Matls Licensing Package for Amend 4 to License 20-20783-02 for T Cell

.- ~ .- , - . - - , _ . . - - - - - . . . .

. . m r' = = = m= =q m =_ % =>i=_======* a; 4 NRC TOMV m = =ma=a1 = = = = 3======y>' * ~ NS q pomL U.S. NUCLE AR REGULATORY COMMISSION g[ MATERI ALS LICENSE Amendment No. 04 (- h og y/ Purniant to the Atomie I nergy Act of 1954. as amended, the linergy Reorganitation Act of 1974 (Publie in 93-43Rh and Tule W. |Q ~ I Cale of I ederal Regulanons. Chapter i, Parts 30, 31, 3133, 34, 35. 39,40 and 70, und m reh.ux e on wtements mal reprocniatsns heretohire [>l - g nude b> ihe hansee a hecme h hereby nsued amhorinng the beensee to recene, auimre, possca ad Hansfer byptabiet, somte, and spesial h i nuelcar materul designated below, to use such inateri.d for the pur1% cts) atal ai the place (s) designated behm to deiner or trarnfer such tnatenal h _ { to perwm amhonfed to recche it m accordarne w uh the regulations of the apphesble Parthd 1 hn hsense shall be deemed to contain the conditions ! { spennca in scolon tx3 of de Atonue i nergy Ad of 1954. n amended. and h suNca to aH appheable ruiew regulanons arat onlers of the Nuclear p j Reputatory romnumou now or hereaf ter in etteet and to any ointhtiinn specined below _ ip : : 'y l__--___._._-_ ij in accordance with letters dated h i November 24, 1992, ih i j 1. -T Cell Sciences Incorporated 3. bcense number 20-20783-02-is amended !% - ; in its entirety to read as follows:

4 1 38 Sidney Street ------@ Cambridge, Massachusetts 02139 4 spiration date March 31, 1997 h , , b ! , 5 Docket or |j I 030-29658 > 1; i Reference No ._ | 1 6 th product, source, and/or 7 Chemkal and/or physical S. hiaitimum amount that licensee . special nuclear inatenal form may possess at any one time h_ i under this twense

i !A. Cesium 137 A. Sealed source (ORNL- A. 600 Curies j! q RAMCO-50 or 150-1000) |1 !| ,|9. Authorized use % 4 k : A. For use in an AECL Gammacell 1000 Model A Irradiator for the irradiation of material N % except explosives and flammable materials. 4 4, in f CONDITIONS. h >1 10. Licensed material may be used only at the licensee's facilities at 38 Sidney Street,-. q Cambridge, Massachusetts. y h I11. A. Licensed Material shall be used by, or under the supervision of, '- Carolyn Pettey, Ph.D., Roseann Glaser, Ph.D., Larry Henry or Karin Evans. g[

, t - - M 4: B. The Radiation Safety Officer for this license is Ellen M. Essigmann, Ph.D. 11 4 hj - L , :12. . Sealed sources or detector cells containing licensed material _ shall not- be opened or- h | i sources removed from source holders or detector cells by the licensee, f1 u : 4 | [13.'A. Sealed sources and detector cells shall be tested for leakage and/or 9 o : contamination at intervals not to exceed 6 months or at such other intervals as L | are specified by the certificate of registration referred to in 10 CFR 32.210, %;N j not to exceed 3 years. !h - h B. -Notwithstanding Paragraph A of this Condition, sealed sources designed to emit- alpha particles shall be tested for leakage and/or contamination'at intervals not to exceed 3 months. p )W]t| 0 0 120134 -OFFICIAL RECORD COPY b BM80M 89it ______,j____jML 10 I y - _ _ _ - ____-_ ___-______- __ - -- - _ - -_.__-_ - _ -_-_---______-___----

dS Er A CO M SS O p W84 q 1icenw nutnter ;j 2 q g MNIliRI ALS LICENSE g g gn;n,n,,0at E M _ - 4 SUPPLEMI NT ARY SHEET ij !q _ _ _ _ .030-29658 - .-- ?{ 4 H

