What’s New at NCC-PDI ?
The University of Maryland (UMD) Fischell Department of Bioengineering and UMD’s Center of Excellence in Regulatory Science and Innovation (M-CERSI) has launched a new Graduate Certificate in Regulatory Science and Engineering, effective fall 2014.
In response to the increasing demand for engineers and technical professionals with graduate-level expertise in both regulatory science and engineering, the new graduate certificate program will focus on medical devices and combination product engineering and regulation, statistical analysis required for Food and Drug Administration (FDA)-regulated clinical trial, legal issues, device classification, medical device reporting, and more. Students in the Graduate Certificate program will complete a total of four three-credit courses: Introduction to Regulatory Affairs: Devices and Drugs, Clinical Study Data Analysis, Regulatory Law – Medical Devices and one three-credit elective from bioengineering, statistics or another focus area within the UMD A. James Clark School of Engineering.
“FDA regulation in the medical device arena is a potential bottleneck for large and small companies trying to bring such products to market,” said Program Director and UMD Fischell Department of Bioengineering Associate Professor Keith Herold. “Our graduates will emerge with direct FDA experience and detailed knowledge of the mindset of the FDA regulators. FDA reviewers follow a well-defined process in arriving at a regulatory decision and our program, taught by reviewers and other FDA experienced instructors, will provide an unmatched view of that process that will enable increased clarity on the testing and analysis needed in a successful FDA submission.”
Students can enroll in courses held at the UMD campus in College Park, Md., or elect to take online courses to fulfill the program requirements. Applications for both the on-campus and online tracks are now being accepted until Aug. 15 via the Office of Advanced Engineering Education website (link is external).
The Graduate Certificate in Regulatory Science and Engineering program is open to technical students, as well as professionals interested in working in regulatory science at government agencies or in industry. Prospective applicants should hold a bachelor’s degree in engineering, or a comparable technical degree, with a GPA of 3.0 or better. Current Clark School students can enroll in any of the available Regulatory Science and Engineering courses to supplement their studies without enrolling in the certificate program. Students should consult their advisor before enrolling.
The Graduate Certificate in Regulatory Science and Engineering is part of the MPowering the State collaborative program, as there is a sister program in Regulatory Science at the University of Maryland School of Pharmacy that focuses on drug and biologic discovery, development, and clinical and post-marketing research. The Clark School of Engineering program focuses on medical devices and combination products. Longer term, the goal is to create a Professional Master of Engineering academic option as a new curriculum is developed.
Those interested in receiving more information about the Graduate Certificate in Regulatory Science and Engineering program can e-mail firstname.lastname@example.org or visit www.cersi.umd.edu.
About the Center of Excellence in Regulatory Science and Innovation The Center of Excellence in Regulatory Science and Innovation (CERSI) focuses on modernizing and improving the ways drugs and medical devices are reviewed and evaluated.
Funded by an initial $1 million grant from the U.S. Food and Drug Administration, CERSI is a collaborative partnership between the University of Maryland, College Park and the University of Maryland, Baltimore. Researchers from both campuses work with FDA staff to support the development of new tools, standards and approaches to assess the safety, efficacy, quality and performance of FDA-regulated products.
Collectively, the FDA, industry and academic scientists all recognize the need for new tools in order to ensure safety and development efficiency in the evaluation of new drugs and medical devices. CERSI draws upon the expertise of researchers from both the College Park and Baltimore campuses to create new mechanisms for scientific exchange, education and training, and regulatory science research in order to meet the needs for these new tools. The center also sponsors seminars and workshops, as well as an open public forum to promote regulatory science exchange, bringing together a network of experts from academia, industrial consortia and FDA scientists.
Drs. Kevin Cleary (Ph.D.) and Peter Kim (M.D., Ph.D.) of the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Medical Center are leading a fall seminar on Medical Device Technology and Research (ENME651) at the University of Maryland in College Park, MD.
This one-credit course offered Wednesdays from 7:00 p.m. to 8:00 p.m. starting September 3 will present information on the state of the art in medical device research, address regulatory issues in developing medical devices and discuss how engineers can work with doctors to develop new medical devices. Topics include medical robotics; interventional cardiology and interventional radiology; general surgery, cardiac surgery, neurosurgery, orthopedics; MR-guided interventions; minimally invasive surgery; and medical device development.
For more information on this seminar, contact Dr. Cleary at email@example.com.
