How to Interact and Communicate with FDA on Quality Issues

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Tanya Clayton, MPH (Acting Division Director, Division I) CDR Bob Gaines, PharmD (Division Director, Division II)

Agenda

• CDER Reorganization • Office of Pharmaceutical Quality (OPQ) • Office of Program and Regulatory Operations

(OPRO) • Regulatory Business and Process Management

(RBPM) • Team-based Integrated Quality Assessment (IQA) • Communication

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Agenda (continued)

• Points to Consider • Contacts • Questions

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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

Quality Office of Compliance

Office of Generic Drugs

Previous Current

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 & Standards Office of

Regulatory Operations

Office of Generic Drug

Policy

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OPQ

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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 Objectives 1. 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

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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 Operations

Acting Director: Giuseppe Randazzo

Immediate Office Acting Director: Janet Woodcock

Deputy Director: Lawrence Yu

Office of Policy for Pharm. Quality

Acting Director: Ashley Boam

Office of Lifecycle Drug Products

Acting Director: Susan Rosencrance

Office of Process and Facilities

Acting Director: Christine Moore

Office of New Drug Products

Acting Director: Sarah Pope Miksinski

Office of Surveillance

Acting Director: Russell Wesdyk

Office of Biotech. Products

Director: Steven Kozlowski

Office of Testing and Research

Director: 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 …

• Works with 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 and risk

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 – 10d S: 0-14d P: 0-10d

S: 0-30d P:0-20d Within 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

Complete Inspection

Wrap up and Final Review

0 – 60d 4mo – 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 Reviewed

6.5mo – 8.5mo

Review Team

Assignment

Within 70d

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Current state: OPQ and OGD working to meet CY3/4 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 CY 5 timeline:

Review cycle Communication

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Communication ANDA BLA/NDA Notes

74 day letter X Does not apply for ANDAs.

Mid-cycle communication 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 required 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 …

• 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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