Common pitfalls with FDA Medical Device Reporting

1. Best Practices for Medical Device
Reporting
Scott Danzis and Pamela Forrest
February 16, 2017

2. 2
 Overview of the MDR Reporting Regulation and FDA MDR Final
Guidance
 Common MDR Pitfalls and Enforcement Trends
 FDA’s Final Rule on Adverse Event Reporting for Combination
Products
Agenda

3. Overview of the MDR Reporting Regulation

4. 4
 Section 519 of the Federal Food, Drug, and Cosmetic Act (FDCA)
sets forth basic elements for “Records and Reports on Devices”
Every person who is a manufacturer or importer of a device intended for
human use shall establish and maintain such records, make such
reports, and provide such information, as the Secretary may by
regulation reasonably require to assure that such device is not
adulterated or misbranded and to otherwise assure its safety and
effectiveness.
 Part 803 of Title 21 of the Code of Federal Regulations (C.F.R.)
provides FDA’s regulations implementing Section 519.
 In addition to Part 803, 21 C.F.R. Part 806 (Corrections and
Removals) and Part 820 (Quality System Regulation) contain
additional regulatory requirements closely related to MDR
reporting.
MDR Statute and Regulations

5. 5
 March 1997: FDA publishes Final Guidance on MDR reporting.
 July 9, 2013: FDA publishes Draft Guidance.
 33 comments submitted by various stakeholders, including industry
trade associations.
 November 8, 2016: FDA publishes final guidance on Medical Device
Reporting for Manufacturers (“Final Guidance”).
 46 pages, structured in Q&A format.
 Divided into 4 primary sections:
 manufacturer reporting requirements;
 written procedures, recordkeeping and public disclosure;
 specific issues and situations; and
 questions concerning the completion of MDR reports.
 November 30, 2016: FDA webinar on Final Guidance.
FDA Guidance on MDR Reporting

6. 6
 The purpose of the MDR reporting is to signal potential device
safety issues to FDA and the manufacturer.
 Manufacturers, importers, and device user facilities all have MDR
reporting obligations.
 Includes foreign manufacturers.
 Includes a contract manufacturer that “distributes or markets” the
devices that it manufactures on behalf of the specification
developer.
 Distributors must maintain records but are not required to report.
 Firms may allocate reporting responsibilities by contract, but that
does not alleviate regulatory obligation to report.
 Must request an exemption from FDA.
Overview of the MDR Reporting Regulation

7. 7
 An "MDR Reportable Event” is an event about which a manufacturer
has received or "becomes aware" of information that reasonably
suggests one of its marketed devices:
 May have ''caused or contributed'' to a death or ''serious injury''; or
 Has ''malfunctioned'' in a way that, if the malfunction were to happen
again, the malfunctioning device or a similar device marketed by the
manufacturer, would likely cause or contribute to a death or serious
injury. (21 C.F.R. § 803.3(o))
 A firm’s complaint-handling system is the main source of MDR
reportable information. A "complaint" is defined as:
 "Any written, electronic, or oral communication that alleges
deficiencies related to the identity, quality, durability, reliability, safety,
effectiveness, or performance of a device after it is released for
distribution." (21 C.F.R. § 820.3(b))
Overview of the MDR Reporting Regulation

8. 8
 A manufacturer must report all the information specified by 21 C.F.R. §
803.52 that is known, or reasonably known, to the manufacturer, which
includes information:
 That is in your possession;
 That you can obtain by contacting a user facility, importer, or other
initial reporter;
 That you can obtain by analysis, testing or other evaluation of the
device.
 FDA expects manufacturers to make a good faith effort to obtain
information required by the MDR regulation, including, when needed, a
written request for information.
 MDR files must contain an explanation of why information required
by the MDR regulation was not submitted or could not be obtained.
 A manufacturer must submit supplemental reports for information that
was not known or available at the time the manufacturer submitted the
initial report. (21 C.F.R. § 803.10)
Overview of the MDR Reporting Regulation

