# Presentation: 666898

## Advisory Committee for Pharmaceutical ScienceOctober 25-26, 2005

**OPS Update**
**Helen N. Winkle**
**Director, Office of Pharmaceutical Science**

## Outline

- CDER objectives and goals
- Move to White Oak
- Current management structure in OPS
- Reorganizations in OPS
- Important Initiatives for OPS
- Pharmaceutical CGMP for the 21st Century
- CMC Review
- Field and Review Interaction
- Drug Safety Initiative
- Critical Path Initiative
- Follow-on Proteins
- Importance of this meeting
- Agenda for meeting and what hope to accomplish

## CDER State of the Center – Dr. Galson’s Vision for CDER’s Future

- CDER’s leadership
- International scientific leader in drug development and innovative regulatory science
- Many active, robust, productive scientific partnerships with outside groups
- Regulatory programs are consistent, efficient and transparent

## Vision

- CDER’s Organization
- Quality Systems throughout our organization
- Improve communication with the public and health-care community about the risks and benefits of pharmaceutical products
- Electronic vs. paper environment for submission, review, post-marketing surveillance
- Respect and tolerance for differences of opinion
- More mechanisms for involving stakeholders in peer review
- High degree of professionalism in resolving disputes

## Supporting the Vision

- Enhance the ability of the Center to respond to challenges of Critical Path (CP) initiatives and improve regulatory and drug development science
- Locus needed for ownership of CP activities
- Reflect the commitment of CDER to sustain a multi-disciplinary, cross-Center approach to drug safety
- Placement in organization must reflect level of commitment
- Need focus and consistency and improvement in communication about drug risks and benefits
- Need focus for cross-center policy development

## White Oak

## White Oak Offers Opportunity

- Allows for flexibility to reorganize
- Brings OPS together in one location
- Provides opportunity to work closely with all review groups
- Potential for better interaction when rest of CDER moves

## Management Structure

- Deputy Directors
- Ajaz Hussain
- Keith Webber
- Associate Directors
- Nakissa Sadrieh
- Jon Clark
- Office Directors
- Office of Generic Drugs – Gary Buehler
- Office of New Drug Quality Assessment – Moheb Nasr
- Office of Biotechnology – Steve Kozlowski, Acting
- Office of Testing and Research – Cindy Buhse, Acting

## Reorganizations

- Have had several reorganizations in OPS during the past few months
- OGD – new chemistry division
- ONDQA
- Change in organizational structure
- New division
- Other reorganizations in Center that affect OPS

## Pharmaceutical CGMP for the 21st Century

- What is current status?
- Set direction for modernization of pharmaceutical regulation
- Continue to focus on pharmaceutical quality issues through Council on Pharmaceutical Quality
- Still implementing various recommendations

## CMC in OPS – Three Pronged

- ONDQA

- OGD

- OBP

- CMC

## Changing the CMC Review Processes

- Office of New Drug Quality Assessment
- Question-based review
- Integration of biotech products into new paradigm
- All come together as one

## Benefits of Changes to CMC Review

- Quality-by-design and performance-based  specifications enhance product quality
- Understanding of product and process leads to reduced CMC supplements
- Focused review on “highest” risk products
- Risk assessment facilitates continuous improvement
- Standardized review enhances the quality of CMC evaluation
- Better applications and focused questions reduce review time

## CMC Workshop

- Held October 5, 6, and 7
- Over 600 in attendance
- Focused on new paradigm for CMC review
- Discussed quality-by-design (QbD), design space, pharmaceutical development data (PD), continuous improvement (CI) and quality overall summary (QOS)
- Set stage for moving forward with the new processes

## Agreements Reached at Workshop

- Support concept of QbD built into PD
- PD to illustrate product/process understanding to serve as the basis of science and risk-based assessment
- Regulatory flexibility predicated on scientific knowledge and process understanding and is welcomed by industry and regulators
- Concept of regulatory agreement supported
- Improved, streamlined, frequent communications required  -  **We must partner!!**
- Specifications tied to clinical safety/efficacy
- Guidances and training will need to be different

