Critical Role of CMC Project Management
Critical Role of CMC Project Management
Critical Role of CMC Project Management
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<strong>Critical</strong> <strong>Role</strong> <strong>of</strong> <strong>CMC</strong> <strong>Project</strong><br />
<strong>Management</strong><br />
Round Table Session<br />
AAPS -2009<br />
Mike Yelvigi<br />
Sr. Director<br />
<strong>CMC</strong> <strong>Project</strong> <strong>Management</strong><br />
Pfizer Inc,<br />
Pearl River, NY
<strong>Critical</strong> <strong>Role</strong> <strong>of</strong> <strong>CMC</strong> <strong>Project</strong> <strong>Management</strong><br />
The Wyeth Model <strong>of</strong> Small Molecule Development<br />
Wyeth Model: The Way it Was<br />
Applies to small molecules development Similar systems<br />
exists for Biotech, Vaccine & Consumer Products divisions<br />
3 Tiered approach to <strong>CMC</strong> <strong>Project</strong> <strong>Management</strong><br />
<br />
<br />
<br />
Early Development Teams (<strong>CMC</strong> <strong>Project</strong> Leader-TAL)<br />
Global Technology Team (Operational Team Leader-<br />
NPL)<br />
Supply Chain Team (Supply Chain Team Leader-SPL))<br />
2
The Development Process<br />
Discovery<br />
Pre-Development<br />
Teams<br />
DT<br />
Transition period<br />
Learn Phase (P1-P2)<br />
Global Learn Teams<br />
DP3<br />
Transition period<br />
DISCOVERY L E A R N C O N F I R M<br />
Confirm Phase<br />
Global Confirm Teams<br />
Phase 3-launch<br />
Design Phase<br />
Optimize Phase<br />
Continuous Improvement<br />
FIH<br />
API route Formulation<br />
and scaleup<br />
Toxicology<br />
Formulation<br />
API Characterization<br />
‣ PhysicoChemical<br />
‣ Permeability<br />
‣ Material Properties<br />
Process<br />
Design<br />
QbD/PAT<br />
IVIVC<br />
Risk Assessment<br />
‣ Technology Platform<br />
‣ To-Be Marketed<br />
Formulation Design<br />
Transfer To<br />
operations<br />
Transfer<br />
to Plants<br />
Process<br />
Optimization
<strong>Role</strong> <strong>of</strong> <strong>CMC</strong> <strong>Project</strong> <strong>Management</strong> in Development Process<br />
Discovery<br />
Pre-Development<br />
Teams<br />
DT<br />
Learn Phase (P1-P2)<br />
Learn Teams<br />
DP3<br />
Confirm Phase<br />
Confirm Teams (P3-Launch)<br />
Transition period<br />
Design Phase<br />
Transition period<br />
Optimize Phase<br />
Continuous Improvement<br />
IND<br />
<strong>CMC</strong> <strong>Project</strong> Team Leader<br />
(TAL*)<br />
NDA<br />
Building the Basics<br />
•API Route scouting<br />
Operations Team Leader<br />
(NPL*)<br />
Supply Chain Leader (SPL)<br />
•API Impurity identification<br />
•API solid form selection<br />
•Initial risk assessment<br />
•Tox Formulation<br />
•FIH Formulation<br />
4<br />
Building Robustness<br />
•API Alternate route scouting<br />
•Technology platform<br />
•To-Be Marketed, Formulation Design<br />
•Site transfer<br />
•QbD/PAT<br />
•IVIVC<br />
*TAL:Therapeutic Area Leader, NPL-New Products Leaders)<br />
Continuous Improvement<br />
•Process optimization<br />
•Design-space defined<br />
•PAT in production<br />
•Post-launch support / Trouble-shooting<br />
•Optimization within filed ranges<br />
•Life Cycle strategy
<strong>CMC</strong> <strong>Project</strong> Team Leader (TAL)-<br />
External Collaboration Activities:<br />
<br />
Represents line functions (Chemical Pharmaceutical Development) at<br />
multidisciplinary project meetings & manages information flow,<br />
facilitates decision making and keeps regulatory time lines.<br />
<br />
Coordinate activities with alliance partners<br />
