1. Entering the US Market: Medical Devices
Carole C. Carey BSEE, M.Engineering
Director, International Staff
US Food and Drug Administration
Center for Devices and Radiological Health

2. Topics Brief FDA Organizational Structure
Regulatory Paradigm, Device Classification
Two Most Common Pathways to Market
Levels of Regulatory Control (General Controls & Special Controls)
Importing into the U.S.
CDRH Databases and Resources
Organizational structure, mission, authority, CDRH risk-based regulatory paradigm, TPLC
Definition of a medical device (3 steps to obtain marketing clearance – medical device? class, application)
New vs. Improved Device
Device classification – preamendment (predicate devices) and postamendment [513g request for classification and 513f deNovo]
Forms (R&L, fees, etc)
Investigational studies (IDE)

3. The U.S. Food and Drug Administration is
Scientific, Regulatory, Public Health Agency
Mission is to protect and promote public health.
Authority to regulate medical devices
Federal FD&C Act
Established regulatory controls for medical devices (May 28, 1976)
21 CFR Parts
FDA Mission
FDA's public health protection role and mission were incorporated into the Federal Food, Drug, and Cosmetic Act by the FDA Modernization Act of 1997 (PL ). The Act outlined bold and innovative approaches to meet the increasingly complex public health challenges of the 21st century. FDA is committed to the successful implementation of this plan and believes success is within reach with the resources and support of its stakeholders. The FDA's statutory mission is:
To promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner. 
With respect to such products, to protect the public health by ensuring that:
foods are safe, wholesome, sanitary, and properly labeled;
human and veterinary drugs are safe and effective; 
there is reasonable assurance of the safety and effectiveness of devices intended for human use; 
cosmetics are safe and properly labeled, and; public health and safety are protected from electronic product radiation. 
To participate through appropriate processes with representatives of other countries to reduce the burden of regulation, harmonize regulatory requirements, and achieve appropriate reciprocal arrangements; and, 
As determined to be appropriate by the Secretary of the Department of Health and Human Services, to carry out these activities in consultation with experts in science, medicine, and public health and in cooperation with consumers, users, manufacturers, importers, packers, distributors, and retailers of regulated products.
Edited 3/1/2000

4. Department of Health & Human Services

5. FDA Centers and Regulated Products*
Food
Drugs　
Medical Devices *
Biologics
Animal Feed and Drugs
Cosmetics
Radiation-Emitting Products *
Combination Products (drug-device*, biologic-device*, drug-biologic)
Primary mode of action
RFD (Request for Designation)
Origins
The U S. Food and Drug Administration is a scientific, regulatory, and public health agency that oversees items accounting for 25 cents of every dollar spent by consumers. Its jurisdiction encompasses most food products (other than meat and poultry), human and animal drugs, therapeutic agents of biological origin, medical devices, radiation-emitting products for consumer, medical, and occupational use, cosmetics, and animal feed. The agency grew from a single chemist in the U.S. Department of Agriculture in 1862 to a staff of approximately 9,100 employees and a budget of $1.294 billion in 2001, comprising chemists, pharmacologists, physicians, microbiologists, veterinarians, pharmacists, lawyers, and many others. About one-third of the agency's employees are stationed outside of the Washington, D. C. area, staffing over 150 field offices and laboratories, including five regional offices and 20 district offices. Agency scientists evaluate applications for new human drugs and biologics, complex medical devices, food and color additives, infant formulas, and animal drugs. Also, the FDA monitors the manufacture, import, transport, storage, and sale of about $1 trillion worth of products annually at a cost to taxpayers of about $3 per person. Investigators and inspectors visit more than 16,000 facilities a year, and arrange with state governments to help increase the number of facilities checked.
HISTORY
The legislation having failed to develop, the Secretary of HEW commissioned the Study Group on Medical Devices, which recommended in 1970 that medical devices be classified according to their comparative risk, and regulated accordingly. The 1976 Medical Device Amendments, coming on the heels of a therapeutic disaster in which thousands of women were injured by the Dalkon Shield intrauterine device, provided for three classes of medical devices, each requiring a different level of regulatory scrutiny--up to pre-market approval.
1976
MEDICAL DEVICE AMENDMENTS passed to ensure safety and effectiveness of medical devices, including diagnostic products. The amendments require manufacturers to register with FDA and follow quality control procedures. Some products must have pre-market approval by FDA; others must meet performance standards before marketing.
Office of Regulatory Affairs (ORA)
is the lead office for all field activities.