- - - ____ _ - _ - 1- - /sendment.No._01 _ __

(13. Continued) CONDIT 1014S N h:. a fl C. In the absence of a certificate from a transferor indicating that a test has jii V been made within six months prior to the transfer, a sealed source or detector :M / cell received from another person shall not be put into use until tested, l. l f. i !! D. Each sealed source fabricated by the licensee shall be inspected and tested for ! h construction defects, leakage, and contamination prior to any use or transfer asl i a sealed source. !i i's E. Sealed sources and detector cells need not be leak tested if: !!' # !A|p h (i) they contain only hydrogen 3; or {- (ii) they contain only a gas; or j

# (iii) the half-life of the isotope is 30 days or less; or ! h ! f (iv) they contain not more than 100 microcuries of beta and/or gamma emitting ! f material or not more than 10 microcuries of alpha emitting material; or h Il ( (v) they are not designed to emit alpha particles, are in storage, and are not jf being used. However, when they are removed from storage for use or | @{ transfer to another person, and=have not been tested within the required | 4 leak test interval, they shallibe tested before use-or transfer. No sealed $ source or detector. cell shall;be istored for a period of more than 10 years without being tested for' leak'agefand/or_ contamination. b ( F 4 ,

$ F. The test shall be capable of detecting the presence of 0.005 microcurie of k _ radioactive material on the test sample. Records of leak test results shall be p kept in units of microcuries and shall be maintained for inspection by the !p j}f, Commission. If the test reveals the presence of 0.005 microcurie or more of |ti removable contamination, a report shall: be filed with the U.S. Nuclear !N 4|i4 Regulatory Commission and the source shall be removed from service and h l$ decontaminated, repaired, or disposed of in accordance with Commission k regul ation s . The report shall be filed within 5 days of the date the leak test i,1 g result is known with the U.S. Nuclear Regulatory Commission, Region I, ATIN: M k Chief, Nuclear Materials Safety Branch, 475 Allendale Road, King of Prussia, ti Pennsylvania 19406. The report shall specify the source involved, the test %{[ results, and corrective action taken. j|1"j !q 'M y G. The licensee is authorized to collect leak test samples for analysis by Bolton |y k and Galenek, Inc. Alternatively, tests for leakage and/or contamination may be pi % performed by persons specifically licensed by the Commission or an Agreement f! 9 State to perform such services. h 4 h 14. The licensee shall not perform repairs or alterations of the irradiator involving removal of shielding or access to the licensed material. Removal, replacement, and hp (g disposal of sealed sources in the irradiator shall be performed by a person li k specifically licensed by the Commission or an Agreement State to perform such N services. g V v bttw wmEvittttic wmyx%tte wachte mtymith h xr e r.zhttism N

-_ _-- _------_ - - - f *1r m sm ?x x x= E L 7 2=5'2?s?1*1 1 U:S NU AR~1?riiim?53*2CFMa*&*WL*Msm?W}) REGUL ATORY COMMISSION :3*%ITL'KW3?2*L*375?3?FR3*y NitC F o.rp J14 A * (_ J AGr 3 OF_ _3 D "8 PAGR.f (| Luenw number ;P,

M A'I Elll ALS LICENSE * 4 SUPPLEMENTARY SHEET - - - -20:20783:02 _ _ _ f;.h 4 030-29658__ _...._ k i ;Y - _ Ampndment No.. OL F $______._..______|h i (Continued) CONDITIONS t 'g 15. The licensee may transport licensed material in accordance with the provisions of 10 ! I 4 CFR Part 71, " Packaging and Transportation of Radioactive Material". ! Ji i 4! 16. Except as specifically provided otherwise in this license, the licensee shall conducti 4j its program in accordance with the statements, representations, and procedures J p; contained in the documents including any enclosures, listed below. The Nuclear !, j Regulatory Commission's regulation shall govern unless the statements, !' i representations and procedures in the licensee's application and correspondence are |, ft| more restrictive than the regulations. . f 1 i! A. Application dated December 8, 1986 |i B. Letter dated February 5, 1987 h f! j} C. Letter dated October 26, 1988 p Letter dated December 2, 1988 W D. ;>'| |4I E. Letter dated February 28, 1989 i> % F. Letter dated February 25, 1992 h $ G. Letter dated March 27, 1992 H. Letter dated November 24, 1992 y!I lip! }@( k !>l|b !Ii 4{i M / ;tbi A