Tentative Course Schedule (some topics and lecturers may change):
- September 3: Peter Kim, MD/PhD: Introduction to Surgery
- September 10: Kevin Cleary, PhD: Medical Robotics: Technology Focus
- September 17: Raj Shekhar, PhD: Introduction to Medical Device Research
- September 24: Craig Peters, MD: Urology Robotics: Clinical Focus
- October 1: Matthew Oetgen, MD: Orthopaedics
- October 8: Charlie Berul, MD: Cardiology
- Oct 15: Josh Kanter, MD: Interventional Cardiology
- October 22: Karun Sharma, MD/PhD: Interventional Radiology
- October 29: Marius Linguraru, PhD: Quantitative Imaging
- Nov 5: Kanishka Ratanayaka, MD: MRI guided interventions
- Nov 12: Diego Preciado, MD/PhD: ENT surgery
- Nov 19: Kevin Cleary, Raj Shekhar: review and discussion
- Nov 26: no class: Thanksgiving
- Dec 3: Robert Keating, MD: Neurosurgery
- Dec 10: Ray Sze, MD: Radiology
- Dec 17: TBD
The course is presented on a pass/fail basis. To pass the course, you need to attend all the lectures but two and participate in the discussion (ask at least two questions during the semester). There will be a sign in sheet at each class so be sure to sign in each time to get credit.
From the Principal Investigators
Dear friends and colleagues,
It is our pleasure to send you the inaugural edition of the National Capital Consortium for Pediatric Device Innovation (NCC-PDI) quarterly newsletter, “Pediatric Devices Spotted and Reported.”
Established in September 2013 and led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Medical Center and the University of Maryland A. James Clark School of Engineering, NCC-PDI is built on a focused commitment for collaboration and innovation in pediatric device development. Together, Children’s National and UMD researchers and their partners have worked to develop medical devices for children and support pediatric medical device progression through all stages of development – from ideation to manufacturing, marketing and commercialization. As such, NCC-PDI provides a platform of experienced regulatory, business planning and device development services to foster the advancement of medical devices for pediatric patients. Even more, as evidenced by several projects highlighted in this newsletter, NCC-PDI research and product development efforts are highly translatable to other populations – including underrepresented patient groups, such as those impacted by rare diseases.
As we close in on the one-year mark of NCC-PDI’s founding, we are excited to provide you with a look at recent initiatives supported by the consortium. With each edition of this newsletter, we look forward to highlighting how the latest advances in pediatric device development will impact human health and the field of medical device development at large. Additionally, we will provide you with a calendar of upcoming NCC-PDI-affiliated events addressing topics in medical device development, bioengineering, pharmaceuticals, regulatory science, orphan drug development and more.
We thank you for your continued support, and we invite you to learn more about how you can get involved with NCC-PDI.
All the best,
Peter Kim, M.D., Ph.D.
Vice President, Sheikh Zayed Institute for Pediatric Surgical Innovation
Children’s National Medical Center
William E. Bentley, Ph.D.
Robert E. Fischell Distinguished Professor and Chair
Fischell Department of Bioengineering
A. James Clark School of Engineering
University of Maryland
Shortages of Injectable Drugs: Manufacturing Issues and Potential Solutions
September 12, 2014
FDA-White Oak Building 2, Room 2031
10903 New Hampshire Ave
Silver Spring, MD 20993
Speaker: Lori Hertz, Ph.D., Professor of Practice, Chemical Engineering Lehigh University, Bethlehem, PA
Contact: Ann Anonsen firstname.lastname@example.org Research Coordinator University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI)
Drug shortages have been a serious concern in the healthcare community for the past several years, sometimes impacting the care of the patients who need these products. The majority of drugs affected by shortages are injectables, and, of those, most are produced by generics manufacturers. The causes of this problem are numerous, and include both manufacturing issues and economic constraints. Manufacturing challenges associated with finish and fill operations for sterile products include the need for specialized facilities, as well as stringent controls and production conditions. Additionally, economic concerns have resulted from a competitive market, as well as the small number of manufacturing facilities capable of producing injectables. The FDA has taken actions to mitigate the shortages, such as asking other companies to increase production, expediting review, and increasing staffing. The aims of this seminar are to discuss common technical issues during the manufacture of injectable products, suggest approaches for troubleshooting and problem solving to help identify root causes for production problems, and to find potential solutions. The issues are sometimes associated with the product itself, such as microbial contamination or the presence of particulates, or there may be process-related challenges, which can include equipment failures and utilities not meeting established specifications. It is beneficial to track and analyze product and facility data via quality metrics to determine root causes of problems, and several organizations have taken such an approach. Just as importantly, a fundamental understanding of the processes and operations used to manufacture injectables is needed. Production facilities, as well as the processes by which injectable products are manufactured, should be evaluated from an engineering perspective, such that operations can be critically assessed. For example: Where in the process are the inefficiencies? What are the opportunities to improve key steps in the process and how can they be implemented? What equipment upgrades and novel technologies will be economically beneficial in the long run? Lastly, the importance of corporate culture and employee education will be discussed, as these factors play major roles in producing high quality pharmaceutical products.
