Module 1 - FDA Overview.pdf

Medical Device Regulation and
the Food and Drug Administration:
What is it trying to Achieve?
Medical Device Regulatory Purpose, Overview
and Regulatory Structure
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BME 4803 "Regulatory and Quality Issues in
Medical Device Design"

The FDA: Overview & Regulatory Structure
Questions to Answer:
1. What is Medical Device Regulation trying to achieve?
2. What gives the FDA power to regulate Medical Devices?
3. How is the FDA organized?
4. What does the FDA consider be a Medical Device?
5. What does the FDA consider to be a Combination
Product?
6. What does “regulate” mean?
7. How does the FDA classify Medical Devices?
8. What are the pathways to regulatory approval?
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Outline
1. Ultimate Goal of Medical Device Regulation: Medical
Device Safety & Efficacy
2. The Framework to obtain this goal
3. What does the FDA do?
4. How does the FDA have the power to regulate Medical
Devices?
5. How is the FDA organized?
6. What is a Medical Device?
7. What is a Combination Product?
8. What does “regulate” mean?
9. How does the FDA classify Medical Devices?
10. What are the pathways to regulatory approval?
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Medical Devices: Striving for Safety & Efficacy
8/20/2022 4
BMED 4803 "Regulatory Issues in Medical
Device Design" ‐ Design Control Overview

What does the FDA do?
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How many people are employed by the FDA?
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What is Medical Device Regulation Trying to
Achieve? A Balance
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Patient
Safety
Device
Efficacy
Business
Risk:
Need profit to
bring device to
market/patients
Innovation:
new treatments
Risks:
1) Patient death/disability
2) Costly, non‐effective treatments
Risks:
1) No profit, no devices
2) Lack of innovation
also harms patients
Medical Device Regulation must:
• Protect patient health safety
• Ensure device efficacy
• Not impede device innovation
• Not impose too onerous
burden
Device
Manufacturer
Primary
FDA Primary

What gives the FDA power to regulate Medical
Devices?
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The FDA: History of Legislation
1902: Biologics Control Act –
• Passed to ensure purity and safety of
serums, vaccines, and similar products used to
prevent or treat diseases in humans.
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1906: Pure Food and Drug Act –
• Prohibited interstate transport of unlawful food and drugs
under penalty of seizure of questionable products and/or
prosecution of responsible parties.
• Contributing fact “The Jungle” by Upton Sinclair, describing
unhealthy sanitary conditions in meat packing industry
• Signed by President Theodore Roosevelt
1927: Regulatory name changed to the “Food, Drug and
Insecticide Agency”
1930: Agency named shortened to “Food and Drug
Administration” ‐ FDA
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1938: Food, Drug and Cosmetic Act –
• Cosmetics and Medical Devices under FDA
control
• Mandated pre‐market approval of all new
drugs; Manufacturer had to prove to FDA that a
drug was safe before it could be sold
• Prohibited false therapeutic claims for drugs
• Formally authorized factory inspections
• Device regulation limited to mislabeling; no
pre‐market safety review
• Signed by President Franklin D. Roosevelt
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1944: Public Health Service Act –
• Established certification of laboratories
• Expanded oversight of biologics
1968: Radiation Control for Health & Safety Act –
• Intended to minimize exposure to electronic product
radiation and intense magnetic fields
• Applied to radiation emitting products, e.g. X‐ray
machines, CT, MRIs microwave, ultrasound, etc.
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1970: Cooper Committee –
• Chaired by Theodore Cooper, MD (head of
NHLBI) to study need for medical device
legislation
• Introduced concept for risk‐based device
classification
• Recommended new legislation targeted at
devices separate from drugs
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1976: Medical Device Amendment of 1976 –
• Defines a Medical Device
• Establishes classifications of medical devices (I,II,III)
• Gives FDA authority to determine pre‐market safety of
medical devices
• Establishes 510k pre‐market approval
• Establishes Pre‐Market Approval (PMA) pathway for high
risk devices
• Authorizes FDA to define Good Manufacturing Practices
(GMP)
• Establishes adverse event reporting & allows FDA to ban
devices
• Sparked by large number of injuries to women by Dalkon
Intra‐uterine Device (IUD)
• Signed by President Gerald R. Ford
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1990: Safe Medical Devices Act –
• Authorizes FDA to levy civil penalties and recall devices
• Enables FDA to monitor device throughout its clinical
life under post‐approval controls ‐> post‐market
surveillance
• Enables FDA to require traceability of medical devices
• Created Humanitarian Use Device
(HUD)/Humanitarian Device Exemption (HDE) to encourage
device development for rare/orphan diseases and
conditions
• Defined Substantial Equivalence for 510k
• Signed by President George HW Bush
8/20/2022 15
BME 4803 "Regulatory and Quality
Issues in Medical Device Design"