,,< : N : I t i 9 i k|4: 'b 4 F! k !bi b kl # i a}> (4 9 h !>l N Ib'i Lt hj F !Fj For the U.S. Nuclear Regulatory Commission

: _ 0+ inn! Sirmed Em M

Date DEC Z D 1992 By aEr a. x:nemmt_ j Nuclear Materials SiTety Branch , 'hi t Region I |Pj King of Prussia, Pennsylvania 19406 11 fP h bTs' Tav.T&r_TassdmTjsssTmTJs5/rsersrars#smT.samfrirhamsmTm"tr.TakaN$

______- ______- ______- - - _ _ _ _ * ^ - ; : . O O

DEC 291992

License No. 20-20783-02 Docket No. 030-29658 Control No. I17471

T Cell Sciences, Incorporated ATTN: Patrick C. Kung, Ph.D. Executive Vice President 38 Sidney Street Cambridge, hfassachusetts 02139 i

Dear Dr. Kung:

Please find enclosed an amendment to your NRC hiaterial License.

Please myiew the enclosed document carefully and be sure that you understand all conditions, if there are any errors or questions, please notify the Region I hfaterial Licensing Section, (215) 337-5093, so that we can provide appropriate corrections and answers. | Please be advised that you must conduct your program involving licensed radioactive i materials in accordance with the conditions of your NRC license, representations made in ! your license application, and NRC mgulations. In particular, please note the items in the

enclosed, " Requirements for h1aterials Licensees." ;

Since serious consequences to employees and the public can result from failum to comply with NRC requirements, the NRC expects licensees to pay meticulous attention to detail and to achieve the high standard of compliance which the NRC expects of its licenseer.

-You will be periodically inspected by NRC. A fee may be charged for inspections in accordance with 10 CFR Part 170. Failure to conduct your program safely and in accordance with NRC mgulations, license conditions, and representations made in your- license application and supplemental correspondence with NRC will result in prompt and vigorous enforcement action against you. This could include issuance of a notice of - violation, or in case of serious violations, an imposition of a civil penalty or an order suspending, modifying or revoking your license as specified in the General Policy and Procedures for NRC Enforcement Actions,10 CFR Part 2, Appendix C. ~

! | | | OFFICIAL RECORD COPY m ic 3

[ _ - . -- .-

' * ' ~ .. . O O

T Cell Sciences, Inc. -2-

We wish you success in operating a safe and effective licensed program.

Sincerely,

'J ; -cM Sinies Ev: A: D.10n ee.nna

John K. Kinneman, Chief Research Development & Decommissioning Section

Division of Radiation Safety _ and Safeguards

Enclosures: 1. Amendment No. 04 2. Requirements for hiaterials Licensees

I ~ D SS:RI R p RI Oberg/mlb 1 mneman

12/ q /92. 1-2 % 2

OFFICIAL RECORD COPY - G:\WPS\h1LTR\L2020783.02 - 12/09/92

. .. _ _ _ - ______- _ _ - ______- ______- ______. . . .

- - - ". O . T CELL O - - SCIENCES

i : , S/

!!ovember 24, 1992

Tara Woidnor 03" liall Control flo. 116503 United States fluclear Regulatory Commission, Region 1 fluclear liatorials Saf ety Section B 475 Allendale Road King of Prussia, Pennsylvar,ia 19406 RE: Amendments to License flo. 20-20783-03 and 20-20783-02 Dear fis. Weidner:

Ar. we discussed by telephone last wook, Denico Aronson, our current ESO has resigned from T cell Sciences, Inc. ef fective !!ovember 16.

