ThinkstockPhotos-499448127-1-1.jpgParagon's Sara Bobbit shares this round-up of hot topics presented at this year’s RAPS Regulatory Convergence and includes a high level recap of innovation and technology: practical applications for regulatory, Zika, real world evidence, faster patient access to innovative and critical medicine, recent developments in off-label promotion and medical devices.

Innovation and Technology: Practical Applications for Regulatory

A panel discussion explored the topic of emerging technology applications in our regulated industry, bringing together Larry Carrier of Verily Life Sciences, Kathy Hibbs of 23andMe, Francine Ratner Kaufman of Medtronic and Bakul Patel of CDRH.

On the innovation front, there was talk about the Internet of Medical Things (IoMT), which offers the possibility for continuous monitoring leading to early interventions, such as Medtronic’s continual glucose monitoring system. They also touched briefly on regulating Software as a Medical Device (SaMD) noting alignment and collaboration with the FDA are keys to success.

The main conclusion was that while these innovations bring vast tangible benefits, there is an urgent need for regulators to keep pace for patient protection. While technology in healthcare can empower and engage patients, it also can expose them to more risk for being hacked or making decisions to share data they may come to regret in the future.


Several sessions were held on the Zika outbreak and how R&D will be critical to addressing this and future emerging diseases. An integrated public-private sector approach is needed to develop the necessary vaccines, therapeutics, diagnostics, devices and novel approaches. Policy and financial considerations must be addressed. The goal is to learn from the mistakes made in dealing with the Ebola outbreak, which exposed weaknesses in the global health system and showed the mechanisms for the establishment of public-private partnerships were lacking.{1}

Puerto Rico is as an ideal ecosystem for Zika R&D as it is endemic for the disease, covered by FDA’s authority, and is one of the top three states for share of highly specialized biopharmaceutical employment. Figure 1 shows the distribution of biotechnology, pharmaceutical, agricultural biology, and medical device employers across Puerto Rico. TransCelerate and Yale University have been key enablers of the Puerto Rico Consortium for Clinical Investigation (PRCCI). PRCCI has a pipeline of eight clinical studies for Zika-related products as of July 2016 so they are likely a group to watch in this space over the coming year.{2}

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Figure 1. Distribution of Highly Specialized Employers Across Puerto Rico.{1}

Real World Evidence

Real World Evidence (RWE) is not new, but there is an evolution occurring to broaden its use, bridging clinical and commercial data silos so that it may be utilized throughout a product’s lifecycle instead of its traditionally exclusive use in post-marketing studies. In order to effectively use RWE, registries for patients, diseases and clinical trials are critical and must be designed and executed with the ability to be linked with key external databases. While high quality data is expected to increasingly assist in regulatory decision making, concerns about data privacy remain at the center of the debate.{3} Three specific bottlenecks were cited as ongoing concerns: the acceptability of RWE across stakeholders, the usefulness of RWE for regulatory use and the feasibility of harnessing big data for evidence collection.{4} Signals from FDA indicate they are willing to work through these challenges, from the inclusion of “enhancing use of RWE in regulatory decision making” as a goal of PDUFA VI to the 27 July release of draft guidance, “Use of RWE to Support Regulatory Decision-Making for Medical Devices.”

Faster Patient Access to Innovative and Critical Medicine

Japan and the EU have followed the lead of FDA’s 2012 Breakthrough Therapy program and are developing their own programs to get drugs to market faster if they show significant improvement over available therapy for serious conditions. Japan’s program, called Sakigake, was introduced in April 2015 and the EU’s PRIME program launched in March 2016. The benefits are similar across programs and include assignment of agency liaisons for more direct communication, accelerated review periods (six months for US and Japan, 150 days for EU). A rolling review process is available in the US and Japan, but PRIME offers early dialogue with the agency. Table 1 provides program comparisons.

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Table 1. Comparison of Programs in US, EU and Japan.{5}

Out of a total 441 requests for the required designation, FDA has approved 145. It is estimated that breakthrough therapies now account for 25% of NDA approvals. While the other programs have not yet approved any products, there have already been eight designations in the EU and 11 in Japan.{6}

Recent Developments in Off-Label Promotion

FDA has lost two recent court cases regarding off-label promotion, setting the precedent where off-label promotion may be allowable if it is “truthful and not misleading.” The subjective nature of this criterion leaves open a number of issues like defining the phrase “truthful and not misleading.” For example, who is responsible to provide such definition when it is in direct conflict with FDA guidance and what type of scientific substantiation is needed to make a claim truthful?

Presenters cautioned companies about loosening their standards when it comes to sharing or promoting information on off-label use, as the practice still carries the potential for billions of dollars in liability. In 2014 alone, $3.5 billion were recovered via the False Claims Act with a total of $26.4 billion since 2009.{7}

Medical Devices

Medical devices and their evolving regulations were a heavy focus of this year’s conference and 75% of attendees were from the device industry. The device market has doubled in the last decade and is forecasted to reach $478 billion globally in coming years with $133 billion in the US alone. It now represents about half of the pharmaceuticals market.{8} Figure 2 provides a 2020 growth analysis by device type.

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Figure 2. Analysis of Market Share and Sales Growth for the top 10 Device Areas by 2020.{9}

The session on Unique Device Identification (UDI) was particularly pertinent as it is a relatively new requirement. The compliance date for Class II devices occurred on 24 September, just a few days after the conference. UDI involves the collection and submission of data elements about the device as well as applying unique identification codes to product labeling and in some cases directly to the device itself. Challenges to compliance that were noted included redesign of packaging, product labels, labeling systems, procedural updates, equipment commissioning and submittal to the GUDID database.{10}


1. Lugo, Ivan. “The Americas Challenges to Stop the Spread to Pandemic Proportions and the Clinical Response.” RAPS 2016 Presentation.
2. Kretsos, Kosmas. "Zika: The Puerto Rico Model of Fast and Efficient Clinical Studies." RAPS 2016 Presentation.
3. Miller, Gloria. “Importance of Real World Evidence.” RAPS 2016 Presentation.
4. Francois, Clement. “Real World Evidence: Why, When and How to Implement.” RAPS 2016 Presentation.
5. Tominaga, Toshiyoshi. “Regulators’ Efforts to Promote Faster Patient Access to Innovative and Critical Medicines: A Comparison of Breakthrough Therapy Designation (FDA), PRIME (EMA) and SAKIGAKE (Japan).” RAPS 2016 Presentation.
6. Ibid.
7. Cooke, Dale. “Avoiding Off-label Promotion.” RAPS 2016 Presentation.
8. Rezende, Maira. “Overview of the World Market for Medical Devices and IVDs.” RAPS 2016 Presentation.
9. Evaluate MedTech World Preview 2015, Outlook to 2020—4th Edition, October 2015. Evaluate Group website. Accessed 31 October 2016.
10. Goode, Roberta. “UDI: Manufacturers’ Challenges and Enforcement Trends.” RAPS 2016 Presentation.

Bobbit, S. “RAPS Regulatory Convergence—2016 Hot Topic Review.” Regulatory Focus. November 2016. Regulatory Affairs Professionals Society.