New medical device & IVD regulations adopted by European Parliament

European Parliament Commission stockIt’s official: regulation of medical devices and in vitro diagnostics (IVD) will undergo significant changes over the next five years. Last week, the EU Parliament approved the proposed changes, disregarding a proposal from the UK Independence Party to reject the new regulations. The new regulations “include stricter premarket review of high-risk devices, strengthened criteria for notified bodies, improved traceability, as well as a risk-based classification system for IVDs… [and are the] result of a multi-year negotiation process between the European Commission, Parliament, and Council to address gaps in oversight that led to several device-related scandals.”1

The new regulations will be published in the Official Journal of the European Union in May. Once published, the new Medical Device Regulations (MDR) will be implemented in three years and the new In Vitro Diagnostics Regulations (IVDR) in five years.

The new medical device and IVD regulations should strengthen transparency of information for consumers, ensuring that vital information is easy to find. For example, patients will receive an implant card containing all essential information; furthermore, a unique device identifier will be mandatory for every product, allowing each product can be found in the new European database of medical devices.2 Elżbieta Bieńkowska, Commissioner for Internal Market, Industry, Entrepreneurship and SMEs at the European Commission, said “I’m extremely happy that our push for stricter controls of medical devices on the EU market will now become a reality. Whether for medical devices, cars, or other products, we must ensure stronger supervision in the interest of our citizens. We should not wait for another scandal instead we should start a discussion how to strengthen European oversight over Member States’ surveillance activities.”2

The regulatory landscape for medical device and in vitro diagnostics will continue to change as products advance and become more connected. Our experts at Pearl Pathways commit themselves each day to driving our clients’ products to market faster. If you have a device or diagnostic in development, contact us today to learn how we accelerate our clients’ product development pathway here in the U.S. market and abroad.




Official press release

Drug master files (DMFs) electronic submission deadline extended

FDA DMFs eCTDOn April 7, the Food and Drug Administration (FDA) announced an extension of the compliance date for submitting drug master files (DMFs) in electronic common technical document (eCTD) format. FDA pushed the deadline back one year to May 5, 2018. The compliance date for submitting new drug applications (NDAs), biologics licensing applications (BLAs), and abbreviated new drug applications (ANDAs) electronically remains unchanged (May 5, 2017).

Shifting to the eCTD format represents FDA’s initiative to make the drug application review process more efficient. eCTD standardizes how the life science industry submits applications, amendments, supplements, and reports. FDA states that implementing electronic DMFs will improve the efficiency of the DMF review process. Electronic drug master files allow FDA to review applications more easily and better meet the associated PDUFA and GDUFA performance goals.

Our team of advisors at Pearl Pathways expertly prepare electronic drug master files for FDA submission. We understand the eCTD format and process. We have already helped several life science companies electronically submit DMFs, NDAs, BLAs, and ANDAs. Contact us today to discuss your submission needs.


Here are some helpful resources to prepare for the upcoming deadlines:

Guidance Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the Electronic Common Technical Document (eCTD) Specifications

New Requirements for Electronic Submissions of DMFs

DMF Tip Sheet

eCTD Submission Requirements: What You Need to Know

FDA Electronic Submissions Gateway

New diagnostics bill could dramatically alter regulations

diagnostic diagnostics lab developed testsDiagnostic and lab-developed test (LDT) regulations could soon receive a significant overhaul. RAPS reported this week that a bipartisan duo, Rep. Larry Buchson, M.D. (R-IN) and Diana DeGetter (D-CO), released a discussion draft for a bill proposing a new path for the US Food and Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS).

The draft, named the Diagnostic Accuracy and Innovation Act (DAIA), would “create a classification system for in vitro clinical tests (IVCTs), require premarket FDA approval for high-risk tests, and create a new center under FDA to regulate these tests.”1 Additionally, the discussion draft would “create a new user fee program…[though] user fees will not be the primary funding source for the new regulatory structure (i.e., user fees will be capped at 30%).” Under this bill, the CMS’ Clinical Laboratory Improvement Amendments (CLIA) program to oversee laboratory operations would be modernized. Furthermore, FDA’s responsibilities would expand to regulate “the design, development, and validation of an IVCT as well as the production of an IVCT for distribution to another facility or third-party”

Assuming the draft discussion advances and FDA issues a full guidance, a transition phase will allow the industry and regulators time to “implement the following framework:

  • IVCTs introduced by laboratories prior to three months before enactment of the bill will be grandfathered and no submission obligations will apply to such IVCTs prior to the effective date of the regulations (i.e. five years after enactment)
  • New regulations would be required to be promulgated within three years of enactment, and compliance would be required no later than two years after that (with some opportunity to take advantage of the new system one year post promulgation).” 1

Regarding other post-market requirements, test developer’s responsibilities will “largely resemble current FDA requirements for in vitro diagnostics, except adverse event reporting will be updates to: (1) limit individual submissions to those events that involve death or imminent threat to public health, and (2) use quarterly summary and trend reporting for all other adverse events, including malfunctions. There will be no overlap of CLIA and FDA requirements.”2 We will continue to monitor the advancement of this draft discussion and the possible impact on diagnostic and lab-developed test regulations. Check back to the Pearl Pathways blog or follow us on Twitter for more immediate updates.




