How to Interact and Communicate with FDA on

Quality Issues

1

Tanya Clayton, MPH (Acting Division Director, Division I)

CDR Bob Gaines, PharmD (Division Director, Division II)

Agenda

• CDER Reorganization

• Organizational Structure (OPQ and OPRO)

• Office of Program and Regulatory Operations (OPRO)

• Regulatory Business and Process Management (RBPM)

• Team-based Integrated Quality Assessment (IQA)

• Communication

• Points to Consider

2

Office of

Biotechnology

Products

Office of

Testing and

Research

Office of

Drug

Security,

Integrity &

Recalls

Office of

Unapproved

Drugs and

Labeling

Compliance

Office of

Manufacturing

and Product

QualityOffice of

Compliance

Office of

Generic Drugs

PreviousCurrent

Office of

Pharmaceutical

Science

Office of

New Drug

Quality

Assessment

Office of

Scientific

Investigations

Office of

Surveillance

Office of

Testing and

Research

Office of Policy

for

Pharmaceutical

Quality

Office of New

Drug Products

Office of

Process

and

Facilities

Office of

Program

and

Regulatory

Operations

Office of

Biotechnology

Products

Office of

Lifecycle

Drug

Products

Office of

Unapproved

Drugs and

Labeling

Compliance

Office of

Drug

Security,

Integrity and

Response

Office of

Scientific

Investigations

Office of

Manufacturing

Quality

Office of

Program

and

Regulatory

Operations

Office of

Computational

Science

Office of

Biostatistics

Office of

Clinical

Pharmacology

Office of Study

Integrity and

Surveillance

Office of

Bioequivalence

Office Research

& StandardsOffice of

Regulatory

Operations

Office of

Generic Drug

Policy

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OPQ

4

Mission

The Office of Pharmaceutical Quality assures that quality medicines are

available to the American public

Vision

The Office of Pharmaceutical Quality will be a global benchmark for regulation

of pharmaceutical quality

One Quality Voice

OPQ Objectives1. Assure that all human drugs meet the same quality standards to

safeguard clinical performance;

2. Enhance science- and risk-based regulatory approaches;

3. Transform product quality oversight from a qualitative to a quantitative

and expertise-based assessment;

– Product Quality Platform and Informatics

– Quality Metrics

– New Inspection Protocol Project

5

OPQ Objectives (cont.)

4. Provide seamless integration of review, inspection, surveillance, policy, and

research across the product life cycle.

– Team-based Integrated Quality Assessment (IQA)

– Lifecycle Management

– Research and Surveillance Empowered by FDA internal laboratories

5. Encourage development and adoption of emerging pharmaceutical

technology

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Office of Pharmaceutical Quality

Office of Program and

Regulatory OperationsActing Director:

Giuseppe Randazzo

Immediate OfficeActing Director: Janet Woodcock

Deputy Director: Lawrence Yu

Office of Policy for

Pharm. QualityActing Director:

Ashley Boam

Office of Lifecycle

Drug ProductsActing Director:

Susan Rosencrance

Office of Process and

FacilitiesActing Director:

Christine Moore

Office of New Drug

ProductsActing Director:

Sarah Pope Miksinski

Office of Surveillance

Acting Director:

Russell Wesdyk

Office of Biotech.

ProductsDirector:

Steven Kozlowski

Office of Testing and

ResearchDirector:

Cindy Buhse

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OPRO Structure

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OPRO

• Mission:

OPRO is a customer‐oriented, regulatory‐focused,

and process‐centered organization that empowers

OPQ with an operational framework fostering

collaboration, efficiency, and quality.

• Vision:

To be the model organization for regulatory and

business operations across FDA centers.

