Proctoring Guidelines and Challenges

FDANEWS — 15

Annual FDA INSPECTIONS vSUMMIT

November 18, 2020

Managing Medical Device Recalls

— Including Conduct of Health Hazard Evaluations

Beverly Lorell, M.D.

Senior Medical & Policy Advisor

FDA & Life Sciences Practice

King & Spalding LLP

blorell@kslaw.com

Steven Niedelman

Lead Quality System & Compliance Consultant

FDA & Life Sciences Practice

King & Spalding LLP

sniedelman@kslaw.com

▪ Brief overview: What is a recall?

▪ Recall classification

▪ Part 806: When to report?

▪ Risk to health: Conduct of a Health Hazard Evaluation

▪ Common challenges, conundrums, and considerations

▪ Roundtable and Q/A

Today’s Discussion

▪ Is there a systemic issue?

– Does the product in distribution fail to meet company

specifications in compliance with FDA Quality System

regulation?

– Is product associated with a risk to health?

▪ Is a field action needed? If so, what type of field action?

▪ Is the field action reportable?

Thought Process

Watch out: Growing Concern Over Recalls

• There is a growing concern within CDRH and ORA regarding the increasing number of

device recalls

• FDA is trying to establish the root cause of this increase.

• Are they design issues?

• Manufacturing issues?

• Advertising/promotion issues?

• Supplier Issues?

• Complaints?

• Are these recalls an indicator of an underlying issue regarding the design of your devices?

• Be sure to read your signal systems - complaints, MDRs, CA/PAs, NCs

• Compare the information with your risk files to see if an adjustment may be needed

• Some firms use heat maps to track complaints; others have stablished thresholds

• Conduct Health Risk assessments to assess patient risk

• A total of 3,348 medical device recalls classified by FDA during FY 2020.

• Of these 348 were classified as Class I, 2, 924 as Class II, and 76 as Class III

Be aware that this may

be a focus of future FDA

concerns at your site

▪ 21 C.F.R. Part 7 Subpart C is guidance, not law. Recalls conducted pursuant

to Part 7 are “voluntary.”

– Defines key terms and provides guidance on recall conduct

▪ 21 C.F.R. Part 806—Reports of Corrections and Removals

– Has the force of law

– Sets out circumstances under which “voluntary” recalls must be reported

to FDA

Recall Regulatory Framework

What is a Recall?

Key Definitions

▪ “Recall means a firm’s removal or correction of a marketed

product that FDA considers to be in violation of the laws it

administers and against which the agency would initiate legal

action, e.g., seizure.”

▪ “Recall” does not include a “market withdrawal” or “stock

recovery.” 21 C.F.R. 7.3(g)

“Recall”

▪ The repair, modification, adjustment, relabeling, destruction, or

inspection (including patient monitoring) of a product without its

physical removal to some other location. 21 C.F.R. 7.3(h)

“Correction”

▪ The physical removal of a device from its point of use to some

other location for repair, modification, adjustment, relabeling,

destruction or inspection. 21 C.F.R. 7.3(i)

“Removal”

▪ “Market Withdrawal”

– A firm’s removal or correction of a distributed product which involves a minor violation that

would not be subject to legal action by FDA or which involves no violation, e.g., normal stock

rotation practices, routine equipment adjustments and repairs, etc. 21 C.F.R. 7.3(j)

▪ “Stock Recovery”

– A firm’s removal or correction of a product that has not been marketed or that has not left the

direct control of the firm, i.e., the product is located on the premises owned by, or under the

control of, the firm, and no portion of the lot has been released for sale or use. 21 C.F.R. 7.3(k)

What is Not a Recall?

▪ A situation in which there is a reasonable probability that use of, or

exposure to, a violative product will cause serious adverse health

consequences or death. 21 C.F.R. 7.3(m)(1) (emphasis added)

‒ “Reasonable probability” means “that it is more likely than not that an event will occur.”

