tae ee ty | dead #5 Engin a4 assessment. : An _inbockeuct reduteenetnt in AR _detenaimation _t6 alg fo or mimits , ao clive on aimed that Coneleter oie or Aiborder in huenonts the dewelefpmaent hoe animal j_—seedels th usually 0 fg iii, - cud _tepensive eaten [> the problems ith these _medels are + ak they tag a | _ Stimulate the diease os _reanifeted hasan ead Aips cud Seme Cancers do not have prechictive animal vaeclch), . 3 One the animal ved i _characten'acl, variows doe _levely jeoad are dented fom either at Strtenieg of bro other Sources, 7 thee dete ane ther aduiniteed > the tart shew to telah & dete redone celeb oe o wos n La ee dow that prowides he Com (ry, eee T | 9 Sdrckeral wnaloge oj ctie dead ne d wag also ede tuted fr Doo a Dthe fead with the Night Lislogrel achwity selected— | - _ : 4 i 7 - oO a _| fee Serther Aeveloprrenct, tee sl od wl 2 Usually.» “thee fheraloyy —ehitin art conducted ja at leat ee He shows thatthe _biclagcal_refonse is ok_shusine | Aepeudent, - | she Deo dose ancl ho - observatle =torie- eject dose ty te Game _animet | Shera are determined -fo_exhimete 4 Aherapencic. 5 index Cratie). oT} the Ahuebeube index 8 4A tte ead 8 Gousideved te_dlratt adverse ebech (AEs) in addrttan ‘othe beneBierad ic ind By ame reFen al AO or more Indicates that oc dead will most dik produce a Loeracolagnd reifonse before Causing doce ctiniling “pesation > these _dewelopurental Yransccdngs Shidig, are (onduckd ot e Shady vote Aas devel utes Ah trdueney of deg debe used in hive bid, is Steals cde = the number ok doses wefured fo reach 2 cheady sleds defends on he leaat's | Vaamacoleinelis ofits in Ba Same |___auimeh wedel. thet nuutliftedose shiditn _prvide infomation | 2 atte edueney of dosing ecesiony fo ize the : bistogreat ropone thos eveluahons el in deciding doce leyels acl ste rouble ond Feaduency a —adwinisbradiin for _freliainang sual ey tive bop cols studien and Woade -T Séfely enh oleance human thetToxitologicat Dain. ee Sladvey exe Gouducleel Ife eS fs, oy day — Godel som Be sludi—tnclud__ defining ne -obserea be nat dee samum tolerated dose CMTD) , potential organs —eh feet ead drake s}able —bidhemical makes _for_detecivg —and stacking —eie pec 1 else =) Before these study »_suffinrent —qusuciby sh the ted it sith, and characterized. inthe Jend , then some of Tf Some changes eve made 4 athe tol doxiapiel Sfudirey are vebcated sotth the neo femutakin 4p delermina, 94 unwanted ettech Jeads Safe profile > Below these shud, do Supbort Claim for the lead os a dwg an IND Submission need do be iniheded, dy 7d Submission rust include subj orking Aste of in vitro and animal exfunmncte eosducted fo _charadenite the ote dowicly of dn Comdidehe J+ thee eit _doviestogiea| sbudhitn ose _covducted in ths Some shes as used in phomacdegy excluchors. > dhe lowe dose vith no _foete'hy | or with _accepinbl $ devel + teieity is Composeel with the dose the frctace Ata _deyred _Pharmacdagieal wapanse de _ebbevn « theaboob indey for that sheaves| DOME |ropeto | | > these early safely shuies ae wsually candace __ssonding ‘ : [> Examples of the carly orivology shudies are y | @ In-vitro toxicology Asasments - Cell based systems L pharmacclogreal target ells ave | i - imeubated 2 Various concerhahons or J the leads i Z + T Cell death or chouge ia Function Z wees set 3 these in _vitvo Systems cannot be used to predict tovicelogy, im ain al _medels or humans @_Acste Single dese doleability. stadia — qualitative sud duanblative Single —dore totiecly of a ead is evalueted Livestigatioal tes Drop Applian =? Ay Twerkgahinal new deg ig a neo d 5 bisloghal drug that ts used tn 2 clywical inveshig, Won, > A shouser who wither do tonduct a claseat tial that tavolves an IND must — Submet an Trverhgahonal Neo Ding Application COND) te she FDA. Tn twp Studies, the IND holder 1s considered fo be sponser. ls Curent Rederat lana _ refutes that dese be the sublect ab aw oppeored maarkehing application before it is sranspeckal4 4 or dicvheled across Hate lines birauies Sener " i frobatly wand te ship._the invetlpatvnal doug jp Cig ij mevesigatore in any Hates jf must Seele an reopen (hy, | Few the legal vequivements i *s he IND is dhe means Ahwough whieh the Spon cey i oad decknica lly chtajne his exenpl’on from -the Fp, fe pianaen: 5 — whi diug carly frecdinital development , 4p, a 4_Shonsen' Jprinnary — goal is te determing i the brodact 1 is_veasently safe oe initial use in humans y and Py th _tompoune__ ecb brs phamacological activity that ache, jaa Commereial development. a ce jt then a preduct is tdentifed as a —_yrable Candidate fo, | ___arther