News & Views: 2019 Opioid Agenda, Quality for Continuous Manufacturing, Task Force for Public Health Emergencies, Brain Computer Interface devices, Quantifying Oncology Patient Experience


2019 policy and regulatory agenda for continued action to forcefully address the tragic epidemic of opioid abuse

New actions to build on 2018 efforts and also adapt to changing nature of threat

  • Reducing Misuse and Abuse of Opioid Drugs: Appropriately prescription, dose, quantity, treatment duration, disposal, REMS effectiveness
  • Support Addiction Recovery and Reduce Overdose Deaths:  OTC naloxone with model Drug Facts Labels with easy directions for use
  • Research and Innovation in Non-Addictive Pain Treatments: Non-opioid drugs, abuse-deterrent features
  • Strengthen Enforcement Against Illicit Opioids: Partnership with U.S. Customs and Border Protection


CaptureQuality Considerations for Continuous Manufacturing

Continuous technology is foundation for improving  overall quality of products and availability to patients

  • Integrated process with fewer steps , shorter processing times, smaller equipment footprint, enhanced development approach e.g., quality by design (QbD) and use of process analytical technology (PAT)

Quality considerations

  • Key Concepts: Process dynamics, Defining batches for continuous manufacturing processes
  • Control Strategy: Input material, Process monitoring, Material diversion, Real Time Release, Specification, Equipment, System integration, Data processing, and Management
  • Process Validation: Stage 1 – Process  Design, Stage 2 – Process  Qualification, Stage 3 – Continued Process Verification
  • Additional Pharmaceutical Quality System Considerations: Scale-Up,  Stability, Bridging existing batch to Continuous Manufacturing
FDA requesting comments on
  • data storage and handling from process analytical technology systems
  • potential approaches for situations where direct attribute measurement is not possible (e.g., low dose compounds)
  • contract manufacturers employing continuous manufacturing
  • risk-based reporting of routine model maintenance and updates
  • statistical approaches using large samples (e.g., Large N)



FDA, CDC, and CMS launch task force to help facilitate rapid availability of diagnostic tests during public health emergencies

The Tri-Agency Task Force for Emergency Diagnostics (TTFED)ompsed of FDA + CDC + CMS

  • Collaborate on future emergency diagnostic response needs
  • Convene, provide timely recommendations to laboratories for rapid implementation of FDA’s Emergency Use Authorization (EUA) assays

Focus to

  • establish efficient communication channels between TTFED members
  • formalize and document interagency process for rapid implementation of EUA IVD assays in public health emergency
  • provide timely recommendations during emergencies



Implanted Brain-Computer Interface (BCI) Devices for Patients with Paralysis or Amputation – Non-clinical Testing and Clinical Considerations

Implanted BCI devices have potential to bring benefit to people with severe disabilities by increasing their ability to interact with their environment, and consequently, providing new independence in daily life

  • Implanted BCI devices are neuroprostheses that interfaces with central or peripheral nervous system to restore lost motor and/or sensory capabilities in patients with paralysis or amputation

Pre-Submission/IDE recommendations:

  • Device description
  • Software
  • Biocompatibility
  • Sterility
  • Pyrogenicity
  • Shelf life and packaging
  • Electrical safety and Electromagnetic compatibility
  • Wireless technology
  • Magnetic resonance compatibility
  • Non-clinical bench testing
  • Risk analysis
  • Electrodes
  • Leads and connectors
  • Implanted casing and electronics
  • Output simulation measurements
  • Output stimulation safety
  • Programmrrs/control unit
  • Radiofrequency transmitter and receiver
  • System level testing
  • Referencing Master Files
  • Animal testing scope
  • Clinical study considerations



Oncology Center of Excellence — Quantifying the Patient Experience

Collaboration between FDA Centers and external stakeholders involved in patient outcomes research in cancer populations

  • Actively engaging with patients and advocacy groups
  • Fostering research into measurement of the patient experience
  • Generating science-based recommendations for regulatory policy

Goals to assess patient experience that complement existing survival and tumor information

  • Learning from Patient Experiences
  • Collaborating with Patients, Public and Private Sectors
  • Fostering Continued Engagement


Image credit: CMS, FDA

News and Views: Voluntary Consensus Standards, Stopping Illicit Opioids, Device Inspection Nonbinding Feedback, Ebola Virus Pathogenesis



