FDA Emergency Use Authorization (EUA)

FDA Emergency Use Authorization(EUA)Presented on:November 5, 2020Presented by:Amanda Johnston, J.D., R.A.C., Senior AttorneyBrynn Stanley, J.D., Associate Attorney

SpeakersAmanda Johnston, J.D., R.A.C.Senior AttorneyBrynn Stanley, J.D.Associate Attorney-- Former quality engineer- 15 years in health care- Former: Monteris, Super Dimension-Covidien(Medtronic), American Medical Systems, St.Jude Medical (Abbott), Boston ScientificFormer compliance officerRegulatory Affairs Certification9 years in health careFormer: Coloplast, Medtronic, United HealthGroupEmail: ajohnston@gardner.lawPhone: 763-639-6951Email: bstanley@gardner.lawPhone: 763-458-1295

Agenda FDA’s Emergency Use Authorization (EUA) authority &overview Preparing & submitting EUA requests COVID-19 guidance documents & policies Quality Management System (QMS) considerations FDA enforcement trends: COVID-19 PREP Act & CARES Act Key takeaways Q&A

FDA’s EUA Authority& Overview

FDA’s EUA Authority FDA’s EUA authority is triggered only when the following twodeterminations are made:1. Public Health Emergency Declaration: Secretary of Health andHuman Services determines that a public health emergencyexists; and2. EUA Declaration: Secretary of Health and Human Servicesdetermines that circumstances exist justifying FDACommissioner’s issuance of EUAs, provided other statutorycriteria are met.

EUA Overview FDA Commissioner may issue an EUA to :– Allow a medical countermeasure (MCM) to be used in anemergency to diagnose, treat, or prevent serious or lifethreatening diseases or conditions caused by a chemical,biological, radiological, or nuclear (CBRN) agent (includinginfectious disease threats) when there are no adequate,approved, and available alternatives. Separate and distinct from investigational applications, e.g.,Investigational Device Exemption (IDE), Investigational NewDrug (IND).

Statutory Criteria for EUA Issuance1. Serious or Life-Threatening Disease or Condition–As declared by the Secretary of DHHS, COVID-19 is capable of causinga serious or life-threatening disease or condition.2. Evidence of Effectiveness–FDA uses the “may be effective” standard, which is lower than“effectiveness” standard FDA uses for product approvals/clearances.3. Risk-Benefit Analysis–FDA must determine that the known and potential benefits of theproduct outweigh the known and potential risks (totality of thescientific evidence).4. No Alternatives–No adequate, approved, and available alternatives. Insufficient supplymay be considered “unavailable.”

Individual vs. Umbrella EUAs Individual EUA: Manufacturer submits EUA Request to FDA.FDA reviews and authorizes individual product. Umbrella EUA: FDA issues general EUA on product categorythat outlines certain criteria and steps to follow forauthorization. Either:1. Company submits EUA, and if authorized, FDA adds theproducts authorized under the umbrella EUA to “Appendix A.”– E.g., Surgical mask, Non-NIOSH approved filtering facepiece respirators2. Product is authorized if it meets the requirements in the EUA.No submission or specific FDA authorization required.– E.g., Face shields, Gowns and other apparel

Current EUAs (as of November 2, 2020) In Vitro Diagnostic Products (n 288)– Templates for some EUA submissions are available– Individual products authorized via Letter of Authorization (LOA) Personal Protective Equipment and Related Devices (n 22)– Umbrella EUAs (surgical masks, gowns, face shields, etc.)– Individual products authorized via LOAs Ventilators and Other Medical Devices (n 26)– Templates for some EUA submissions are available– Individual products authorized via LOAs Drug and Biological Products (n 5)– Individual products authorized via LOAs E.g., Remdesivir, convalescent plasma

Preparing & SubmittingEUA Requests

Preparing an EUA Request FDA encourages early engagement via “pre-EUA” before EUARequest. Check to see if FDA has an EUA template– Make sure you use the current EUA template!– FDA requires FDA Form 3514 for some EUA submissions. Write concisely, clearly, and accurately.Submission should be well-organized.Write for your audience. Follow FDA’s instructions!Contact the appropriate FDA COVID-19/EUA email address withsimple, concise questions.– They may provide general information but will not give you legaladvice or tell you how they would classify or regulate your product.

EUA Request Review Process Review timelines are not standardized, often unpredictable basedon (not exhaustive):–––––Product type;Whether there are similar products with pending applications;Organization and completeness of the EUA request submission;Workload of FDA review staff; andAgency priorities. Respond promptly to FDA questions and requests. Ask for the name/email of lead reviewer assigned. Check-in often. If authorized, FDA will issue a letter of authorization (“LOA”)– LOA will cover conditions of authorization, e.g., labeling, required FactSheets for patients and HCPs, advertising, CGMPs.

Termination of EUA When EUA Declaration ends, all EUAs issued under thatdeclaration will end.– Secretary of HHS will provide “advance notice . . . sufficient to allowfor the disposition” of EUA product and labeling. FDA can revoke (or modify) individual and umbrella EUAs(e.g., Hydroxychloroquine Sulfate and Chloroquine Phosphate) Products that are legally-marketed under “typical” FDAregulations (e.g., meets QSR, obtains clearance/approval orexempt) will not be impacted by termination of EUADeclaration.

Obtaining FDA Approval/Clearance Seek appropriate regulatory clearance:––––––510(k)De NovoPMANDA510(k) ExemptEtc. Recommend evaluating and seeking regulatoryapproval/clearance in parallel to minimize disruption tobusiness.

