A-Mab Case Study:Still A Few Challenges!!

Amit Banerjee, Ph.D

Pfizer Inc

1

Goal For Todays Presentation

Brief recap of the A-Mab case study

Implementation Challenges

Current State

Slide 2

A-Mab: a Case Study in Bioprocess Development

CMC Biotech Working Group

Background and GoalTo create a case study that provides a guideline

Started in August 2008

Concluded in October 2010

7 companiesGlaxoSmithKline, Abbott, Lilly, Pfizer, Genentech, MedImmune, Amgen

John Berridge, Sam Venugopal, and Ken Seamon, co-facilitators

Focused on science and risk-based approaches

Slide 4

To illustrate options to achieve enhanced product and process understanding

Demonstrate Industrys vision for QbD as applied to biotech product

Creating a Biotech Case Study:A-Mab

Why Monoclonal Antibody?

Represents a significant number of products approved and in development

Good product and process experience in development and manufacture

Slide 5

Based on a monoclonal antibody drug substance and drug product

A-Mab

Humanized IgG1IV Administered Drug (liquid)

Expressed in Cho Cells

Treatment of NHL

Is freely available as a teaching tool for industry and agencies

Outline and Intent of Case Study

ContentStructure

Introduction

Quality Attributes

Upstream

Downstream

Drug Product

Control Strategy

Regulatory

Intent

Contains pieces/ sections that appear realistic and represent selected QbD principles

Illustrates the benefits of a QbD development approach

Information represents real data or appropriate fictitious data

Not a mock CTD

Not a Gold Standard

Slide 6

Whats Next??

7

From Theory to Practice!

Critical Quality Attributes

Risk Assessment Tools

Design Space

Critical Parameter Designation

Control Strategy

An evolution8

Target Product ProfileDrug substance properties; prior knowledge

Proposed formulation and manufacturing process to meet desired product attributes

Determination of Cause Effect relationships

(Risk Identification with subsequent Risk Analysis)

Risk-based classification (Risk Evaluation)

Parameters to investigate (e.g. by DOE)

FORMULATION DESIGN SPACE

PROCESS DESIGN SPACE

CONTROL STRATEGY

Formulation understanding

Proc

ess

unde

rsta

ndin

g

F. Erni EFPIA Working Group9

A Road Map

Road Map for Process Understanding And Characterization

QA3 CQA1

QA5 CQA2

PP4 CPP4?

PP5 KPP5?

PP1 CPP1?

CriticalityOf PP

Describe inS2/P2 Section

Design SpaceCQA3 = f (KPP1, CPP4, KPP5 )

CQA5 = f (CPP2, KPP5 )Criticality of QA

PlanExecution

(DOE, Models,SOS)

QAQA

QAQA QA

QA QAQA

QA1 associated with PP1,nQA2 associated with PP1,nQA3 associated with PP1,nQA4 associated with PP1,nQA5 associated with PP1,n

RiskAssessment

QA1 = f (PP2, PP3, PP6)QA2 = f (PP4)QA3 = f (PP1, PP4, PP5)QA4 = f (PP1, PP3, PP4, PP6)QA5 = f (PP2,KPP5)

?

?

QA1 = f (PP2, PP3, PP6)QA2 = f (PP4)CQA3 = f (PP1, PP4, PP5)QA4 = f (PP1, PP3, PP4, PP6)CQA5 = f (PP2, PP5)

QA1 = f (PP2, PP3, PP6)QA2 = f (PP4)CQA3 = f (KPP1, CPP4, KPP5)QA4 = f (PP1, PP3, PP4, PP6)CQA5 = f (CPP2, KPP5)

C&E DOE/ExperimentalStrategy Output

Knowledge Space

Quality AttributeCriticality Assessment

FMECA

Con

trol

Str

ateg

y

QTPP

PP

PP

PP

PPPP

PP

PP

10

Align With Target Product Profile!

Developability AssessmentUnderstand Safety, Immunogenicity and CMC risks

Aid in Molecule Selection

11

Quality Attributes and the Criticality Continuum

12

A-Mab Case Study (2009): http://www.casss.org/associations/9165/files/A-Mab_Case_Study_Version_2-1.pdf

http://www.casss.org/associations/9165/files/A-Mab_Case_Study_Version_2-1.pdf

Process Understanding = Design Space?

Risk Assessment Methodologies

Equivalence of scale down models

Multivariate DOE studies

CPP and non-CPP designation

Experience from clinical batches

13

Comprehensive Control Strategy:Minimize Risk

14Establishment of Quality Systems

Where Are We??FDA Pilot Program

FDA approved Gazyva (!) including the QbD based control strategy and Design Space Nov 1, 2013. Lynne Krummen, Ph.D.

VP, Global Head Roche Technical Regulatory, Biologics2013 ISPE Annual Meeting

More to come????

15

A Case Study for Vaccines?

16

Look at the impact of A-mAb case

study!!Yes, of course, we must explore QbD for vaccine development!

CMC-Vaccine Working Group QbD Case Study

17

Thank you for your attention!

Questions??

18

A-Mab Case Study:Still A Few Challenges!!Goal For Todays PresentationA-Mab: a Case Study in Bioprocess DevelopmentBackground and GoalCreating a Biotech Case Study:A-MabOutline and Intent of Case StudyWhats Next??From Theory to Practice!Slide Number 9Slide Number 10Align With Target Product Profile!Quality Attributes and the Criticality ContinuumProcess Understanding = Design Space?Comprehensive Control Strategy:Minimize RiskWhere Are We??A Case Study for Vaccines?CMC-Vaccine Working Group QbD Case StudySlide Number 18