development, the sponser then focuses om Cellechng the data and information necessary fo erlatlah thot s the _poedud vill not expose humans +e _unsearonat! risk | aos then used im —_ limited gory — stage clinteal —_shuckies, {=> [on IND application mush _coulsin information in three broad ete Animal phamacclegy tad Tovivdlogy Studies — Preclinical data _f>_ thether the product & reasons efor tial tegting tn humans: Alo included are ey —}_prewious expertonce with athe dng in humans (often Foreign us 1 Henfecacrg defecation Infrmshion — ferlaincng athe Gabe = meanfacturer ) stabi ity dunch Controls scat -for__mawfacheing he ——}- ding __Subtance aad ‘the das ‘J_preduct dhis _ifermahion 5 — assessed do ensure that the Gupany can adequately pels ike Any assessment 9 and oa Sia230M |e Na 74 and Supply Consistent halche of the dew. *_clinteal__profocols 4 Saves hgator_informahion -— Detailed protocels for proposed clinical Studies fo _acsess whether the inihal - phase 2 Analy will expose subjects 4p unnecessary risks. Also, infomation a en dhe _quatificaWons of clinical investiqalers ~ bro fessionals ice Cy ererat_phoy sresans) ushe oversee the adminishabien of the experimental compound - fo assets _eehether they ave _duatiReel fo — falH MN thers clinical bial duties. . =P Finally Commitments 4° _ebtain _inforined Censcatt__-tom _ the E research Subjects, Fo obtain review of the shudy by an I jnstitevonal revéer board CIRB) , and A> adhere to the inushgakinnl nes dig vegulation |= EDA receipe of the IND = | upon ceceipt ok tne IND by FDA, an IND number ail be assigned 1 and the abplicatien will be forwarded 40 the | Sbproprrate reviewing diviscon. i | go the Ease division sil) send 4 letter _4o the shonsor- Thveshig a tor providing notihiation of the ID number assigned , date of vecapt 6 the original ap}ticab'on » addres: where { Future submissions te the WO should be Seat, and the name and telephone number of the EDA person to schom questions about ‘the application should be directed. = 9 0A will shy ctne sponser twtr the date __jt_reeeiver “the application Abvough ah IND acknowledgment leer, INDE appt ation st ve gol seco eS eae[Gn _eavlier notification by. FDA [pone >! + 80 days aller FDA receives the Appice ten mh described iw Y he sponser that ah inveshiqa Hone The abby ne ave subject (a dinical Hold What the clinical ivelga how, Inthe IND may begins sisi ‘Www Once an _ IND application iy in effect y a dag _manfactue ,, new dng 1 the Invehgaby — Haine | Shih the: invtshigahondl ut | Administer an iy —— _ahe_a}plication. An inveshgator ray nok administer on inves | Wee drug ce human subject: until the IND Speeder oe iB |__n \e ints effect. S shee an too IND Categories: + Commercial + Research (non-cemmertia) D> _ there are three IND _yhes ¢ © Tovestigator IND - An investigator IND is submitted bya Jus whe both initiates and Conduch an _investigahion | ond ander sshost Immediate _divechion “the inveshigabional drug 15 adwinistond Or __dishensed- AL _plysigian might Submit’ a esearch INO fo propose studying gn _unapprored drug oy an apbroved _fmduct for anes jmestiqnh Indication or in 8 heww ahent _pepuladsn @_Emogenay Use IND - TH stlows the EDA to authorize _use_of sn__exhuimental dng in _an emergency situahion that does 4 het allow fiw for _submision olan IND _auondene with a) CFF 32-23 or gia.20, m3 Hic alse used ty patients sho do not met theStudy rolpcel, or | Approved Study rotacel or if £m _abprved | docs not exist. Haag an ce | @ Treatment WD = i ~Subsitled for _ ex) perimental drags thous in clinica _ Aeshing for ee —Sevians_or_ immediately _( |__ Threatening Condi — cite a Devi —chinreal tock és —Grducted ancl EDA review taker place Note - > _TH_is_sthe investigator's reshomsibilhy 4o dekermine ahether an IND is _necessarg for a study cthat involves a marketed deag. exempt from the IND regulations if they meet all five | the Criteria [uted o ¢ ZI CER 312-2¢bX4). > Studies of Jeeofully marketed dnugs are + The Stud y is wot intended to Subpert _ablroval of a hed indication or _a Significant change yy the product's Labelteg , othe studi’. “is not“ jakeadea Jo Support a Feant. 2 Uv ———Significantty tnaeasg the risks (or der tae wept, ofp the ish) change inthe products adverbiing | ‘The _shudy conducted in Comfliante th IRB and _intemed Consent regulations : + the shdy will not be wed te fromote non approved indices ~s_ the tinal Giteion, however veefuires inter retakion. + the inveshgahon docs not__involve 2 voule sl, adiminishahon, desage level, use ina pationtopulshion sox other factor that ~ Assodated With the use of the drag. } Ee