21 C.F.R. 810.2(h)

‒ However, FDA does not rely on this definition – i.e., a likelihood of greater than 50% – in

its conduct of HHE and recall classifications.

“Class I Recall”

▪ A situation in which use of, or exposure to, a violative product

may cause temporary or medically reversible adverse health

consequences or where the probability of serious adverse health

consequences is remote. 21 C.F.R. 7.3(m)(2)

“Class II Recall”

▪ A situation in which use of, or exposure to, a violative product is

not likely to cause adverse health consequences. 21 C.F.R. 7.3(m)(2)

“Class III Recall”

▪ Required for any correction or removal of a medical device if the

correction or removal was initiated

– To reduce a risk to health posed by the device or

– To remedy a violation of the FDCA caused by the device which may

present a risk to health

▪ Report must be submitted with 10 working days of initiating the

correction or removal. 21 C.F.R. Part 806

Part 806 Reporting Requirements

▪ Part 806 definition of “risk to health” tracks the definitions for Class I and

Class II recalls.

– “A reasonable probability that use of, or exposure to, the product will

cause serious adverse health consequences or death”; or

– “That use of, or exposure to, the product may cause temporary or

medically reversible adverse health consequences, or an outcome where

the probability of serious adverse health consequences is remote.”

21 C.F.R. 806.2(j)

“Risk to Health” and Part 806

▪ Is the change being made to a “violative” device?

– Fails to meet specifications

– Fails to perform as intended – such devices are “of a quality below what they

purport or are represented to possess”

– Changes being made to false or misleading labeling

▪ FDA guidance advises that a design change to improve the safety and

effectiveness of a device is not reportable under Part 806 if the design

change is not done to remedy a violative device

Is a Change to a Device a Recall or a “Product Enhancement”?

▪ The FDA’s HHE determines

– The recall classification

– How FDA communicates information about the recall to the public, including

issuance of a press release

▪ A manufacturer’s HHE guides decision-making and the conduct of a voluntary recall

– Should a voluntary recall (i.e., a correction or removal) be conducted?

– If so, is it reportable to FDA under Part 806?

– Input to CAPA (Should design, including user interface, or manufacturing be

modified for future products?)

Health Hazard Evaluations

Consider aligning your approach with CDRH HHE process

I. Product Data

Name, Model, Lot/Serial Numbers, PMA or 510(k) Number, Total

Number in Distribution, Number Subject to Review or Recall,

Manufacturer, Product Description (including Intended Use from

Labeling)

II. Problem Definition and Analysis, including

Reason for Recall or Conduct of Risk Assessment

CAPA Investigation (if available)

III. Health Risks

“TO BE COMPLETED BY MEDICAL OFFICER OR COMMITTEE”

http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHTranspare

ncy/ucm217880.htm

Conduct of an HHE by Manufacturer

Reason for the Recall or Health Risk

▪ Description of the “Defect, Malfunction, or Error in Use”

▪ Root Cause (if known)

▪ Factors That May Contribute to Risk (“i.e., device design, manufacturing, or user

error”)

▪ Design Factors That Might Mitigate Risk

▪ If Device Failure Occurs, Is it Easily Recognized by User (e.g., health care provider,

caretaker, or patient)

II. Problem Definition and Analysis

CDRH HHE Guidance Version 3-1

Include user error in the

analysis

Data Input from CAPA Investigation

▪ Estimate of number of devices that will develop the defect

and/or fail, with date of analysis

– Number of devices from Affected Lots that are expected to

have or develop the defect

– For implants or reusable devices, number of devices likely

to exhibit the failure over lifetime of the device

– Of those devices that fail, how many are likely to cause injury

if used [i.e., upon patient exposure to the defective device]

II. Problem Definition and Analysis

CDRH HHE Guidance Version 3-1

What about devices

provided as a set? For

example, a cartridge of

surgical staples?