This letter constitutes a request for amendments to liatorials , Licenso 20-20783-01 and Irradiator License 20-20783-02. The requested changes are that the Radiation Safety Officer named on our licences be changed from Denise Aronson to Ellen 14. Essigmann. I am also requesting that this amendment bo ovaluated on an expedited approval basis. A check for the amount of $940 is enclosed, the fee for the processing of those amendments. 4 A summary of my training and experience, as it relates to work with radioisotopes, is attached along with a copy of my curriculum yhig . Please note that I have hold the positions of Assistant Radiation Safety Officer and Radiation Safety Of ficer at a previous place of employment. As Chairman of the Safety Committee at T poll Sciences, Inc., I worked closely with the previous RSO, Jorry Carson, on matters relating to compliance with !1RC requirements. In addition, I supervised D7niso Aronson, the current Radiation Safety Officer, for a period of two years.

Please lot me know if you require any additig al i n f ormat-icn ' regarding my training and experience. ' @anh_ _you - f or--your - assistance in this matter. w.r ..x c .cm ------s e n t c r _ ' _ _ _ - .=- , ------Sincere 1y, Ch:ek noel 2EQtE ,- ---- Amount 924 J_#f fld2LL'DM- in C:Mr;ary --.. ------y ; N, ,y . . 10 e c,t M _ _ _ _7 ------Ellen fi. Essigmann, Ph.D. j D"to Chak Rec'di p Mi- --- - Associato Director, Regulatory Affairs : Date Cqmpktod ntm/f'------a Byj n P_CZ; _ - -- :------Enclosures (2) ZC ( d (- 330 B. no w 11,v,1,,1, OFFICIAL ImCgl}yglg33 E 01 E

T Cell Sciences. Inc 38 Sidney Street Cambndge. MA 02139 4135 USA 617-621 1400 Telex 9102401560 lelefax 1-617-621-1420

______. - _ _ _ _ . . . . _ . . . _.- ._-_.- . - . _ - _ - ._. .- - - . - - .. - - _

- ...... o 9

. .

RELEVANT EXPERIENCE WITH RADIOISOTOPES: i Ellen M. Essigmann, Associate Director, Regulatory Affairs and Chairman, Safety Committee Hausachusetts Institute of Technology: 1976 - 1980

Trainina - Rocnived MIT general radiation safety orientation and on job training in use of radioisotopes, autoradiography and radiometric techniques. Cource matorials covered the following areas:

. principlos and practicos of radiation protection; biological offects of radiation; . emergency . written proceduros for routine and operations; and relevant NRC . NRC license requirements and regulations. Work experience -

Worked with 3 H, "C from 1977 - 1980. Possessed quantitics of up to 150 mC1.

H.G. Pars Pharmaceutical Laboratories, Inc.: 1980 - 1986 Trainina - Received general radiation safety orientation and on job training in use of radioisotopos. Courso matorials covered the following areas

, principles and practices of radiation protection;

. biological effects of radiation; for routine and emergency . Written procedures operations; and and rolovant URC . NRC license requirements regulations.

Work experience - Worked with "C , 3H and 123 I from 1980 to 1986. Possessed quantities of up to 200 mci. Study Director for weekly evaluations of 123I-labeled fibrinogen which included rabbit blood clearance assays, rabbit pyrogen tests - and general safety tests conducted in mico and guinea pig. Wrote a comprehensive set of in-house standard operating proceduros for the safe handling of radioisotopos and for work involving animal injections with radioisotopos.

, . _ -. . . - - - _ _ _ . . . _ . --. . _ . _ _ . - . . _ _ . _ -. ------_ _ _ - _ _ _ _ _ - ______- ______

- - - '. . o o

. . Assistant Radiation Safety Officor, from 1982 to 1983, with responsibility for wipe testing, radiation waste management and manifouting. Radiation Safety Officer from 1983 to 1986.

T Cell Sciences, Inc.: 1987 - present Work Experience - Chairman of Safety Committee from 1987 to present. Supervised Assistant Radiation Safety Officer and Safety Officer from 1990 to present. Assisted Radiation Safety Officers in matters of !JRC compliance and oniployee saf ety, from 1987 to present.