9. 9
 In general, a manufacturer is required to submit an MDR report to FDA within
30 calendar days of when it receives or otherwise becomes aware of
information, from any source, that reasonably suggests that one of its
marketed devices was involved in an MDR Reportable Event. (21 C.F.R. §
803.50)
 A manufacturer must report within 5 working days where:
 The event necessitates remedial action to prevent an unreasonable risk of
substantial harm to the public health; or
 FDA has made a written request for the submission of a 5-day report. (21
C.F.R. § 803.53).
 FDA generally considers that a manufacturer becomes aware of an adverse
event whenever any employee becomes aware of an adverse event.
 For 5-day reports, timeline begins the day after an employee with
“management or supervisory responsibilities over persons with regulatory,
scientific, or technical responsibilities, or a person whose duties relate to the
collection and reporting of adverse events,” “becomes aware” of the event.
Overview of the MDR Reporting Regulation

10. 10
 Manufacturers are required to establish and maintain written MDR
procedures. (21 C.F.R. § 803.17).
 Procedures must address:
 Timely and effective identification, communication, and
evaluation of potentially reportable events;
 Standardization of the review steps for determining whether an
event is reportable;
 Timely submission of complete reports; and
 Requirements for documentation practices and recordkeeping.
(21 C.F.R. § 803.17)
 Manufacturers should train all employees to recognize and
immediately forward adverse event information to the appropriate
person appointed by those entities to submit MDR reports.
Overview of the MDR Reporting Regulation

11. Common Pitfalls and Enforcement Trends

12. 12
 MDR reporting regulations apply to any device “manufacturer”
 Contract manufacturers do not always recognize when MDR reporting
requirements apply to their operations.
 Final Guidance clarifies that a contract manufacturer that does not
distribute or market the devices it manufactures for a specifications
developer would not need to submit MDR reports.
 This is a change in approach as compared to the Draft Guidance,
which would have required reporting by all contract manufacturers.
 If contract manufacturer “distributes or markets” the devices, both
must submit MDR reports.
 If the two firms want only one firm to file MDRs, they should file a
joint request for an exemption, specifying which firm will submit the
reports.
Common Pitfall:
Failure of Contract Manufacturers to Report

13. 13
 Information must be reviewed and evaluated to determine if it
constitutes a "complaint." A "complaint" is defined as:
 "Any written, electronic, or oral communication that alleges
deficiencies related to the identity, quality, durability, reliability,
safety, effectiveness, or performance of a device after it is
released for distribution." (21 C.F.R. § 820.3(b))
 Frequently overlooked sources of potential complaints include:
 Service reports
 Social media
 Scientific journal articles
 Returned goods
 Clinical investigations of marketed devices
Common Pitfall:
Failure to Treat All Complaints as Complaints

14. 14
Warning Letter Example
“Your firm’s procedure…does not ensure that oral complaints
are documented upon receipt…you stated to the FDA
investigator that your firm has received a number of
complaints that you referred to as easily rectified by
telephone. However, your firm failed to document these
complaints.”

15. 15
 All complaints must be evaluated to determine if the complaint
constitutes an MDR reportable event. (21 C.F.R. § 820.198(a)(3))
 Firms sometimes review for MDR reportability only those
complaints that involve obvious harm to the patient, but neglect to
review complaints that do not involve patient injury/death, but do
involve a device malfunction.
Common Pitfall:
Failure to Review All Complaints for Reportability

16. 16
 Frequent issues include:
 Failure to incorporate key regulatory definitions (e.g., “Become
Aware,” “Caused or Contributed,” “Malfunction,” “Serious Injury)
and requirements (e.g., supplemental reports, 5-day reports)
 Lack of a comprehensive “Decision Tree” outlining the analytical
process for determining reportability.
 Failure to appropriately train on MDR procedures and
responsibilities.
Common Pitfall:
Lack of Effective MDR Procedures

