Transforming ORA’s Operations and Organization and Advancing Product

Quality

Douglas Stearn Director

Office of Enforcement and Import Operations Food and Drug Administration

FDA Inspections Summit

Bethesda, MD November 6, 2015

ORA’s Transformation

FDA/ORA’s Drivers of Change

Program Alignment

Implementing Legislation and Center Initiatives

ORA’s Strategic Priorities

Program Alignment - Commitments

1. Establish Commodity-Based and Vertically Integrated Regulatory Programs

2. Increase Specialization

3. Enhance Training

4. Revamp Agency Work Planning

5. Improve Compliance Policy and Enforcement Strategies

6. Enhance Import Operations

7. Advance Lab Optimization

8. Address Delayering/Streamlining

ORA Organizational Chart - Current ACRA

Deputy ACRA &

Partnerships & Policy

IT Staff

Communication, Quality Systems Management &

Project Management

Executive Secretariat

Office of Partnerships

Office of Policy

Assistant Commissioner for Operations

Human & Animal Food Operations

Office of Enforcement & Import Operations

Medical Products &

Tobacco Operations

Office of Regulatory Science

Audit Staff Northeast

Region

Central Region Southeast

Region

Southwest Region

Pacific Region

Office of Criminal Investigations Office of Resource Management

ORA Operations - Current Structure Operations

Central Region

Baltimore District

Cincinnati District

Chicago District

Detroit District

Minneapolis District

New Jersey District

Philadelphia District

Detroit Laboratory

Forensic Chemistry Center

Philadelphia Laboratory

Northeast Region

New England District

New York District

Northeast Regional Laboratory

Winchester Engineering Analytical Center

Southeast Region

Atlanta District

Florida District

New Orleans District

San Juan District

San Juan Laboratory

Southeast Regional

Laboratory

Southwest Region

Dallas District

Denver District

Kansas District

Southwest Imports District

Arkansas Regional Laboratory

Denver Laboratory

Kansas Laboratory

Pacific Region

Los Angeles District

San Francisco District

Seattle District

Pacific Regional Laboratory Northwest

Pacific Regional Laboratory Southwest

San Francisco Laboratory

Human & Animal Food Operations

Medical Products & Tobacco Operations

Enforcement & Import Operations

Regulatory Science

Audit Staff

ORA Operations - Future Structure

Operations

Pharmaceutical Quality Operations

Director, Alonza Cruse

Four Management

Teams

Biologics Operations

Director, Anne Reid Acting

Two Management

Teams

Medical Devices Operations

Director, Jan Welch

Three Management

Teams

BIMO Operations

Two Management

Teams

Tobacco Operations

Human and Animal Food Operations

Director, Joann Givens

12 Management Teams

Audit Staff

What does this mean for me?

Inspectorate specialized by program

Expanded technical expertise

Increased ability to keep pace with changes in manufacturing

Goal of reduced timeframes for decision-making through both streamlining as well as team-based approaches

Quality Focus for FDA

Principles for change

More clear standards for review and inspection

More clear enforcement policies

Same standards for all drugs: lifecycle approach

Specialization and team review: integration of review and inspection for a quality assessment

Clinically relevant standards

Surveillance using quantitative metrics

Overall QMS and evaluation system

FDASIA-User Fees

The first 4 titles relate to user fees:

Gives FDA authority to collect user fees from industry

Steady & reliable income to bring new products to market safely & quickly

Prescription Drug User Fee Amendments (PDUFA)

Medical Device User Fee Amendments (MDUFA)

Generic Drug User Fee Amendments (GDUFA)

Biosimilar Products User Fee Amendments (BsUFA)

Quality Focus for Industry

Commitment to quality

Essential… from the top down and bottom up

Cannot settle on “meeting regulators standards”

Must meet YOUR standards to reliably produce high quality products

Elements

proactively identify & promptly correct issues

design/qualify robust operations

maintain equipment and facilities

Implement robust quality management systems

Significant impacts to the public’s health

Cost of poor quality – $$$$$$$$$$$$$

Cost to patients – shortages, adverse events, etc.

