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.


1 https://blogs.fda.gov/fdavoice/index.php/2017/03/this-is-not-a-test-rmat-designation-goes-live/?source=govdelivery&utm_medium=email&utm_source=govdelivery

New FDA draft guidance points to problems with multiple endpoints in clinical trials

FDA clinical trials draft guidanceThe US FDA released draft guidance this week on the “problems posed by multiple endpoints in the analysis and interpretation of study results and how these problems can be managed in drug and biologic clinical trials,” Zachary Brennan of RAPS reports. The FDA justifies the guidance due to the greater likelihood of making false conclusions about the effects of a given drug as the number of endpoints in a single clinical trial increases.

The FDA states that the guidance serves to “describe various strategies for grouping and ordering endpoints for analysis and applying some well-organized statistical methods for managing multiplicity within a study in order to control the chance of making erroneous conclusions about a drug’s effects.” (FDA Draft Guidance). Efficacy endpoints measure a drug’s effects. They may include assessments of clinical events (e.g. mortality, pulmonary exacerbation), patient symptoms (e.g. pain, depression), measures of function (e.g. ability to walk or exercise), or surrogates of these events or symptoms. The draft guidance lists the three families for classifying endpoints within a clinical trial: primary, secondary, and exploratory. To demonstrate the study objective of effectiveness, a statistical analysis must be performed to rule out chance as the explanation for a trial’s results. The guidance goes on to discuss the test of hypothesis and several other statistical methods used within clinical research to test against the probability of chance.

The FDA’s explanation of various statistical models and their usage cases dominates the rest of the draft guidance. However, this in-depth analysis drives home the message of this guidance. The FDA states that “the chance of making a false positive conclusion, concluding that a drug has a beneficial effect when it does not, is of primary concern” (FDA Draft Guidance). Our team of experts at Pearl IRB strive to stay up to date with FDA’s guidance to ensure that our clients remain informed about the necessary regulations. This allows clinical trials to run smoothly as our clients march towards product commercialization. If you have a study that needs reviewed or are in the beginning phases of research for a new treatment, please contact us today.

FDA Issues Official Withdrawal of Proposed Rule Concerning Public Disclosure of Unapproved Gene Therapies

Two weeks ago, the US Food and Drug Administration (FDA) announced the withdrawal of a proposed rule from 2001. The rule would have required the public disclosure of summaries of safety and effectiveness data from pre-market clinical trials of gene therapies and transplanted non-human tissues to humans.

In its notice of withdrawal, the FDA announced “[we have] reconsidered our position on the issue and deemed our concerns from 2001 outdated. We will continue to assess whether rulemaking in this area is necessary, and if so, we will proceed with a new proposed rule.”

RAPS explains that “non-proprietary and non-trade secret information and data related to investigational new drug applications (INDs) for xenotransplantation and gene therapies would have been disclosed.” RAPS goes on to detail the categories of information that would have been disclosed under the rule:

  1. product and patient safety data and related information, including results from preclinical and clinical studies and tests that demonstrate the safety and/or feasibility of the proposed procedures
  2. the name and address of the sponsor
  3. the clinical indications to be studied
  4. the protocol for each planned study, including a scientific abstract and a nontechnical abstract, a statement of the objectives, purpose, and rationale of the study, the name and address of each investigator, the name and address of the official contacts of each local review body as appropriate (IRB, IBC) and dated copies of approval by each group, the criteria for patient selection and exclusion, an estimate of the number of patients to be studied, a description of the treatment that will be administered to patients, and the clinical procedures, laboratory tests, or other measures to be taken to monitor the safety and effects of the drug in human subjects and to minimize risk
  5. written informed consent forms
  6. identification of the biological product(s) and a general description of the method of production, including a description of product features that may affect patient safety
  7. IND safety reports
  8. information submitted to FDA in an annual report
  9. the regulatory status of the investigation, the date of such action and the reason for such action
  10. other relevant data and information that the director of the Center for Biologics Evaluation and Research determines as necessary for the appropriate consideration of the public health and scientific issues, including relevant ethical issues

The FDA closed their notice of withdrawal by stating “the withdrawal of these proposals identified in this document does not preclude the Agency from reinstituting rulemaking concerning the issues addressed in the proposals listed in the chard. Should we decide to undertake such rulemakings in the future, we will re-propose the actions and provide new opportunities for comment.” If your company needs help navigating the FDA’s ever-changing rules and the complex regulatory landscape, please contact us.

