Getting your device approved or cleared by FDA is a critical step, of course, but it's only the beginning of your relationship with US federal regulatory agencies. Specifically, this presentation will cover: -What you should know about FDA inspections -An overview of Quality System Inspection Techniques (QSIT) -QSR and design issues that may surface in the domestic production or importation of devices or components -Understanding the intersection between FDA and US Customs -What does you company need to do if things do go wrong with FDA You can watch the presentation here: https://www.greenlight.guru/webinar/life-with-fda-after-clearance

1. You've gained FDA market clearance
…
…
Now what?
Presented by: Thomas C. Knott John F. Johnson III
Senior Regulatory Advisor Senior Associate Attorney
FDAImports.com Benjamin L. England & Associates

2. Today’s Agenda
Introduction …………………………………………………………… 5 min.
Basics of FDA Regulatory Regime …………………………… 10 min.
FDA’s Facility Inspection and QSRs …………………………. 20 min.
FDA’s Import Regime and the
Appearance Standard …………………………………….. 10 min.
Concluding Thoughts and Questions ……………………… 15 min.

3. About the Presenters
Thomas C. Knott provides
regulatory assistance to companies of all
sizes through his role as a Senior
Regulatory Advisor with
FDAImports.com, LLC. His work with
clients ranges from FDA pre-market steps
to device and biologics labeling and
developing Quality Systems for
manufacturers.
Mr. Knott has over 30 years of experience
at FDA serving in a wide range of
capacities at the Agency’s Districts,
Headquarters, and the Center for Devices
and Radiological Health (CDRH) including
as a Branch Chief in the Office of
Compliance in CDRH.
John F. Johnson III, Esq.
practices FDA and Customs law at
Benjamin L. England & Associates, LLC
with a focus on integration of the two
agencies’ regulatory compliance
requirements, and has extensive
experience with representing FDA-
regulated clients before FDA, USDA,
Customs and other regulatory agencies.
Mr. Johnson aptly deals with FDA
Compliance Officers, Headquarters
Officials, Customs Officials, laboratories,
warehouses, and brokers to remove
obstacles at every step along the way, thus
minimizing the risk of FDA scrutiny and
enforcement action.

4. Work so hard for

5. But that’s just the beginning
Taken from Sally A. Hoyvat, Issues in Clinical Trial Design for Companion Diagnostic Devices

6. FDA regulation of devices
• Is it safe [and effective]? Not “adulterated”
• Is it labelled appropriately? Not “misbranded”

7. What if Non-compliant
• Form FDA 483, Inspectional Observations
• Administrative Enforcement
• Warning Letters or Untitled Letters
• Recall (voluntary, recommended, mandatory)
• Import refusal and import alerts
• Judicial Enforcement
• Seizure
• Injunction
• Prosecution
• Civil money penalties

8. FDA’s surveillance tools
• Inspecting a facility
• Inspecting an import shipment
• Reviewing
• labeling, promotions, and advertising
• recalls and market withdrawals
• trade and consumer complaints
• Medical Device Reporting (MDRs)
• Conducting sample analysis

9. The Facility Inspection

10. The FDA Inspection
• Class II and III devices inspected every 2 years
• FDA Investigator will inspect:
• Quality System (21 CFR 820)
• Medical Device Reporting (21 CFR 803)
• Corrections and Removals/Recalls (21 CFR 806)
• Device Tracking (very few firms)
• Sterilization
• Registration and Listing
• Imports/Exports
• Significant changes in manufacturing/device
• Correction of any previous observations

11. Quality System Inspection
Technique
• Knowing FDA’s plan is a key to preparation
• “CAPA plus” approach
• FDA CSO always looks at CAPAs and complaints
• CSO will follow the trail to the root problem
• What do you do when things go wrong?