1997: Food and Drug Administration Modernization
Act –
• Created “least burdensome” provision for pre‐market
review
• Permitted use of data from studies of earlier versions of
devices in premarket submissions for new versions of
device
• Increased patient access to investigational devices
• Created “De Novo” program for new low to moderate
risk devices to be classified I or II instead of automatically
being classified as a class III device
• Signed by President Bill Clinton
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2002: Medical Device Fee and Modernization Act‐
• Fees assessed to medical device manufacturers
• Establishes Office of Combination Products for
products that cross multiple FDA jurisdictions (e.g. drug
eluting stents)
•Current Good Manufacturing Practice (cGMP)
established to focus public health risks arising from
manufacturing, endure quality standards don’t impede
innovation
• Signed by President George W Bush
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2007: Food and Drug Administration
Amendment Act ‐
• Required all registration and listing performed
electronically
• Required FDA to establish Unique Device
Identification (UDI) for medical devices, i.e. all
medical devices require label with unique
identifier
• Signed by President George W Bush
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2012: Food and Drug Administration Safety
and Innovation Act ‐
• Created dire De Novo pathway of classification
to I,II without submitting 510k first
• Permitted FDA to work with foreign
governments to harmonize regulatory standards
• Expanded “least burdensome” principle to
premarket review
• Signed by President Barack Obama
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2012: Food and Drug Administration Safety and
Innovation Act ‐
• Increased HUD/HDE designation from 4,000 to
8,000 patients per year
• Expedited review program for breakthrough
devices
• Streamline process for exempting device from
510k requirement
• Codify process for recognition/non‐recognition of
standards (i.e. ASTM, ISO, etc.)
• Signed by President Barack Obama
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How is the FDA organized?
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FDA Overall Organization
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FDA CDRH Organization
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What does the FDA consider to be a Medical
Device?
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What is a Medical Device?
A Medical Device is anything that:
• diagnoses, cures, lessens, treats or prevents disease
• affects the function or structure of the body
• does NOT achieve primary intended purposes
through chemical action (i.e. not a drug or biologic)
Examples:
Elastic bandage, hearing aid, CT scanner, total joint
replacement, breast pump, microbial analyzer, cochlear
implant, pacemakers
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What does the FDA consider to be a
Combination Product?
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What is a Combination Product?
A Combination Product is defined by the FDA as:
1. A product comprised of two or more regulated
components, i.e. drug/device, biologic/device,
drug/biologic, or drug/device/biologic, that are
physically, chemically, or otherwise combined or
mixed and produced as a single entity
2. Two or more separate products packaged together in
a single package or as a unit and comprised of drug
and device products, device and biological products,
or biological and drug products
8/20/2022 27

What is a Combination Product? (Continued)
3. A drug, device, or biological product packaged
separately that according to its investigational plan or
proposed labeling is intended for use only with an
approved individually specified drug, device, or
biological product where both are required 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,
e.g. to reflect a change in intended use, dosage form,
strength, route of administration, or significant
change in dose
8/20/2022 28

What is a Combination Product? (Continued)
4. Any investigational drug, device, or biological product
packaged separately that according to its proposed
labeling is for use with another individually specified
investigational drug, device, or biological product,
where both are required to achieve the intended use,
indication or effect.
Examples:
drug‐eluting stent, nicotine patch, surgical mesh with
antibiotic coating, titanium spine cage with collagen
sponge and BMP2
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What does “regulate” mean?
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What does “regulate” mean?
The FDA regulates or controls many aspects of medical device
engineering, manufacturing, and monitoring, specifically:
1. Establishment Registration
2. Medical Device Listing
3. Premarket Safety/Efficacy Evaluation through
‐ Premarket Notification 510k
‐ Premarket Approval (PMA)
‐ Humanitarian Device Exemption (HDE)
4. Investigational Device Exemption (IDE) for clinical studies
5. Quality System Regulation (QSR) to impart quality in design
and manufacturing
6. Labeling Requirements
7. Medical Device Reporting and Postmarket Surveillance
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Establishment Registration
• All owners or operators of places of business (also
called establishments or facilities) that are involved in
the production and distribution of medical devices for
use in the United States are required to register annually
with the FDA.
• All registrations must be submitted electronically
• A fee of $3,313 (2014) must be paid
• Registration form is at:
http://www.fda.gov/MedicalDevices/DeviceRegulationan
dGuidance/HowtoMarketYourDevice/RegistrationandListi
ng/default.htm
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Medical Device Listing
Manufacturers and other establishments must
register their devices with the FDA:
• Establishments include manufacturers, contract
manufacturers, contract sterilizers, remanufacturers,
US manufacturers of export only devices
• All proprietary names under which the device is
marketed must be listed
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Premarket Safety and Efficacy Evaluation
All medical devices United States must be
approved by the FDA for safety and efficacy
prior to marketing and distribution. The path
by which a medical device is approved takes
one of three pathways:
1. Premarket Notification (510k)
2. Premarket Approval (PMA)
3. Humanitarian Device Exemption (HDE)
8/20/2022 34