About the Speaker
Lori Herz, Ph.D. is currently a Professor of Practice of Chemical Engineering at Lehigh University. She is the Associate Director of the Bioengineering Program at Lehigh, where she teaches the Metabolic Engineering and Biotechnology Laboratory courses. Additionally, she is affiliated with the Integrated Product Development program, for which she has advised student teams working on their capstone design projects.
Prior to joining Lehigh, Dr. Herz worked at Bristol-Myers Squibb Company for nine years. She started in Technical Operations, supporting technology transfer and the manufacture of sterile liquid and lyophilized drug products. She later managed early-phase clinical operations and process scale-up of protein therapeutics. In addition to her position at Lehigh, Dr. Herz is the owner of Herz Biotechnology Consulting, which she started in 2011.
She received her B.S. in Chemical Engineering from Cornell University and her Ph.D. in Chemical and Biochemical Engineering from Rutgers, the State University of New Jersey. She is currently the faculty adviser for the Lehigh chapter of Alpha Omega Epsilon, as well as a member of AICHE and the Society for Biological Engineering.
Pediatric Surgical Innovation Symposium
October 24, 2014
Newseum – Knight Conference Center
555 Pennsylvania Ave NW
Washington, D.C. 20001
Contact: email@example.com Visit: www.pediatric-surgery-symposium.org
Considerable progress has been made to advance pediatric drug research and to ensure appropriate drug product labeling for children. The Best Pharmaceuticals for Children Act (BPCA) provides drug manufacturers with significant incentives to pursue pediatric drug research. Analogous efforts have been made in the pediatric device arena. Namely, the 2007 Pediatric Medical Device Safety and Improvement Act (PMDSIA) was a well-intentioned step to narrow the gap. Great strides have been made and still much needs to be done. Among the 22 medical devices approved through the PMA process for use in a pediatric subpopulation, only one device was indicated for use in patients under age 18 and few pediatric patients were exposed to the devices before market availability.
To address this challenge, the Sheikh Zayed Institute for Pediatric Surgical Innovation will be hosting a conference on October 24, 2014 in Washington DC. The conference theme is: “Lessons from Drugs to Devices: A Pediatric Perspective.” The conference will bring together a diverse group of experts representing multiple disciplines (life sciences, medicine, engineering, law, and regulatory affairs) and sectors (industry, government, academe, and advocacy).
The objectives of the conference are:
- To forge consensus on critical issues germane to pediatric surgical innovation;
- To identify concrete, achievable action items and assigning them to relevant parties;
- To establish a set of scientific, clinical, regulatory, and policy recommendations required to advance the field;
- To agree upon a select and targeted publication, presentation, legislative, regulatory, appropriate media strategy and targeted outreach campaign to forward conference objectives.
Identifying Novel Selective Cancer Drug Targets
October 15, 2014: 10:00 a.m. – 11:00 a.m.
FDA-White Oak Building 2, Room 2047E
10903 New Hampshire Ave
Silver Spring, MD 20993
Eytan Ruppin, Ph.D., Professor, School of Computer Science & Sackler Faculty of Medicine
Tel Aviv University
University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI)
The Epilepsy Foundation has awarded a New Therapy Research Grant of $95,000 to Dr. Tammy Tsuchida, a clinical neurophysiologist and neonatal neurocritical care neurologist at Children’s National Health System, and co-principal investigator Dr. Walid Soussou, Vice President of Research at Quantum Applied Science and Research (QUASAR). Children’s National and QUASAR have partnered to develop a Dry Sensor based Neonatal EEG Monitor (“NEMO”) system intended as a reliable and easy-to-use EEG system that will increase availability of neonatal EEG monitoring at all hours of the day and to hospitals that typically lack this capability.
Neonatal seizures are a common neurologic diagnosis in the Neonatal Intensive Care Unit (NICU), occurring in some 14,000 newborns annually in the US. They are frequently associated with long-term deleterious consequences including intellectual disability, cerebral palsy, epilepsy, and other neurodevelopmental disabilities. Early detection and treatment can result in more effective seizure control and decreased rates of epilepsy and may also lead to reduced morbidity and mortality.