6. CDRH

7. 16 Classification Regulations 21 CFR (part 800-1299)
Clinical chemistry and clinical toxicology
Hematology and pathology
Immunology and microbiology
Anesthesiology
Cardiovascular
Dental
Ear, nose and throat
Gastroenterology & urology devices
General and plastic surgery
General hospital and personal use
Neurological
Ophthalmic
Orthopedic and physical medicine
Obstetrical and gynecological
Radiology
Medical Device Definition in Sec 201(h) of the FD&C Act

8. Regulatory Paradigm: Balancing Risks and Benefits
… while ensuring that devices currently on the market remain safe and effective.
Getting safe and effective devices to market as quickly as possible…
Benefits
Risks
Helping the public get science-based accurate information about medical devices and radiological products needed to improve health.

9. Risk-based Classification, Level of Reg Control, & Submission Type
1700 generic type of devices
510(k) Exempt
Class I
Class II
Class III
Very low
Low (~782)
Medium (~799)
High (~119)
General Controls (may or may not be GMP exempt)
General Controls
Premarket Notification or 510(k)
General & Special Controls
510(k) submission
Premarket Approval
1700 generic types of devices
16 classification regulations
21 CFR
e.g. 870 = Cardiovascular
Classification determines extent of regulatory control
Level of Risk & Level of Regulatory Control

10. Class I / II Exemptions FD&C Act 513(d)(2A)
Over 800 generic types of Class I devices and 60 Class II devices are exempted from the premarket notification requirement (Federal Register)
510(k) Exempt Devices - approximately 47%
Class I 93%
Class II 9%
Devices exempt from 510(k) are:
“preamendment devices” not significantly changed or modified; or
Class I/II devices specifically exempted by regulation.
The Food, Drug and Cosmetic Act under section 513(d)(2)(A) authorizes FDA to exempt certain generic types of Class I devices from the premarket notification [510(k)] requirement. FDA has exempted over 800 generic types of Class I devices and 60 class II devices from the premarket notification requirement.  The 510(k) exemption is with certain limitations, which are so noted in ".9" of each chapter. It is important to confirm the exempt status and any limitations that apply with 21 CFR Parts or the PRODUCT CODE CLASSIFICATION DATABASE or subsequent FR announcements on class I exemptions and class II exemptions. If a manufacturer's device falls into a generic category of exempted Class I devices as defined in 21 CFR Parts , a premarket notification application and FDA clearance is not required before marketing the device in the U.S.

11. Examples of Device Classes
Medical Device Classes:
Class I
General Controls
Most exempt from premarket submission
Class II
Special Controls
Premarket Notification [510(k)]
Class III
Require Premarket Approval [PMA]

12. What are General Controls?
Establishment registration and device listing
Premarket notification or 510(k), if not exempt
Labeling
Misbranding
Adulteration
Quality Systems
Records and Reports / Medical Device Reporting (MDR)
Basic authorities that provide FDA with the means to regulate medical devices.
Applies to all medical devices regardless of classification, are subject to premarket and postmarket regulatory controls.
Generally synonymous to Class I device. General controls include:
Establishment Registration (use FDA Form 2891) of companies which are required to register under 21 CFR Part , such as manufacturers, distributors, repackages and relabelers. Foreign establishments, however, are not required to register their establishments with FDA.
Medical Device Listing (use FDA Form 2892) with FDA of devices to be marketed.
Manufacturing devices in accordance with Good Manufacturing Practices (GMP) in 21 CFR Part 820.
Labeling devices in accordance with labeling regulations in 21 CFR Part 801 or 809.
Submission of a premarket notification [510(k)] before marketing a device.
Misbranding is False or Misleading labeling
Manufacturers. Importers and distributors must maintain records of reports to assure that devices are not adulterated and misbranded