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Regulatory Business Process

Manager (RBPM)

• Centralized project managers for:

• The Quality Assessment for all applications

submitted to CDER

• Specialized projects

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RBPMs value to

OPQ and Industry

• Centralized POC in OPQ for information regarding

the quality portion of applications

• Provides a focal point for communication external to

the review team

• Provides expert regulatory knowledge to the OPQ

review team

• Facilitates teams to ensure the timely completion of

work products

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RBPM value continued 0

• Works with subject matter experts (SMEs) to

identify and facilitate process improvement

opportunities

• Streamlines communication with the sponsor

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Team-based Integrated Quality Assessment (IQA)

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Drug

Product

Biopharm

Process

facility

Microbiology

Surveillance

Inspection

Drug

Substance

Team-based Integrated

Quality Assessment

BLA/NDA Original Process

Initial filing Assessment

Review Team

assignment

Inspection requested

Final Filing Review

and 74 day letter –

may include IRs

1st

Cumulative IR

Mid-cycle Review and

2nd

Cumulative IR

Inspection Finalized

Wrap up and Final Review

0 – 10dS: 0-14d

P: 0-10d

S: 0-30d

P:0-20dWithin 60d

S: 5.25mo

P: 3.25mo

S: 7mo

P: 4mo

S: 8.0mo

P: 5mo

Team Kick-off

Meeting

S: 0-45d

P:0-30d

3rd

Cumulative IR

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Prior to MC As needed

In collaborating with Industry, OND and associated review offices, have

experienced an increase in 1st cycle approvability rate from approximately

23% in 1992 to 73% in 2013/2014. This increase has been possible due to

improved processes and the increased quality and completeness of

original NDAs/BLAs submissions.

Filing Review (OGD)

IR #1 Response Received

and Reviewed

CompleteInspection

RBPM finalizes

IQA/sends to OGD

0 – 60d4mo –

6.5mo

Within

7.0mo

Within

9.0mo

Kick-Off Meeting

Within 90d

Assessment #1 and

Cumulative IR #1

Within 120d

IR #2 Response Received and Final Review

completed

6.5mo –

8.5mo

Review Team

Assignment

Within 70d

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Current state: OPQ and OGD working to meet

Cohort Year (CY) 3/4 15 mth GDUFA date.

OPQ believes, in working with OGD and Industry, by CY5 the 1st

cycle approvability rate for ANDAs can be improved. This goal is

achievable provided the ANDA submissions we receive are of high

quality and complete upon first submission.

Proposed example of 10 mth CY 5 timeline:

ANDA Original Process

Review cycle Communication

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Communication ANDA BLA/NDA Notes

74 day letter X Does not apply for ANDAs.

Cumulative IR #1 (ANDA);

Mid-cycle communication

(NDA – program products)

X X ANDA: OPQ/OPRO RBPM

sends comments directly to

sponsor and notifies OGD/RPM.

BLA/NDA: OPQ/OPRO RBPM

sends comments to OND RPM

and sends to sponsor.

Wrap-up communication X X Not required, only as needed

Information Request (IR) X X Process includes cumulative IR

letters; however, to prevent

delays during review cycle

additional IRs can be sent as

needed.

Important points to consider

• Contact the RBPM for all questions related to Quality-only

correspondences received (IR).

• Continue to use the OGD/OND RPM as the point of contact

for general inquiries.

• Be aware of your information request response deadline.

• Only respond to IR with requested information. Additional

unsolicited information may impact review time and goal

dates.

• Correctly code all submissions and amendments to ensure

accurate triage and goal dates applied.

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Important points continued 0

• Clearly identify all facility changes for all

submissions

• Ensure all facilities and their responsibilities are

clearly listed on the 356h

• Reach out to your assigned RBPM for any

quality specific areas of uncertainty when

submitting information

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OPRO Contacts

• For all Quality related questions/communications, contact your assigned

OPQ/OPRO RBPM

• For additional questions:

Tanya Clayton: Tanya.Clayton@fda.hhs.gov

Bob Gaines: Robert.Gaines@fda.hhs.gov

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Questions?

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