Office of Biotechnology Products

Steven Kozlowski, Director, OBPEdward Max, Assoc. Dir. Research, OBP

Site Visit Report Cellular, Tissue, and Gene Therapies

Advisory Committee Meeting April 17, 2013

Office of Biotechnology Products (OBP) Steven Kozlowski, MD, Director

Edward Max, MD,PhD, Assoc Dir Research

Division of Monoclonal Antibodies (DMA)

Division of Therapeutic Proteins (DTP)

Amy Rosenberg, PhD, DirectorGibbes Johnson PhD, Deputy

Lab of Molecular and Developmental Immunology

Lab of Cell Biology

Lab of Immunology

Lab of ChemistrySerge Beaucage, PhD, Chief

Lab of Molecular Oncology

Kula Jha, PhD

Jacek Cieslak, PhD

Serge Beaucage, PhD

Gibbes Johnson PhD

Office of Biotechnology ProductsSteven Kozlowski, MD, Director

Edward Max, MD, PhD, Assoc Dir for Research

Division of Monoclonal Antibodies

Kathleen Clouse, PhD, Director

Division of Therapeutic Proteins

Amy Rosenberg, MD, Director

Monoclonal Antibodies

mAb FragmentsFab, sFv, diabodies

mAb ConjugatesRadionuclide, drug, toxin

Fc-Fusion Proteins

Enzymes

Cytokines

Growth Factors

Toxins

Rituxan

ReoPro

Bexxar

Enbrel

Fabrazyme

Avonex

Epo

Botox

OBP PRODUCTSHAVE MANY CLINICAL

INDICATIONS

OBP Product Approvals/Year

Linear fit

App

rova

ls/

Yea

r

Approvals/Yr

0

2

4

6

8

10

1980 1985 1990 1995 2000 2005 2010

5 Year Running Avg.

Yervoy ipilimumabNulojix belatacept

Challenges in OBP Product Review• Variety of Cell Substrates• microbiology (virus, prion), host cell molecules• Heterogeneity• glycosylation, oxidation, PEGylation• Higher order structure : structure/function

• receptor interaction and signaling

• Manufacturing Issues• scale-up, solubility, aggregation• Mechanism of Action: sometimes unclear• design of bioactivity/potency assays• Immunogenicity: • safety and efficacy Issues• Comparability: manufacturing changes• Counter Bioterrorism: Animal Rule, stockpiles

Challenges in OBP Product Review• Variety of Cell Substrates• microbiology (virus, prion), host cell molecules• Heterogeneity• glycosylation, oxidation, PEGylation• Higher order structure : structure/function

• receptor interaction and signaling

• Manufacturing Issues• scale-up, solubility, aggregation• Mechanism of Action: sometimes unclear• design of bioactivity/potency assays• Immunogenicity: • safety and efficacy Issues• Comparability: manufacturing changes• Counter Bioterrorism: Animal Rule, stockpiles

BIOSIM

ILARS

OBP Research• Protein structure/function• Biotechnology manufacturing science• Mechanism of action

– Bioassays, Biomarkers, etc.• Immunogenicity• Adventitious Agents

RESEARCH

REVIEW &REGULATION

Researcher/Reviewer Model

Advantages for all reviewersAdvantages for all reviewers

•Scientific knowledge to evaluate:Scientific knowledge to evaluate:– Mechanisms of actionMechanisms of action– Potency assaysPotency assays– Adverse eventsAdverse events– Drug-drug interactionsDrug-drug interactions

•Hands-on technical experienceHands-on technical experience– State-of-the-Art scienceState-of-the-Art science– Product developmentProduct development– Analytical techniquesAnalytical techniques– Manufacturing methodsManufacturing methods

Definitions of Research Personnel

Temporary Employee

Permanent Employee

Independent Investigator

Tenure-trackPrincipal Investigator

“Converted”Principal Investigator= Senior Investigator

Dependent Investigator

Staff Fellow Staff Scientist

Research Career Paths

Site-Visit Team: Evaluate individual PIs and Service Fellows in a Laboratory Unit

• RESEARCH accomplishments since last review cycle• RESEARCH proposals for next four years

– Novelty and originality– Mission Relevance– Independence of the candidate– Productivity relative to time for research and research support

available

• Administrative/Management comments welcome• Regulatory activities and regulatory work quality NOT

assessed by Site Visit Team

Thank you!

To the Site Visit reviewers for your

time, expertise, and suggestionstime, expertise, and suggestions

to improve OBP’s research programs

Your input is critical to fulfilling our regulatory mission!