------_ _ _ ,

- ...... o o ! ,

b ! ' CURRICUWH VITAE

ELLEN M. ESSIGMANN 15 Thatcher Street , | Brookline, Massachusetts 02146 617 566-3886 -1 I

EDUCATION! , ' . i PhD 1980 Massachusetts Institute of Technolo67e Department of Applied Biological Sciences Major field: Biochemistry and Metabolism ' Minor field: Experimental Animal pathology MS 1974 Northeastern University, Department of Biology BS 1970 Northeastern University, Department of Biology Major field: Biology Minor iield: Chemistry

PROFESSIONAL EXPERIENCE: ! 1987 to Present: Associate Director / Director of Regulatory Affairs and Chairman, Safety Committee; T cell Sciences, Inc., Cambridge, Massachusetts Established and directed a regulatory affairs department, Department responsibilities included company regulatory compliance, FDA documentation and submissions, clinical research, and employee health and safety. 1985 to 19861 Vice President of Clinical and Regulatory Affairs, H.'O. Pars Pharmaceutical Laboratories, Inc. , Cambridge, Massachusetts

Established _and directed a new Regulatory and Clinical Affairs Department- , consisting of seven full time employees. Department's responsibilities incluJed regulatory compliance, FDA documentation and submissions, and clinical research.

: Routinely prepared long range development programs (preclinical and. clinical * research, regulatory affairs) for company drugs, including financial proj ec tions . Identified qualified Principal Investigators and performed pre-investigation -visits. Established a team of clinical research scientists for monitoring of planned studies. Prepared and initiated a large Phase I and II'U.S. clinical program for the development of oral and~ parenteral forms of a mixed agonist / antagonist analgesic.

, !

. . _ . . .._,,,-u-,,.,_. _ . . . . , . . ._..,,...... - , _ . . .__a,- . _ , , . . . - , . . - , , _ . . ~ . . . _ - ' .. ' ., . . . . O O .

Project Director for preparation of New Drug Application for Delta-9-THC-for < use as an antiemetic for nausea and vomiting secondary to treatment with cancer chemotherapeutic agents. Direct responsibility for preparation of preclinical overview and for individual summaries of animal pharinacology and toxicology studies.

Supervised a Data Management Specialist in developing and providing support services for the department and the company.

1983 (November) to 1985 (Janusry): Director of Clinical Pharmacology. H. G. Pars |' Pharmaceutical Laboratories. Inc.

' Supervised clinical research program for in-house drug candidates, j Responsibilities included maintenance of INDs for all Para drCgs: preparation j and filing of INDs, IND supplements, safety reports and annual reports to the i FDA.

, Overall responsibility for sponsoring new clinical investigations (protocol.and | case report form design, selection and evaluation of prospective investigators , and investigation sites) and monitoring and reporting of trials. Drafting and ' revision of Investigator Brochures.

Vrote a comprehensive set of standard operating procedures for the sponsoring ! and monitoring of clinical investigations, reporting of adverse events and documentation of manufacture and disposition of clinical supplies according to Good Clinical Practice guidelines and regulations.

1983 (November) to 1985 (January): Acting Director of Preclinical Pharmacology, H. C. [ Pars Pharmaceutical Laboratories, Inc.

Supervised the completion and reporting of a $50,000 Phase.I Small Business Innovation Research (SBIR) program designed to select a candidate analgesic for further developtnent. Research included performance of primary dependence assays. and screens for antinociceptive and CNS activity. Responsible for preparation of a two year Phase 11 SBIR proposal for the development of the selected ; analgesic. The proposal was awarded $500,000 over two years by the National < Institute for General Medical Sciences. Acted as overall project director for-

this development program. Directly supervised design and reporting of ^ preclinical research aspects of this program. , Project director for a $50,000 SBIR project designed to select a leading candidate for development as' an antihypertensive agent.- Supervised six-month evaluation of four compounds for antihypertensive-and CNS activity. ,