The only reliable means of detecting and treating neonatal seizures is with an EEG recording; however, many neonates do not get an EEG or there are delays to getting an EEG due to lack of skilled EEG technologists to apply EEG electrodes to delicate neonatal skin, poor recording quality due to improper skin preparation and electrical artifact, and extensive time needed to apply electrodes.
Recognizing this, NEMO leverages QUASAR’s innovative dry sensor technology that has been demonstrated in adults to record high fidelity EEG signals that are immune to electrical artifacts, without the need for skin abrasion or the use of conductive gels. These dry sensors are embedded into a headset that is gentle to neonatal skin and can be rapidly applied by nursing staff.
While competitor EEG manufacturers are developing easy-to-don caps, there are currently no dry EEG sensors on the medical market. Caps using wet electrodes require longer preparation times or maintenance of wet electrodes every four hours in order to do an overnight EEG recording. As the only dry sensor system for neonates, NEMO will allow it to be used when EEG technologists are unavailable and at hospitals that currently lack neonatal EEG, leading to more neonates at risk for seizures being quickly screened and appropriately treated, which in turn is expected to shorten hospital stays and improve outcomes. NEMO will be a first-in-category neonatal dry sensor EEG monitor that will address the cost and logistical inefficiencies that currently inhibit adequate neonatal care.
Vittamed Corporation, a neurodiagnostics medical device company that has received NCC-PDI funding, announced in late July that it has received the CE Mark of approval for two novel neuromonitoring devices: the Vittamed 205 for non-invasive intracranial pressure (ICP) measurement, and the Vittamed 505 for non-invasive Cerebrovascular autoregulation monitoring.
Both devices are ultrasound based. The Vittamed 205 offers non-invasive ICP measurement for conditions such as traumatic brain injury, concussion, hydrocephalus, stroke, brain tumors and other neurological diseases.
“CE approval for both devices is not only an important milestone for our company as we move toward commercialization but also an important advance in patient care,” stated Dr. Remis Bistras, the CEO of Vittamed. “Invasive options for intracranial pressure measurement and for cerebral perfusion monitoring have historically been limited by risk, inconvenience, and high costs. Our monitors, in contrast, add no material risk. They are totally non-invasive and may be deployed routinely whenever and wherever indicated, including the outpatient setting.”
The ICP meter is clinically validated in prospective clinical trials, provides accurate and precise measurements and does not require an individual patient specific calibration. The device uses safe Doppler ultrasound and measures absolute ICP value in mmHg using the ophthalmic artery as a natural ICP sensor.
The Vittamed 505 non-invasively monitors cerebrovascular autoregulation. It allows clinicians to monitor cerebrovascular autoregulational and evaluate cerebral blood flow after traumatic brain injury, in stroke, during cardiac surgery, in the critical care unit and in the outpatient clinic.
“We have been very encouraged with the results of non-invasive diagnostic devices. This platform gives us, neurosurgeons, the possibility to understand what is happening in the brain without invasion and any increase in risk for patient. We can also, for the first time, easily monitor conscious individuals and outpatients. Vittamed’s instruments enable clinicians to obtain safer, faster, and accurate measurements of absolute intracranial pressure values,” said Saulius Rocka, MD, Ph.D., principal investigator and Head of Neurovascular Center at Neurology and Neurosurgery Clinic at Vilnius University, Lithuania.
Medical device firm Procyrion, Inc. is working to develop the first catheter-deployed circulatory assist device intended for long-term use in the treatment of chronic heart failure.
Procyrion’s Aortix™ is a small, continuous-flow pump mounted within a self-expanding anchoring system and delivered via catheter through the femoral artery to the descending thoracic aorta. Once the catheter sheath is pulled back, nickel-titanium anchors deploy to anchor the pump to the aortic wall. Aortix functions by accelerating a portion of the native aortic flow, resulting in reduced work of the ehart and increased blood flow to vital organs.
In partnership with Maxon Precision Motors, Inc., Procyrion is using grant funds to modify the adult Aortix device for use in children born with single ventricle heart defects. Earlier this summer, Procyrion was awarded a $50,000 NCC-PDI grant.
“The commercialization path of pediatric medical devices presents unique challenges due to limited market size,” said Christopher Blake, President of Maxon Precision Motors, Inc. “Maxon Precision Motors is proud to help meet those challenges and work with Procyrion to develop an efficacious tool for this important unmet clinical need.”
“Many devices for adults are not suitable for pediatric use, but the small form factor of Aortix makes it very useful for the pediatric patient. With minor modifications, we hope to create a first-in-class device for pediatric patients with failing Fontan circulation. Receiving this grant reflects confidence our product can impact the underserved pediatric medical device market,” said Ben Hertzog, president and CEO of Procyrion.
