Introduction to US FDA Regulatory Framework NSF SB SF SBIR Pha - - PowerPoint PPT Presentation

Introduction to US FDA Regulatory Framework

NSF SB SF SBIR Pha Phase I I Grant ntee Pr Program Arlin lingto ton, V , VA Septem ember 20, 0, 2 2017 17 Dinesh esh V V Patwar ardhan an P Ph.D.

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Agenda

• FDA Organization
• Introduction to Centers within FDA
• Combination Products
• Medical Devices Amendments
• Benefit-Risk Paradigm
• Quality System (QSR)
• Resources & Initiatives

– Guidance Documents – Software as a Medical Device – Medical Device Development Tools (MDDT)

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FDA in news

FDA touches 20-25 % of US economy

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Departm tment o

• f Health

th an and H Human S Ser ervice ces

Food a d and Drug A g Admin ministratio ion

Cen ente ter for Devic vices an and d Radio adiolo logic ical Healt Health (CDR CDRH)

Cent nter f for D Drug ug E Evalua uation

• n

and R Resear earch ( (CDER) Cent nter f for B Biol

• log
• gics

Evalua uation

• n and R

Research (CBER) R) Center f r for V Veteri rinary ry Medicine ( e (CVM) M) Center fo for F Food S Safe fety And A Applied N Nutrition

• n

(CFSAN AN) Nationa

• nal C

Cent nter f for Toxico cological cal R Resear earch

Cente enter f for

• r T

Tob

• bacco

co Prod

• ducts

ts (C (CTP)

FDA Organizational Chart

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Legislative History

1902 Biologics Control Act 1906 Food & Drug Act (F&D Act) 1938 Federal, Food, Drug, and Cosmetic Act (FD&C Act) 1968 Radiation Control for Health & Safety Act (RCHSA) 1976 Medical Device Amendment of 1976 1988 Clinical Laboratory Improvement Amendments (CLIA) 1990 Safe Medical Devices Act (SMDA) 1992 Mammography Quality Standards Act (MQSA) 1992 Medical Device Amendments 1997 Food & Drug Administration Modernization Act (FDAMA) 2002 Medical Device User Fee and Modernization Act (MDUFMA) 2005 Medical Device User Fee Stabilization Act (MDUFSA) 2007 Food and Drug Administration Amendments Act of 2007 (FDAAA) 2012 FDA Safety and Innovation Act (FDASIA) 2017 FDA Reauthorization Act (FDARA) 2017

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Medical Device Defined

• Sect

ection 201( 201(h) of the FD&C Act defines a medical device as: (…in part…)

• A medical device is "an instrument, apparatus, implement,

machine, contrivance, implant, in vitro reagent, or other similar or related article

• ..intended for use in the diagnosis of disease or other

conditions, or in the cure, mitigation, treatment, or prevention of disease in man….

• ..intended to affect the structure or any function of the

body,..

• and does not

not achieve its principal intended purpose by chem emical cal a action

• n or by being metaboliz

lized.

• As

As simple as as a a tong tongue d depressor or

• r a

a the thermometer

• As complex a

as roboti

• tic s

c surger ery d devices ces

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Definition (regs)

• Drug

(in part)…...A substance recognized by an official pharmacopoeia or

• formulary. A substance intended for use in the diagnosis, cure,

mitigation, treatment, or prevention of disease. A substance (other than food) intended to affect the structure or any function of the body….. [FD&C Act, sec. 201(g)(1)]

• Cosmetic

(in part) ….articles intended to be rubbed, poured, sprinkled, or sprayed

• n, introduced into, or otherwise applied to the human body...for

cleansing, beautifying, promoting attractiveness, or altering the appearance….[FD&C Act, sec. 201(i)]. And so on…

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• 21 CFR 3.2(e): Combination products

are therapeutic and diagnostic products that combine drugs, devices, and/or biological products

• Lead center is based on “primary mode
• f action” (PMOA)
• Office of Combination Products

Combination Products Definition

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• Device coated or impregnated with a

drug or biologic

• Drug-eluting stent; pacing lead with

steroid-coated tip; catheter with antimicrobial coating

• Examples of combination products

where the components are packaged together

• Drug or biological product packaged

with a delivery device

Combination Products

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Combination Products

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Departm tment o

• f Health

th an and H Human S Ser ervice ces

Food a d and Drug A g Admin ministratio ion

Cen ente ter for Devic vices an and d Radio adiolo logic ical Healt Health (CDR CDRH)