RMAT Designation from the 21st Century Cures Act now live

21st Century Cures Act regenerative medicineThe 21st Century Cures Act, signed into law on December 13, 2016, includes several provisions related to regenerative medicine. Regenerative medicine covers a wide range of innovative products including cell therapies, therapeutic tissue engineering products, human cell and tissue products, and certain combination products using such therapies. Examples of regenerative medicine include chimeric antigen receptor T-cell (CAR-T cell) treatments (FDA recently granted IND approval to the first gene-edited CAR-T cell therapy in the US), human tissues grown on scaffolds for subsequent use, and more.

The Regenerative Medicine Advanced Therapy (RMAT) Designation is a product of the Cures Act. The RMAT designation builds on FDA’s existing expedited programs available to regenerative medicine products and was established to foster the development and approval of these products. In an FDA blog, Peter Marks, M.D., Ph.D. (director of the Center for Biologics Evaluation and Research at the U.S. Food and Drug Administration), explains that “sponsors of certain products may obtain RMAT designation for their drug product if the drug is intended to tread serious or life-threatening diseases or conditions and if there is preliminary clinical evidence indicating that the drug has the potential to address unmet medical needs for that disease or condition.”1 The RMAT designation applies to:

  • Certain cell therapies
  • Therapeutic tissue engineering products
  • Human cell and tissue products
  • Certain combination products

Marks goes on to explain the process and benefits of the RMAT designation, which is summarized below:

  • Sponsors may make such a request with or after submission of an investigational new drug application and the agency then will take action on the requests within 60 calendar days of receipt
  • Sponsors of RMAT-designated products are eligible for increased and earlier interactions with the FDA
  • Sponsors may be eligible for priority review and accelerated approval
  • Once approved, the FDA can permit fulfillment of post-approval requirements under accelerated approval through the submission of clinical evidence, clinical studies, patient registries, or other sources of real world evidence, when appropriate

The FDA has already begun receiving RMAT designation requests and they will likely receive more as regenerative medicine research and treatments continues to advance. Our experts work diligently with our clients to accelerate the product development process. We have helped countless sponsors receive priority review and expedited approval for their product, such as with the Breakthrough Therapy Designation. Contact us today to discuss how we can help with your next investigational new drug application.



Tobacco products escape FDA final rule on intended use, for now

FDA final rule tobaccoLast Friday, the US Food and Drug Administration (FDA) announced it will not implement its final rule specifying when tobacco products are regulated as medical products until March of 2018, RAPS reports. The delay comes in the wake of a petition presented by biopharmaceutical industry groups. These groups voiced concerns regarding the rule’s impact on the current definition of intended uses for drugs and medical devices. The petition’s backers included the Medical Information Working Group (MIWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the Biotechnology Organization (BIO). The filed petition calls for FDA to “stay the final rule and revert back to language found in the proposed rule1.

Why the delay?

  • FDA intends to collect more feedback on its final rule from the public. Stakeholders now have 60 days to respond to the final rule before FDA works to finalize the rule once again.

Why the petition?

  • The proposed rule (September 2015) defined when tobacco products are regulated as drugs, devices, or combination products.
  • It also proposed to amend FDA’s definition of intended use found in 21 CFR Sections 202.128 and 801.4 by deleting a clause that had “long troubled the industry… under the clause, FDA is not only able to regulate products based on their intended uses, but on their actual uses based on whether a manufacturer ‘knows, or has knowledge of facts that would give him notice, that a drug or device introduced into interstate commerce…is to be used for conditions, purposes, or uses other than the ones for which he offers it’”1
  • Industry professionals expressed concern over the knowledge clause, fearing the provision could allow FDA to require new marketing applications based on a company’s knowledge of a product’s off-label use.
  • Language in the final rule amended the knowledge clause to read: “And if the totality of the evidence establishes that a manufacturer objectively intends that a drug introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than ones for which it is approved (if any), he is required, in accordance with section 502(f) of the Federal Food, Drug, and Cosmetic Act, or, as applicable, duly promulgated regulations exempting the drug from the requirements of section 502(f)(1), to provide for such drug adequate labeling that accords with such other intended uses.”2

Pearl Pathways will monitor this situation as it develops. Check out our blog in the coming weeks for updates on amendments to the final rule once the 60-day feedback period concludes. Our team has helped several companies navigate the difficult regulatory pathway tobacco products face under the Family Smoking Prevention and Tobacco Control Act. Contact us today to discuss what regulatory pathway your tobacco product falls under. We can help with your premarket tobacco application (PMTA), modified risk tobacco product (MRTP), and more.





