Quality by Design & Question-Based Review: Observations by the Generic

Pharmaceutical Industry

Advisory Committee for Pharmaceutical Science

October 5, 2006

Gordon Johnston

Generic Pharmaceutical Association

Outline

• Introduction

• Quality by Design

• Question-Based Review

• Summary

Introduction

• QbD/QbR – Requires significant changes to cross-functional

coordination within firms– Shift to QbR content represents a major change

• Cautiously optimistic• A steep learning curve for industry• Conversion to CTD format• Aggressive implementation schedule by FDA• ~ 800 ANDAs expected in CY 2006

– Increased burden for industry

Quality by Design

• Extensive manufacturing expertise in the industry– Generic firms often manufacture 50 - >100

products– Product and process understanding is critical for

efficiency

• Concepts of QbD have been in use by industry for many years– QbD represents a more organized and

integrated approach to product development

Quality by Design

• Opportunities– Value in ‘prior knowledge’– Extensive experience with common

formulations• Excipient properties well understood• Critical attributes impacting manufacturing

process known

Quality by Design

• Opportunities (cont’d)– Keen knowledge of equipment and

common manufacturing processes• Blending, coating, etc.

– Potential for reduced review time– Potential for reduced post-approval

burden

Quality by Design• Are QbD expectations clearly

defined?– GMP implications?

• Experience to date is mixed• ICH Q8 concepts still being integrated by

Field• Field often expects full design space

validation• Prior knowledge not universally accepted

by investigators at this time

Quality by Design• Should FDA modify its focus?

– Generic industry still required to accept FDA dissolution specifications

– Continued requirements to set specifications typically based on process capabilities and not product performance

• For example, residual solvents

– More guidance on non-oral dosage forms needed

Question-Based Review

• Represents a tool to efficiently assess QbD approach

• Industry is supportive of the initiative

• Industry and OGD still learning

Question-Based Review

• OGD Model QOS– 2 years in the making– Open dialogue between OGD and

generic industry during evolution– OGD responsive to Q&A sessions

Question-Based Review

• OGD Model QOS– OGD-industry collaboration has

accelerated industry’s understanding of QbR

– Ongoing communication critical during full implementation

Question-Based Review

• OGD Model QOSs– Help industry recognize issues OGD

generally considers critical – Guide industry toward quality by design– Assist industry to prepare a high quality

QOS

Question-Based Review

• OGD Questions– Allow industry to address some

questions with prior knowledge

– Industry has been active in submitting QbR applications• Over 35 ANDAs

• First ANDA Approval last month

Question-Based Review

• Challenges– Simultaneous conversion to CTD format

and QBR data elements– Implementation schedule has been

challenging for some companies• Some companies have been submitting QbR

applications since this summer

– Substantial internal training and coordination required for implementation

Question-Based Review

• Challenges– Still uncertain on OGD expectations for

QOS and product development reports– Oct 20 OGD training on how to

prepare a high quality QOS• Initial response is very positive

– More OGD training if needed

Question-Based Review• Recommendation

– Post-approval reduction in regulatory burden?

• Industry requests clarity on types of supplements where regulatory burden may be ‘downgraded’

– Extending QbR concept to already approved products (>8000)?

– Extending QbR concept to drug substance DMF

Summary

• Excellent communications by OGD– Numerous meetings, webcasts,

teleconferences during development phase of QbR

– Ongoing industry-OGD communications critical

• Increased burden

Summary

• Need to expand QbR to already approved ANDAs and drug substance DMF

• Post-approval regulatory relief a critical outcome of initiative

• Industry remains cooperative and hopeful

• Reassess in a year