Principal Investigator for a $50,000 Phase _I SBIR project designed to evaluate , the choline-deficient rat model for use as a bioassay for identifying potential ( chemical carcinogens. | Supervised preclinical research conducted on a cannabinoid antiglaucoma-drug- ! | .. ! candidate, including: use of ocular normotensive and ' ocular hypertensive rabbits for determining the mechanism of action of the compound; use of ocular

, 2

|. ' ' ;

- , . , . _ . . , . _ _ . . _ _ _ . . _ - _ . _ . - . __ _ 2._ ,__ . _ . _ - _ _ - .--_ _.u .J _

- . o o

normotensive rabbits in the conduct of biocquivelence assays and ocular irritation assessments for various formulations of the comPeund. 1983 to 1985 (January): Director of Toxicology,11. C. Pars Pharmaceutical Laboratories, Inc. Supervised the Manager of Toxicology in the operation of the Toxicology De p a r t:te n t . Interacted with sponsors during preinvestigational stage of studies. lleld overall responsibility for the scientific integrity of protocols and reports. Interacted with Quality Assurance Officer to ensure adequate compliance of department with relevant state and federal regulations. 1983 to 1986: Additional Experience,11. G. Pars Pharmaceutical laboratories , Inc.

Drug Enforcement Administration (DEA) Ofilcer. Overall n sponsibility for _ assuring that research quantities of Schedule I to V substances were handled in compliance with federal regulations. Radiation Safety Officer. Responsible for assuring that radioisotopes utilized in research and safety assays were handled and disposed of in cottpliance with stato and federal regulations. Wrote a comprehensive set of in-house standard operating procedures for the safe handling of radioisotopes. Chai rman of Anittal Vel f are Committee. Responsible for assuring that animals were handled and cared for in compliance with the Animal Welfare Act and relevant Nill USDA, and Massachusetta Department of Public llealth regulations. Directed the Supervisor of Animal ilusbandry. Obtained and maintained AAAlAC accreditation during this period. 1980 to 1983: Senior Toxicologist, Sisa Toxicological Laboratories , Inc. (A wholly owned subsidiary of it.G. Pars Pharmaceutical Laboratories, Inc.) Project Coordinator and Study Director on acute, sub-chronic, and reproductive toxicity studies. Responsibilities included involvement at virtually every L stage of the toxicity assessment of chemicals, pharmaceuticals and clinical diagnostic agents. This involved direct interaction with clients and, when necessary, regulatory officials. During the course of toxicity evaluations, responsibilities included supervision of technical personnel, direct implementation of some facets of experimental procedures, assurance of

compliance with protocol requirements and CLP/GMP regulations, evaluation of ~

interim results, and liaison with both client and in-house departments (i.e. ' Quality Assurance, Clinical Pathology, llistopathology and Analytical Chemistry). After study completion, duties included compilation and statistical analysis of data, interpretation of results and preparation of final reports. Other major responsibilities included; staf f training; preparation of project cost analyses; preparation of Drug Master Files for FDA submission; preparation of preclinical toxicology sections of IND applications; and preparation of in-house standard operating procedures for Animal Welfare, handling of hazardous substances and performance of sub-acute and sub-chronic saf,ty studies.

3 . - - .

...... o o :

1982: Institute of Applied Pharmaceutical Sciences Attended a three-day course offered by the Center for Professional Advancement, i entitled " Preparing Investigative New Drug and New Drug Applications and The ; ' Mechanics of FDA Regulations". i 1980: Internship in Industrial Toxicology Toxicol Laboratories, Ltd. ;

! I Two month internship in quality assurance and performance of acute, sub-acute and sub-chronic toxicity studies at site of sister company in Ledbury, England. 1974 to 1976: Research Assistant, Howe Laboratory of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts

Participated in the conduct of ocular-perfusion studies designed to investigate < the causative factors of several types of human glaucoma, particularly open-angle glaucoma and glaucoma associated with vitreous hemorrhage. Characterized the ultrastructure (transmission and scanning electron microscopy) of pathological specimens from the hwnan anterior segment. 1972 to 1974: Biology Instructor, Bridgewater State College, Bridgewater, Massachusetts