Indy tech jobs continue to flourish

indy tech jobs top 5Perhaps you haven’t noticed the flurry of articles written about Indianapolis lately. Journalists and analysts continue to praise Indianapolis’ airport, food scene, and tourism. These are praiseworthy aspects of Indiana’s growing capital, but a strong, diverse job market will keep young talent in the state and encourage experienced professionals to make the Hoosier state their home. Fortunately, when it comes to tech jobs, Indy is rolling.

Forbes recently reported on the cities creating the most tech jobs in 2017. Regarding methodology, half the ranking is based on employment growth at companies in high-technology industries (e.g. software, engineering services), with the other half based on changes in the number of workers classified as having STEM (science, technology, engineering, and mathematics) occupations. Data analyzed spanned one decade (2006-2016), with added weight given to 2014-2016 growth to account for current momentum. Here’s a look at the top 5:

  1. San Francisco-Oakland-Hayward, California
  2. Charlotte-Concord-Gastonia, North Carolina
  3. Austin-Round Rock, Texas
  4. San Jose-Sunnyvale-Santa Clara, California
  5. Indianapolis-Carmel-Anderson, Indiana

Even the Forbes author seemed puzzled by the results, admitting that “another surprising up and comer is Indianapolis in fifth place.”1 The share of STEM jobs in the Indianapolis region sits close to the national average at 5%, but STEM employment is up nearly 18% since 2006. Internet-based jobs experienced an astounding 1,700% growth in the past decade. A few more noteworthy statistics from the report:

  • Tech Industry Job Growth (2006-2016): 68.1%
  • Number of tech jobs (2016): 30,646
  • STEM occupation growth (2006-2016): 17.8%
  • Number of STEM jobs (2016): 53,181

Silicon Valley still holds a commanding lead for the number of tech jobs, but Indy seems poised to continue climbing the ranks. Tech and STEM related jobs include some strong Indiana life science sectors, such as medical device manufacturing. Pearl Pathways’ President and CEO, Diana Caldwell, recently provided her perspective on the medical device industry in Indiana in an article published in the 2017 edition of BioFutures. Check out her article and learn more about the best health science companies, technologies, and talent.




RAPS seeking nominations for 2018-2020 Board of Directors

raps indianaRegulatory Affairs Professionals Society (RAPS) is seeking qualified individuals to serve on the RAPS board of directors for the 2018-2020 term. RAPS, the largest global organization of and for those involved with the regulation of healthcare and related products (e.g. medical devices, pharmaceuticals, biologics, and nutritional products). Board members serve as the strategic governing and policy body of RAPS and identify opportunities that advance the profession and improve/expand association programs that support the profession globally.

2018-2020 Board Position Openings:

  • President-Elect (one open position)
  • Directors (four open positions)

Learn more about the nomination process and open positions here

Gretchen Bowker, COO and co-founder of Pearl Pathways, currently serves as the chair of the RAPS Indiana Chapter. Bowker states that the “RAPS Indiana Chapter conducts a number of professional development and networking activities throughout the year to help members connect, build relationships, and increase knowledge, competence, and performance… RAPS is a volunteer-driven organization and I’ve found that the more I put into it, the more I get back.”

Interested in joining RAPS? Find your local chapter here and learn how to get involved today!

Alzheimer’s drugs keep failing, but why?

Assorted_Pills_Alzheimer'sLast November, Eli Lilly abandoned its leading Alzheimer’s drug after recent failures during clinical trials. It’s not that the drug didn’t fulfill its mission of clearing out plaques in the brain; the problem was that plaques were removed but patients experienced no relief from their symptoms.

