regulatory basics for small businesses - ctsi · submission (we don’t need to know regulatory...

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19th Annual HHS SBIR/STTR Conference

Regulatory Basics for Small Businesses

Chris Sasiela, PhD, RACNational Heart, Lung, and Blood Institute

Office of Translational Alliances and Coordination

By the end of this presentation you should be able to answer the following questions about your innovative technology:Which branch/division within the FDA would

review your technology?

What is the expected regulatory pathway for your technology?

What regulatory uncertainties/challenges do you foresee for your technology?

Learning Objectives

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Learning Objectives

Center for Biologics Evaluation and

Research (CBER)

Center for Drug Evaluation and

Research (CDER)

Center for Devices and Radiological Health (CDRH)

FDA Biomedical Review Centers

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CBER

(Biologics)

Office of Blood Research and Review

Office of Vaccines Research and Review

Office of Tissues and Advanced Therapies

Center for Biologics Evaluation and Research Review Offices

Offices organized by therapeutic modality

What CBER Reviews

Blood and blood components used for transfusion

Medical devices and tests used to safeguard blood, blood components, and cellular products

Vaccines and viral products

Bacterial, parasitic and allergenic products

Human tissue for transplantationCellular products (stem and somatic cells)Gene therapy products (incl. thx vaccines)Xenotransplantation productsHematology and plasma protein therapeuticsAntivenins

Office of Tissues and Advanced Therapies

Office of Vaccines Research and Review

Office of Blood Research and Review

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Review of certain biologic technologies moved to CDER in 2002.

Monoclonal Antibodies

Recombinant Therapeutic Proteins

EXCEPTIONS!!!

Center for Drug Evaluation and Research Review Offices

Offices generally organized by disorder or organ system

Office of New Drugs

Office of Drug Evaluation I (ODE I)

Office of Drug Evaluation II (ODE II)

Office of Drug Evaluation III (ODE III)

Office of Drug Evaluation IV (ODE IV)

Office of Antimicrobial Products

Office of Hematology and Oncology Products

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CDER Review Divisions

ODE I

ODE II

ODE III

ODE IV

Cardiovascular and Renal ProductsNeurology ProductsPsychiatry Products

Anesthesia, Analgesia, and Addiction ProductsMetabolism and Endocrinology ProductsPulmonary, Allergy, and Rheumatology Products

Gastroenterology and Inborn Errors ProductsDermatology and Dental ProductsBone, Reproductive, and Urologic Products

Medical Imaging ProductsNon-prescription Clinical Evaluation (OTC)Non-prescription Regulation Development (OTC)

Center for Devices and Radiological Health Review Offices

Center for Devices and Radiologic Health

(CDRH)

Office of Device Evaluation (ODE)

Office of In Vitro Diagnostics and

Radiologic Health (OIR)

Offices generally organized by disorder or organ system

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Office of Device Evaluation Review Panels

OD

EAnesthesiology , General Hospital, Respiratory,

Infection Control, Dental

Cardiovascular

Ophthalmic and ENT

Neurological and Physical Medicine

Orthopedic

Surgical, Reproductive, Gastro-renal, Urological

Office of In Vitro Diagnostics and Radiological Health Review Panels

OIR

Chemistry and Toxicology Devices

Immunology and Hematology Devices

Molecular Genetics and Pathology

Microbiology Devices

Radiological Health

Mammography Quality Standards

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Learning Objectives

New Drug(including new

uses for existing drugs)

Biological License Application

New Drug Application

Abbreviated New Drug Application

Investigational New Drug Application

Drugs / Biologics

Pre

clin

ical

Clin

ical

tria

ls

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Drug Approvals Databases

http://www.fda.gov/Drugs/InformationOnDrugs/default.htm

Information to guide your drug development work can be found in the public domain.

Finding Approved Drugs@FDA

http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm

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Approval Doucmentation Links

FDA Reviews

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Review Letters

Redacted summary letters for all review disciplines

B/R Assessment found in reviews

The Benefit-Risk Assessment is a great resource describing how FDA thought about the new product during their review processes. This section goes beyond the information presented in the marketing application and places a real-world-use context around the product.

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Basic Anatomy of a B/R Assessment

Example B/R Summary

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208684,208685Orig1s000MedR.pdf

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Example B/R Summary

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208684,208685Orig1s000MedR.pdf

Biologic Approval Information

http://www.fda.gov/BiologicsBloodVaccines/ucm133705.htm

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The Orange Book

http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm

For a primer on finding and using approval documentation from similar technologies to understand the likely regulatory path for your technology please view

“Developing a Target Product Profile” At

http://bit.ly/SmallBizHangouts-YouTube

MORE INFO!!!!

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Medical Device

Class I510(K) Exempt

510(K)

Class II510(k) Exempt

510(K)

Class IIIDe novo 510(K)

Premarket Approval

Devices / Diagnostics

CDRH Product Classification Database

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Start with general terms

Results of broad search

From this search – 17 Class I, 184 Class II, 11 Class III

Can increase # of returns/page

Links provide greater detail

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Product Code Detail

Researching a 510(k) Device

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Device Clearance / Approval Databases

Use your product code to learn more about the regulation of your technology in these databases

Combination products contain at least 2 of the following: Biologic, Drug, Medical Device (Tx or Dx)

Regulation led by primary mechanism of action Drug Eluting Stent – stent opens vessels

Cell impregnated bioresorbable mesh?- It’s still very case-by-case

- Submit a Request for Designation

What About Combination Products?

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Guidance Documents – More Information

http://www.fda.gov/RegulatoryInformation/Guidances/default.htm

Use broad search terms

Number of returns updates as you type

Links to documents appear as you type

What About Health IT?

http://www.fda.gov/downloads/MedicalDevices/.../UCM263366.pdf

http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm429674.pdf

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Don’t know where to look?