Investigational Device Exemption (IDE)
An Investigational Device Exemption (IDE) allows an investigational device to be
used in a clinical study in order to collect safety and effectiveness data. It is most
often used to support a PMA or HDE, but may be required if clinical data is
needed for a 510k. The components of an IDE include:
• purpose of the study, including intended use of device
• Clinical Study protocol
• Risk analysis
• Description of device
• monitoring procedures
• Description of facilities used to manufacture, process, pack, sterilize, and store
device
• Institutional Review Board (IRB) approval
• informed consent from all patients
• labeling of device for investigational use only
8/20/2022 35

Quality System Regulation (QSR)
Quality System Requirements are requirements by the FDA that a system be in place to ensure
standards and reproducibility for activities related to producing the medical device, including
designing, purchasing, manufacturing, packaging, labeling, storing, installing, sterilizing, and
servicing the device. The components of such a system include:
1. Design Controls – including Design Reviews and a Design History File
2. Process Validation ‐ manufacturing
3. Personnel Education and Training
4. Buildings and Environment
5. Equipment and Calibration
6. Device Master Record – specifies standards for making the device
7. Document and Change Control
8. Purchasing and Acceptance Activities
9. Labeling
10. Product Evaluation
11. Packaging
12. Storage, Distribution, and Installation
13. Complaints
14. Servicing
15. Quality System Audits
8/20/2022 36

Labeling Requirements
Labeling includes all labels on the device as well as
descriptive and informational literature that accompany
the device:
1. Should include indications and contraindications for
use of the device
2. Should include schematics of device
3. Part of QSR
4. Should be able to withstand sterilization
5. If device is investigational, must state so on the
labeling
6. Labeling guidance document:
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/
GuidanceDocuments/UCM095308.pdf
8/20/2022 37

Medical Device Reporting (MDR)
• Requirement that incidents in which device contributed to
death or serious injury must be reported to the FDA
• Certain malfunctions must also be reported
• MDR is the mechanism to identify and monitor adverse
events, with the goal of detecting and correcting problems
in a timely manner
• Health professionals and consumers can also submit
reports of adverse events
8/20/2022 38

Additional Postmarket Requirements
• In addition to MDR, medical device manufacturers must, as part of
QSR, be able to track devices, and determine conditions for
manufacturer and release
• Manufacturers must register new establishments in which devices
are produced or distributed
• In addition, postmarket requirements may be put in place as part of
a PMA or HDE approval for high risk devices
• Devices with history of failure are subject to tracking, including
glenoid fossa prosthesis, mandibular condyle prosthesis, TMJ
prosthesis, Abdominal Aorta Aneurysm stent grafts, pacemaker
electrode, mechanical heart valves, implantable cerebellar stimulator,
implantable infusion pumps and silicone gel‐filled breast implants.
8/20/2022 39

How does the FDA classify Medical Devices?
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How does the FDA classify Medical Devices?
The Medical Device Amendment Acts of 1976
established three classes of Medical Devices:
1. Class I General Controls
‐ with exemptions
‐ without exemptions
2. Class II General and Special Controls
‐ with exemptions
‐ without exemptions
3. Class III General Controls & Premarket Approval
8/20/2022 41

Class I Devices
• Present a low risk of harm to the user and
are subject to general controls to protect the
user. Most are exempt from premarket
notification
• Examples: tongue depressors, arm slings,
hearing aids, breast pumps, microbial
analyzers, elastic bandages
8/20/2022 42

Class II Devices
• More complicated than Class I and require
special controls for guidance, standards, labeling,
performance standards, and postmarket tracking.
Require QSR. Typically don’t require clinical trials.
• Approval through 510k Premarket Notification
pathway
• Examples: powered wheelchairs, CT scanners,
bone void fillers, certain spine cages
8/20/2022 43

Class III Devices
• Sustain or support life, are implanted and/or present
potential unreasonable risk of illness or injury. Most devices
require Premarket Approval (PMA) or HDE if applicable.
Require special clinical investigations because general and
special controls are not adequate to assure safety and
effectiveness. Require QSR
• Approval through PMA or HDE
• Examples: mechanical heart valves, cochlear implants, all
combination products, artificial hearts, implantable weight
loss devices
8/20/2022 44

