Advisory Committee for Pharmaceutical Science

April 13, 2004

OPS Update

Helen WinkleDirector, Office of Pharmaceutical ScienceCenter for Drug Evaluation and Research

Food and Drug Administration

Outline of Presentation

• OPS Mission, Vision and Goals• Developing a new paradigm for CMC review

in ONDC– Building on the Pharmaceutical Quality Initiative

for the 21st Century• New Personnel in OPS• Meeting Agenda

Mission Statement To ensure timely availability of high quality

drug products to the US patients through

– effective and efficient scientific assessment of relevant pharmaceutical and biotechnology information in regulatory submissions and

– by facilitating those scientific and technological innovation that improve understanding of product performance, quality and efficiency of development, manufacturing, and quality assurance processes

Vision

OPS is an international champion and leader in regulatory application of contemporary scientific knowledge of design, development, manufacture, and clinical performance of pharmaceutical and biotechnology products

Goals and Objectives OPS programs and projects will support the

achievement of the following attributes of drug products: Drug quality and performance is achieved and assured

through design of effective and efficient development and manufacturing processes

Regulatory specifications are based on a mechanistic understanding of how product and process factors impact product performance

Continuous "real time" assurance of quality

http://www.fda.gov/cder/gmp/21stcenturysummary.htm

Goals and Objectives OPS will implement a review quality system and

procedures that will: Recognize the level of scientific knowledge supporting

product applications, process validation, and process capability

Apply a risk based regulatory scrutiny that will relate to level of scientific understanding of how formulation and

manufacturing process factors affect product performance, and the capability of process control strategies to prevent or mitigate risk

of poor product performance

http://www.fda.gov/cder/gmp/21stcenturysummary.htm

Setting the Stage For the

Future

• FDA Strategic Action Plan• Pharmaceutical Quality for the 21st

Century• Resources• Other Influences

FDA Strategic Plan - Responding to Challenges and Opportunities• Efficient risk management - the most public

health bang for our regulatory buck• Empowering consumers - improving health

through better information• Improving patient and consumer safety• Protecting America from terrorism• More effective regulation through a stronger

workforce

FDA’s Initiative on Pharmaceutical Quality for the 21st Century

FDA Unveils New Initiative To Enhance Pharmaceutical Good Manufacturing Practices http://www.fda.gov/bbs/topics/NEWS/2002/NEW00829.html (August 21, 2002 )

Strong Public Health

Protection

Integrated quality systems orientation

Science-based policies and standards Risk-based orientation

International cooperation

Time

Directional Vectors

• Ensure regulatory review and inspection policies are based on state-of-the-art pharmaceutical science

• Encourage new technological advances• Encourage risk-based approaches that focus both industry and

Agency attention on critical areas • Facilitate modern quality management techniques, including

implementation of quality systems • Enhance the consistency and coordination of FDA's drug quality

regulatory programs, in part, by integrating enhanced quality systems approaches into the Agency's business processes and regulatory policies concerning review and inspection activities

Second Progress Report and Implementation Plan. http://www.fda.gov/cder/gmp/2ndProgressRept_Plan.htm (September 3, 2003)

Covering the Space Defined by the Directional Vectors

Risk

Science

Preapproval Inspection Compliance Program

Dispute Resolution Process

Comparability Protocol

PAT PAT

Pharmaceutical Inspectorate

Product Specialists on Inspection Process

Aseptic Processing

Guidance on CFR Part 11

Systems/

Integrat

ion ICH P2, QbD, & Risk ICH P2, QbD, & Risk ManagementManagement

Opportunities• Develop strategy for ensuring product quality • Revisit processes - all aspects of pharmaceutical quality - incorporate best

practices• Focus more on manufacturing and associated issues relating to quality of

products• Focus both review and inspection more on science• Enhance interactions between review, inspection and compliance• Foster communication with industry