17. 17
Warning Letter Example
“Failure to develop, maintain, and implement MDR procedures, as
required by 21 CFR 803.17…the following issues were noted:
a. …does not establish internal systems that provide for
timely and effective identification, communication, and
evaluation of events that may be subject to MDR
requirements. For example… the exclusion of definitions
… for the terms ‘become aware,’ ‘caused or contributed,’
‘malfunction,’ ‘MDR reportable event,’ ‘serious injury,’
‘reasonably known,’ and ‘reasonably suggests’…may lead to
an incorrect reportability decision…
b. …does not establish internal systems that provide for a
standardized review process... For example, there are no
instructions for conducting a complete investigation of each
event and evaluating the cause of the event. The procedure,
as written, does not specify who makes the decision for
reporting events to FDA...”

18. 18
 ''Become Aware''
 Generally speaking, manufacturers are considered to have "become
aware" of an MDR reportable event when "any employee" becomes
aware of it. (21 C.F.R. § 803.3(b))
 MDR reports typically are due to FDA within 30 days of the "become
aware" date. (21 C.F.R. § 803.50(a))
 Firms frequently miss reporting deadlines due to:
 Waiting until complaint information reaches the regulatory
department before starting the ''MDR clock.“
 Delays in receiving complaint information from
contractors/consultants.
 Lack of contingency planning -- internal timelines should be tighter
than regulatory requirements so as to ensure that reporting deadlines
are met.
 Lack of resources to evaluate and process sources of information for
potentially reportable information.
Common Pitfall:
Missing Reporting Deadlines

19. 19
Warning Letter Example
“[O]n July 27, 2015, your firm became aware of an event
…Your firm did submit an MDR related to this event...,
received by FDA on September 23, 2015. However, this MDR
was not submitted within the required 30 calendar day reporting
timeframe. “

20. 20
 ''Caused or Contributed” means:
 A death or serious injury was or may have been attributed to a
medical device, or a medical device was or may have been a factor
in a death or serious injury, including events occurring as a result of:
 Failure;
 Malfunction;
 Improper or inadequate design;
 Manufacture;
 Labeling; or
 User Error. (21 C.F.R. § 803.3(c))
 Firms sometimes:
 Overlook the “contributed” portion of “caused or contributed.”
 Disregard “user error.”
 Take at face value a physician's statement that the device did not
"cause or contribute," without independently confirming.
Common Pitfall:
Misinterpretation of “Caused or Contributed”

21. 21
 "Serious Injury“ means
 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. (21 C.F.R. § 803.3(w))
 Firms sometimes focus only on whether the patient or user actually
died or was badly hurt, and neglect to consider whether
medical/surgical intervention was performed to prevent a death or
serious injury.
Common Pitfall:
Incomplete Understanding of “Serious Injury”

22. 22
Warning Letter Example

23. 23
 ''Malfunction”
 The failure of a device to meet its performance specifications or
otherwise perform as intended.
 Performance specifications encompass not only technical operating
specifications, but also include all claims made in the labeling for the
device.
 Intended performance refers to intended use for which the device is
labeled or marketed. (21 C.F.R. § 803.3(k))
 A malfunction is reportable if, upon recurrence, the device or a
similar device marketed by the manufacturer would be likely to
cause or contribute to a death or serious injury. (21 C.F.R. §
803.50(a)(2))
Common Pitfall:
Improper “Malfunction” Analysis

24. 24
 Frequent issues include:
 Assessing the likelihood that a malfunction will recur, rather than
assuming the malfunction will recur, as is required by the
regulation.
 Failing to report a malfunction because there was no patient
involvement.
 Failing to recognize how conservative FDA can be in deciding
that the recurrence of a malfunction is "likely" to cause or
contribute to death or serious injury.
Common Pitfall:
Improper “Malfunction” Analysis (cont’d)