COVID-19 Guidance Documents& Policies

FDA’s COVID-19 Guidance Documents & Policies FDA has issued 64 policies and guidance documents tosupport rapid COVID-19 response efforts to COVID-19.– Immediately implemented without prior comment, but you maysubmit comments. “Enforcement Policies” and “Temporary Policies” expandavailability of products and address urgent public healthconcerns.– FDA waives certain requirements; exercises enforcement discretion ifconditions are met. Must fully meet the requirements. Effective only for the duration of the public health emergency(per DHHS).

Enforcement Policies & Temporary Policies (36 ) Non-Invasive Remote Monitoring DevicesFace Masks and RespiratorsRemote Digital Pathology DevicesImaging SystemsNon-Invasive Fetal and Maternal Monitoring DevicesTelethermographic SystemsDigital Health Devices for Treating Psychiatric DisordersExtracorporeal Membrane Oxygenation and Cardiopulmonary Bypass DevicesRemote Ophthalmic Assessment and Monitoring DevicesInfusion Pumps and AccessoriesClinical Electronic ThermometersGowns, Other Apparel, and GlovesSterilizers, Disinfectant Devices, and Air PurifiersVentilators and AccessoriesHand Sanitizer, etc

IMPORTANT: Know which paths are availableFace MasksSurgical maskRespirators510(k) clearance510(k) clearanceNIOSH approval

Identify the most appropriate path(s)Face maskunder EUARespirator underumbrella EUAFace mask rSurgical maskunder EUASurgical mask underEnforcement PolicyNIOSH-approvedrespiratorFDA-clearedsurgical mask

Considerations Product designHow FDA classifies and regulates the productMaterial compositionCountry of manufactureSupply chainWhat standards the product currently meets (if any)Product’s intended useHow you want to label the productWhat claims you want to makeWhat testing you have already completed (if any)What testing would be requiredQSR requirements and company’s QMS statusBusiness objectives (current and future)Customer requirements (e.g., “on Appendix A” or “510(k) cleared”)TimingResourcesMarket demand

Quality Management System Considerations

EUA and QSR Regulatory requirements are waived for many EUA pathways––––21 CFR 807 Registration and listing requirements21 CFR 820 Quality System Regulation (QSR)21 CFR 806 reports of corrections and removals21 CFR 830 and 21 CFR 801.20 Unique Device Identification Under some enforcement policies, e.g., surgical gowns,manufacturers must still have a QSR compliant QualityManagement System (QMS). Manufacturers will need to meet all regulatory requirementsupon termination of the EUA declaration.

Quality Management System There are 7 subsystems of a QMS:1. Management2. Design Controls3. Corrective and Preventive Actions4. Production and Process Controls5. Equipment and Facility Controls6. Records, Documents, and Change Controls7. Material Controls

Quality Management System Even if not required under the Policy/EUA, a QMS should beimplemented as soon and as much as possible in order to:––––Provide assurance products meet requirements;Reduce timelines for clearance or approval;Choose the most appropriate suppliers or contract manufacturers; andContinue marketing products upon termination of the EUA. Implementing a QMS may be time and resource intensive– Weeks to months depending on complexity of the business andproducts. Recommend a parallel path for EUA and implementation of aQMS.

Considerations Status of a QMS for contract manufacturers or suppliers– The manufacturer is responsible for product quality– Choose and evaluate suppliers carefully Dedicated resources for QMS maintenance– The QMS must be maintained as long as product is being marketed– Continuous improvements for product and the QMS

FDA Enforcement Trends

FDA’s Operation Quack Hack Focusing on cracking down on fraudulent and unprovenCOVID-19 claims/products. Combat companies exploiting or taking advantage of fearamong consumers during COVID-19 pandemic. FDA/FTC are reviewing websites and social media activity. Identified 1,127 fraudulent and unproven products sinceMarch 2020. FDA has issued 128 warning letters– Test kits, teas, essential oils, vitamins, nasal sprays, hand sanitizer,inhalers, etc. 270 reports to virtual marketplaces 225 complaints to domain registrars

FDA Enforcement Adulterated and/or misbranded if not approved, cleared,or authorized.– Must meet all conditions in LOA, EUA, Policy, etc. FDA may pursue warning letters, seizures, injunctions, orcriminal prosecutions against companies/individuals. FDA has issued multiple safety alerts on hand sanitizerissues:– Methanol contamination– Microbial contamination– Improper packaging (resembling food/beverage container)

PREP Act & CURES Act

Public Readiness and Emergency Preparedness Act “PREP Act” authorizes the Secretary DHHS to issue adeclaration that provides immunity from liability related tocertain medical countermeasures (“MCM”)—EXCEPT willfulmisconduct. Declaration for MCM against COVID-19 issued February 4,2020. Immunity generally applies to those involved in thedevelopment, manufacture, testing, distribution,administration, and use of certain MCM.

Coronavirus Aid, Relief, and Economic Security Act “CARES Act” introduced new shortage notification and riskmanagement plans for medical product manufacturers tomitigate shortages of important equipment. Added personal protective equipment (PPE) to the list ofproducts to be included in the strategic national stockpile. Added respiratory protective devices as a coveredcountermeasure (MCM) eligible for liability protections underPREP Act.

Key Takeaways Do your homework. Stay up to date with FDA COVID-19 news. Consider all options and identify most appropriate path.– EUAs, Enforcement Policies, clearance/approval, etc. Consider future business objectives after EUA Declarationterminates. Engage FDA early in the process. Submit a pre-EUA (if applicable). Follow FDA’s instructions! Ensure all claims are accurate, not misleading, and substantiated. Understand time/effort/resources that may be required. Beprepared. Consult with legal/regulatory/quality experts.

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