PhRMA Perspective PhRMA Perspective on FDA Final Reporton FDA Final Report

FDA Advisory Committee on Pharmaceutical Sciences

October 20, 2004

G.P. Migliaccio, Pfizer Inc

Discussion TopicsDiscussion Topics

Culture Change General Comments on Report Quality Systems Guidance Risk-Based Inspection Model ONDC Risk-Based Quality Assessment

System Summary

Three Years of Culture Three Years of Culture ChangeChange• An unprecedented period of

communication and learning for both FDA and Industry.

• The culture change has been driven by open communications and a shared vision of the desired state.

• PAT was the model, much has followed.

Two Years of Culture Two Years of Culture ChangeChange Industry is moving from a fear of data to a

passion for process understanding. Science, not blind compliance, is winning

the day more often. Innovation is accelerating throughout

industry. Interactions during inspections are

changing.

General Comments on Final General Comments on Final ReportReport This is not the end, it is the beginning! PhRMA applauds the magnitude of what has

been accomplished and the rigor in which it was accomplished.

FDA and Industry Leadership must continue to work together to ensure that the guidance and position papers are fully understood, modified as appropriate, and implemented.

Much remains to be accomplished to realize our shared vision.

Quality Systems GuidanceQuality Systems Guidance

Comprehensive and of great utility. Companies are already using to assess Quality

Systems infrastructure. Key outstanding issue is defining the level of

process understanding required to achieve flexible continuous improvement.

Imperative that these concepts be addressed at global level and the FDA guidance provide a starting point for ICH discussions relative to the proposed Q10.

Quality Systems GuidanceQuality Systems Guidance

FDA and Industry must move away from current “Compliance Systems” to be able to achieve all elements of Quality Systems Guidance. e.g. Trending of data Some data generated for compliance purposes

can not be trended to gain process understanding.

Current specification system must evolve to allow reporting of meaningful data on CTQs.

Risk-Based Inspection Risk-Based Inspection ModelModel Solid step forward to allow FDA to focus

on higher risk sites. Elements of the algorithm require further

discussion – e.g. volume. PhRMA has serious concerns about

transparency.

Risk-Based Inspection Risk-Based Inspection ModelModel “Survey results were analyzed and process

control and contamination weights were assigned to each product category identified in the expert elicitation survey.”

“Individual risk-factor weights and final scoring information, as well as specific information used to generate the weights and scores, are intentionally not provided in this paper. FDA does not intend to publish or disclose such details of a site’s individual score or ranking, in order to effectively enforce the law.”

Risk-Based Inspection Risk-Based Inspection ModelModel “FDA’s customer relationship with industry will differ

depending on the transactions involved. At one end of the spectrum, industry clearly is a direct customer of FDA’s products or services. For example, when FDA develops guidance documents representing the agency’s current thinking on a particular subject, we provide clarity and understanding to firms that manufacture FDA regulated products. With this information, industry has a better understanding of the agency’s expectations about their products, and this may enable companies to manufacture products more effective or approach regulatory milestones with greater certainty.”

From Defining the Customer in a Regulatory Agency, Appendix B

Risk-Based Inspection Risk-Based Inspection ModelModel “FDA will now be using a Quality Systems

approach to improve the predictability, consistency, integration and overall effectiveness of our entire regulatory operation.”

from “Final Report”

Risk-Based Inspection Risk-Based Inspection ModelModel If FDA and Industry do not have a mutual

understanding of what processes/unit operations are higher risk, how can FDA and Industry appropriately focus their respective resources on high risk areas?

Transparency is essential.

ONDC Risk-Based Quality ONDC Risk-Based Quality Assessment SystemAssessment System Represents a profound change in the

organization and review process. PhRMA supports the objective, but much

work is required to achieve the end state. Will FDA approach this change with the

same level of leadership commitment and reviewer availability as demonstrated with the PAT and GMP initiatives?

Will FDA work with industry to ensure that the objectives can be achieved?

ONDC Risk-Based Quality ONDC Risk-Based Quality Assessment SystemAssessment System ONDC proposal could create expectations that

there will be a significant increase in the knowledge provided “up front”. Companies will provide different information resulting

in a greater degree of process understanding, but at NDA submission, the level will be limited.

Process knowledge will be sufficient to establish that a robust process has been developed.

Process understanding is a continuum, and will accelerate post approval.

ONDC Risk-Based Quality ONDC Risk-Based Quality Assessment SystemAssessment System FDA should work through ICH to establish

a global partnership for the risk-based quality assessment system.

We should not exacerbate the current differences in assessment systems but work to establish a global assessment approach.

ONDC Risk-Based Quality ONDC Risk-Based Quality Assessment SystemAssessment System Pre- and Post-Marketing approach

requires further evaluation. Process understanding significantly increases during first 1-2 years of marketing and potential for continuous improvement is highest. There is value to having the NDA reviewer also review these continuous improvement changes.

ONDC Risk-Based Quality ONDC Risk-Based Quality Assessment SystemAssessment System FDA has implied that there will be two

assessment systems, one for applications including manufacturing science/process understanding, the other without. Process understanding is not a “yes” or “no”,

it is a continuum. Every application will have a different level of

process understanding. How will a reviewer determine where any

application is in this continuum?

SummarySummary

The infrastructure is in place – some modification required.

The culture is changing. The desired state is on the horizon.