25. 25
 FDA reiterated criteria included in the Draft Guidance describing when
a malfunction is reportable because it would likely cause or contribute
to a death or serious injury if it were to recur.
 Malfunction is reportable if any of the following is true:
 Chance of death or serious injury occurring is “not remote”;
 Malfunction affects the device in a “catastrophic manner” that may
lead to death or serious injury;
 Malfunction results in failure of the device to perform its essential
function and compromises the device effectiveness, which could
cause or contribute to death or serious injury;
 Malfunction involves long term implant or device that is life-supporting
or life-sustaining;
 Manufacturer takes, or would be required to take, action under
section 518 (mandatory recalls) or 519(g) (reportable correction or
removal)
Final MDR Guidance on Reportable Malfunctions

26. 26
Warning Letter Example
“Your firm became aware of two events…that associate your
firm’s device…with a malfunction…There is no evidence to
justify whether the malfunctions would not be likely to cause
or contribute to a death or serious injury, if they were to recur.
Your firm did not submit MDR reports within 30 days of
receiving…the referenced events.”

27. 27
 Background:
 1997 Guidance: once a malfunction had caused or contributed to
a death or serious injury, FDA would presume that the
malfunction was likely to cause or contribute to a death or serious
injury until two years had passed during which the malfunction
did not contribute to a death or serious injury.
 Draft Guidance: eliminated the two-year period for lifting the
presumption, recommending that manufacturers file MDRs
indefinitely for reports of that malfunction unless FDA approved
an exemption from further reporting of the malfunction.
 Final Guidance restores the so-called “Two Year Rule,” but with a
new notification procedure.
Final Guidance: FDA Reintroduces “Two-Year Rule”

28. 28
 If a manufacturer wishes to cease reporting at the end of two years:
 Should submit “notification to FDA with a summary of the data and
rationale to cease reporting at the end of two years.”
 Do not need to wait for FDA’s response before stopping reporting,
but FDA may request additional information.
 If a manufacturer wishes to cease reporting before end of two years:
 Should request an exemption under 21 C.F.R. § 803.19(d).
 The firm should continue reporting to FDA until the agency
responds and grants the exemption request.
 A manufacturer could consider requesting such an exemption if
data suggest that the malfunction has not “caused or contributed
to” further deaths or serious injuries and that “the likelihood of
another death or serious injury” due to the malfunction is remote.
Final Guidance: FDA Reintroduces “Two-Year Rule”

29. 29
 A supplemental report must be submitted when required
information is received that was not known or not available at the
time the initial MDR report was submitted.
 Supplemental reports must be submitted within 30 days of a
manufacturer's receipt of the new information. (21 C.F.R. §
803.56).
 Firms sometimes neglect to submit supplemental reports due to:
 An incorrect belief that their reporting obligations end with the
submission of the initial report.
 Lack of processes/procedures to ensure that newly obtained
information is assessed for reportability.
Common Pitfall:
Failure to Submit Supplemental Reports

30. 30
Warning Letter Example
“Your firm’s MDR procedure does not establish internal systems
that provide for timely transmission of complete MDRs.
Specifically, the circumstances under which your firm must
submit supplemental or follow-up reports and the requirements for
such reports are not addressed.”

31. 31
 Frequent issues include:
 Failing to include all required information.
 Inconsistencies within the MDR report and with related
documents.
 Use of speculative/emotional language.
Common Pitfall:
Failure to Properly Complete the MedWatch Form

32. 32
Warning Letter Example
“[Y]our firm submitted 33 MDRs to the FDA that did not
identify the "Date of event" in Block B3 of the FDA Form
3500A. In addition, your firm did not include in Block H11-
"Corrected data", of the associated 3500A forms, an explanation
of why the required information was not provided and the steps
taken to obtain such information.”