Voluntary Consensus Standards to promote the adoption of innovations in drug manufacturing that can improve quality and lower drug costs

Recognizing “voluntary consensus standards” based on nationally and internationally accepted standards for drug quality

  • New draft guidance  to propose pharmaceutical quality standards for potential recognition by the FDA, providing industry with additional options for pharmaceutical development and manufacturing
  • Promote and expedite  development, streamline FDA review of drug product applications
  • Provide list of recognized standards on website; reduce regulatory uncertainty



Efforts to stop the spread of illicit opioids, further secure the U.S. drug supply chain and forcefully confront opioid epidemic

Efforts to stopping spread of illicit opioids and  securing all aspects of supply chain

  • Enforcement and interdiction of illegal shipment through US Postal Services
  • Work closely with U.S. Customs and Border Protection and U.S. Department of Justice
  • Warning Letters for illegal online marketing
  • Online Opioid Summit with appropriate stakeholders for stronger action
  • Warning letter under the Drug Supply Chain Security Act (DSCSA) McKesson Corp
  • New guidances
    • Risk/benefit framework to opioid analgesics including illicit use risks
    • Modernize development pathway for non-opioid analgesics for specific clinical conditions
    • Packaging requirements to limit number with single prescription
  • Continue work in accordance with Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act


Nonbinding Feedback after Certain FDA Inspections of Device Establishments

Standardized method for communicating and submitting requests for nonbinding feedback and describes how FDA evaluates and responds to such requests

  • Request for nonbinding feedback submitted by device establishment to FDA regarding firm’s proposed actions to address Form 483 inspectional observations

Firm’s proposals for addressing Inspectional Observations related to

  • release of violative product that may cause death or serious injury
  • production of nonconforming, violative, and/or defective finished devices
  • release of devices likely to cause 196 death or serious injury

FDA informal feedback on whether proposals

  • address inspectional observations
  • partially adequate or inadequate with explanation
  • recommend what may be needed to be adequate


Capture.JPGNew approach for understanding Ebola Virus Pathogenesis

Contract with Broad Institute to conduct the largest Ebola virus and host gene expression (i.e., transcriptomics) study

  • Assess how Ebola virus evolves and spreads within the body
  • Identify mechanisms and biological pathways altered in immune cells and tissues during infection
  • Inform natural history of Ebola virus disease in humans
  • Characterize nonclinical models necessary for testing
  • Utilize fordeveloping medical countermeasures (MCMs) to prevent and treat Ebola virus disease


Image credit: FDA

Youth Tobacco Prevention Plan


FDA’s Youth Tobacco Prevention Plan—a key component of the agency’s Comprehensive Plan for Tobacco and Nicotine Regulation—to stop youth use of tobacco products, especially e-cigarettes

  • Preventing youth access to tobacco products
  • Curbing marketing of tobacco products aimed at youth; and
  • Educating teens about the dangers of using any tobacco product, including e-cigarettes, as well as educating retailers about their key role in protecting youth


Image credit: FDA

News & Views: Patients First, Least Burdensome Provisions, Drug Supply Chain security, 510(K) exemptions

Capture.JPGFDA’s Patient Affairs Staff (PAS)-  FDA Puts Patients First

PAS works with patients, caregivers, and advocates in 2019
  • Understanding patient experience and incorporating patient feedback into FDA’s work

PAS launched several initiatives to support and connect with patients


The Least Burdensome Provisions: Concept and Principles

Final guidance on use of least burdensome approach to medical device regulation
  • Support timely patient access to high quality, safe and effective medical devices
  • Remove or reduce unnecessary burdens throughout total product lifecycle
  • Maintaining statutory requirements for clearance and approval
  • Principles are based on sound science, intent of the law, use of alternative approaches, efficient use of resources to effectively address regulatory issues

Guiding principles

  • FDA to request minimum information necessary to adequately address regulatory question or issue at hand
  • Industry should submit material, including premarket submissions, that are least burdensome for FDA to review
  • FDA to use most efficient means to resolve regulatory questions and issues
  • Right information provided at right time (e.g., just-in-time data collection) to address right questions
  • Regulatory approaches designed to fit technology, taking into account unique innovation cycles, evidence generation needs, timely patient access
  • FDA to leverage outside US data to the extent appropriate and feasible



Improving security of Drug Supply Chain through innovations that improve tracking and tracing of medicines


Intent to Exempt Certain Unclassified Medical Devices from Premarket Notification Requirements

Intent to exempt certain unclassified medical devices from premarket notification requirements

  • Devices are sufficiently well understood
  • Do not require premarket notification (510(k)) to assure their safety and effectiveness.

