book called Design Controls for the Medical Device Industry. This book assists in the development of an effective design control program, and it includes templates that can be used by a small company. The book is slightly outdated and does not include information on Unique Device Identifier (UDI) regulations. This book is great for medical device engineers.

FDA’s New ISO 10993-1 Biocompatibility Evaluation Guidance

On June 16th, 20016, FDA published a final guidance on biocompatibility evaluation called, Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process.

Special consideration should be paid to Attachment A of the guidance document which provides a framework for the development of a biocompatibility testing plan. FDA claims Attachment A is not a “checklist” for testing, but rather a checklist of considerations that need to be made when thinking about the biocompatibility of a device in its final finished form (FFF). FDA’s expectation is that all submissions to the FDA address all of the “Xs and Os” on in the biocompatibility safety evaluation (Attachment A). Information such as existing data, additional endpoint-specific testing, or rationales can be used. If testing is performed, the guidance document includes additional information on endpoint considerations for the following: cytotoxicity, sensitization, hemocompatibility, pyrogenicity, implantation, genotoxicity, carcinogenicity, reproductive & development toxicity, and degradation assessments. New materials used in a device might require additional evaluations beyond those mentioned in Attachment A, and devices with multiple types of exposure should include information to address each exposure category. It is critical to understand this guidance when commercializing a medical device.

To read the guidance, click the link here:
FDA also published a webinar which can be found here:

Posted by Spencer Kimber

FDA’s Pre-Submission Program

FDA’s Pre-Submission (Pre-Sub) Program allows for sponsors to meet with FDA to get feedback on medical device submissions (e.g., IDEs, PMAs, HDEs, and 510(k)s). The main purpose of the program is to provide the sponsor with a mechanism to obtain feedback from FDA prior to an IDE or marketing application, allowing a sponsor to understand the path from device concept to market. Questions that can be answered include specific questions related to product development, proposed clinical study protocols, or data requirements for submissions.

According to the FDA Guidance Document, Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff, Pre-Subs can be useful in the following circumstances:

  • “Before conducting clinical, nonclinical, or analytical studies, or submitting an IDE, IND, or marketing application when:
    • the new device involves novel technology and it may be helpful to familiarize the FDA review team with the technology in advance of the submission;
    • you are proposing a “first of a kind” indication or a new indication for an existing device;
    • the new device does not clearly fall within an established regulatory pathway, and you desire informal input on a proposed regulatory strategy;
    • the new device is a multiplex device capable of simultaneously testing a large number of analytes;
    • the new device is an in vitro diagnostic (IVD) device that contains a new technology, a new intended use, a new analyte, new clinical questions, complex data/statistical questions, and/or where the predicate19 of or the reference method is unclear or uncertain;
    • you desire FDA guidance on specific issues related to nonclinical study protocols and/or animal study protocols, before initiating your studies; or FDA input on your proposed testing is especially encouraged for studies that will have a long duration or for which there is no single clearly established consensus method for collecting the data, such as when there is no recognized consensus standard or are multiple standards from which to choose;
    • you desire FDA input on specific issues related to your planned clinical studies, especially if they involve complex or novel statistical approaches;
    • you desire FDA input on the extent that existing data may be leveraged in preparing a PMA submission for your device in accordance with section 520(h)(4) of the FD&C Act; and/or;
    • you desire FDA input on a clinical protocol before conducting a clinical study that does not require FDA review of an IDE or IND, such as for a nonsignificant risk device or a study you plan to conduct entirely outside the US (OUS).
  • Before submitting a marketing application:
    • to apprise the FDA review team on the particulars of the device and clinical study (if there have been changes since initiation of the IDE or IND);
    • to obtain feedback on the use of data collected from an OUS study to support clearance or approval;
    • to obtain our feedback on preferred data presentation and to ensure clarity with respect to our expectations regarding the elements to be included in the marketing application; and/or
    • to gain insight into potential hurdles for approval or clearance (e.g., numerous protocol deviations, missing data, or a failed study endpoint), some of which could require additional data or analyses.

Pre-Subs can be a useful way of clearing up any ambiguity associated with bringing a product to market; however, they should not be used to replace the use of guidance associated with a medical device. To learn more about Pre-Subs, read FDA’s guidance here: Requests for Feedback on Medical Device Submissions:  The Pre-Submission Program and Meetings with Food and Drug Administration Staff. If you have questions or believe you could benefit from a Pre-Sub, feel free to contact one of our knowledgeable consultants at the KAS Group.

