FDA Regulations and Medical Device Pathways to Market | Kevin Daly | Lunch & Learn

FDA Regulations and Medical
Device Pathways to Market
Kevin Daly Consulting, LLC
October 28, 2016

Kevin Daly Consulting, LLCOctober 28, 2016 2
Determining Regulatory Requirements
• Definition of a Medical Device
– An instrument, apparatus, implement, machine, contrivance, implant, in
vitro reagent, or other similar or related article, including a component part,
or accessory which is:
• Recognized in the official National Formulary, or the United States
Pharmacopia, or any supplement to them,
• intended for use in the diagnosis of disease or other conditions,
or in the cure, mitigation, treatment, or prevention of disease, in man or
other animals, or
• intended to affect the structure or any function of the body of man or
other animals, and which does not achieve its primary intended
purposes through chemical action within or on the body of man or
other animals and which is not dependent upon being metabolized
for the achievement of any of its primary intended purposes.

• Step 1 - Define “Intended Use” and “Indications for Use”
– Example: A scalpel’s Intended Use is to cut tissue, and may have
Indications for Use for “for making incisions in the cornea”
• Step 2 - Find FDA Regulation Number and Product Code
– Find matching description of the device and its Intended Use in Title 21 of
the Code of Federal regulations (CFR) Parts 862-892, or FDA “Product
Code” database
• FDA has classified and assigned regulation numbers to over 1,700
distinct types of devices within 16 medical specialties

– Description will include:
• Device class (i.e. Class I, II, or III), and
– Information about premarket requirements (i.e. 510(k) exempt,
510(k) required, PMA required)
– GMP requirements of QSR (Quality System Regulation) - exempt
or non-exempt
862 = Chemistry/Toxicology
864 = Hematology/Pathology
866 = Immunology/Microbiology
868 = Anesthesiology
870 = Cardiovascular
872 = Dental
874 = Ear, Nose and Throat
876 = Gastro/Urology
878 = General Plastic Surgery
880 = General Hospital
882 = Neurological
884 = Obstetrical/Gynecological
886 = Ophthalmic
888 = Orthopedic
890 = Physical Medicine
892 = Radiology
21 CFR Sections within 16 Medical Specialties

• Step 3 - Find information on previously cleared/approved
devices
– FDA maintains databases listing all previously cleared/approved devices
– 510(k) Summary or PMA Summary of Safety and Effectiveness provide
helpful information as to the required data submission requirements for
new devices
• If no appropriate match can be found
– Submit 513(g) Request for Information to the FDA
• FDA will respond within 60 days as to the risk classification and other
requirements of the FD&C act
• FDA responses DO NOT constitute FDA clearance or approval for
distribution

FDA Medical Device Regulatory Requirements
• Class I device requirements
– Typically exempt from Premarket Notification (510(k)) submission
requirements
– Subject to “General Controls” (i.e. provisions that relate to adulteration,
misbranding, facility registration and device listing, records and reports,
recall reporting, adverse event reporting, custom devices, and good
manufacturing practices)
– Exempt from compliance with design controls (21 CFR 820.30), except for
devices with “automated with computer software”
– May or may not be exempt from GMP requirements of QSR
• All Class I sterile medical devices are not exempt from the GMP
requirements of the QSR (all provisions except design controls)

• Class II device requirements
– Most require Premarket Notification (510(k)), but some are exempt
– Full compliance with QSR (including design controls)
• Register manufacturing facility and list devices within 30 days after
510(k) clearance
• Class III device requirements
– Most require Premarket Approval (PMA)
– Full compliance with QSR (including design controls)
• FDA facility pre-inspection required before distributing first device

510(k) Submissions
• What “510(k)” means
– Refers to Section 510(k) of the Food, Drug, and Cosmetic Act
– Regulations defined in 21 CFR §807 Subpart E
– Must demonstrate that new device is “substantially equivalent” to a
predicate (legally marketed in U.S.) device
• 3 types: Traditional, Abbreviated, Special
– Traditional – for any “original” 510(k), or modification to a previously
cleared device
• FDA clearance typically in ~4-6 months
– Abbreviated – use data summaries showing compliance with FDA
recognized consensus standards and guidance documents
• FDA clearance typically in ~4-6 months
– Special – for a modification to a device that has been previously 510(k)
cleared
• Uses summary information from design control process as basis for
clearance
• Faster clearance times (~30 days)