Device categories

  • Ear, Nose, and Throat
  • Gastroenterology-Urology
  • General and Plastic Surgical
  • Neurological
  • Obstetrical and Gynecological Devices
  • Physical Medicine Devices


Image credit: FDA

Obesity Prevention Game


Obesity Prevention Game Challenge

  • 2 out of every 3 women overweight or with obesity problems in US
  • 1 in 3 girls (2-19 years old) overweight or with obesity problems
  • Create engaging web- or mobile-based game that helps women or girls build healthier exercise and eating habits to prevent obesity
  • Chance to win up to $77,000 in prize money!


Image credit: FDA

Market Authorizations: ULTOMIRIS for paroxysmal nocturnal hemoglobinuria, Personal Genome Service (PGS) for Cervical Cancer screening


ULTOMIRIS (ravulizumab-cwvz) injection

Alexion Pharmaceuticals
INDICATION: Treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH)
  • PNH is a rare acquired disorder that leads to the rupture or destruction of red blood cells (hemolysis)
  • Prior to this approval, treatment required every two weeks, which can be burdensome for patients and families
  • Novel formulation so patients only need treatment every eight weeks, without compromising efficacy

MECHANISM OF ACTION: Terminal complement inhibitor specifically binds to complement protein C5 with high affinity; inhibits terminal complement-mediated intravascular hemolysis in patients with PNH

  • First randomized clinical trial, n=246 PNH patients (treatment naïve), Ultomiris vs. eculizumab, current standard of care for PNH
  • Non-inferiority on endpoints: Transfusion avoidance and hemolysis directly measured by normalization of LDH levels
  • Second randomized trial, n=195 PNH patients clinically stable after eculizumab treatment, Ultomiris vs. continue eculizumab
  • Similarity on several clinical measures including hemolysis and avoiding transfusion
  • Common side effects: Headache, upper respiratory infection
  • Boxed Warning: Risk of life-threatening meningococcal infections and sepsis
  • Priority Review designation, Orphan Drug designation
  • Postmarketing commitments: Data from clinical trials in patients with paroxysmal nocturnal hemoglobinuria (ALXN1210-PNH-301 and ALXN1210-PNH-302) to include the extension period of up to 2 years of follow-up

Personal Genome Service (PGS) Genetic Health Risk Report for
MUTYH-Associated Polyposis for Cervical Cancer screening


INTENDED USE: PGS uses qualitative genotyping to detect select clinically relevant variants in genomic DNA isolated from human saliva collected from individuals ≥18 years for the purpose of reporting and interpreting genetic health risks, including the 23andMe PGS Genetic Health Risk Report for MUTYH-Associated Polyposis (MAP)

INDICATION FOR USE: The 23andMe PGS Genetic Health Risk Report for MUTYHAssociated Polyposis is indicated for reporting of the Y179C and the G396D variants in the MUTYH gene. The report describes if a person is at increased risk of developing colorectal cancer. The two variants included in this report are most common and best studied in people of Northern European descent and may not represent the majority of the MUTYH variants found in people of other ethnicities. The test report does not describe a person’s overall risk of developing any type of cancer, and the absence of a variant tested does not rule out the presence of other variants that may be cancer-related.

This test is not a substitute for visits to a healthcare provider for recommended screenings or appropriate follow-up and should not be used to determine any treatments.


  • The core components of the PGS are unchanged from the de novo authorization for the predicate device, the PGS Genetic Health Risk Report for BRCA1/BRCA2 and also the additional de novo Authorizations of the PGS for Carrier Screening Tests for Bloom Syndrome and PGS Genetic Health Risk Reports including saliva collection kit, reagents and beadchip, instrumentation, software, test processes, procedures
  • Novel components: (a) specific variants to be reported (b) qualitative reporting of risk for MAP, as opposed to the BRCA related cancer risks

REGULATORY PATHWAY: Traditional 510(k)

  • Trade/Device Name: MUTYH-Associated Polyposis (MAP)
  • Regulation Number: 21 CFR 866.6090
  • Regulation Name: Cancer Predisposition Risk Assessment System
  • Regulatory Class: Class II
  • Product Code: QAZ


Image credits: Alexion, 23andMe