– Early discussion of CMC questions– Dispute resolution

• Leverage resources to get “best bang for buck”• Simplify regulatory requirements and reduce regulatory burden• Eliminate “check box” approach

More Opportunities• Enhance training opportunities

– Plant residency – Cross training opportunities– Pharmaceutical inspectorate

• Enhance FDA’s knowledge regarding new technologies in manufacturing and encourage innovation

• Develop processes which are more focused on product risk• Revisit how quality of product relates to ensuring safety and efficacy - ensuring clinical relevance• Alleviate industry’s concerns regarding “reprisal”• Enhance international involvement

– Pharmaceutical Development– Risk Management

Resources

• CMC Workload for FY 2003– 159 NDAs (103 originals and 56 resubmitted)– 342 commercial INDs– 507 research INDs– 1858 CMC supplements, not including efficacy

and labeling– 1132 annual reports

• Fewer review staff

Other Influences

• 1995 - ONDC established - collocated with clinical divisions

• Shorter PDUFA deadlines• FDAMA• Harmonization/globalization• SUPAC, BACPAC • New technologies in pharmaceutical

manufacturing

Other Influences• PAT• Counterterrorism• Counterfeit products• BSE• Focus on generic products• Changes in industry - more global, mergers, etc.• Electronic submissions• Focus on risk management and quality systems

How to Achieve the Future CMC Review Paradigm

• Develop risk-based CMC review• Establish quality systems which help set framework

for ensuring dynamic organization• Focus resources towards efforts that improve quality

- not hinder or interfere with innovation• Focus on all aspects of CMC - chemistry -

manufacturing - controls

Advantages of New Paradigm in CMC Review

• FDA– More product and process knowledge shared by

industry for a better understanding of products and where manufacturing processes are in control

– More efficient resource allocation for review and inspection

– Increased trust and understanding of industry decision making

Advantages - cont.

• Industry– Fewer, more efficient, science based inspections– Faster, more consistent reviews– Potential for reduced regulatory burden– Manage changes with less FDA oversight– Focus resources on critical issues– Flexibility to focus on what should be done, not what

can be done– Improve communication with FDA

Advantages - cont

• Ultimate beneficiary - The public– Increased availability of drugs on the market– Faster approval of new products– Continued assurance of high quality products– Increased confidence– {And hopefully, reduced costs}

What the New Paradigm Will Include

• Develop strategies to recruit and train reviewers with expertise in drug discovery, analytical chemistry, pharmaceutical engineering, etc.

• Build a learning organization“A learning organization is an organization skilled at creating, acquiring, and transferring knowledge, and at modifying it behavior to reflect new knowledge and insight”

• Set specifications based on science and process understanding• Reengineer process

– Best practices– Metrics– Customer oriented

New Paradigm• Increase emphasis on manufacturing science - ask the “right”

questions at the “right” time• Implement peer review by FDA scientists and clinicians• Establish a program to better integrate review and inspection -

team approach - product specialists on inspection• Develop processes which ensure regulatory relief based on:

– Process understanding and control– Quality systems in manufacturing processes– Continuous improvement

• Create better work environment and promote job satisfaction

Challenges to Moving Ahead

• Current culture - both inside and outside of FDA• Hiring• Establishing performance metrics• Identify gaps in requirements• Reevaluate review process to determine right questions to ask to

ensure product quality• Understanding what is relevant science• Determine what needed from pharmaceutical development data to

assist in better understanding of manufacturing process• Develop a science-based risk model• Integrate better into inspection process including participating on

inspections

OPS New Additions

• Dr. Vincent Lee (OPS)• Dr. Mansoor Khan (DPQR/OTR/OPS)

ACPS Meeting Topics• Day 1

– Subcommittee Report– Proposal for PTIT (Parametric Toleerance Interval Test for

Dose Content Uniformity)– PAT Update and PAT for Office of Biotechnology

Products• Day 2

– Bioequivalence topics (highly variable drugs, bioINequivalence, and topical products)

– Awareness topic - Nanotechnology