Posted by Spencer Kimber

Is It a Medical Device?

Often, a company wonders if their product is a medical device and what that means for them. What are the FDA requirements for a particular product and how difficult will it be to get the FDA’s blessing?

To discover this information, the first step is to look at the encompassing definition of a medical device and question the product:

“A medical device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or some other similar 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 its 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.”

If any of this criteria applies, then it is time to search the CDHR Classification Database – it is likely that the device already exists in some shape or form in the database.

The Classification Database contains products that are already established as medical devices. The Classification Database also has useful information that one will need to know before marketing a device. For example, the database contains information on the device classification (i.e., Class I, Class II, or Class III).  Based on the device classification, certain levels of control are necessary to “provide reasonable assurance of [the device’s] safety and effectiveness.” Once the device classification is known, one can then have an idea of what regulations will need to be met.  Click hear to learn more about classifications and regulatory controls. Furthermore, the Classification Database, will provide information such as additional Special Control requirements, or whether the device requires a 510(k) for clearance or a PMA for approval.

If it is still not clear whether your product is a medical device, one can contact the FDA directly for an informal device determination. At the time of this writing, the email to contact FDA for device classification questions is

Posted by Spencer Kimber

Mobile Medical Apps

The many benefits that technology – and particularly information technology – provides to other industries has yet to be realized in healthcare, although it is the popular belief that the adoption and use of Healthcare Information Technology (HIT) will have a large positive effect on the clinical outcomes and the economy. Recent legislation has attempted to embrace HIT. For example, the Health Information and Technology for Economic and Clinical Health (HITECH) Act and the Affordable Care Act (ACA) both include financial incentives through Medicaid and Medicare for implementing HIT.  One side effect of new legislation has been the increased interest in developing new technologies such mobile medical apps, devices regulated by the FDA. In fact it is estimated that by 2015, 500 million smartphone users will be using mobile medical apps, and by 2018, approximately 50 percent of users will have downloaded some form of a mobile health application.

Unfortunately, the regulatory landscape for mobile medical apps is still not well defined. It is clear that mobile medical apps fall under the jurisdiction of the FDA, but the FDA is still working out how it will enforce its regulatory authority. Last year, CDRH attempted to clarify their stance on medical mobile apps by issuing a guidance called “Mobile Medical Applications Guidance for Industry and Food and Drug Administration Staff.” However, FDA is still publishing information on their website to further fine tune their stance.

If you are a stakeholder in mobile medical apps, the guidance is worth a read. It clarifies where FDA gets their authority to regulate mobile medical apps, and what is considered a mobile medical app. In addition, there are numerous mobile apps that meet the regulatory definition of a “device” but pose minimal risk to patients and customers. For these devices FDA exercises “enforcement discretion.” In other words, FDA will not regulate the device but may choose to do so in the future – read about the changes in LDT regulations in “New LDT Regulations on the Horizon.”

If you want to find more information on mobile medical apps, visit or contact one of our knowledge consultants at the KAS Group.

Posted by Spencer Kimber

New LDT Regulations on the Horizon

Technological advances are leading to the increased relevance of personalized medicine and genomic testing. Over the next few decades we will see a rapid development of these technologies which will result in improved medicinal efficacy and a reduction in the overall economic burden of the healthcare costs in the US. The FDA is aware of this trend, and as a result, has been forced to rethink the regulations concerning technologies such as Laboratory Developed Tests (LDTs) which will become increasingly more relevant as healthcare evolves. In 2013, companies such as 23andMe were selling Direct-To-Consumer LDT genomic testing services, which served as a catalyst for recent FDA actions. These tests fall under the definition of a medical device under Section 201(h) of the Federal Food, Drug and Cosmetic Act (FD&C Act), but the FDA has traditionally practiced “enforcement discretion” on LDTs. The only exception has been LDTs which contain analyte specific reagents (ASRs); ASRs are regulated as a class I device. The increased importance of LDTs has raised Public Health concerns. Specifically, the FDA is worried about how people will use data in making health decisions from services like 23andMe, which is not validated under FDA or Clinical Laboratory Improvement Amendments (CLIA) regulations. For example, someone may decide to have preventative surgery based on a genomic test result which is not backed by scientific evidence. This has caused controversy in how LDTs should be regulated, and it is now apparent that FDA intends to change their outlook on the regulations.