Two projects put forth by Sheikh Zayed Institute (SZI) researchers receive Pilot Research Awards from the Clinical and Translational Science Institute at Children’s National (CTSI-CN). Dr. Rohan Fernandes’ Prussian blue nanoparticles for laser-induced photothermal therapy of neuroblastomas and Dr. Brian Reilly’s A New Surgical Approach to Otitis Media: Dissolvable On Demand Tympanostomy Tubes each earned a $50,000 grant, designed to accelerate projects that show promise for future and in-depth investigations that have the potential to improve human health.
Responding to an Urgent Need Neuroblastomas are one of the most common types of childhood cancer and account for approximately 7 percent of all newly diagnosed cases of childhood cancer. Despite advances in the management and treatment of this disease, the survival rate for patients with advanced neuroblastomas is very poor – five-year rates reach just 30-40 percent. As such, there is an urgent need for the development of novel therapies that can be used to treat children with advanced neuroblastomas.
Recognizing this, Dr. Fernandes and his team are developing Prussian blue nanoparticles as novel agents for laser-induced photothermal therapy of neuroblastomas. Prussian blue is a dye that was synthesized in the early 18th century, and it contains nanoparticles capable of absorbing light at near-infrared wavelengths invisible to the naked eye. At these wavelengths, the human body exhibits a “window” allowing greater penetration of light. The Prussian blue nanoparticles are injected into neuroblastoma tumors and, when irradiated with a near-infrared laser, they are heated by a process known as photothermal conversion, which converts the irradiated light into heat. This results in the “ablation” of turmos only when both treated by the nanoparticles and irradiated by the laser.
Fernandes’ team is developing methods to intravenously administer the Prussian blue nanoparticles so that they specifically target neuroblastomas by honing in on markers only expressed on neuroblastomas and not normal cells and tissue. The team is also investigating the response of the immune system to this ablative therapy with the long-term goal of not only ablating the tumors, but also eliciting a favorable anti-tumor immune response that prevents recurrence of the tumors post-ablation.
Minimizing the Number of Ear Surgeries Needed Tympanostomy tubes are commonly used to treat otitis media – inflammation of the middle ear – but use of these tubes can require surgical removal. Worse yet, patients sometimes endure ear perforations or secondary hearing loss as the result of tympanostomy tubes.
Knowing this, Dr. Reilly, Co-Director of the Cochlear Implant Program at Children’s National Health System, has worked to develop an ear tube that can be dissolved “on demand,” addressing many of the problems caused by the current generation of such implants. Because dissolvable ear tubes do not have to be surgically removed, there would be no need for further procedures under general anesthesia. This is particularly important since preliminary research has suggested that excessive general anesthesia may affect learning in children under three years of age, Reilly noted.
“Additionally, an ear tube that can be dissolved ‘on demand’ would provide the potential benefit of lower perforation rates, particularly from tubes implanted over 24 months while awaiting spontaneous extrusion,” he said. “Our design could remain for the desired duration that clinicians deem necessary for children to outgrow the otitis media prone time period. The clinician would then apply ear drops to patients as a simple medical procedure once they determine that the risk of ear infections has decreased, or that the child’s Eustachian tube has developed enough to adequately drain middle ear fluid on its own.”
Even more, Reilly’s research could translate well to other medical applications.
“The materials and fabrication processes optimized for the dissolvable ear tube will establish a foundation for the development of a broader range of biological and dissolvable materials for medical devices,” he said. “For example, our technology can be translated to other medical applications such as stents, catheters and mesh, which are used in many medical fields including urology, cardiology, pulmonology, gastroenterology and neurosurgery.”
The annual individual and societal costs of sleep loss and sleep disorders are estimated to be in billions of dollars in both direct and indirect costs related to co-morbid medical conditions, hospitalization, accidents, and productivity loss. Wearable, wireless systems are said to be a revolutionary technology for health and wellness management.
As such, Dr. Madhvi Upender and a team of researchers at Awarables, Inc. have worked to apply such technologies to specific groups, such as children with ADHD or autism spectrum disorder. By extension, the group foresees such applications can be used to help the elderly and people with depression, schizophrenia, addiction and other mental and physical disorders. Nevertheless, the team’s efforts this year have earned Awarables National Science Foundation (NSF) and Department of Defense (DOD) Small Business Innovation Research (SBIR) Phase I grants.
