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.





United States sees first gene edited CAR T-cell receive an IND approval

human T-cellThe United States Food and Drug Administration (FDA) approved its first Investigational New Drug (IND) submission for a gene-edited chimeric antigen receptor (CAR) T-cell product for clinical trials. CAR T-cell therapy involves using a virus to edit an immune cell (T-cell) extracted from an individual patient, instructing the cell to attack cancer cells within that patient. This autologous process requires individualized treatments for each new patient. Cellectis’ new product (UCART123), which the FDA granted IND approval, is an allogenic CAR-T immunotherapy, meaning it is non-patient specific or “off the shelf.”

Cellectis plans to initiate Phase 1 trials this year. UCART123 targets CD123, an antigen expressed at the surface of leukemic cells in acute myeloid leukemia (AML) and tumorous cells in blastic plasmacytoid dendritic cell neoplasm (BPCDN). AML is characterized by “uncontrolled proliferation and accumulation of leukemic blasts in bone marrow, peripheral blood and, occasionally, in other tissues” and accounts for an estimated 19,950 new cases each year in the U.S alone.1 BPDCN, categorized by the World Health Organization (WHO) under AML, typically presents with features of both lymphoma and leukemia. It impacts bone marrow and blood cells but the most frequently involved site of disease is the skin.2

Pearl Pathways can help your company navigate the complex regulatory landscape towards a pre-IND meeting, new IND filing, 510k submission, and more. Please contact us today to schedule a conversation with our team of industry experts.




New drug approvals stumble, total filings hit mark in 2016

new drug approvals 2016Record approvals of new drugs in 2014 and 2015 likely won’t continue in 2016. Even so, the total number of filings remains just above the average. FierceBiotech examined the numbers yesterday and tried to uncover the meaning.

According to John Jenkins, the soon-to-be retired director of the Center for Drug Evaluation and Research (CDER) at the FDA, approvals of new molecular entities (NMES) currently stand at 19, well below the 45 NMEs approved in 2015. Novel drugs and biologics currently being reviewed by the FDA will also fall short of the 2015 numbers but align close with 2014. Jenkins attributes 2016’s underwhelming numbers in part due to five drugs that were slated for 2016 approval that received a green light ahead of schedule in 2015. A significant increase in applications resulting in a complete response letter (CRL), meaning they did not achieve the adequate approval mark, also increased from 2 in 2015 to 12 this year (so far). The FierceBiotech article notes that the hike in CRLS could be the effect of a “greater use of speedier approval pathways designed to accelerate access to new medicines [that] is raising the risk of failure at the first hurdle.”

Jenkins felt encouraged by this year’s large share of innovative medicines in the total number of approvals. Over one third are designated for rare diseases, 37% are first-in-class drugs, and 8/10 received clearance in the US ahead of other markets. Pearl Pathways is well equipped to support your NME NDAs/BLAs submissions to help your organization receive approval efficiently and expedite your product’s pathway to market.

FDA officials double down on stem cell therapy regulations

stem cell therapyStem cell research and therapy understandably accounts for much excitement and caution within the life science community and general population. The potential applications of stem cell therapy, from regenerating organs and limbs to fighting cancer, seem endless. The Food and Drug Administration (FDA) recognizes the exciting potential benefit that stem cell therapy poses, but also weighs the potential risks and defends its stance on regulations in an article recently published in The New England Journal of Medicine.

Safe use and efficacy of stem cells certainly exists. For example, the successful use of stem cells derived from peripheral blood or bone marrow for hematopoietic reconstruction is well established. However, expanded use into new areas does not have strong empirical support. The FDA argues that “despite the absence of compelling evidence from adequate, well-controlled clinical trials, some practitioners assert that stem cells have a unique capacity to restore health because they can sense their environment and differentiate in a manner that repairs any defect…[this] assertion… is not based on scientific evidence.”

The FDA admittedly worries about the lack of evidence, stating that “the literature is replete with instances of therapeutic interventions pursued on the basis of expert opinion and patient acceptance that ultimately proved ineffective or harmful when studied in well-controlled trials comparing them with the standard of care.” The FDA expresses the dangers of therapies derived from anecdotal success stories and cited a time in the United States’ history in which such therapies were rampant, and patients unfortunately suffered the consequences. Researchers and companies developing therapeutic products argue that current and/or additional regulations will stifle creativity and delay the cycle of getting potential life-saving therapies to patients. According to the FDA, this fear stems from the lack of familiarity with the available pathways for developing cellular therapy products and the lack of a “systematic, facilitated approach to assembling the clinical data necessary to support the licensure of stem cell therapies produced by individual practitioners at different sites.” The FDA closes its argument by restating its mission of facilitating the development of safe and efficacious therapies that are readily available for patients while maintaining a process that supports future scientific advances.