510(k) Submissions
• What is Substantial Equivalence (SE)?
– Demonstration that a new device, as compared to a predicate device,
has…
• The same intended use and
• The same technological characteristics, or
– that differences in technological characteristics do not raise
different questions regarding safety and effectiveness.
• What is a Predicate Device?
– A legally marketed device, previously cleared through the 510(k) process
(mainly), that is used for comparison to a new device for the purpose of
determining substantial equivalence (21 CFR 807.92(a)(3)).
• When is a 510(k) Typically Required?
– Introducing a device to the market for the first time
– Changing the indications for use of a previously cleared device
– Making significant modification(s) to a previously cleared device

10Kevin Daly Consulting, LLCOctober 28, 2016
1. Medical Device User Fee Cover
Sheet (Form FDA 3601)
2. CDRH Premarket Review Submission
Cover Sheet
3. 510(k) Cover Letter
4. Indications for Use Statement
5. 510(k) Summary or 510(k) Statement
6. Truthful and Accuracy Statement
7. Class III Summary and Certification
8. Financial Certification or Disclosure
Statement
9. Declarations of Conformity and
Guidance Documents
10. Executive Summary
11. Device Description
12. Substantial Equivalence
Discussion
13. Proposed Labeling
14. Sterilization and Shelf Life
15. Biocompatibility
16. Software description
17. Electromagnetic Compatibility and
Electrical Safety
18. Performance Testing – Bench
19. Performance Testing - Animal
20. Performance Testing - Clinical
510(k) Submissions
20 Elements (not trivial):

510(k) Submissions
• 510(k) Test Data
• Typically requires side-by-side testing to predicate device unless an FDA
recognized consensus standard or device-specific FDA guidance document
exists
• Need statistically valid sample size
• 510(k)s typically 100-200 pages long
• Includes completion of 24-page FDA “Acceptance Checklist”
• FDA will refuse to accept if information missing
• Reusable devices
• Manufacturer must validate cleaning, disinfection, and sterilization
procedures
• Duodenoscope infections and deaths have heightened FDA validation
requirements

510(k) Submissions
• Upon FDA receipt
– By day 7 – FDA acknowledgement letter
– By day 15 – FDA conducts “Acceptance Review”
– By day 60 – FDA conducts “Substantive Review”
• Requests for minor additional information frequently by email
• Requests for major additional information – FDA sends deficiency
letter, and 510(k) review is placed on hold
– By day 90 – FDA sends final decision, or
– By day 100 – FDA provides “Decision Communication” identifying
outstanding issues.

Other FDA Market Clearance Pathways
• De Novo Submission (21 CFR §513(a)(1)) of FD&C Act
– Entirely new devices automatically considered Class III
– Includes devices of low risk
– File de novo submission for marketing approval as Class I or II device
– Must contain all known information on safety and efficacy of the device
– When approved, may serve as a “predicate” device for future 510(k)
submissions.
– Average time to complete FDA review is ~1 year
– No FDA user fee

Other FDA Market Clearance Pathways
• Humanitarian Device Exemption (“Orphan Device”)
– Applies if intended to treat a disease in <4,000 patients annually
– No comparable device currently available
– Similar to PMA (clinical trials needed)
– Must demonstrate safety and “probable benefit” (as opposed to safety and
“efficacy”)
– Long approval times (~1-1.5 years)
• Premarket Approval (PMA) Application
– Required for highest risk (Class III) devices
– Large clinical studies normally required
– Must demonstrate device safety and “effectiveness”
– FDA “approves” or “disapproves” the PMA
– Long approval times (~1-1.5 years)

FDA Pre-Submissions
• FDA Q-Sub (Request for Pre-Submission meeting)
– Relatively new opportunity to obtain FDA input on adequacy of bench,
animal, and clinical test protocols
– Highly valuable for obtaining confirmation of adequacy of planned bench,
animal, and/or clinical trials
– No user fee
– FDA meeting, teleconference, or written reply within ~90 days
– FDA response does not provide marketing clearance; for information only

Quality System Requirements
• Class I devices – if exempt from GMPS
– Subject to compliance with FDA “General Controls”, “General
Controls”
• Adulteration
• Misbranding
• Facility registration and device listing
• Recalls
• Unique device identifier (UDI)
• Class I devices – if not exempt from GMPS
– Comply with “General Controls” and all GMP elements of Quality
System Regulation (21 CFR §820), except (unless specified) Design
Controls (21 CFR §820).