12. Quality System Inspection Technique

13. Quality System
• Management Controls
• CAPA/Complaints/MDR/Reports of C&R/Medical
Device Tracking
• Design Control
• Production and Process
Control/sterilization/calibration/validation
• Others
• Records/Documents/Change controls
• Material Controls/Purchasing Controls/Acceptance
Activities
• Facility and Equipment Controls

14. Management Controls
• Commitment permeates all systems
• Establish quality policy and planning
• Establish an adequate organization
• Provide sufficient resources
• Train sufficient personnel
• Ongoing quality audits and reviews
• Appoint a management representative

15. Corrective and Preventive Action
• Constantly analyze/trend
• Detect nonconformity/quality problem
• Investigate the (root) cause
• Identify actions to correct and prevent
• Verify/validate actions
• Implement changes
• Communicate changes
• Management review
• Document
• Appropriate statistical methodology

16. Complaint Files
• Formally designated unit
• Receive, review, evaluate all complaints
• Evaluate for Medical Device Reporting
• Investigate possible failures of the device, labeling, or
packaging to meet specifications
• Document

17. Medical Device Reporting
• Within 30 calendar days of becoming aware
• Report incidents that reasonably suggest that your
device:
• May have caused or contributed to a death or serious
injury
• Malfunctioned and could cause death or serious injury if
it happens again
• Document

18. Corrections and Removals
• Correction - without removing device
• Labeling change
• Removal – remove from its point of use
• C or R to reduce the risk to health; violative
• Report to FDA within 10 working days
• Device recalls
• Class I, II or III recalls
• Risk – severity and probability of occurrence
• Health Hazard Evaluation

19. Design Control
• Is design control used to evaluate changes in the
device that might arise from a CAPA, Recall/C&R,
complaint investigation?
• Design change procedure
• Verification/validation
• Risk management
• New 510(k) required?
• Document

20. Production and Process Controls
• SOPs for production control
• Change procedure
• Environmental control
• Personnel practices
• Contamination control
• Buildings
• Equipment
• Automated processes

21. Production and Process Controls
• Calibration
• Process validation

22. Inspectional Observations
Inspections ending between 10/1/2015 and 9/30/2016
ISSUES 21 CFR REGULATION Rank
Reg Combine
HANDLING
PROBLEMS
820.100 CAPA 1
1820.198 Complaints* 3
820.90
Nonconforming
Product**
6
MANUFACTURING
820.70 P&PC 4
2820.72 Calibration 13
820.75 Validation 7
PRODUCT CHANGES 820.30 Design Control 2 3
*Additionally Medical Device Reporting
**Additionally Corrections and Removals
934 FDA 483s for 2027 class II and III inspections

23. Since FDA will look at CAPAs and
Complaints:
• Create strong CAPA/complaint processes:
• Review at management reviews and meetings
• Capture all applicable sources of quality
• Investigate/determine root cause
• Act timely/document extended time frames
• Allot sufficient resources
• Address root cause with corrective/preventive action(s)
• Perform a risk analysis
• Verify/validate actions in light of risk analysis