Learning Objectives

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Is there something about your technology that FDA has not seen before? First in class

New manufacturing method

No current therapy

Is there something about your technology that FDA has seen before? Known adverse event profile

What’s Different About Your Technology?

Risk for Drugs / Biologics

http://www.fda.gov/Drugs/InformationOnDrugs/default.htm

What does FDA know about your potential drug or biologic’s target, indication, chemical or biological class?

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Risk for Devices / Diagnostics

What does FDA know about your proposed device or diagnostic’s characteristics and potential failure rates?

CBER Office of Communication, Outreach, and Development [email protected]

(800) 835-4709 or (301) 827-1800

CDER Small Business and Industry Assistance [email protected]

(866) 405-5367 or (301) 796-6707

CDRH Division of Industry and Consumer Education [email protected]

(800) 638-2041 or (301) 796-7100

Double Check Your Plan!

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For information about requesting a meeting with FDA please view

“First Contact with FDA” At

http://bit.ly/SmallBizHangouts-YouTube

MORE INFO!!!!

You should now be able to answer the following questions about your innovative technology:Which branch/division within the FDA will




Learning Objectives

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CASE STUDY

!!BONUS INFO!!

Ultrasound imaging of blood flow in peripheral vasculature

Research plan SA1: Develop prototype new device

SA2: Perform clinical studies

SA3: Refine device and get FDA OK

Hypothetical Case Study (Research Plan)

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Commercialization Plan Peripheral artery disease (PAD) is an unmet need

with anticipated growth due to population aging

There is limited (device) competition in this space

IP protection is solid

We will license or sell the technology prior to FDA submission (we don’t need to know regulatory stuff) OR

We will submit a 510(K) application (with few or no details about what is required)

Hypothetical Case Study (Commercialization Plan)

Center for Devices and Radiological Health Review Offices

Center for Devices and Radiologic Health

(CDRH)

Office of Device Evaluation (ODE)

Office of In Vitro Diagnostics and

Radiologic Health (OIR)

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ODE Review Panels

OD

EAnesthesiology , General Hospital, Respiratory,

Infection Control, Dental

Cardiovascular

Ophthalmic and ENT

Neurological and Physical Medicine

Orthopedic

Surgical, Reproductive, Gastro-renal, Urological

OIR Review Panels

OIR

Chemistry and Toxicology Devices

Immunology and Hematology Devices

Molecular Genetics and Pathology

Microbiology Devices

Radiological Health

Mammography Quality Standards

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Researching your Class II Device

>500 hits! – Narrower / alternate search?

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Guidance Documents!

http://www.fda.gov/RegulatoryInformation/Guidances/default.htm

Search “ultrasound” “imaging” or “PAD”

5 returns for “ultrasound”

Links to guidance documents

Guidance for Industry and FDA Staff -Information for Manufacturers Seeking Marketing Clearance of Diagnostic Ultrasound Systems and Transducers Search term “ultrasound”

Guidance for Industry: New Contrast Imaging Indication Considerations for Devices and Approved Drug and Biological Products Search term “imaging”

Example Guidance Documents

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Researching a Radiation-Emitting Technology

Regulated products A-Z list continued

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Information for Industry!

Case Study – Ultrasound for PAD

Info on regulations / law

Info on policy

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Case study – Ultrasound for PAD

Overview of Guidance Content

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Additional Guidance Information

??

New database search approach!

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Market research leads!

Search FDA site, or 510(K) database for product code and look at already cleared devices

How to decide?

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Anatomy of a 510(K) Summary

Predicate deviceDevice description

Intended Use

Comparison to Predicate

Nonclinical Testing

Clinical Testing

Conclusions

References

We will test our technology for compliance with the following regulations and standards for Track 1 ultrasound devices: Exposure rate limit (21 CFR 1020.10 (c)1)

Thermal and Acoustic Output Indices (AIUM/MENA 2004a)

… as suggested in the FDA Guidance Document “Information for Manufacturers Seeking Market Clearance of Diagnostic Ultrasound Systems and Transducers”

Update to Research Plan

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To access the US market, we will submit a 510(K) premarket notification for our ultrasound device as substantially equivalent to Boston Scientific Corporations AtlantisTM 018 Peripheral Imaging Catheter (K073623) as an Ultrasonic Diagnostic Imaging Catheter, Ultrasonic Diagnostic Transducers (ITX) Intravascular Ultrasound Catheter (OBJ) (regulation no. 892.1570), for review in the Center for Devices and Radiological Health’s Office of Device Evaluation’s Division of Cardiovascular Devices.

Update to Commercialization Plan

Is there something about your technology that FDA has not seen before? First in class

New manufacturing/analytical method

No current therapy/diagnostic

Is there something about your technology that FDA has seen before? Known adverse event profile

What about risks?

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What risk has FDA seen for your “device”?

What does FDA know about your proposed device’s characteristics and potential failure rates?

Based upon the totality of regulatory knowledge about ultrasound technology we do not anticipate specific issues with our technology development. However, we will request a pre-submission meeting* with CDRH prior to our 510(k) filing to ensure that we are compliant with all regulations, policies, and expectations required for market access.

Update to Commercialization Plan

*CDRH Presubmission Program Guidance Documenthttp://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311176.pdf

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For more information on how to use regulatory research to support your small business product development plan and SBIR / STTR application please view

“Integrating Your Regulatory and Research Plans”

Athttp://bit.ly/SmallBizHangouts-YouTube

MORE INFO!!!!

Thank You!

[email protected]

For additional commercialization tidbits check out the

NHLBI Small Biz Hangouts athttp://bit.ly/SmallBizHangouts-YouTube