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.

IRB Written Procedures Draft Guidance released

Institutional Review Board (IRB) Written Procedures: Guidance for Institutions and IRBs draft was released recently by the FDA and the Office for Human Research Protections (OHRP). This new draft guidance includes an IRB Written Procedures Checklist developed with the intent to assure all important activities are considered and completed by IRBs as they ensure the protection of human research subjects.

Pearl IRB strives every day to provide our customers top quality service, unyielding ethics and efficient services.  Protecting human subjects and driving improved value and efficiency in protocol reviews and implementation shapes our behaviors each day.

Contact Pearl IRB – we are assuring all important activities are considered and completed. ✔

Phase I study death in France prompts EMA updated guidelines on FIH trials

In January of 2016, a Phase I drug trial in France, conducted by the French contract research organization Biotrial, left one volunteer dead and five others hospitalized: four with permanent neurological damage. The drug, named BIA 10-2474, is under development, by the Portugal-based pharmaceutical company Bial, for pain relief. This is a therapeutic area where non-addictive drugs are in great need. BIA 10-2474 differs from other medications in this class as it is an inhibitor of fatty acid amide hydrolase (FAAH). This is in contrast to oxycodone (which works on opioid receptors) or naproxen (inhibitor of cyclooxygenase enzymes).  How and why this catastrophe happened has been a focus of significant speculation in the medical and scientific communities. But crucial details, such as in vitro and animal studies, are lacking. At the time of the incident, PubMed listed no publications of any type from Bial on this class of drugs.

Following the Biotrial incident, the EMA updated its guidelines on first-in-human (FIH) clinical trials. Following its review of FIH trials in late May, EMA released a draft concept paper for public consultation through 30 September 2016. EMA states the concept paper will be a foundation for a draft revision to its current guidelines, which it expects to release in late 2016. According to EMA, FIH trials have changed considerably since the last guidance was published in 2007, and current trials often involve more elements, such as multiple ascending doses (MAD), food interactions, and several subject groups. The EMA says it plans to extend its FIH trial guidance to cover issues such as early phase clinical trial design, integration of non-clinical pharmacology and toxicology data, definition of stopping criteria, and the rolling review of emerging human data during the study.

Most testing for the US drug industry’s late-stage human trials is now done at sites outside the country where results often can be obtained cheaper, faster, and with less red tape. A study by Glickman et al (N Engl J Med. 2009 Feb 19;360(8):816-23) reviewed over 300 published Phase 3 trials and found that almost a third of those led by US pharmaceutical companies were being conducted entirely outside the country. The researchers found, at the same time, that the number of FDA-regulated investigators running trials abroad increased by 15% each year, while the number of US-based investigators declined 5.5% annually.

The bureaucracy associated with gaining FDA approval has been in the headlines numerous times over the years. The FDA process was recently questioned following meningitis outbreaks at Princeton University and the University of California, Santa Barbara in 2015. These outbreaks were unique because the meningitis vaccines required by schools didn’t protect against the particular meningitis strain that was determined to be the cause of the outbreak. However, a vaccine for the serogroup B strain, named Bexsero, was approved in 2012 by the European Medicines Agency (EMA) for use in the EU.  The vaccine had also been previously approved for use in Australia and Canada. Within nine months, FDA permitted students on affected campuses to use the vaccine. FDA has not yet approved a design for Novartis’ Phase III trials. Completion of these trials, in addition to the submission of a new drug application to FDA, will take years to complete and cost millions of dollars.

Why doesn’t FDA just approve a product already approved for use in the EU? Do the EMA and FDA have significantly different approval standards? It has been suggested that competition between regulatory authorities could cause a “race to the bottom” as agencies cut regulations to be competitive and draw the most applications.