33. 33
 Over time, firms tend to make reportability decisions without
referring back to the regulations.
 These faulty decisions are then relied upon as precedent,
resulting in more faulty decisions.
Common Pitfall:
"Regulatory Drift"

34. 34
 Of the Warning Letters issued by CDRH in 2016, more than 25%
addressed MDR-related violations.
 The most common issues related to MDRs included:
 Inadequacies in the manufacturer’s written MDR procedures.
 Failure to submit an MDR report within reporting deadlines.
 Examples of other deficiencies cited include:
 Failure to submit MDR reports for device-related deaths/serious
injuries and reportable malfunctions.
 Failure to submit MDR reports for MDR Reportable Events
occurring outside the United States.
Enforcement Trends

35. FDA’s Final Rule on Adverse Event Reporting for
Combination Products

36. 36
 Combination products
 A product comprised of two or more regulated components
(device/drug);
 Two or more separate products packaged together in a
single package;
 Two or more separate products intended for use (by
labeling) for use together, and where both are necessary to
achieve the intended use, indication, or effect and where
upon approval of the proposed product the labeling of the
approved product would need to be changed.
(21 C.F.R. Part 3.2(e))
 Combination products pose unique challenges for adverse
event reporting – when an event arises, what standards and
rules apply for reporting?
Safety Reporting for Combination Products

37. 37
 On December 20, 2016 FDA issued a final rule setting
forth the postmarket safety reporting requirements for
combination products.
 The agency had previously issued a proposed rule in
2009.
 New rule codified at 21 C.F.R. §§ 4.100 to 4.105.
 The final rule became effective on January 19,
2017. But the compliance date is 18 months from the
publication date for certain requirements.
 Overarching framework: Combination products are
subject to the reporting requirements applicable to the
type of application under which the product is marketed,
plus a few additional requirements.
Final Rule for Combination Product Reporting

38. 38
 The final rule is structured around the following two new
definitions:
 “Combination product applicant” defined as “an applicant
that holds the application(s) for a combination product.”
 E.g., drug eluting stent, PMA holder = combination product
applicant.
 “Constituent part applicant” defined as “the applicant for a
constituent part of a combination product the constituent
parts of which are marketed under applications held by
different applicants.”
 E.g., implantable pump + drug. If each are marketed under
different applications (PMA + NDA) and held by different
applicants, each is a constituent part applicant.
Key Definitions

39. 39
 Basic reporting requirements: Constituent part applicants are
subject to the reporting requirements applicable to the constituent
part (e.g., a drug constituent part is subject to reporting under 21
C.F.R. Part 314).
 Information sharing requirement: Constituent part applicants must
also submit adverse event information to the other constituent part
applicant(s) for the combination product within 5 days of receiving
the information.
 Recordkeeping requirement: Constituent part applicants must
maintain records relating to the information shared with other
constituent part applicants.
Constituent Part Applicants

40. 40
 Combination product applicants are subject to the
reporting requirements applicable to the type of
application for the combination product:
 Combination products approved under an NDA are
subject to 21 C.F.R. Part 314.
 Combination products approved under a PMA are
subject to 21 C.F.R. Part 803.
 Combination product applicants are also subject to
additional specific reporting requirements depending on
the constituent parts.
Combination Product Applicants

41. 41
Device Applications Requirements in Addition to Parts 803 and 806
Drug-device combination
product marketed under
device application
 Field alert reports under 21 C.F.R. § 314.81
 15-day reports and follow-up reports described in 21 C.F.R. §
314.80(c), but submitted within 30 days and in accordance with
21 C.F.R. § 803.12(a)
 Reports as specified by the Agency in notice to applicant
Combination Product Applicants
Drug Applications Requirements in Addition to 21 C.F.R. Part 314
Drug-device combination
product marketed under
NDA or ANDA
 5-day reports and follow-up reports described in 21 C.F.R. §§
803.53 and 803.56
 Malfunction reports and follow-up reports described in 21 C.F.R.
§§ 803.50 and 803.56
 Correction or removal reports and records under 21 C.F.R. §§
806.10 and 806.20
 Periodic report under 21 C.F.R. § 314.80(c)(2) must include
summary of 5-day reports and malfunction reports

42. Thank You!
Questions?