Determining the Classification of Your Device
• Need to know regulation number that is the device classification regulation
• To determine regulation number, go to the classification database and enter part
of device name
• Or, go to the listing for the device panel (medical specialty) and identify device and
corresponding regulation
• Each device has a Code of Federal Regulation (CFR) for example, for a clinical
mercury thermometer the CFR classification is:
21 CFR 880.2920 ‐ Clinical Mercury Thermometer
• You may get advice on classification at:
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevi
ce/default.htm
• You may see a listing of device panels (medical specialties) at:
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/Classify
YourDevice/ucm051530.htm
8/20/2022 45

Example CFR for Mercury Thermometer
• The example CFR entry for the Mercury Thermometer is shown below
• From the result, we see that it is a class II device that does not actually require
premarket notification 510k, its classification number is 21CFR880.2920
8/20/2022 46

Listing of Device Panels (Medical Specialty)
• Device regulation citation references the device panel (medical specialty)
• For example, mercury thermometer falls under “General Hospital Part 880”
8/20/2022 47

What are the pathways to regulatory
approval?
8/20/2022 48

Pathways to Regulatory Approval & Marketing
There are 4 pathways to regulatory
approval by the FDA:
1. Exempt
2. Premarket Notification (510k)
3. Premarket Approval (PMA)
4. Humanitarian Device Exemption
(HDE)
8/20/2022 49

Data Used to Support FDA Device Approval
8/20/2022 50
• Class II: Computational, Bench, Animal (typically)
• Class III: Computational, Bench, Animal, Human
• Computational: many scenario, realism uncertain; Bench: more
realism (forces, etc), not in vivo; Animal in vivo cell/tissue not
human age/species, etc; Human real deal, but expensive cannot
get as much information or as controlled as animal/bench

Exempt
• Most class I and a few class II devices are exempt from premarket
notification (510k)
• Specific exempt devices are:
‐ preamendment (pre 1976) devices not
significantly changed
‐ Class I/II devices exempted by regulation
• Examples: Stethoscope, Cast removal equipment, hearing aid, skull
plate screwdriver; see
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm
• Even exempt devices must be manufactured under QSR, be packaged
and labeled properly, have establishment listing, and medical device
listing
8/20/2022 51

Premarket Notification (510k)
• Each person who wants to market a class I, II, or III medical device in
the US, for which a PMA is not required, must submit a 510k unless that
device is 510k exempt
• A 510k is a premarket submission made to the FDA to demonstrate
that the device to be marketed is at least as safe and effective (i.e.
substantially equivalent) to a legally marketed medical device (known as
a predicate device) that itself is not subject to a PMA.
• Substantially Equivalent (SE) means
‐ has the same intended use and has the same
technological characteristics or
‐ has the same intended use and has different technological
characteristics but does not raise any new questions of safety and
effectiveness and demonstrates that the device is at least as safe
and effective as the predicate device
8/20/2022 52

Premarket Approval (PMA)
• FDA process of scientific and regulatory review to evaluate the safety
and effectiveness of class III medical devices.
• Applicant must receive FDA approval of PMA before marketing the
device.
• PMA is a scientific, regulatory documentation to the FDA to
demonstrate the safety and effectiveness of a class III device. It contains
the following components:
1. Non‐clinical Laboratory Studies Section: includes microbiology,
toxicology, biocompatability, mechanical and other laboratory
tests. Also includes pre‐clinical animal tests.
2. Clinical Investigations Section: includes study protocols, safety &
effectiveness data, device failures, patient information, patient
complaints, etc.
8/20/2022 53

Humanitarian Device Exemption (HDE)
• A Humanitarian Use Device (HUD) is a device that is intended to benefit patients
by treating or diagnosing a disease or condition that affects fewer than 4,000
individuals in the US per year
• An HDE is similar in form and content to a PMA, but the HDE is exempt form the
effectiveness requirement of a PMA, that is, an HDE is not required to contain the
results of a scientifically valid clinical investigation showing the device is effective for
its intended purpose. This is due to the difficulty in establishing a clinical trial with
enough patients to prove effectiveness.
• The HDE pathway was established to encourage medical device companies and
developers to create devices for small markets, in which the R & D costs may exceed
expected market returns
• For pediatric HDE devices, the manufacturer may charge for the device during the
clinical trial.
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SUMMARY
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Regulatory Flow
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What is Medical Device Regulation Trying to
Achieve? A Balance
57
8/20/2022
Patient
Safety
Device
Efficacy
Business
Risk:
Need profit to
bring device to
market/patients
Innovation:
new treatments
Risks:
1) Patient death/disability
2) Costly, non‐effective treatments
Risks:
1) No profit, no devices
2) Lack of innovation
also harms patients
Medical Device Regulation must:
• Protect patient health safety
• Ensure device efficacy
• Not impede device innovation
• Not impose too onerous
burden
Device
Manufacturer
Primary
FDA Primary

Module 1 - FDA Overview.pdf

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