Use terms public will

understand, such as

actual numbers or “one

out of 100” rather than

patient-years

Immediate and Long Range Health Consequences

▪ Health consequences that may result from use of or

exposure to the defective device

– “Include known off label uses”

▪ Any clinical factors that may mitigate risk

▪ Segment of the population that is “Most at Risk”

– “e.g., infants, elderly, pregnant women, critically ill

patients, immunocompromised”

▪ Any significant public health impact beyond users

III. Health Risks:

TO BE COMPLETED BY MEDICAL OFFICER OR COMMITTEE

CDRH HHE Guidance Version 3-1

Identify the subgroups of

patients at higher risk if

exposed to the device

defect

Consider off-label uses

Relies on FDA definition of “serious injury” – 21 C.F.R. 803.3

“An injury or illness that:

• Is life-threatening,

• Results in permanent impairment of a body function or

permanent damage to a body structure, or

• Necessitates medical or surgical intervention to

preclude permanent impairment of a body function or

permanent damage to a body structure. Permanent

means irreversible damage to a body structure or

function, excluding trivial impairment or damage.”

FDA HHE Assessment of Health Risks

Definition for

identification of

complaints that must

be reported as serious

injuries in MDRs

III. Health Risks:

TO BE COMPLETED BY MEDICAL OFFICER OR COMMITTEE

CDRH HHE Guidance Version 3-1

Estimate the seriousness of the potential harms

Assess the hazards associated with the use of the defective product

Separately consider the

highest health risk scenarios

and patients, not just

“average patients”

III. Health Risks:

TO BE COMPLETED BY MEDICAL OFFICER OR COMMITTEE

CDRH HHE Guidance Version 3-1

Estimate the probability of the potential harms

For HHE, FDA has not defined

“reasonable probability” or

“remote probability”

Assess the Probability that Use of, or Exposure to, Product under Recall will Cause Adverse Health Consequences

▪ Complaint file (U.S. and global) – not just MDRs

▪ Repair and service history

▪ Publications, case reports, presentations at medical meetings

▪ Training/proctoring

▪ Internal signals: Manufacturing, vendor, supplier

▪ Issues that may have escaped the Quality System

▪ Health risk of recalls of similar products by competitors

▪ What else?

Challenges: Sources of Information

▪ Incomplete or unverified

information

▪ No or few returns of product that is

defective

▪ Uncertain extent of hazard/root

cause not fully identified

▪ Under-reporting of injuries and near

misses

▪ COVID-19 disruption

Conundrums: Incomplete Information

When FDA conducts an HHE with

limited information…

“When forming

conclusions,

clinicians assume a

reasonable worse

case scenario.”

Jacqueline Ryan, MD. Medical

Officer. Office of Compliance.

CDRH. May 10, 2016

▪ What triggers an HHE at the company? How is the HHE escalated?

▪ Who conducts and is responsible for the HHE?

– Who provides clinical input? Who must be at the table?

– Who might provide data but not determine the risk to health or likelihood?

– Who has the final say and sign off on the HHE?

▪ Common sticky assumptions

– Defect is “easily recognizable” by healthcare provider

– “Work-arounds” will consistently prevent patient harm

– Problem is misuse or inexperience (“Experts have no problems”)

Challenges: Conducting the HHE

▪ FDA weighs seriousness of injury more heavily than estimates of the

likelihood of harm

▪ What numbers count?

– In reports to the public, FDA nearly always reports numbers of injuries, not

estimates of probability

– Occurrence of actual injuries to a few is weighted heavily

Elephants in the Room

▪ What about benefit–risk?

▪ Product scarcity if device is recalled (removed)?

▪ Should HHE be provided when company notifies FDA of the recall?

▪ When does the clock start for Part 806 report?

▪ When is a press release needed?

▪ When is an “update bulletin” to users an under-the-table recall?

▪ What is difference between a “Safety Alert” and a recall (correction)?

Challenges: Conduct of the Recall

Panel Discussion and Q&A