Cent nter f for D Drug ug E Evalua uation

• n

and R Resear earch ( (CDER) Cent nter f for B Biol

• log
• gics

Evalua uation

• n and R

Research (CBER) R) Center f r for V Veteri rinary ry Medicine ( e (CVM) M) Center fo for F Food S Safe fety And A Applied N Nutrition

• n

(CFSAN AN) Nationa

• nal C

Cent nter f for Toxico cological cal R Resear earch

Cente enter f for

• r T

Tob

• bacco

co Prod

• ducts

ts (C (CTP)

FDA Organizational Chart

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• “There is reasonable assurance that a device is safe

when it can be determined based on valid scientific evidence that the probable benefits to health from use of the device for its intended uses and conditions of use, when accompanied by adequate directions and warnings against unsafe use,

• utweigh the probable risks.”
• “There is reasonable assurance that a device is

effective when it can be determined, based upon valid scientific evidence, that in a significant portion

• f the target population, the use of the device for its

intended uses and conditions of use, when accompanied by adequate directions for use and warnings against unsafe use, will provide clinically significant results.”

Safety & Effectiveness

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CDRH Mission

The mission of the Center for Devices and Radiological Health (CDRH) is to protect and promote the public health. We assure that patients and providers have timely and continued access to safe, effective, and high-quality medical devices and safe radiation-emitting products. We provide consumers, patients, their caregivers, and providers with understandable and accessible science-based information about the products we

• versee. We facilitate medical device innovation by advancing

regulatory science, providing industry with predictable, consistent, transparent, and efficient regulatory pathways, and assuring consumer confidence in devices marketed in the U.S.

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CDRH’s Mission

Br Bring s saf afe and and effec ecti tive m e medica cal devices ces t to market a et as quickly ly a as possib ible le… … while ile e ensurin ing that m t medical cal d devices ces cur currently on

• n the

the market r et remai ain s n safe e and e effecti ective. *Provide consumers, patients, caregivers, and providers with understandable and accessible science-based information about the products we oversee.

Reference: – CDRH Mission, Vision and Share Values

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The products we regulate…

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Who We Are

CDR CDRH is a team of over 170 700 employees dedicated to public health

• Engineers
• Physicians
• Biologists
• Chemists
• Physicists
• Statisticians
• Epidemiologists
• Microbiologists
• Nurses
• Veterinarians
• Toxicologists
• Public Health Education /

Communication Specialists

>80% of device companies have <50 staff

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CDRH in perspective

• CDRH oversees:

– 175,000 medical devices on US market – 570,000 proprietary brands on the US market – 18,000 medical device manufacturers – 25,000 medical device facilities worldwide – Each year we receive – 22,000 premarket submissions (includes supplements and amendments) – 1.4 million reports on medical device adverse events and malfunctions

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CDRH Ombudsman

Center nter f for D Devices ces a and R Radiol

• log
• gical

cal H Health th

Office ce o

• f In V

n Vit itro Diagnosti tics cs a and Radio iolo logic gical l Heal ealth Office ce o

• f

Compli mpliance Office o e of Sci Scien ence an e and Engin gineerin ring Labor

• rator
• ries

Office ce o

• f

Comm mmunic icatio ion an and Ed Educa cation Office ce o

• f

Survei eillan ance e an and Biometr etrics cs Office ce o

• f

Managem emen ent Ope Operations Office ce o

• f

Device ce Evalu luatio ion

CDRH Organizational Chart

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Office of Science and Engineering Labs (OSEL)

• Ensure readiness for emerging and innovative medical technologies
• Develop appropriate evaluation strategies and understandable public health info.

Our job is to ensure that CDRH never has to say “I don’t know”

• Division of Applied Mechanics; Biology

, Chemistry and Material Science; Biomedical Physics; Imaging, Diagnostics and Software Reliability .