How mature is your quality system? Level 1: Small problems ultimately

snowball into larger ones, and

management becomes aware only when

there is a crisis.

Level 2: Nearly always reactive, but there

is willingness to change. Patchwork

corrections are the norm.

Level 3: More proactive. Increasingly

surfaces major issues and makes lasting

systemic improvements.

Level 4: Routinely acts preventively, and

institutionalizes (rewards) meaningful

process and system improvements.

1

2

3

4

Data Integrity

Data Integrity

Reliable for its purpose: meeting standards to assure complete, consistent, and accurate data

Examples

What of state of mind?

Easier to emerge than you might think . . .

Not necessarily criminal

Not necessarily involving many people

Not necessarily easy to detect

The trinity: rationalization, justification, and denial

Why Data Integrity Matters

Oversight in this area is foundational

Lack of data integrity in one area raises questions about other data and records

Inability to rely upon data raises questions about the ability to assure safety and efficacy

Internal Oversight

A quality system should

prevent errors and defects

assure ongoing state of control

facilitate vigilance, timely action, and early warning of emerging quality issues

Data integrity breaches undermine these abilities

External Oversight

Regulators rely on firm data in

Inspections

Reviewing firm correspondence

Application review

Data integrity breaches undermine these reviews

Antecedents

The Generic Drug Scandal

Numerous prosecutions

Legislation and policy approaches

Prosecutorial approaches

Looking at data integrity with CGMP

Application integrity policy

Debarment

Data Integrity Issues Today and Tomorrow

Prosecution

Criminal objectives: deterrence and retribution

Common statutory approaches

Title 18

False statements within FDA jurisdiction

Obstruction of agency proceeding

Mail and wire fraud

FDCA felonies: “intent to defraud or mislead” extends to FDA

Difficulties of Overseas Prosecutions

Subpoena power in investigations

Cooperation of foreign authorities

Compulsory power at trial

Evidentiary Issues

Jurisdictional Issues

Extradition

The offense (FDASIA 718 (extraterritoriality))

Collateral Consequences

Debarment

Stems from conviction

Clear focus on development work in ANDAs

Applies more broadly as well

Prevents services to applicants

Medicare exclusion and corporate integrity agreements

CGMP Issues

Multiple provisions incorporate data collection and recordkeeping

Process leads to inaccurate or unreliable data

Renders product adulterated

Generally deemed material

Harder to investigate and to remedy

Warning letters and enforcement actions

Application Issues

Implicit requirement of reliability

Not necessarily found fraudulent

Not necessarily found inaccurate

FDA can reject data

Application integrity policy – a subset

Applies to review (rather than rejection)

Applies to a pattern by applicant

Preventing and Limiting Problems

Culture should reinforce rigor of procedures and unacceptability of short cuts

Accountability in systems and procedures

Management knows who did what when

Accountability in electronic data is key

Data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate (ALCOA)

Remediation – Step One

A comprehensive evaluation of data integrity deficiencies generally would include

The extent of the inaccuracy of any reported data

Plan to investigate deficient practices

Examination of management involvement, procedures, and contract agreements

FDA expects detailed, thorough plans addressing people and systems

Remediation – Step Two

A risk assessment of potential effect on drug product quality

Issues

Affected products in marketplace

Potential impact on patients

Nature of preventative controls

Remediation – Step Three

A management strategy that includes CAPA

Potential issues: customer contacts, recalls, revising procedures, implementing new controls, training, etc.

Expectation will be for increased accountability and preventative systems in future

Inspection

A focus on implementation of corrective actions

Mismatch may show problems are not fully addressed

Closing Thoughts

Potentially high stakes consequences

Not always easy to see

Difficult to remediate

Better safe than sorry: controls can prevent and limit data integrity breaches