13. What are Special Controls?
General controls alone are insufficient to assure safety and effectiveness of Class II devices
Existing methods are available to provide such assurances.
Special controls may include special labeling requirements, mandatory performance standards and postmarket surveillance.
A few Class II devices are exempt from the premarket notification.
Postmarket Surveillance Study
Patient Registries
Guidelines (e.g., Glove Manual)
Mandatory Performance Standard
Recommendations or Other Actions
Special Labeling (e.g., , Cranial Orthosis)
Class II - Special Controls
Class II devices are those for which general controls alone are insufficient to assure safety and effectiveness, and existing methods are available to provide such assurances. In addition to complying with general controls, Class II devices are also subject to special controls.
A few Class II devices are exempt from the premarket notification.
Special controls may include special labeling requirements, mandatory performance standards and postmarket surveillance.
Examples of Class II devices include powered wheelchairs, infusion pumps, and surgical drapes.

14. Two Most Common Pathways to Market in the U.S.
Premarket Notification (PMN or 510(K))
Safe and effective to a legally marketed (predicate) device through demonstration of substantial equivalence
Class I, II, or III (pre-amendment)
Premarket Approval (PMA)
Demonstration of safety and effectiveness (supported by clinical data)
Class III (new, high risk devices and no predicate device, new indications)
The primary regulation that allows to conduct clinical trials using unapproved medical devices in the U.S. without complying with the FD&C Act is… the IDE or Investigational Device Exemption (21 CFR Part 812)

15. Use of Consensus Standards & Guidance Documents
CDRH Standards Program
Guidance Documents
They are non-binding but very useful in streamlining the regulatory approval process.

16. Legal Import of Medical Devices into the U. S
Legal Import of Medical Devices into the U.S. Market Section 801(a) – (d) of the FD&C Act
Subject to examination by FDA even if the product is authorized for marketing in another country.
Devices must be safe and effective.
Must contain informative and truthful labeling in English.
Imported products are required to meet the same standards as domestic goods.
Establishment Registration
Medical Device Listing
Compliant Labeling
GMP/Quality Systems
Appropriate Marketing Applications unless exempt
510(k)
PMA
Adverse Event Reporting, Records/Complaint Files

17. Summary
If a product is labeled, promoted or used in a manner defined in section 201(h) of the Federal Food Drug & Cosmetic (FD&C) Act, it will be regulated by the FDA as a medical device.
USFDA CDRH’s regulatory paradigm is risk-based classification. The levels of regulatory control are based on the classification. Unless exempt, they require a premarket notification clearance or a premarket approval application.
In entering the U.S. medical device market,
First determine if it meets definition of medical device.
Then determine how the may FDA classify the device, if known.
Finally, gather your information, collect the necessary data, organize your submission.
Products imported into the U.S. meets the same standards and requirements as domestic goods.

18. CDRH manages risk across the “Total Product Life Cycle” applied across Center activities
TOTAL PRODUCT LIFE CYCLE MODEL (TPLC) is applied across Center activities to promote and protect the public heath.
Total Product Life Cycle (TPLC) is an integrated product development scheme and a conceptual framework for assessing a variety of industrial and clinical models. For the manufacturer TPLC is the market-driven evolution of a device, drug, or biologic from initial conception, through pre-market development, to widespread market use, and finally to obsolescence and replacement by subsequent generations of products.

19. CDRH Databases http://www.fda.gov/cdrh/databases.html
Registration and Listing
Premarket Approvals (PMA)
Premarket Notifications (510(k))
Product Classification
FDA-Recognized Consensus Standards
MAUDE (Manufacturer and User Facility Device Experience)
MDR (Medical Device Reporting) ’92-’96
and others…

20. “Device Advice” (a self-service, interactive Site)
Division of Small Manufacturers, International and Consumer Assistance (DSMICA)
Fax (00)
Phone (00)
Write to us at:
International Staff, Center for Devices
and Radiological Health, HFZ-220
1350 Piccard Drive
Rockville, MD USA
“Device Advice” (a self-service, interactive Site)