FDA is in the process of collecting and reviewing safety information pertinent to FAAH inhibitors under investigation in the US. In the meantime, additional FAAH inhibitors are also under development, including Janssen/Johnson & Johnson’s JNJ-42165279 for social anxiety disorder and Pfizer’s PF-04457845 for osteoarthritis pain. Therefore, updates to the regulations are timely and necessary. And, sponsors must carefully weigh the benefits (both to the sponsor and the study subject) of performing FIH trials in the EU, US or elsewhere.

Share your thoughts with us on EU vs. FDA FIH regulatory hurdles at Pearl IRB.

FDA Guidance on Adaptive Designs released

On July 27th, FDA released final guidance for Adaptive Designs for Medical Device Clinical Studies – a link to the guidance is here.  According to Zachary Brennan in his article posted on RAPS, FDA received 151 comments from industry and most were included in the final guidance.  The guidance explains that “An adaptive design for a medical device clinical study is defined as a clinical study design that allows for prospectively planned modifications based on accumulating study data without undermining the study’s integrity and validity.”  Examples are listed throughout the guidance to provide a better understanding of how to include this in your medical device clinical study planning.  Need help in planning your medical device clinical study?  Contact us here.

Latest updates on Compassionate Use

The FDA has been working to improve the process used by physicians to request Expanded Access — Compassionate Use to investigational drugs and biologics for their patients who need these therapies to stay alive.  In a statement released in early June from FDA Commissioner Robert Califf, M. D., the FDA released 3 guidance documents with information on Compassionate Use drugs and biologics.

The first guidance to note covers Individual Patient Expanded Access Applications – Form FDA 3926.  New Form 3926 is specifically for physicians to use to request access to investigational drugs for their patients who need these therapies to stay alive.  FDA also has instructions for completing the form.

There are 2 additional guidance documents to note that provide additional clarity on Compassionate Use. One of the guidance documents explains Compassionate Use using a Question and Answer format – click here to read.  The other guidance covers how a patient may be charged for these investigational drugs – click here to read.

Pearl Pathways’ and Pearl IRB’s experienced teams are ready to help you with this process. Expediting regulatory pathways is what we are about — contact us.

April 21st, Pearl Pathways’ own Gretchen Bowker speaking at the IMDMC workshop

imdmcThe Indiana Medical Device Manufacturers Council (IMDMC) is hosting a workshop on April 21st targeted for those new to the medical device industry or for those looking for a regulatory refresher. There will be multiple presentations including one from Gretchen Bowker COO & RAC, FRAPS, on, Pathways to Market – 510(K) Requirements at 10:15am. The workshop provides a background in FDA regulations of medical devices.

What: A workshop exploring FDA regulations of medical devices and pathways to market.

When: Thursday, April 21st, 2016, 8:00 AM to 5:00 PM EDT

Where: The Montage – 8580 Allison Pointe Boulevard, Indianapolis, IN 46250

New to the medical device industry and want to learn more about the FDA regulations? Register here today! (Lunch will be provided.)

Click here to learn more about the workshop and to register for both workshops, REG 101 & 102. We hope to see you on April 21st!

FDA’s COA Compendium — a tool for patient focused drug development

Ed Miseta of Clinical Leader, recently wrote an excellent article about FDA’s pilot Clinical Outcome Assessment (COA) Compendium and hit on some good points about what you need to know about it.

The FDA defines a COA as a “measure of a patient’s symptoms, overall mental state, or the effects of a disease or condition on how the patient functions. COAs can be used to determine whether or not a drug has been demonstrated to provide treatment benefit.” Understanding a disease from a patient perspective, developing a treatment that benefits the patient, and measuring the outcome in clinical trials are all parts of patient focused drug development.

Take a look at the COA Compendium table, it provides COA information for many diseases and conditions that can be useful information in future drug development. CDER is gathering public comment on the current pilot. Visit FDA to comment here. Read Miseta’s article here for more details. Contact us at Pearl IRB to help you in your patient focused drug development and clinical research.