Presented on:November 5, 2020

Presented by:Amanda Johnston, J.D., R.A.C., Senior Attorney

Brynn Stanley, J.D., Associate Attorney

FDA Emergency Use Authorization (EUA)

Speakers

Amanda Johnston, J.D., R.A.C. Senior Attorney

- Former compliance officer- Regulatory Affairs Certification - 9+ years in health care- Former: Coloplast, Medtronic, United Health

Group

Email: ajohnston@gardner.lawPhone: 763-639-6951

Brynn 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 Scientific

Email: 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 two determinations are made: 1. Public Health Emergency Declaration: Secretary of Health and

Human Services determines that a public health emergency exists; and

2. EUA Declaration: Secretary of Health and Human Services determines that circumstances exist justifying FDA Commissioner’s issuance of EUAs, provided other statutory criteria are met.

EUA Overview

• FDA Commissioner may issue an EUA to :– Allow a medical countermeasure (MCM) to be used in an

emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by a chemical, biological, radiological, or nuclear (CBRN) agent (including infectious disease threats) when there are no adequate, approved, and available alternatives.

• Separate and distinct from investigational applications, e.g., Investigational Device Exemption (IDE), Investigational New Drug (IND).

Statutory Criteria for EUA Issuance

1. Serious or Life-Threatening Disease or Condition– As declared by the Secretary of DHHS, COVID-19 is capable of causing

a 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 the

product outweigh the known and potential risks (totality of the scientific evidence).

4. No Alternatives– No adequate, approved, and available alternatives. Insufficient supply

may 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 category that outlines certain criteria and steps to follow for authorization. Either:1. Company submits EUA, and if authorized, FDA adds the

products authorized under the umbrella EUA to “Appendix A.”– E.g., Surgical mask, Non-NIOSH approved filtering facepiece respirators

2. 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 & Submitting EUA Requests

Preparing an EUA Request

• FDA encourages early engagement via “pre-EUA” before EUA Request.

• 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 with

simple, concise questions.– They may provide general information but will not give you legal

advice or tell you how they would classify or regulate your product.

EUA Request Review Process

• Review timelines are not standardized, often unpredictable based on (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; and– Agency 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 Fact Sheets for patients and HCPs, advertising, CGMPs.

Termination of EUA

• When EUA Declaration ends, all EUAs issued under that declaration will end. – Secretary of HHS will provide “advance notice . . . sufficient to allow

for 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” FDA regulations (e.g., meets QSR, obtains clearance/approval or exempt) will not be impacted by termination of EUA Declaration.

Obtaining FDA Approval/Clearance

• Seek appropriate regulatory clearance:– 510(k)– De Novo– PMA– NDA– 510(k) Exempt– Etc.

• Recommend evaluating and seeking regulatory approval/clearance in parallel to minimize disruption to business.

COVID-19 Guidance Documents & Policies

FDA’s COVID-19 Guidance Documents & Policies

• FDA has issued 64+ policies and guidance documents to support rapid COVID-19 response efforts to COVID-19.– Immediately implemented without prior comment, but you may

submit comments. • “Enforcement Policies” and “Temporary Policies” expand

availability of products and address urgent public health concerns. – FDA waives certain requirements; exercises enforcement discretion if

conditions 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 Devices• Face Masks and Respirators• Remote Digital Pathology Devices• Imaging Systems• Non-Invasive Fetal and Maternal Monitoring Devices• Telethermographic Systems• Digital Health Devices for Treating Psychiatric Disorders• Extracorporeal Membrane Oxygenation and Cardiopulmonary Bypass Devices• Remote Ophthalmic Assessment and Monitoring Devices• Infusion Pumps and Accessories • Clinical Electronic Thermometers • Gowns, Other Apparel, and Gloves• Sterilizers, Disinfectant Devices, and Air Purifiers• Ventilators and Accessories • Hand Sanitizer, etc…

IMPORTANT: Know which paths are available

Face Masks Surgical mask Respirators

510(k) clearance

NIOSH approval510(k) clearance

Identify the most appropriate path(s)

Face mask under EUA

Face mask under Enforcement

Policy

Surgical mask under EUA

Surgical mask under Enforcement Policy

Respirator under umbrella EUA

FDA-cleared surgical

respirator

NIOSH-approved respirator

FDA-cleared surgical mask

Considerations

• Product design• How FDA classifies and regulates the product• Material composition• Country of manufacture• Supply chain• What standards the product currently meets (if any)• Product’s intended use• How you want to label the product• What claims you want to make• What testing you have already completed (if any)• What testing would be required• QSR requirements and company’s QMS status• Business objectives (current and future)• Customer requirements (e.g., “on Appendix A” or “510(k) cleared”)• Timing• Resources• Market demand

Quality Management System Considerations

EUA and QSR

• Regulatory requirements are waived for many EUA pathways – 21 CFR 807 Registration and listing requirements– 21 CFR 820 Quality System Regulation (QSR)– 21 CFR 806 reports of corrections and removals– 21 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 Quality Management System (QMS).

• Manufacturers will need to meet all regulatory requirements upon 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 be implemented 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; and– Continue 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 and

products.

• Recommend a parallel path for EUA and implementation of a QMS.

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 unproven COVID-19 claims/products.

• Combat companies exploiting or taking advantage of fear among consumers during COVID-19 pandemic.

• FDA/FTC are reviewing websites and social media activity. • Identified 1,127+ fraudulent and unproven products since

March 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, or criminal prosecutions against companies/individuals.

• FDA has issued multiple safety alerts on hand sanitizer issues:– 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 a declaration that provides immunity from liability related to certain medical countermeasures (“MCM”)—EXCEPT willful misconduct.

• Declaration for MCM against COVID-19 issued February 4, 2020.

• Immunity generally applies to those involved in the development, manufacture, testing, distribution, administration, and use of certain MCM.

Coronavirus Aid, Relief, and Economic Security Act

• “CARES Act” introduced new shortage notification and risk management plans for medical product manufacturers to mitigate shortages of important equipment.

• Added personal protective equipment (PPE) to the list of products to be included in the strategic national stockpile.

• Added respiratory protective devices as a covered countermeasure (MCM) eligible for liability protections under PREP 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 Declaration terminates.

• 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. Be

prepared.• Consult with legal/regulatory/quality experts.

Copyright Gardner Law 2020. All Rights Reserved.

Questions?

Thank you!

• Amanda Johnston, JD, RACPhone: 763-639-6951Email: ajohnston@gardner.law

• Brynn Stanley, JDPhone: 763-458-1295Email: bstanley@gardner.law