1. Office of Biotechnology Products
Site Visit Report
Cellular, Tissue, and Gene Therapies
Advisory Committee Meeting
April 17, 2013
Steven Kozlowski, Director, OBP
Edward Max, Assoc. Dir. Research, OBP

2. 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, Director
Gibbes Johnson PhD, Deputy
Lab of Molecular and
Developmental Immunology
Lab of Immunology
Lab of Chemistry
Serge Beaucage, PhD, Chief
Lab of Cell Biology
This is an abbreviated organizational chart to illustrate the general structure of the Division and to show the relative positions of those being reviewed today within that structure.
Dr. Bonvini is serving as the Acting Deputy Director of the Division and Dr. Patrick Swann is in charge of the full-time reviewers in the Regulatory Science & Policy Branch.
The 3 research labs are here headed by Dr. Clouse, Dr. Bonvini, and Dr. Kozlowski.
Dr. Markovic is a Staff Fellow in Dr. Clouse’s lab and Dr. Frucht and Dr. Feldman are Staff Scientists in the LCB and LIB, respectively.
Serge Beaucage, PhD
Lab of Molecular Oncology
Jacek Cieslak, PhD
Gibbes Johnson PhD
Kula Jha, PhD 2

3. Rituxan Fabrazyme ReoPro Avonex Bexxar Epo Enbrel Botox
Office of Biotechnology Products
Steven Kozlowski, MD, Director
Edward Max, MD, PhD, Assoc Dir for Research
Division of
Monoclonal Antibodies
Kathleen Clouse, PhD, Director
Therapeutic Proteins
Amy Rosenberg, MD, Director
mAb Fragments
Fab, sFv, diabodies
mAb Conjugates
Radionuclide, drug, toxin
Fc-Fusion Proteins
Enzymes
Cytokines
Growth Factors
Toxins
Rituxan
ReoPro
Bexxar
Enbrel
Fabrazyme
Avonex
Epo
Botox

4. OBP PRODUCTS HAVE MANY CLINICAL INDICATIONS

5. OBP Product Approvals/Year
Linear fit
Approvals/Year
Approvals/Yr 2 4 6 8 10
1980
1985
1990
1995
2000
2005
2010
5 Year
Running Avg.
Yervoy
ipilimumab
Nulojix
belatacept

6. 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

7. 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
BIOSIMILARS

8. OBP Research Protein structure/function
Biotechnology manufacturing science
Mechanism of action
Bioassays, Biomarkers, etc.
Immunogenicity
Adventitious Agents
RESEARCH
REVIEW &
REGULATION

9. Researcher/Reviewer Model
Advantages for all reviewers
Scientific knowledge to evaluate:
Mechanisms of action
Potency assays
Adverse events
Drug-drug interactions
Hands-on technical experience
State-of-the-Art science
Product development
Analytical techniques
Manufacturing methods
Extra edge of knowledge that can be disseminated to the whole office

10. Definitions of Research Personnel
Temporary Employee
Permanent Employee
Independent Investigator
Tenure-track
Principal Investigator
“Converted”
= Senior Investigator
Dependent Investigator
Staff Fellow
Staff Scientist

12. Research Career Paths

13. 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

14. Thank you!
To the Site Visit reviewers for your time, expertise, and suggestions to improve OBP’s research programs Your input is critical to fulfilling our regulatory mission!