The Less Burdensome Pathways to US FDA Approval

Medical Device Regulatory Rules

The most contentious hurdle that steals competitiveness and commercial opportunities for medical devices is the regulatory review process. It has already been very challenging for regulators to strike a balance between assuring device safety and ensuring access to the best treatment. However, where regulations threaten to stifle innovation and deprive the medical device industry of its value, this becomes the critical turning point for a change to take place. Leading the way in finding the least burdensome approach (FDA Modernization Act of 1997) to regulatory scrutiny is the US FDA. In 2011, it introduced the Innovation Pathway to facilitate device innovation and expedite the review of breakthrough technologies. Through this programme, the FDA aims to engage with innovators much earlier and more interactively during device development to identify just the right investment of time, efforts and resources to achieve regulatory compliance. The three programmes already proposed to reduce time and cost of the regulatory process are detailed below.

1. Downclassification of PMA devices

The US FDA classifies medical devices into three categories – Class I, Class II and Class III – based on the products perceived risks. The higher the risk (Class II and III) the greater is the degree of regulatory control. The level of risk in a product depends on its intended use. However, under the US FDA, assigning classification to a medical device based solely on intended purpose is not enough. For example, to secure the lighter 510(k) approval route for Class I and Class II devices, a manufacturer must further demonstrate substantial equivalence (SE) to a predicate legally marketed device of the same classification; failing which, the device will be regarded as a new technology classified under Class III and subject to the more stringent Pre-Market Approval (PMA) review. In a recent review of PMAs approved before 2010, the US FDA has proposed the loosening of controls on 44 device types. This regulatory relief is given in the following forms:

  • Reclassification to the Class II category
  • A shift from pre-market data collection to postmarket controls or postmarket data collection
  • A reduction or shift in data collection and/or reclassification in 2014, during the review

The Center for Devices and Radiological Health (CDRH) has made it their strategic priority for 2014/2015 to explore ways to expedite the evaluation of new device technology, especially where it is of particular importance to public health. The 21 devices candidated for downclassification to Class II includes short-term and semi-permanent invasive devices, but does not include permanent implants. This brings the US FDA slightly closer to the way these devices are classified under the EC rules, within which they already fall under either Class IIa or Class IIb devices. However, the reason for downclassification is less for harmonisation purposes and more because the device technology has become the standard, effective, safe and highly demanded mode of treatment. It would not be wrong to presume that these devices would also need to meet some essential criteria such as:

  • Have sufficient clinical data and post-market experience
  • Demonstrate exemplary safety records
  • Have been in the market for 5 years or more
  • Are widely available and used on/by patients

On the other hand, the shift from pre-market data collection to post-market controls for breast implants may be counter-intuitive for a device that has been subjected to recalls and scandals. However, this is clear proof that lengthy pre-market review would not necessarily increase the safety and effectiveness of a medical device. In this case, the US FDA is wise to employ a “bootstrap” strategy that applies just the right amount of review with more specific end-points continuously throughout the commercial lifetime of the device. The right balance of assumption (pre-market) and fact (post-market) will help create a more complete safety and effectiveness picture for a medical device.

2. Expedited review process

For PMA devices not targeted for downclassification, the US FDA has introduced two programmes: the De Novo device classification and the Expedited Access Pathway (EAP). Both pathways are voluntary, meaning manufacturers need to make a submission to the US FDA requesting for the devices to be considered under these programmes. The De Novo classification allows what would normally be a Class III device to be reviewed via the Class I or Class II routes despite having no substantial equivalence to a legally marketed device. These devices approved under general controls or 510(k) will then be classified as Class I or Class II. They can be marketed immediately and serve as the predicate device. To qualify for the De Novo process, a device must meet the following criteria:

  • The device should demonstrate a risk level equivalent to a Class I or Class II medical device, meaning low to moderate risk.
  • A comprehensive risk-benefit analysis must be performed. The manufacturer must be able to understand, explain and mitigate all known risks as well as provide assurance of effectiveness using general or special control principles.

An EAP designation, on the other hand, allows a shift from the pre-market data collection approach to a post-market data collection approach. It is an interactive review process, in which the US FDA and manufacturer work hand-in-hand to establish the appropriate data development plan under either a PMA or De Novo route. The data development plan should adequately describe the pre-market and post-market data (clinical and non-clinical) to be collected and analysed within agreed timelines. Devices that qualify for consideration under the EAP should meet the following criteria:

  1. The device is intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition.
  2. AND

  3. The device meets at least one of the following criteria:
    • No appropriate alternative treatment or means of diagnosis exists.
    • The device represents a breakthrough technology that provides a clinically meaningful advantage over existing legally marketed technology.
    • The device offers significant, clinically meaningful advantages over existing legally marketed alternatives.
    • The availability of the device is in the best interest of patients.


  4. The sponsor submits an acceptable draft Data Development Plan.

    1. 3. Foreign clinical data

      More recently, the US FDA has released a draft guidance for the acceptance of clinical data obtained from studies conducted outside the United States (OUS) to support pre-market submissions. In making this move, the FDA acknowledges the increasing globalisation of clinical trials and seek to find ways to prevent unnecessary duplication of clinical studies. For the FDA to accept OUS clinical data, certain criteria needs to be met:

      1. The clinical studies are conducted under an investigational device exemption (IDE)
      2. Sites in the United States are included as part of the clinical study
      3. Clinical studies conform with the Declaration of Helsinki or a similar declaration under the laws or regulations of a country
      4. Valid scientific evidence is produced from a well-controlled studies presided by qualified experts
      5. Compliance with Good Clinical Practice
      6. Considerations have been given to:
        • Differences in clinical conditions
        • Differences in Study Populations
        • Differences in regulatory requirements
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