Through their project, Upender and collaborators Dr. Jeanne Geiger-Brown (University of Maryland School of Nursing) and Dr. Daniel Lewin (Children’s National Medical Center) address the need for safe, effective measures for assessing and understanding sleep in the home and promoting sleep literacy among consumers. The first component of the project focuses on Data acquisition (DAQ) using low-cost, unobtrusive wearable sensor technology to monitor activity, sound – such as snoring and speech, heart rate, respiration rate, pulse transit time, temperature and so forth over a 24-hour period or longer. Their DAQ methods employ mobile technology to support use at home.
The second component of the project incorporates signal processing and feature extraction tools that employ nonlinear, complex systems analysis to harvest clinically relevant sleep quality, quantity and health information from variables such as sleep stage transitions and heart rate variability. In addition, development of neurocognitive tests, including reaction time tests similar to psychomotor vigilance tests (PVT), will evaluate the impact of sleep quality and quantity on cognitive performance.
The group plans to design such devices and tools for use by consumers and clinicians to assess the effectiveness of treatment systems such as Cognitive Behavior Therapies (CBT) intended to improve sleep.
The due date for the next cycle of National Institute of Neurological Disorders and Stroke (NINDS) funding opportunities is Oct. 21, 2014. Answers to commonly asked questions regarding this unique funding opportunity are listed below:
If I am applying to develop a device, to which program should I apply? Investigators who propose projects that focus on preclinical and pilot clinical studies for therapeutic devices should apply to the CREATE Devices program. There are three tracks for devices all using UH2/UH3 or SBIR U44 mechanisms:
- Translational and Clinical Studies to Inform Final Device Design will support development of a device to test scientific hypotheses that are not feasible or practical to conduct in animal models but are critical to enable next-generation devices. Preclinical work should lead to an Investigational Device Exemption (IDE) to support a clinical study, or a Non-Significant Risk (NSR) study that does not require an IDE. It is expected that the clinical study will inform a final device design that would have to go through most, if not all, of the bench-top and preclinical animal testing on the path to clinical trials and market approval. Activities supported in this program include implementation of clinical prototype devices, preclinical safety and efficacy testing, design verification and validation activities, pursuit of regulatory approval for the clinical study, and a clinical study.
- PAR-14-300: For small businesses that are SBIR eligible (http://www.ninds.nih.gov/funding/small-business/small_business_STTR_SBIR_eligibility_summary.htm)
- PAR-14-297: For academic and businesses that are not SBIR eligible
- Translational and Clinical Studies on the Path to 510(k) will support preclinical studies and the following IDE-enabled or NSR studies. It is expected the immediate next steps upon completion of the clinical study will be a 510(k)/510(k) De Novo submission or a larger clinical trial that will lead directly to a 510(k)/510(k) De Novo submission. Activities supported in this program include implementation of clinical prototype devices, preclinical safety and efficacy testing, design verification and validation activities, pursuit of regulatory approval for the clinical study, and a clinical study.
- PAR-14-296: For small businesses that are SBIR eligible (http://www.ninds.nih.gov/funding/small-business/small_business_STTR_SBIR_eligibility_summary.htm )
- PAR-14-295: For academic and businesses that are not SBIR eligible
- Translational and Early Feasibility Studies on the Path to Pre-Market Approval (PMA) or Humanitarian Device Exemption (HDE) will support applications to pursue preclinical studies for an IDE submission, with the option of also supporting the following Early Feasibility Study. It is expected the immediate next steps upon completion of the Early Feasibility Study will be a full Feasibility Study and a Pivotal Trial in support of a PMA (Pre-Market Approval) or HDE (Humanitarian Device Exemption). Activities supported in this program include implementation of clinical prototype devices, preclinical safety and efficacy testing, design verification and validation activities, pursuit of regulatory approval for the clinical study, and an Early Feasibility Study.
- PAR-14-299:, For small businesses that are SBIR eligible (http://www.ninds.nih.gov/funding/small-business/small_business_STTR_SBIR_eligibility_summary.htm)
- PAR-14-298: For academic and businesses that are not SBIR eligible
How many years and how much funding can I request in my device application (UH2/UH3 or SBIR U44)?
- For the UH2/UH3, application budgets are not limited but must reflect the actual needs of the proposed project. For the pre-clinical UH2 phase an applicant should rarely exceed $1M direct cost per year for up to 3 years. For the UH3 phase an applicant should rarely exceed up to $1.5M direct cost per year for up to 4 years. The combined UH2/UH3 phase may not exceed 5 years. Additional justification is needed for exceptions.