Navigating the current regulations surrounding stem cell therapies is a necessary step in the product development cycle. However, expedited pathways do exist for the treatment of life-threatening diseases that currently have an unmet medical need. Pearl Pathways is equipped to support you during this process and alleviate the burden that regulations seemingly impose. Contact us today for support.

The 21st Century Cures Act passes through the House with resounding support

The 2st Century Cures Act, a nearly 1,000 page bill that details changes for the Food and Drug Administration (FDA) and National Institute of Health (NIH), passed by a vote of 392-26 today in in the House of Representatives. A Senate vote could come as soon as next week.

Assuming the bill prevails in the Senate, the NIH will be the recipient of $4.8 billion in funding over the next 10 years, though money allocation must be reauthorized each year. This money is “earmarked for the three landmark big science initiatives of President Obama’s time in office: the cancer moonshot, the BRAIN Initiative, and the Precision Medicine Initiative” (FierceBiotech).

The passing vote of 392-26 came as a shock to some critics of the bill, “showing a bipartisan spirit that has been rare in recent years” ( If the bill passes, it would also “gives states $1 billion to fight the opioid crisis, and deliver an additional $500 million to the FDA.”

FDA’s list of emerging tech requests topped by continuous manufacturing and sterile production innovations

The US FDA’s Emerging Technology program was established as a catalyst for new technologies to help modernize pharmaceutical development and manufacturing in areas where the FDA has limited review or inspection experience. Thomos O’Connor from the FDA’s Office of Pharmaceutical Quality explains that “this is technology with the potential to modernize the body of knowledge associated with pharmaceutical development to support more robust, predictable, and cost-effective processes or novel products… our vision is to have a maximally efficient, agile, flexible pharmaceutical manufacturing  sector that reliably produces high quality drugs without extensive regulatory oversight ” (

O’Connor is a member of the committee formed to facilitate the program and assist the industry with applications. The committee, known as the Emerging Technology Team (ETT), has already received 20 applications this year, doubling the number requested last year. The in-PharmaTechnologist article breaks down the submissions: continuous manufacturing technologies for drug product, substance, and biologics represent 30% of all requests, another 30% consists of the use of robotics and container closure systems for sterile injectable production, biotechnology processes and analysis represent 22%, and the final 17% include other areas of innovation such as new dosage forms and 3D printing.

What implications, if any, do these numbers say about the future of the life sciences industry? One could look at the breakdown as a compass for where future demand (and funding) will be. Though continuous manufacturing and robotic/container closure technologies led the way with a majority share of submissions, the numbers represent a fairly even and robust spread of emerging technologies. If your firm is looking to participate in the Emerging Technology program and need guidance with your IND, NDA, ANDA, or BLA application, our dedicated team of experts at Pearl Pathways is here to help.

FDA Halts Finalization of Lab-Developed Test Draft Guidance

Last Friday, the FDA halted the finalization of guidance that would have changed the way lab-developed tests (LDTs) are regulated. The reason? The presidential election. The current administration now enters its waning hours and the FDA decided to suspend guidance until the new regime takes office.

As RAPS reported, the press office for the FDA, Tara Goodin, defended this position because the “FDA believes that patients and health care providers need accurate, reliable, and clinically valid tests to make good health care decisions – inaccurate or false tests results can harm individual patients. We have been working to develop a new oversight policy for laboratory developed tests… and realize just how important it is that we continue to work with stakeholders, our new Administration, and Congress to get our approach right. We plan to outline our view of an appropriate risk-based approach in the near future.”

The agency released draft guidelines two years ago outlining a risk-based framework for regulating LDTs that would be phased in over nine years. LDTs have historically been regulated by the Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments. The FDA’s decision, though praised by some, creates uncertainty for the industry and may leave a lot of companies in limbo. To learn more about this topic, see our industry whitepaper. Need assistance navigating the regulatory guidance for IVDs or LDTs, contact us and our experts can help.

Gretchen Bowker to lecture at Tools & Techniques in Translational Research course

new-ctsi-logoOn November 22nd, Pearl Pathways COO, Gretchen Bowker, MS, RAC, FRAPS will lecture on the topic “Drug Development:  Goin’ to the FDA” for the Indiana Clinical and Translational Sciences Institute (CTSI) Fall 2016 course – Tools and Techniques in Translational Research. The course is designed to provide an understanding of the basic technologies and techniques used in translational research today. Translational Research is the application of basic discovery to human health and disease. Bowker is one of the faculty lecturers helping Purdue, Notre Dame and IU Bloomington advanced graduate students, clinical and research based postdoctoral fellows gain the skills needed to succeed in translational research. Check out Indiana Clinical and Translational Sciences Institute (CTSI) to learn more about their role in accelerating clinical and translational research.