# Presentation: 280359

## GPhA MeetingJune 26, 2003

- Welcome Remarks

## Current Focus in OPS

- Supporting core business
- Enhancing scientific underpinning of decision making
- Supporting Center/Agency mission through numerous initiatives (e.g., cGMP)

## Office of Pharmaceutical Science

- Helen N. Winkle, Director
- Ajaz S. Hussain, Ph.D. Deputy

- Office of Biotechnology Products
*Yuan-yuan Chiu, Ph.D.*

- Office of Clinical Pharmacology and Biopharmaceutics
- Lawrence Lesko, Ph.D.

- Office of Generic Drugs
- Gary Buehler

- Office of New Drug Chemistry
*Moheb M. Nasr, Ph.D.*

- Office of Testing and Research
*Frank D. Sistare, Ph.D.*

- Div. of Monoclonal Antibodies
- Keith Webber, Ph.D.

- Div. of Therapeutic Proteins
- Amy Rosenberg, M.D.

- Div. of Bioequivalence
- Dale Conner, Pharm.D.

- Div. of Chemistry I
- Rashmikant Patel, Ph.D.

- Div. of Chemistry II
- Florence Fang

- Div. of Labeling and Program Support
- Peter Rickman

- Div. of Chemistry III

- Div. of Pharmaceutical Evaluation I
- Mehul Mehta, Ph.D.

- Div. of Pharmaceutical Evaluation II
*Henry Malinowski, Ph.D.*

- Div. of Pharmaceutical Evaluation III
- John Lazor, Pharm.D.

- Div. of New Drug Chemistry I
- John Simmons, Ph.D.

- Div. of New Drug Chemistry II
- Eric Duffy, Ph.D.

- Div. of New Drug Chemistry III
- Chi-Wan Chen, Ph.D.

- Lab. of Clinical Pharmacology
- Jerry Collins, Ph.D.

- Div. of Applied Pharmacology Research
*Joseph Hanig, Ph.D*.

- Div. of Pharmaceutical Analysis
*Lucinda Buhse, Ph.D.*

- Div. of Product Quality Research
*Robbe Lyon, Ph.D.*

- New Drug Microbiology Team
- Peter Cooney,PhD

- Informatic Computational
- Safety Analysis
- Joe Contera, PhD

- Quality Implementation
- Staff
- Nancy Sager

- Process
- Analytical Technologies
- Raj Uppoor, Ph.D.

*Acting positions in italics*

- Approximately 600 staff

## Core Business

- Keeping the freight moving
- Individual product issues
- Congressional/ administrative activities
- Better communication
- Industry
- Public
- Better internal interactions
- Quality systems approach

## Enhancing Science

- Lawrence and his staff
- Advisory Committee for Pharmaceutical Science
- Improved interaction with field/Office of Compliance
- Research
- Standards/guidance
- PQRI and similar venues

## Priority Initiatives

- Drug Quality Initiative (cGMP for the 21st Century)
- Process Analytical Technologies (PAT)
- Transition (CBER/CDER)

## Drug Quality Initiative for the 21st Century

**Covers both cGMP and other aspects of ensuring product quality including review**
**Applies to pharmaceuticals, biological human drugs and veterinary drugs**
**Focuses on a quality systems orientation**
**Continues to ensure strong public health protection**
**Will not interfere with current enforcement activities**
**Strives toward international harmonization**

## What Trying to Accomplish at FDA with the Initiative and How

- Clarify the scope of FDA’s electronic recordkeeping requirements (Part 11)
- Facilitate continuous improvement and innovation in manufacturing
- Changes without prior approval/comparability protocols
- Identify inconsistencies across program
-    areas - both review and inspections
- Understanding manufacturing science
- PAT

## What Accomplish - cont.

- Ensure state-of-the-art pharmaceutical science underpins the regulatory review and inspection programs
- Inspectional cadre
- Product specialists
- Dispute resolution
- Scientific review of warning letters
- Understanding manufacturing science

## What Accomplish- cont.

- In implementing a risk-based approach, develop a better understanding where the risks actually are and apply resources accordingly
- Risk management
- Understanding manufacturing science
- Improved communication with industry
- 483 communication
- Dispute resolution

## What Accomplish - cont.

- Enhanced consistency and coordination of drug quality oversight activities
- International
- Product specialists
- Inspection cadre
- Quality systems
- Warning letter review

## A Giant Step for All

## Why Process Analytical Technologies?

- PAT provides an opportunity to move from the current “testing to document quality” paradigm to a “Continuous Quality Assurance” paradigm that can improve our ability to ensure quality was “built-in” or was “by design” - ultimate realization of the true spirit of cGMP!
- Greater insight and understating of processes
- At/On/In-line measurement of  “performance” attributes
- Real-time or rapid feedback controls (focus on prevention)
- Potential for significant reduction in production (and development) cycle time
- Minimize risks of poor process quality and reduce (regulatory) concerns

## Regulatory Incentives

**Not a requirement**
**Research exemption**
**Continuous improvement without the fear of being considered non-compliant**
**Regulatory support and flexibility during development & implementation**
**Eliminate the fear of delayed approval**
**Dispute avoidance/resolution**
**Science & Risk based regulatory approach**
**Low risk categorization based on a higher level of process understanding**

## PAT: Conceptual Framework

- Incoming
- Materials.
- Specifications
- Relevant to
- “Process-ability”

- Incoming material attributes
- used to predict/adjust
- optimal processing parameters
- within established bounds
- (more flexible bounds)

***PAC***

***PAC***

***PAC***

***PCCP***

***LT***

***CM***
***IT***

***Direct or inferential***
***assessment of quality***
***and performance (at/on-line)***

- Control of process critical
- control points (PCCP).
- Process end point (PEPs’) range
- based on “performance” attributes.

***   ******PEP’s***

- Chemometrics (CM)
- and IT Tools
- for “real time”
- control and decisions

- At-line

- In/On-Line

- Process Analytical
- Chemistry Tools

- Laboratory
- or other
- tests

***LT***

- Development/Optimization/Continuous Improvement
-  (DOE, Evolutionary optimization, Improved efficiency)

- Multivariate
- Systems
- Approach
- Risk
- Classification
- and
- Mitigation
- Strategies

## Consolidation - CDER/CBER

- Why consolidate?
- Improvement of Agency efficiency and consistency
- PDUFA
- Reduce redundancy
- Enhance scientific expertise/knowledge and product understanding (e.g., immunogenicity)
- Establishment of quality systems - best practices

## Consolidation - cont.

- Next steps
- Detail of CBER folks to CDER - June 30
- Integration of CBER folks into CDER programs
- Examination of review models and practices
- Finalize organizational structure
- Continue to work closely to enhance science and processes

## Slide 18