## Challenges Realized as Result of Workshop

- Lack of adequate scientific understanding of products and processes both by FDA & industry
- Implementation – “devil is in the details”
- Setting specifications
- Legacy products
- Culture change
- Industry buy-in for new processes (in many cases industry resistant to make changes)
- Global harmonization

## Integration of Field and Review“The submission review program and the inspection program operate in a coordinated and synergistic manner” 

**Compliance** - Sets standards for quality systems and reviews inspectional findings

**Field** - Inspects
- against standards

**Review** - Sets standards
- for product quality

## Roles and Responsibilities

- Review side (lead)
- Scientific assessment of product and process design
- Evaluate product quality in light of established FDA standards (e.g., impurities, stability, etc.)
- Set and maintain product quality standards

## Roles and Responsibilities

- Field (lead)
- Evaluate implementation of process design
- Evaluate quality system
- Implement enforcement actions
- Set certain compliance policies

## Roles and Responsibilities

- Compliance Offices (lead)
- Establish and maintain quality system standards for cGMPs
- Establish and maintain risk management system for inspections
- Establish and maintain compliance policies and standards

## Drugs Safety and How it Relates to Product Quality

- Many issues related to drug safety are caused by product quality problems (e.g., alcohol-induced dose dumping)
- Safety is an important aspect when focusing on product risk
- CMC specifications linked to safety and efficacy

## Drug Safety –How Focused in Center		

- Drugs safer than they have ever been
- FDA as organization learns well from experience with large number of products
- What we’ve heard:
- More info – address gap between FDA and others
- Improve internal processes to manage safety issues
- Involve outside experts more
- Secretary Leavitt recently announced a new drug safety initiative
- Promote a culture of openness and
- Enhanced oversight within the FDA

## Drug Safety Initiative

- New drug safety information initiative
- Proposed Drug Watch Program
- Patient Information Sheets
- Healthcare Professional Sheets
- Drug Safety Oversight Board
- Focus on product quality

## Critical Path Initiative

## FDA’s Role in Critical Path

- FDA has a significant role in enhancing product development and manufacturing
- We are involved in review during product development -- they see the successes, failures, and missed
-        opportunities
- We have no preconceived thoughts on how products need to be developed and manufactured - we are not a competitor, but instead can serve a crucial convening and coordinating role for consensus development between industry, academia and government
- We set the standards that need to be met
- Critical Path research can make a difference in how we regulate CMC

## Examples of Critical Path Projects Focused on CMC

- Proposed CRADAs to collaborate with industry and academia to better understand manufacturing science and new technologies and their application
- Determining how PAT can be applied in product manufacturing to improve efficiencies
- Gathering information on determining critical product and process parameters and quality attributes - CMC pilot
- Other

## Follow-on Proteins

- Moving toward follow-on proteins, but there are a lot of issues to address
- Terminology
- Legal
- Science
- Administrative/process
- We need to be more open in our thinking and not have preconceived ideas as to how follow-ons should be regulated
- Process will evolve – as we learn more – and we will incorporate into regulatory processes

## Follow-on Proteins (cont.)

- We need to incorporate thinking from the new paradigm – looking at early on in developing regulatory framework
- Finalizing guidances to help lay the path for moving forward
- It will take all of us working together to make this happen successfully

## Importance of this Meeting

- Step closer to understanding quality-by-design – especially as it relates to dissolution
- Showcasing the progress that has been made in changes to CMC review
- Introducing several new topics
- Saying farewell to Dr. Ajaz Hussain

## Advisory Committee Meeting Topics

- Quality-by-Design and control of drug dissolution
- Continuation of discussion from May
- Several presentations from outside organizations
- FDA presentations on tactical plan
- Update from PTIT working group
- Fact finding group on dose content uniformity for inhalation products
- Alcohol-induced dose dumping
- Awareness topic
- Basis of concern and our current thinking on regulatory approach

## Advisory Committee Meeting Topics

- Transitional changes in CMC review
- Presentations by all three OPS CMC programs
- Implementation of risk-based approach
- Laboratory research - developing “peer review” program
- How best to handle scientific “peer review” for all laboratory research
- State of US pharmaceutical science and engineering education
- Important as we move toward new paradigm