- For SBIR, only Fast-track (combined Phase I and II) are accepted through the CREATE programs. There is no direct to Phase II option through the CREATE program and Phase I applications that are not part of a Fast-track application are not permitted. NIH has received a waiver from the Small Business Administration (SBA) to exceed the SBIR hard cap for specific topics such as the translational programs CREATE and BPN. Generally, NINDS will not fund SBIR Phase I applications through this program requesting more than $2M total funding support, with no more than $1M total cost in any year or project periods greater than 2 years. In addition, NINDS does not generally fund Phase II applications through this program requesting more than $4.5M total funding support, with no more than $1.5M total cost in any year, or project periods greater than 3 years. Additional justification is needed for exceptions. Applicants are strongly encouraged to contact program staff before submitting an application.
Orphan Device Development Provides Hope for Underrepresented Disease Populations | Lex-Schultheis | By Lester Schultheis | September 3, 2014
Nearly $80 million has poured into the ALS Association since July 29 due to the overwhelming popularity of the Ice Bucket Challenge, a grassroots campaign to raise awareness and funding for amyotrophic lateral sclerosis (ALS) treatment and research.
Participants in the challenge dump ice water over their heads and donate an amount of their choosing to support the ALS Association or similar foundation, and the campaign picks up steam as participants challenge peers to do the same. Those who fail to complete the challenge within a 24-hour window are asked to donate $100 to an organization benefiting those impacted by ALS.
Prior to the campaign’s viral success, few without a direct connection to ALS may have known the facts about the neurodegenerative disease commonly known as Lou Gehrig’s disease. As such, the campaign has directed a spotlight on efforts put forth to combat ALS, which affects as many as 30,000 Americans at any given moment.
Long before the launch of the Ice Bucket Challenge, Dr. Eva Chin, Assistant Professor of Kinesiology at the University of Maryland School of Public Health, and fellow researchers set out on a mission to develop early diagnostic tools for ALS. Chin, along with Dr. Justin Kwan, Assistant Professor of Neurology at the University of Maryland School of Medicine, and Dr. Lyle Ostrow of Johns Hopkins School of Medicine, have worked to develop a clinical assay for the early diagnosis of ALS, to distinguish between molecular defects in different ALS sub-types and to help develop personalized treatments for the ALS sub-types in the future. The team of researchers will determine which proteins are relevant to patients with ALS and develop a test that uses a muscle biopsy sample that is analyzed for the specific proteins that are defective in ALS. Because no molecular-based laboratory tests for ALS yet exist, the process to diagnose and treat the disease can take 12-18 months to initiate.
“Similar to cancer, the earlier you treat ALS, the more you slow down disease progression,” Chin noted.
According to the ALS Association, the life expectancy of an ALS patient averages just two to five years from the time of diagnosis, although the disease is variable.
Nevertheless, the recent spike in public awareness of a disease that has a tremendous impact on a relatively small population – when compared with certain cancers or heart disease – has demonstrated the need for research benefiting small patient populations, such as those impacted by rare diseases.
As the Ebola outbreak in West Africa and the Democratic Republic of Congo has tragically demonstrated, funding and support for the treatment of rare diseases and medical conditions can be difficult to come by when there are relatively few advocates for the cause. Yet, researchers at the University of Maryland (UMD) and the National Capital Consortium for Pediatric Device Innovation (NCC-PDI) are working to attack many diseases which commonly lack representation and research support.
Since its launch, NCC-PDI has worked to advance orphan products development for a variety of causes impacting pediatric populations. NCC-PDI’s foundation traces back to September 2013, when the Food and Drug Administration (FDA) Office of Orphan Products Development awarded the FDA P50 grant to the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System (SZI) and the University of Maryland A. James Clark School of Engineering to establish NCC-PDI. The 2013 grants were awarded to consortia that brought together teams with excellence and expertise in delivering business, regulatory, legal, scientific, engineering, and clinical services for children. All consortia work collaboratively with the FDA to help innovators effectively navigate existing laws, regulations and agency guidance to protect the health and safety of children.
“It is particularly interesting that NCC-PDI is working so hard to address the needs of small patient populations because many in industry focus resources primarily on large populations, such as those impacted by cancer or heart disease,” said Dr. Lester W. Schultheis, Director, Regulatory Science Initiative at the University of Maryland. “Patients with rare diseases have relatively few advocates interested in the research community despite the compelling harm that these rare diseases cause to individual patients and their families. Therefore, the initiatives put forth by UMD and SZI researchers is significant.
“A secondary benefit, in addition to the potential for NCC-PDI to help the unfortunate few patients with rare diseases, is the opportunity our researchers have to learn about very complex machinery within the human body,” he continued. “The study of rare diseases can inform medical science to improve our understanding of fundamental mechanisms of metabolism that may be relevant for diagnosis and treatment of more prevalent disease.”