ACADEMIC EXPERIENCE:

' 1976 to 1980: Doctoral Candidate in Experimental Antoni Pathology, Massachusetts Institute of Technology

. Thesis Title: House Hepatic Neoplasia. This research consisted of an investigation of the morphology, biochemistry and biological behavior of spontaneous and induced mouse hepatic nodules for the purpose of (1) determining the malignant potential of the nodules, (2) determining new diagnostic criteria for nodule classification, and (3) evaluating the mouse as a carcinogen bionssay system. | The following research techniques were utilized in the conduct of the thesis research: light and transmission electron microscopy, development and use of a double-perfusion apparatus for the in vivo perfusion / fixation of the liverc autoradiography,-enzyme histochemistry, iscenzyme analysis (cellulose acetate and polyacrylamide gel electrophoresis, and spectrofluorometric, radiciaetric ^ and_ histochemical methodologies), tumor transplantation studies, tumor angiogenesis factor analysis and_ computer analysis of data using BMDP biomedical statistical: programs.

.. _ .. ... - _ . _ _ . . _ . . . _ . _ _ . _ . . _ _ _ _ _ - , _ . _ _ _ . . . . _ . - _ . - _ _ _ - . ' .. ' . .. - . O O

Additional Research Experience:

Assisted in the des 1& n and supervision of a 1200 animal chronic feeding study designed to determine the carcinogenic potential of an organochlorino pesticide. Assured performance of study in accordance with proposed EPA guidelines for Cood Laboratory Practice. Assisted in the design and supervision of a pilot study designed for the purpose of developing an animal model for arsenic-induced lung tumors. Utilized neutron activation analysis for detection of low levels of arsenic in the tissues of treated rats. Assisted in the de61gn and conduct of a histopathology study for assessing the acuto cifects of inhaled ozone on guinea pig bronchial epithelium and the rate of pinocytosis in intestinal epithelium overlying lymphold tissue in the large intestine.

Additionni Experience: Instructor for an EPA sponsored course in toxicology held at MIT (July, 1979). Authored a manual for MIT use, entitled " Manual for the Safe llandling of Carcinogens in the Research Laboratory." 1970 to 1974: Northeastern University, Graduate Student in Biology Ibesis Pesenrch: A light and electron microscope study of the morphology and light adaptation mechanisms of.the eye of a marine molluse,

PROFESSIONAL SOCIETIES. ACADEMIC HONORS Phi Sigma Society (Biology honor society) 1970 - 1971 President 1969-1970 Vice-President Sigma Xi Electron Microscopy Society- The Academy of Northeastern University Drug Information Association Regulatory Affairs Professionals Society

PUBLICATIONS AND PRESENTATIONS

llowes, J. F. , Villarreal, J . _ E. , liarris, L.S. , Essigmann, E.M. and Cowan, _ A. Xorphanel. In: Druc_ and Alcohol Denendence. 14. Elsevier Scientific Publishers, Ireland, 1985, 373-380, Elsevier Scientific Publishers Irciand Ltd.

Razdan, R. K. , Ilarris, L. S . , Dewey, W. L, , Essigmann, E. ' M. Heltzer _ P. Pars . ll. G. C. and Cowan, A. Analgesic and Narcotic Antagonist Activity of Synthetic Cannabinoids. Presented at American Society of Pharmacology and Experimental Therapeutics Boston (August, 1985).