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OSEL Contributions

• Providing scientific/engineering expertise, data,

and analyses

• Conducting laboratory-based regulatory research

(Regulatory Science Programs)

• Facilitate Innovation & Collaboration

https://www.fda.gov/AboutFDA/CentersOffices/Offi ceofMedicalProductsandTobacco/CDRH/CDRHOf fices/ucm115989.htm

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How to Market a Medical Device

• 1. Device Determination
• 2. Device Classification
• 3. Determine Appropriate Regulatory

Pathway

• 4. Establishment Registration and

Device Listing

• 5. Other Requirements

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Product Classification

Product Classification Data Base https://www.accessdata.fda.gov/scripts/cdrh/c fdocs/cfPCD/classification.cfm

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Determination & Classification

• Cannot determine Device (Y/N)

DeviceDetermination@fda.hhs.gov

• Cannot determine Classification
• 513 g

https://www.fda.gov/downloads/medicalde vices/deviceregulationandguidance/guid ancedocuments/ucm209851.pdf

• Written Response

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Class of Medical Devices

Class ss Risk sk Contr ntrol

• ls

Su Submiss ssion T Typ ype

I Low Lowest Gener eral al

• Exe

xempt

• 510(

510(k) II II Mo Moderate te Gener eral al an and Speci cial al ( (if avai ailable) e)

• Exe

xempt

• 510(

510(k) III III High ighest Gener eral al an and PM PMA

• PM

PMA

• HDE

References: – Regulatory Controls – Class I/II Exemptions

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Valid Scientific Evidence

• Establish safety and effectiveness
• Progressive Paradigm:
• 4. Clinical
• 3. Animal (in vivo)
• 2. Bench (engineering)
• 1. Descriptive information (no new)

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FDA Quality System Regulation (QSR) (Good Manufacturing Practice)

Discovery /Ideation Proof of Concept Prototyping Scale Up Manufacturing /Launch Monitoring/Im provement

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…FDA QSR…

• Does it work?
• How does it work?
• How well does it work? (Consistency)
• How well does it need to work?

(Patient)

• How good is good enough? (Risk)

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…FDA QSR…

• The design is good enough if . . .
• . . . regulatory and supporting business

processes are grounded in quality management and risk management standards, and

• decisions are based on legal, scientific,

and engineering principles, as evidenced by textbooks, professional literature, consensus standards, past experience.

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequ irements/QualitySystemsRegulations/default.htm

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FDA QSR

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Resources & Initiatives

• Guidance Documents
• Medical Device Development Tools
• Digital Health Initiative

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Guidance Documents

• In some cases Intersection of Regulatory

Policy and Science/Engineering

• Guidance documents represent FDA's current

thinking on a topic. They do not create or confer any rights for or on any person and do not operate to bind FDA or the public

• You can use an alternative approach if the

approach satisfies the requirements of the applicable statutes and regulations

• Draft and Final Guidance
• Comment Period for Guidance

https://www.fda.gov/RegulatoryInformation/Guidances/

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Guidance Documents

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Guidance (E.g.) ….

• Additive Manufacturing (Technical)

https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidan ce/GuidanceDocuments/UCM499809.pdf (DRAFT Guidance)

Ultrasound

• Diagnostic Ultrasound

https://www.fda.gov/RegulatoryInformation/Guidances/ucm070856.htm

• Ultrasound Wound cleaners

https://www.fda.gov/RegulatoryInformation/Guidances/ucm071551.htm

• Aesthetic HIFU

https://www.fda.gov/RegulatoryInformation/Guidances/ucm263709.htm

• Lithotripsy: https://www.fda.gov/MedicalDevices/ucm073712.htm
• Ultrasound physiotherapy/diathermy

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=1050

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Medical Device Development Tools (MDDT)

• Medical Device Development Tools (MDDT)

program is a way for the FDA to qualify tools that medical device sponsors can use in the development and evaluation of medical devices

• Clinical outcome assessment
• Biomarker test
• Nonclinical assessment model

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….MDDT…

• Clinical

al o

• utco

come a e asses sessm smen ent: measures of how a patient feels or functions. These could be patient-reported or clinician- reported rating scales like the NIH stroke scale, measures based on clinical decision- making, observer-reported outcomes such as from a parent or caregiver, or performance outcome measures, such as measures of gait speed or memory recall.

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• Bi

Biomarker er te test: a lab test or instrument used to detect or measure an indicator of biologic processes or pharmacologic responses to a treatment (biomarker). Examples of tools that might be eligible for qualification include:

• tests used as an aid in diagnosis, for patient

selection, or as

• clinical study endpoints, such as instruments or

methods for measuring blood pressure; or

• instruments or methods for measuring certain

concentrations of serum proteins, such as an assay to detect the level of a specific hormone in a patient in order to determine enrollment eligibility for study population in a clinical trial.

