Learning Objectives

• Explain the new drug development and review process in the United States.

• State how to obtain current drug information from the FDA.

NCTR CBERCDRH

CFSAN CVM

Food and Drug Administration

Center for Drug Evaluationand Research

CDER

ORA

OFFICE OF REGULATORY AFFAIRSOVER 160 OFFICES NATIONWIDE

NORTHEASTPACIFIC CENTRAL

SOUTHEAST

SOUTHWEST

REGIONAL OFFICES - 5DISTRICT OFFICES - 20RESIDENT INSPECTION POSTS –100+OCI FIELD OFFICES - 6OCI RESIDENT OFFICES - 4OCI DOMICILES - 4

CA

NV

WA

MT

ORID

AL

HI

AZ

UT

WY

CO

NM

TX

OK AR

MO

IANE

KS

TN NC

GAALMS

LA

FL

SC

PR

MEVT

NY

NH

MA

CTRI

MN

WI

IL

MI

INOH

PA

WV

KYVA

NJ

ND

SD

MDDE

Office of the Center Director

Office of Information Technology

Office of Compliance

Office of Management

Office Training and Communications

Office of Pharmaceutical ScienceOffice of New Drugs

Office of Testing andResearch

Office of New Drug Chemistry

Office of Generic Drugs

Office of Drug Evaluation I

Office of Drug Evaluation II

Office of Drug Evaluation III

Office of Drug Evaluation IV

Office of Counter Terrorism and Pediatric Drug Development

Office of Pharmacoepidemiologyand Statistical Science

Office of Drug Evaluation V

Office of Medical Policy

Office of Clinical Pharmacologyand Biopharmaceutics

Office of Regulatory Policy

Office of Executive ProgramsOffice of Drugs Evaluation VIOffice of Biotechnology

Products

Office of Information Management

A drug is defined as:

(A)articles recognized in the official USP, HPUS or NF or any supplement to any of them,

(B)articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals, (C)articles (other than food) intended to affect the structure or any function of the body of man or other function of the body of man or other animals…..

What is a Biologic?

Any virus, therapeutic serum, toxic, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or its derivatives, applicable to the prevention treatment or cure of diseases or injuries of man.

http://www.access.gpo.gov/nara/cfr/

IndustryGuidance

IndustryGuidance

PRE-CLINICALRESEARCH

FDA & INDUSTRY TIME

FDA TIME

INDUSTRY TIME

SPONSOR/FDA MEETINGS ENCOURAGED

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GSYNTHESISAND PURIFICATION

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GPRE-CLINICALRESEARCH

SYNTHESISAND PURIFICATION

ANIMALTESTING

SHORT-TERM

LONG-TERM

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CLINICAL STUDIES

NDAFDA & INDUSTRY TIME

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CLINICAL STUDIES

PHASE 3

PHASE 1

PHASE 2

FDA REVIEW

SHORT-TERM

LONG-TERM

IND NDA/ BLAFDA & INDUSTRY TIME

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SPONSOR/FDA MEETINGS ENCOURAGED

FDA TIME FDA ACTION

PHASE 1 PHASE 2 PHASE 3

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FDA REVIEW

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CLINICAL STUDIES

ADVERSEREACTION

SURVEILLANCEPRODUCT DEFECT

REPORTING

POSTMARKETING

SURVEYS/SAMPLINGTESTING

POST APPROVALINSPECTIONS

SHORT-TERM

LONG-TERM

FDA REVIEW

PARALLEL TRACK

TREATMENT USE

ACCELERATED APPROVAL

ACCELERATED REVIEW: SUBPART E

ACCELERATED REVIEW

EEXPANDED ACCESS:

PARALLEL TRACKTREATMENT USE

IND NDA/BLA FDA ACTIONFDA & INDUSTRY TIME

INDUSTRY TIME

SPONSOR/FDA MEETINGS ENCOURAGED

FDA TIME

New Drug Application (NDA) or Biologic License Application

(BLA) contains the following:

• Pre-clinical studies

• Human clinical studies

• Manufacturing details

• Labeling

• Additional information

A Better Way

The equivalent of 50,000 paper pages of data..

ODE I ODE II ODE III ODE IV ODE V

Neuro-pharmacological

Oncology

Cardio-Renal Metabolic andEndocrine

Pulmonary

Gastrointestinal and Coagulation

Anesthetic, Critical Care,

and Addiction

Medical Imaging and

Radiopharmaceuticals

Anti-Viral

Anti-Infective

Special Pathogen

and Immunologic

Anti-Inflammatory, Analgesic and Ophthalmologic

Dermatologic and Dental

Over-the-Counter

Reproductiveand Urologic

ODEVI

TherapeuticBiologicalOncology

TherapeuticBiological

InternalMedicine

ReviewManagement &

Policy

DRUG PRODUCT DIVISIONS

Review Team

Project ManagerMedical OfficerChemistMicrobiologistStatisticianPharmacologistEstablishment/Facility ReviewerSupport Personnel

• Panel of OUTSIDE experts• Provide advice and opinions to the FDA drug review team • FDA advisory committee

information, 1-800-741-8138 or 301-443-0572

ADVISORY COMMITTEE

http://www.fda.gov/oc/advisory/default

Prescription DrugUser Fee Act (PDUFA)

http://www.fda.gov/oc/pdufa/default.htm

• Permits CDER/CBER to charge pharmaceutical manufacturers a fee to review drug applications