21 CFR §820 – Early Development Requirements
• 820.30 Design Controls
– Applicable to all class II and III and the following class I devices
– Describe design and development activities
– Design input
• Note: Standard practice is to initiate a Risk Analysis early in the
design and development process in accordance with ISO 14971
– Design output
– Design review
– Design verification
– Design validation

21 CFR §820 – Quality System Regulation
Why Design Controls?
How the Customer
Explained it
How the Project
Manager
Understood It
How R&D
Designed It
What the Customer
Really Needed

19Kevin Daly Consulting, LLCOctober 28, 2016
IDE (Investigational Device Exemptions)
• 21 CFR §812 Investigational Device Exemptions (IDEs)
– Requirement for conducting clinical trials
– 2 Types of IDEs
• Significant Risk (SR) IDE – Requires FDA pre-approval (30 days)
• Non-Significant Risk (NSR) IDEs – Requires only Institutional Review
Board (IRB) approval
– IDE Sponsor (e.g. Company) determines risk
– If IRB disagrees and believes is significant risk study, Sponsor
must report to the FDA

FDA Regulation of Medical Device Apps (MMAs)
• Mobile Application is a “Medical Device” if it:
– Is used as an accessory to an already-approved medical device
– Transforms a mobile device such as a smartphone or tablet into an actual
medical device providing diagnostic or therapeutic assistance
• Will my medical mobile app be regulated as a medical
device?
– Key FDA Guidance at:
http://www.fda.gov/downloads/MedicalDevices/.../UCM263366.pdf
– States: When the intended use of a mobile app is for the diagnosis of
disease or other conditions, or the cure, mitigation, treatment, or
prevention of disease, or is intended to affect the structure or any function
of the body of man, the mobile app is a device.

• Examples of MMAs Regulated by the FDA
– Sensor connected to mobile platform to measure and display
electrocardiograph (ECG)
– Use accelerometer to measure degree of tremor caused by certain
diseases.
– Use sensor to monitor physiological parameter (e.g. limb movement,
electrical activity during sleep) for use in diagnosing disease or conditions
such as sleep apnea.
– App as attachment to mobile platform to measure blood glucose levels

• Examples of MMAs NOT Regulated by the FDA
– Medical dictionaries or encyclopedias of first-aid or emergency care
information
– Apps used for medical training (e.g. anatomy diagrams, games that
simulate cardiac arrest scenarios for health professional training
– Help manage shifts for doctors or manage schedules
– Tools, quizzes, games, questionnaires to help patient general health and
wellness (e.g. calorie consumption, benefits of physical activity)
– Provide information about gluten-free food products or restaurants

• Examples of MMAs With FDA “Enforcement Discretion”
– MMAs meet regulatory definition of “device” but pose minimal risk
– From FDA Guidance Document and
http://www.fda.gov/MedicalDevices/DigitalHealth/MobileMedicalApplication
s/ucm368744.htm
• Track a normal baby’s sleeping and feeding habits
• Educational reminders or motivators to smokers trying to quit
• Track asthmatics inhaler usage
• Allow patient to collect, track, and share trend data such as blood
pressure, blood glucose with health care provider or upload to online
database
• Allow patient or caregiver to call pre-specified emergency call center
• Lists of signs and symptoms on when to consult a health care provider

• What to do when unsure…
– There is no definitive list
– Check FDA website for new guidance documents (key words: “mobile
medical applications”)
– 513(g) request for classification information ($1,583 for small business)
• Other Issues to consider
– FDA guidance documents on software design and validation
– FDA guidance on cybersecurity
– FDA guidance on human factors and usability
– AAMI ANSI IEC 62304:2006 - Medical Device Software - Software Life
Cycle Processes
– IEC 60601-1 requirements for Programmable Electrical Medical Systems
– Other (biocompatibility, sterilization, packaging, labeling, etc.)

Thank you!
Questions?
Email: kevinedaly@gmail.com

FDA Regulations and Medical Device Pathways to Market | Kevin Daly | Lunch & Learn

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