Shortly after Lilly’s drug failed, a “small company called Accera touted an alternative: a drug to improve how the brain processes sugar.”1 Accera’s hypothesis marks an alternative to the longstanding theory that a buildup of a toxic protein called amyloid causes Alzheimer’s disease. Plaques formed by the protein were thought to kill nerves and lead to confusion, memory loss, etc. Unfortunately, Accera’s drug suffered the same fate as Lilly’s. Outcomes did not improve for any participants in their study involving 413 volunteers, Accera announced two weeks ago.2

Multiple drugs from a variety of companies continue failing, and now some of the dominant theories behind the cause of Alzheimer’s are being called into question. An MIT Technology Review article cited that a 2014 review study found more than 99% of 413 different Alzheimer’s drugs tested showed no benefits for patients.3 These failures are forcing researchers and drug developers to rethink Alzheimer’s disease altogether; what the majority once theorized to be the cause has not held up during clinical trials. Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California School of Medicine, fears that drug companies strive to “hit a home run too fast” when “we don’t quite have the illness or target down.”1

Accera and others plan to continue pursuing the alternative theory that “plaques associated with Alzheimer’s develop when the brain starts losing its ability to metabolize blood sugar, or glucose, a key energy source for cells.”1 2017 and beyond will certainly bring about new hypotheses to test and novel mechanisms of action if new drugs continue to fail during clinical trials. If your company is initiating a human study and needs IRB support or help navigating the regulatory pathway for the development of a new drug, please contact our team of experts today.





Life science event: Pearl Pathways presents “The Impact of Software in Medical Device Development” forum

Pearl Pathways, along with Barnes & Thornburg Law LLP and Indiana Medical Device Manufacturers Council (IMDMC), will host an educational forum on the morning of Tuesday April 11, 2017. Key topics impacting the medical device industry will be addressed and attendees will have the opportunity to network with other leaders in the Indiana life science community. You may find agenda and registration information below.


  • 8:30 – 9:00  Registration & Breakfast
  • 9:00 – 9:45  My Medical Device Has Software: What Are My Next Steps?
  • 10:00 – 10:45 Regulatory Landscapes, Considerations and Pitfalls: Emerging Trends for Embedded Software in Medical Devices and Capital Equipment.
  • 11:00 – 11:45 – PANEL DISCUSSION – Best Practices in Developing Medical Devices Containing Software
  • 11:45 – 12:00 Q&A and Networking


Session #1 will be led by Marshall Parker, Principal Software Engineer & Owner at Gale Force Software
Session #2 will be led by John Lockwood, RAC, CWA, CSQE, Senior Advisor at Pearl Pathways


Heidi Hancock Strunk, Senior Director, Quality & Regulatory Affairs at PTS Diagnostics
Cathy Wilburn, Director of Quality Assurance & Compliance at The RND Group
Marshall Parker, Principal Software Engineer & Owner at Gale Force Software
John Lockwood, RAC, CWA, CSQE, Senior Advisor at Pearl Pathways
*Moderated by Lynn Tyler, Intellectual Property Litigator & FDA Practice Chair at Barnes & Thornburg Law LLP


Tuesday April 11, 2017


Barnes & Thornburg Offices

11 S. Meridian Street

Indianapolis, IN 46204

Learn more and register now!


IMDMC life science event

Barnes & Thornburg life science event

21st Century Cures Act deadlines approaching

21st Century Cures ActThe 21st Century Cures Act passed with resounding bipartisan support in the final days of President Barack Obama’s second term. The bill, which includes initiatives impacting several federal organizations and the clinical research ecosystem, will be implemented over the next several years primarily by the US Food and Drug Administration (FDA) and National Institutes of Health (NIH). The Regulatory Affairs Professionals Society (RAPS) recently reported, some provisions of the bill must be implemented in the next two weeks.

March 13, 2017 marks 90 days since the law’s passing and subsequently includes some required actions. The RAPS article points out some of the upcoming deadlines:

  • “Tom Price, the new Secretary of Health and Human Services, shall establish a task force, called the “Taskforce on Research Specific to Pregnant Women and Lactating Women” to provide guidance on “gaps in knowledge and research regarding safe and effective therapies for pregnant women and lactating women, including the development of such therapies and the collaboration on and coordination of such activities.”1
  • Price also must publish a notice in the Federal Register containing a list of each type of Class II device that no longer requires a report “to provide reasonable assurance of safety and effectiveness.”1
  • Another portion of the bill requires NIH officials to “consult with stakeholders, including FDA and the Office of the National Coordinator for Health Information Technology, as well as patients, researchers, physicians, industry representatives, and developers of health information technology to receive recommendations to further enhance”2

These deadlines undoubtedly arrive during a time of change for the FDA and NIH, yet the Cures act was passed with the intention of improving patient care, expanding clinical research programs in the United States, and finding a cure for cancer by the year 2020. With more deadlines approaching at the 180-day mark, or June 13, the new administration officials entering the impacted agencies must come together and work quickly to support the goals of the bill.

Stay tuned to our blog or follow us on Twitter for updates on the 21st Century Cures Act, new legislation, and other current events impacting the life science industry. Do you need assistance with your NIH funded research? Please contact us today.