1. LIB site visit January 24, 2002 Jay E. Slater, MD Laboratory of Immunobiochemistry FDA/CBER/OVRR/DBPAP

2. History of LIB n Laboratory of Allergenic Products, Division of Bacterial Products n Laboratory of Immunobiochemistry, Division of Allergenic Products and Parasitology Allergenic Products Testing LabAllergenic Products Testing Lab Allergenic Products Research LabAllergenic Products Research Lab n Laboratory of Immunobiochemistry, Division of Bacterial Parasitic and Allergenic Products

3. LIB mission LIB supports the regulatory mission of CBER and FDA in assuring the safety and efficacy of allergenic products in the US by 1. performing original research in the fields of allergen structure and function, and immunomodulation 2. responding to specific regulatory needs with directed research projects 2. responding to specific regulatory needs with directed research projects 3. providing expert advice and support for CBER and FDA staff regarding allergy and allergenic products 4. reviewing, confirming and approving lot release data from allergenic product manufacturers 5. assisting in the review of BLAs and INDs that relate to allergenic products

4. LIB is in NIH, Building 29, in the basement and on the 2 nd floor 211 B3 B1 214-218212203

5. Equipment n tissue culture hoods n chemical hoods n centrifuges n CO 2 incubators n light microscopes n thermocyclers n vertical and horizontal electrophoresis apparatuses and power sources n UV and light spectrophotometers n balances n pH meters

6. More equipment n mouse plethysmograph n fluorescent imager n magnetic cell sorter n flow cytometer (room 513)

7. Core facilities (Buildings 29, 29A and Nicholson Lane) n DNA sequencing n oligonucleotide primer synthesis n peptide synthesis n N-terminal sequencing n mass spectrometry analysis n amino acid composition n lyophilization

8. Shared equipment n gene expression microarray n circular dichroism spectrometer (Building 5) n NMR spectrometers (300 MHz and 500 MHz; 700 MHz on order)

9. Scientific goals n Allergen structure and function n Immunomodulation of allergic responses n Preparation and preservation of reference standards

10. Scientific goals Allergen structure and function Modifying allergic responses Extract preservation and potency determinations Latex, cockroach, hymenoptera LPS RSV, MDR Lyophilization Precipitates in allergen extracts MALDI-TOF of allergen extracts Cross-reactivity between foods and latex SELDI technology in identification of allergens PAR-2 activation in mast cells

11. Scientific goals Allergen structure and function Modifying allergic responses Extract preservation and potency determinations Latex, cockroach, hymenoptera LPS RSV, MDR Lyophilization Precipitates in allergen extracts MALDI-TOF of allergen extracts Cross-reactivity between foods and latex SELDI technology in identification of allergens PAR-2 activation in mast cells

12. Scientific goals Allergen structure and function Modifying allergic responses Extract preservation and potency determinations Latex, cockroach, hymenoptera LPS RSV, MDR Lyophilization Precipitates in allergen extracts MALDI-TOF of allergen extracts Cross-reactivity between foods and latex SELDI technology in identification of allergens PAR-2 activation in mast cells

13. LIB research program ResearchRegulatory Latex, cockroach, hymenoptera Regulation of recombinant allergens; immunotherapy options LPS Adjuvant safety and efficacy Extract potency determination methods Lot release for current and future products Extract preservation US standard reference maintenance RSV Parameters of effective immunomodulation MDR Novel approaches to immunotherapy

14. Technical capabilities Project Primary tools and capabilities latexhymenoptera protein analysis DNA amplification/analysis cloning and mutagenesis cockroach combinatorial IgE library LPSplethysmography RSVMDR flow cytometry cell sorting

15. LIB technicians are involved in research and regulation Position Research activity Marc Alston Biologist RSV, lyophilization Mona Febus Microbiologisthymenoptera Albert Gam Biologisthymenoptera Melissa Patterson Biologist latex, cockroach, precipitates Cherry Valerio Biologist LPS, lyophilization

16. Rabin presentations n Characterization of responses to RSV by T- cells from human tonsil (Rabin and Alston) n Modification of multidrug resistance protein activity as a potential mechanism of immunomodulation (Rabin and Huang)

17. Soldatova presentations  Glycosylation and the allergenicity of honeybee venom hyaluronidase (Soldatova, Gam and Dobrovolskaia)  Cloning of a new bee venom allergen, acid phosphatase (Soldatova and Dobrovolskaia)

18. Slater presentations n The effects of LPS on allergen responses (Slater, Valerio and Trivedi) n Modification of the latex allergen Hev b 5 for the immunotherapy of latex allergy (Slater and Patterson) n Molecular characterization of the immune response to cockroach allergens (Finlay, Slater and Patterson)