One such technology put forth by UMD and Children’s National Medical Center researchers is a point-of-care device to measure blood ammonia levels.
Hyperammonemia, a life-threatening condition, is characterized by elevated blood ammonia levels and causes severe neurodevelopment complications. The condition originates from metabolic disturbances in the urea cycle caused by several different inborn errors of metabolism collectively referred to as Urea Cycle Disorders (UCDs). Following a diagnosis, patients are given strict dietary limitations to reduce protein intake and they are treated with ammonia scavenging drugs. Nevertheless, patients must monitor their blood ammonia levels throughout the span of their lifetime. Without a system in place to allow patients and their caregivers to rapidly measure blood ammonia levels, families endure a great deal of stress as any sign of the patient feeling ill prompts concern of a hyperammonemic episode, warranting a trip to the doctor or emergency room for testing.
Recognizing this, Drs. Peter Kofinas (UMD, Fischell Department of Bioengineering) and Marshall Summar (Children’s National Medical Center) have developed a prototype of point-of-care device for detecting ammonia in a drop of blood, obtained by pricking the finger – or heel for newborns – to be used at home, in clinics, and in hospitals, in a fashion similar to a glucometer. Consolidating this system into a small, easily manufactured device and test cartridge will provide rapid point-of-care detection with minimal training. Additionally, a rapid point-of-care sensor would allow for at home and bedside testing, reducing the large burden on children with UCDs and their caretakers.
The high sensitivity of the developed point-of-care device allows for accurate and reliable differentiation between the colorimetric responses produced by elevated (100-500 mM) or normal (40-70mM) levels of ammonia in blood. Consolidating this system into a small, easily manufactured device and test cartridge provides rapid point-of-care detection with minimal training. It is expected that such sensor device could be used to screen all newborns for diagnosis at hospitals.
The device would also allow families or primary care facilities that have a child or patient with hyperammonemia to frequently monitor ammonia levels and use the results of the test to manage the child’s diet and treatment.
While UMD and SZI researchers work tirelessly to develop diagnosis and treatment options for many of today’s most underrepresented diseases, a great need for continued research and funding remains.
At both the undergraduate and graduate level of study, UMD students continue to work to develop new systems for monitoring rare conditions such as methyl malonic academia – a rare inherited disorder of the metabolism – and tyrosinemia – a serious metabolic disease that is rare in the United States but more common among the French Canadian population.
Expanding beyond the reach of the D.C.-metropolitan area, UMD is collaborating with the Children’s Hospital of Philadelphia to offer educational opportunities to FDA scientists interested in the development and adoption of next-generation sequencing technologies for diagnostic testing of genetic disease, such as in pediatric disorders including hearing loss, epilepsy, Noonan syndrome, Rett syndrome, paraganglioma and neuroblastoma.
Moving forward, NCC-PDI continues to build on its commitment for collaboration and innovation in pediatric device development, and many of the projects undertaken by UMD and SZI researchers promise to make a significant impact on human life, even beyond the scope of pediatrics. While currently, UMD researchers have not formulated a coordinated effort to specifically target rare diseases, recent research trends – both within and outside the university – have indicated this as a recurring theme.
About the Author: Lester Schultheis
Lester Schultheis Born and raised in Maryland, Dr. Lex Schultheis has made the state his home for most of his life. His undergraduate and Ph.D. training in Bioengineering at Johns Hopkins University focused on studies of adaptive control systems and signal processing in the brain. While in graduate school, he attended clinical rounds and observed patients whose illnesses could only be explained by mathematical models. In medical school at the University of Pennsylvania, his interests in modeling physiology expanded to studies of artificial environments, such as patients under anesthesia and humans in space flight. Dr. Schultheis completed a residency in anesthesiology with a clinical fellowship caring for cardiac surgical patients at Johns Hopkins. He has over twenty years of experience as an active physician, including direction of a subspecialty division of cardiac anesthesiologists and Chairman of a Department of Anesthesiology at the Washington Hospital Center. Dr. Schultheis has also been a principal investigator for NASA. Most recently, Dr. Schultheis has been an expert medical officer in the Center for Drug Evaluation and Research, and Branch Chief in the FDA Center for Devices and Radiation Health where he reviews anesthesia and respiratory medical technology. His team was awarded four Critical Path grants from FDA. Nominated by his team, Dr. Schultheis received the 2013 John Villforth Leadership Award in engineering by the Commissioned Corps of the US Public Health Service.