5 . _ _ . . . _ _ _ . ______. _ . _ . _ . _ _ _ . _ _ _ . . _ _ _ . _ _ _ .. i .. .- ; ...... o 9 ! . . ; ! Cowan, A. , Pars,11. G. , Razdan, R. K. , llarris, L. S. , Dewey, V. L. and Essigmann, f E.M. Antinociceptive activity of Menabitan. In: Marihuana '84. Proceedinrs of the j 0xford Syrmosium on Cannabis. Edited by D.J. Marvey, W. Paton and G.G. Nahas, IRL | Press Ltd, Oxford England pp 693-699. 1985. ; Fox, J. C. , Ackerman, J . l. , Maxwell, K. and Essigmann, E.M. Campylobacter jejuni associated diarrhea in juvenile beagle dogs. Presented at the 24th Annual Session of the American Association for Laboratory Animal Science in San Antonio. Texas. ,

(November 1983). I Essigmann, E. M., McConnell, R. G. and Newberne, P. M. Transplantation studies on induced and spontaneous nodules from B6C3F1 mouse liver, Ig,& oloric Patholor.y 12:

211-220, 1984. ' , , Essigmann, E. M. The evaluation of a synthetic polymer " Wipe On" burn covering in the miniature pig. In: Burn t'ound Coverinrs, Vol. II, CRC Press, Boca Raton, Fla. ,1984

Essigmann, E.M. and Newberne, P.M. Transplantation studies with mouse hepatic * nodules. Presented at the Annual Meeting of the Society of Toxicology Boston (February 1982). ' Essigmann, E.M. and Newberne, P.M. Enzymatic alterations in mouse hepatic ncidules. induced by a chlorinated hydrocarbon pesticide. Cancer Research 41: 2823-2831 1981. !

- Essigmann, E. M., McConnell, R.G. and Newberne, P.M. A comparison of aryl hydrocarbon hydroxylase activity in spontaneous and chemically induced mouse hepatic nodules. Presented at the Annual Meeting of the Society of Toxicology, New Orleans (March, , 1979). Campbell, D. C. and Essigmann, E. M,, llemolytic Chost cell glaucoma, further studies. Archives of Ophthalmology 97 241-246, 1979.

Essigmann, E.M. and Campbell, D. C., Chost cell glaucoma, further studies. Presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla. (April, 1974). t t

" mmie w ,ImCoat COM - 117471

. . _ _ _ _ ;. - _~.-.,_____._,_-,,.,.._..,._,._,4 _ . . . . - - , _. , , _ , . . . - _ , . - , _ , . - - , _ . . . - _ . , - , . _ ,_ . _ ,_ . ._ ,

* . ,. . . e 7 , ,

e . : (FOR LFMS USE) : INFORMATION F00M LTS SETWEENt * ***-****"*-~~~~--"** : LICrNSE F EE MANAGEMENT t' R A tiCH , A2M : PROGRAM CODE: 03510 f. N D : ST ATUS CODE: 0 R EGION AL LIC ENLING SECTIONS : FEE CATEGORY: 3E : Exp. DATE: 19970331 t FEE C0MMENT$: ...... DECOM FIN ASSUR REQD: N. : : : : ::: :: : : :: : : : ::: : : : : : : :: :: : :: :::: :: LICENSE FEE ToAN5MITTal

A. R E GIO N

_ 1. ArcLIC AT ION ATTACHED APPLICA9T/ LICE 15EE: 1 CELL SCIENCES, INC. 2ECEIvt? DATE: 921201 00CKET NO: 30296 % CONTFDL NO.: 117471

LICENSE ND.: 2 C-20 7 3 3- 0 2 . ACTION IYP!: AMENOMENT

2. FEE ATTACHED ANGUNT: .[ ..... CHECK O.: ......

3. COMMENTS 6 e.9eren c.e. I17 4 'IO y2 ,sj' ,dwuno

ms-o 0A ?"e"- - g j v------p ,33gc7 enbd ^f['^"9 f . m ......

3. LICENSE FE? MANAGEMENT BRANCH (CHECK WHEN MIL ES T ONE 03ISENTERED/h./) _ , ,f - 1. FEE C AT~ GOR Y AND AMOUNT: df ...... j...... f ) y c

2. CORFECT FEE PAID.gAPPLICATION MAY BE PROCE3 SED FOR: 5 MEN 3ME9T ......

RCNEwAL ......

LICEN55 ......

3. OTHER ...... # p1

e oATE ,...e129.rx...... / !

w. .,