• These fees provide appropriate resources to accelerate the review of applications

• Not the only source of funds for CDER/CBER

• Funds go directly to CDER/CBER, not individuals

DIS

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RY/S

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NIN

GPRE-CLINICALRESEARCH

SYNTHESISAND PURIFICATION

ANIMALTESTING

PHASE 3

PHASE 1

PHASE 2

PHASE 4

CLINICAL STUDIES

ADVERSEREACTION

SURVEILLANCEPRODUCT

DEFECTREPORTING

POSTMARKETING

SURVEYS/SAMPLINGTESTING

POST APPROVAL

INSPECTIONS

SHORT-TERM

LONG-TERM

FDA REVIEW

IND NDABLA

ACTIONFDA & INDUSTRY TIME

INDUSTRY TIME

SPONSOR/FDA MEETINGS ENCOURAGED

FDA TIME

PARALLEL TRACK

TREATMENT USE

ACCELERATED APPROVAL

Post-market Surveillance

Office of Drug Safety

• Division of Drug Risk Evaluation

• Division of Medication Errors and Technical Support,

• Division of Surveillance, Research, and Communication Support

MedWatch Website

• Safety Information Retrieval

• Adverse Event Reporting for Drugs,Devices, Biologics and Dietary Supplements

www.fda.gov/medwatch

• Database

• Internationally compatible

Adverse Event Reporting System (AERS)

Office of Drug Safety (ODS) uses AERS to:

• triage

• review

• assess risk

Potential Regulatory Action for Postmarketing Safety Issues

• Labeling Change

• Scientific publication

• "Dear Doctor" letter (for specific warnings)

• Restricted use

• Restricted distribution

• Patient Medication guide

• Product withdrawal

FDAevaluatesbenefits/risksfor the population

Providerevaluatesbenefits/risksfor a patient

Patientevaluatesbenefits/risksin terms of

personal values

B B B BB B B B

RRR

Benefits

Benefits

Risks

Risks

DDMAC (Division of Drug Marketing Advertising and Communications)

• Promotional Materials Review Guidances and policy development

• Research

• Surveillance and enforcement

CDER’s Office of Compliance

• Sets labeling, manufacturing, and testing standards

• Monitors the quality of marketed drugs

• Evaluates, classifies, and recommends human drug recalls

Generic Drug Review Process

Application Application submitted submitted to Office of to Office of

Generic Generic DrugsDrugs

Bioequivalence Review

Plant Inspection

Chemistry/Micro Review

Labeling Review

FDA reviews FDA reviews and decides if and decides if

product is product is approved or approved or

not approvablenot approvable

Determine if application is acceptable

Definition of Bioequivalence

• The rate and extent of absorption do not show a significant difference from listed drug, or

• The extent of absorption does not show a significant difference and any difference in rate is intentional or not medically significant

A generic drug is considered to be bioequivalent if:

APPROVED DRUG PRODUCTS WITH THERAPEUTIC EQUIVALENCE EVALUATIONS “Orange Book”

http://cdsmlweb1/ob/index.htm

Orphan Drug Productswww.fda.gov/orphan

• Rare diseases or conditions affecting fewer than 200,000 people in the U.S.

• 7 years exclusively after approval

• Special financial incentives

• Grants

• Protocol Assistance

Three Regions, Six Parties

EuropeEU EFPIA

JapanMHLW JPMA

United States of AmericaFDA PhRMA

Observers: WHO, Canada, EFTAObservers: WHO, Canada, EFTA

OTC Drug Review ProcessFDA reviews active ingredients and finds they are safeand effective. http://www.fda.gov/cder/Offices/OTC/industry.htm.

New OTC drugThe sponsor/manufacturer submits a new drug application(NDA) as an OTC drug.

Prescription to OTC SwitchThe drug company submits a supplement to the new drugapplication NDA to “switch” to OTC.

Panel reviews all known data or any submitted by company

Agency inputcat. Icat. IIcat. III

ingredientsamountscombinationslabeling claims

-Public Comment- Change in category could occur

Advisory Panel Review

ANPR FR(Panel Report)

Agency review

Agency addresses comments

OTC

D

RU

GR

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OTC

D

RU

GR

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Codified in CFR [April]

-Public Comment-

cat. I monographcat. II nonmonograph

FR(Final Monograph)

PR(Tentative Final Monograph)

Agency review/address comments

OTC

DR

UG

REV

IEW

OTC

DR

UG

REV

IEW

The New OTC Label

• Customize and Expand Enforcement Efforts

• Partner with Federal, State and other Organizations

• Engage in Public Outreach

http://www.fda.gov/oc/buyonline/default.htm

• Cooperate Internationally

• E-mail webcomplaints@ora.fda.gov

Counterterrorism

• Help prevent or alleviate shortages of medically necessary drug products

• Public Health Security and Bioterrorism Preparedness and Response Act of 2002

• Counterterrorism Drug Development– Radiation emergencies

– Anthrax

– Chemical agents

Working with Partners to Meet

the Challenge

www.fda.gov/cder

/http://www.fda.gov/cder/handbook/

www.fda.gov/cder

CDER’s Internet Home Page http://www.fda.gov/cder

Drug Information

888-INFO-FDA or 301- 827-4573

druginfo@cder.fda.gov