….MDDT…

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….MDDT…

• Nonclinical assessment model: a nonclinical test

method or model (e.g. in vitro “bench,” animal or computational model) that measures or predicts device function or performance in a living organism. Examples of tools that might be eligible for qualification include: models used to measure a parameter of interest or to substitute for another generally accepted test or measurement, such as computer modeling to assess conditions typically evaluated through human, animal or bench testing to evaluate a device instead of collecting data from human subjects; use of tissue and other material phantoms to evaluate imaging devices; or In vitro models to replace animal testing.

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…MDDT…

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Advancing Digital Health Innovation

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Digitalization Across the Health Care Continuum

Leveraging computing pow er, sensors, connectivity and softw are. Moving health care from the Clinic to the Patient. Understanding patient’s behavior and physiology “In the wild”. Focusing on prevention for early/smaller interventions.

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Risk Based

Functionality Focused

Platform Independent Promote Innovation

Narrowly Tailored

Promote Patient Engagement Protect Patient Safety

Smart Regulation Principles for Digital Health Technologies

FDA Pre-Cert for SaMD

A voluntary program that allows manufacturers of Software as a Medical Device (“SaMD”) to demonstrate their embedded Culture of Quality and Organizational Excellence (CQOE) to ultimately participate in a streamlined and predictable FDA regulatory pathway.

Purpos

• se/Go

Goal

Allows manufacturers of SaMD with FDA DA P Pre-Cert t status (demonstrated culture of quality and

• rganization excellence):
• To have the ability to get SaMD to market faster;
• To iterate based on real world experience;
• To have an excellent regulatory experience; and
• To have regulatory predictability.

Pub ublic heal c health/ h/inno novation

• n outcom
• utcomes
• 1. Companies strive for excellence rather than

compliance;

• 2. Promotes high quality and effective innovation;
• 3. Transparent FDA

DA P Pre-Cert t status increases user confidence beyond regulatory oversight; and

• 4. Allows FDA to focus resources on higher risk

digital health products.

Providing safe patient experience Being clinically responsible Being cybersecurity responsible Being proactive v/s reactive Delivering highest product quality

Exa xample of

• f CQOE

QOE scorecard elements of interest where a company shows commitment towards ...

https://www.fda.gov/medicaldevices/digitalhealth/

Entrepreneur-in-Residence Program

• Analyze software industry business

processes and key performance indicators to identify reliable predictors of product quality and organizational excellence;

• Develop and test models of data

collection and analysis;

• Collaborate with external stakeholders,

pilot participants, and internal staff to identify requirements and input for a new digital health paradigm;

• Identify opportunities to improve

processes and policies on data sharing and access;

• Participate in scheduled and ad hoc

meetings with the Digital Health Unite team and/or Senior Office Staff; and

• Provide additional counsel or services

related to the EIR program as directed by the CDRH Center Director.

Duties

 Launched September 6

• Posted on Digital Health website
• Blast email to XX

 Applications will be accepted through September 29, 2017  May be hired by FDA as contractors, special government employees, or full employees, dependent on qualifications and type of expertise  Commit to participate in the program for a minimum of 6 months, and not to exceed a period of two years

Recruiting up to 6 of the best innovators and entrepreneurs from the digital health technology industry or academia to work with DH Unit on complex challenges https://www.fda.gov/medicaldevices/digitalhealth/

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• 1. CDRH Learn – Multi-Media Industry Education
• https://www.fda.gov/Training/CDRHLearn/default.htm
• ver 80 modules
• videos, audio recordings, power point presentations, software-based “how to”

modules

• mobile-friendly: access CDRH Learn on your portable devices
• 2. Device Advice – Text-Based Education
• https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/default.htm
• comprehensive regulatory information on premarket and postmarket topics
• 3. Division of Industry and Consumer Education (DICE)
• Contact DICE if you have a question
• Email: DICE@fda.hhs.gov
• Phone: 1(800) 638-2014 (Hours: 9 am-12:30 pm; 1 pm-4:30pm EST)
• Web: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ContactUs--

DivisionofIndustryandConsumerEducation/default.htm

Industr try E Educati tion R

• n Resour
• urces

Thank you dinesh.patwardhan@fda.hhs.gov