Chem.Pharm.Line Mgt.<br />
Pre-development<br />
teams<br />
Drug Safety<br />
and Metabolism<br />
<strong>CMC</strong> <strong>Project</strong><br />
Team Leader<br />
Manufacturing<br />
Group<br />
Medical Research<br />
Global <strong>Project</strong><br />
<strong>Management</strong> Team<br />
(Learn Team)<br />
Clinical<br />
Pharmacology<br />
Global<br />
Regulatory Affairs<br />
Commercial<br />
Alliance partners<br />
Patent Law<br />
5
<strong>CMC</strong> <strong>Project</strong> Team Leader (TAL)-<br />
Internal Collaborations Activities:<br />
Internal line function Collaborations (Chemical Pharmaceutical<br />
Development)<br />
Develops <strong>CMC</strong> strategy<br />
Coordinates activities across line functions, sites<br />
Quality<br />
Unit<br />
Stability<br />
Clinical<br />
Pharmacy<br />
Global <strong>Project</strong><br />
<strong>Management</strong> Team<br />
Pharmaceutical<br />
Development<br />
Clinical Supply<br />
Manufacturing<br />
<strong>CMC</strong> <strong>Project</strong><br />
Team Leader<br />
Chem .Pharm Team<br />
<strong>CMC</strong> Regulatory<br />
Submissions<br />
Analytical<br />
Quality & Sciences<br />
Chemical<br />
Development<br />
Documentation<br />
Services<br />
6
Seamless Transition and Knowledge Transfer<br />
from Phase 0 to Launch and Beyond<br />
•<strong>CMC</strong> <strong>Project</strong> Team Leader (TAL) Leads Chemical and Pharmaceutical Development<br />
Teams and ensures filing <strong>of</strong> IND, Phase 2 & 3 starts, continuity <strong>of</strong> clinical supplies, and<br />
project timeline maintenance<br />
Product Life Cycle <strong>Management</strong><br />
Stage I Transition, NPL to SPL<br />
•Operations Team Leaders (NPL) designated ~3 months before end <strong>of</strong> Phase 1 & leads<br />
Global Technology Teams until first regulatory approval and remains on Team (ad-hoc)<br />
1 year post approval-<br />
Supply Chain Leader (SPL) Leads Supply Chain Team and remains on the project for<br />
life cycle management (designated at GTT formation)<br />
<strong>CMC</strong> <strong>Project</strong> Leader (TAL) Assigned at Lead Selection<br />
Operations Team Leader ( NPL)<br />
Supply Chain Leader (SPL)<br />
Chem Pharm Team dissolved<br />
GTT dissolved<br />
Lead<br />
IND<br />
Selection<br />
Submission<br />
Establish GTT -<br />
early/mid<br />
phase 2<br />
Start <strong>of</strong><br />
phase 3<br />
Scale-up /<br />
registration<br />
batches<br />
1 st NDA<br />
Launch<br />
/MAA Launch<br />
approval<br />
12 months<br />
post<br />
approval<br />
1<br />
7
Mean Duration in Months<br />
Number <strong>of</strong> INDs<br />
Time Lines From Lead Candidate Identification to IND Filing<br />
25<br />
20<br />
15<br />
23<br />
17<br />
15<br />
6 Plus 6 Initiative<br />
Small Molecules<br />
12<br />
12.4<br />
12.6<br />
10<br />
5<br />
12<br />
9<br />
8<br />
12<br />
12<br />
8<br />
0<br />
2003 2004 2005 2006 2007 2008<br />
Year<br />
Coordination <strong>of</strong> all <strong>CMC</strong> activities toward initial IND submissions allows<br />
consistent completion <strong>of</strong> Pre-Dev to FIH activities in ~12 months
<strong>Critical</strong> <strong>Role</strong> <strong>of</strong> <strong>CMC</strong> <strong>Project</strong> <strong>Management</strong>-<br />
Round Table Session<br />
ACKNOWLEDGEMENTS<br />
Pfizer & Wyeth <strong>Management</strong>s<br />
Dr. Mahdi Fawzi<br />
Dr. Galen Radebaugh<br />
Dr. Richard Saunders<br />
Dr.Micheal Kolb<br />
Dr. Parimal Desai<br />
Dr. Debbie Cooper<br />
Dr. Ron Michalak<br />
9<br />
Thank You
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