24. Import Inspections
and Consequences

25. Section 801(a)
The Secretary of the Treasury shall deliver to the Secretary of Health and Human Services, upon his request, samples of food, drugs, devices, tobacco
products, and cosmetics which are being imported or offered for import into the United States, giving notice thereof to the owner or consignee, who
may appear before the Secretary of Health and Human Services and have the right to introduce testimony. The Secretary of Health and Human
Services shall furnish to the Secretary of the Treasury a list of establishments registered pursuant to subsection (i) of section 360 or section 387e(h)
of this title and shall request that if any drugs, devices, or tobacco products manufactured, prepared, propagated, compounded, or processed in an
establishment not so registered are imported or offered for import into the United States, samples of such drugs, devices, or tobacco products be
delivered to the Secretary of Health and Human Services, with notice of such delivery to the owner or consignee, who may appear before the
Secretary of Health and Human Services and have the right to introduce testimony. If it appears from the examination of such samples or otherwise
that (1) such article has been manufactured, processed, or packed under insanitary conditions or, in the case of a device, the methods used in, or the
facilities or controls used for, the manufacture, packing, storage, or installation of the device do not conform to the requirements of section 360j(f) of
this title, or (2) such article is forbidden or restricted in sale in the country in which it was produced or from which it was exported, or (3) such article
is adulterated, misbranded, or in violation of section 355 of this title or the importer (as defined in section 384a of this title) is in violation of
such section 384a of this title, or prohibited from introduction or delivery for introduction into interstate commerce under section 331(ll) of this title,
or (4) the recordkeeping requirements under section 2223 of this title (other than the requirements under subsection (f) of such section) have not
been complied with regarding such article, then such article shall be refused admission, except as provided in subsection (b) of this section. With
respect to an article of food, if importation of such food is subject to, but not compliant with, the requirement under subsection (q) that such food be
accompanied by a certification or other assurance that the food meets applicable requirements of this chapter, then such article shall be refused
admission. If such article is subject to a requirement under section 379aa or 379aa–1 of this title and if the Secretary has credible evidence or
information indicating that the responsible person (as defined in such section 379aa or 379aa–1 of this title) has not complied with a requirement of
such section 379aa or 379aa–1 of this title with respect to any such article, or has not allowed access to records described in such section 379aa or
379aa–1 of this title, then such article shall be refused admission, except as provided in subsection (b) of this section. The Secretary of the Treasury
shall cause the destruction of any such article refused admission unless such article is exported, under regulations prescribed by the Secretary of the
Treasury, within ninety days of the date of notice of such refusal or within such additional time as may be permitted pursuant to such regulations,
except that the Secretary of Health and Human Services may destroy, without the opportunity for export, any drug refused admission under this
section, if such drug is valued at an amount that is $2,500 or less (or such higher amount as the Secretary of the Treasury may set by regulation
pursuant to section 1498(a)(1) of title 19) and was not brought into compliance as described under subsection (b)..[The Secretary of Health and
Human Services shall issue regulations providing for notice and an opportunity to appear before the Secretary of Health and Human Services and
introduce testimony, as described in the first sentence of this subsection, on destruction of a drug under the sixth sentence of this subsection. The
regulations shall provide that prior to destruction, appropriate due process is available to the owner or consignee seeking to challenge the decision
to destroy the drug. Where the Secretary of Health and Human Services provides notice and an opportunity to appear and introduce testimony on
the destruction of a drug, the Secretary of Health and Human Services shall store and, as applicable, dispose of the drug after the issuance of the
notice, except that the owner and consignee shall remain liable for costs pursuant to subsection (c). Such process may be combined with the notice
and opportunity to appear before the Secretary and introduce testimony, as described in the first sentence of this subsection, as long as appropriate
notice is provided to the owner or consignee. Clause (2) of the third sentence of this paragraph shall not be construed to prohibit the admission of
narcotic drugs the importation of which is permitted under the Controlled Substances Import and Export Act [21 U.S.C. 951 et seq.].

26. That’s ugly
• 1 paragraph with 11 sentences using a total of ~850 words
• Practically speaking:
• FDA can examine any device shipment.
• Owner and consignee has the right to introduce testimony as to
compliance
• Based on FDA’s examination or otherwise the product appears to
violate the Act, then FDA shall refuse it
• This is an in rem action

27. Detention
• Importer/consignee given notice that it appears the article
is subject to refusal (appears that it appears non-
compliant…)
• At this stage, FDA refers to the product being “detained,” a
word that does not appear in FDCA or CFR.
• In formal hearing where importer can submit testing as to
compliance
• Failure to respond will result in a default judgment of sorts

28. Release, recondition, or refusal
• Release: Detention an error, or issues resolved (like
registration/listing)
• Recondition: Fixed the problem
• Refusal: Continues to appear violative

29. Enforcement – Customs Bond
• To import, the importer must file a bond with
Customs, which should be of a value to cover 3x
the value of the goods
• Failure to redelivery or do it appropriately, FDA will
instruct Customs to collect “liquidated damages”

30. Bans and restrictions: Import Alerts
• “or otherwise” strikes back – import alerts
• Burden shifts essentially: product subject to refusal
unless the importer can provide testimony as to
compliance (usually testing)
• There are per se bans where no testimony will
persuade FDA (a failed FDA facility inspection)

31. Imports in Practice
Taken from Jessica Aranda & Gayle Gehrman, Importing FDA-Regulated Products in ACE

32. Considerations
• Know why you are importing the product
• Make sure the documents are clear and concise
• Actively track any import holds and detention
• Don’t ignore import detentions

33. Concluding Thoughts

34. •The best defense is a good offense
• Ensure that you have a robust compliance program
• Ensure that you respond to nonconformities/quality
issues; timely and effectively
• Ensure that you deal with nonconforming product
• Do what you require (don’t shoot yourself in the foot)
• Complete change processes
• Document, document, document
• Make your quality policy visible

35. Questions?