In July of 2014 the FDA publically announced that it would begin regulating LDTs, saying that the tests used to make important treatment decisions need to be subject to FDA oversight before they go into use. In addition, the FDA announced that they would be releasing two guidance documents regarding oversight of LDTs which should emerge soon. These documents, which will be first issued as draft guidance, are “Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)” and “FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs).” If you are a stakeholder in LDTs, you should pay close attention to the development of these regulations.

You can find more information on LDTs on FDA’s website here:

Posted by Spencer Kimber

Notified Bodies’ Unannounced Audits

On September 24, 2013 the European Commission published a recommendation that Notified Bodies perform unannounced audits in addition to annual and recertification audits. Unannounced audits are already being performed by Notified Bodies and will become common practice over the next couple of years. If you would like to read more about the recommendation, follow the link here:

If you are a manufacturer of medical devices and sell in the EU, than you should be preparing for these surprise visits. Auditors could show up sooner than you expect. The KAS Group has already had some experience with the new unannounced audit recommendation.

KAS Group recently had experience with one of these audits. The Notified Body representatives began by asked to see the manufacturing area. Next, they gathered a sample of lots numbers and announced that they intended to perform lot traceability all the way back to the raw materials. If the trail lead them to other departments such as inspection, quality, purchasing, etc., they would then review those processes as well — this process which is not typical of a surveillance audit. The audit consisted of 5-10 lots which were traced back to the raw materials level, and the audit lasted one day.

The auditors mentioned that their organization would be performing 450 audits this year with the intention of increasing that number to 1500 in 2015. Moreover, these audits will include subcontractors. If a subcontractor refuses an audit, it could jeopardize the certificates of the manufacturer.

If your company is not preparing for audits, it should do so immediately; an audit might be just around the corner. In addition, these audits stress the importance of external audits and communication. It is imperative that your employees and subcontractors are aware of the EU recommendation and that they are prepared. It is also important to communicate with employees and subcontractors what unannounced audits mean for them and your business.

Posted by Spencer Kimber

Approval to Market or Distribute a Medical Device in the US: A Brief Overview

Gaining market approval is not easy. Commercializing a product in the United States requires a significant amount of time and money. In addition, device manufacturers must navigate the complex and time-consuming requirements enforced by the Food and Drug Administration (FDA). When attempting to market a new device, a manufacturer must assess the regulatory requirements and work with the Center for Devices and Radiological Health (CDRH) – a division of the FDA – and its many different offices. Fundamentally, no matter what device a manufacturer is trying to market, it boils down to two questions:

  1. Do the benefits outweigh the risks?
  2. Does the FDA agree with your assessment of the benefits outweighing the risks?

FDA classifies devices based on risk. There are three different classifications of devices: Class I, Class II, and Class III. The proper classification of a device is critical since the class impacts regulatory requirements.  Most devices require that manufacturers establish compliance with current Good Manufacturing Practices (that is, Quality System Regulations (21 C.F.R. part 820)).  Interestingly, the FDA will typically not classify a device until the device has been reviewed in a marketing application (510(k) or PMA).  So, it is up to the manufacturer to ensure that the classification is correct.  The FDA does offer informal assistance, though, through the Division of Small Manufacturers, International and Consumer Assistance (DSMICA).  If a manufacturer wants a formal device classification before filing a marketing application, the manufacturer may submit a 513(g) Request for Information to the FDA (along with a fee).

Depending on the risk associated with a new device, the FDA may require one of two premarket applications to be filed. The first application, and the most common, is called a 510(k) (pronounced “five-ten-K”).  510(k)s generally involve less regulatory burden, costs, and time. These applications are most often required for Class II and some Class III devices. The second type of application the FDA might require is called a Premarket Approval Application (PMA). These applications require a great deal of resources and time, and are generally only required for high-risk (e.g., life sustaining) or devices which apply significant, new technology.  PMAs, especially original PMAs, are not common.  Most Class I devices do not require premarket approval or clearance.

It is important to note that there are a number of other FDA regulatory requirements which are not discussed here. Some of these requirements include device registration and listing (DRLM), labeling requirements, unique device identifiers (UDI), and post-market surveillance. These may be the subject of subsequent blogs.  For more detailed approval advice, visit or contact one of our knowledgeable consultants at the KAS Group.

Posted by Spencer Kimber