FDA Guidance for Industry 1 Extended Release Solid Oral Dosage forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations

Abstract

This guidance provide. \ " 1"cco'IJ/mf!ndations to pharmm:ellticti/ sponson ' 'wbo intend to develop dOCfIllIl'llfatioll ill .mpp011 ofllJl in Vih'o/in vivo cor'relatiol1 (lVrVC) fl1" {111 07'al extended reiease (ER) dmg prodllct for minllission in a 1Iew d17lg application (NOli), abbreviated lmv drug a/lplimtion (IINDII), 01' antibiotic dmg appliclltion (IIA 011). The gaidam:e preselllJ a comprehemive pe1:fpective 011 (1) '/IIetbods of developing an I Vl VC (lilt! eVlllllming its predictability; (2) /Ising {/II I V1VC to set dissoilltion specifications; 01111 (3) applying all I VIVC a:i II sll1Togate for in vivo bioequivalel1ce when it is 7lecesstl1"Y to docu-JIIent bioequival'llce during tbe initial approval process or becallse of certain pre-01' postflpproval changes (e.g., j"o11J/ltiatioll, eqllipme17l, Pl"OceSS, find manu/act/wing site Cbll1lgCJ), BACKGROUND T he concept of IVIVC, particularly for ER dmg products, has been extensively discussed by phannaccutital scientists. The ability to predi ct, accurately ,mel precisely, expected bioavailability charocteristil~ for an ER product from dissolution profi le characteristics is a long sought after goal. Several workshops and publications have provided information in support of this goal. These are discussed briefly as follows: o A report from a 1987 ASCPT/DWAPSI FDA-sponsored workshop entitled Rep011 of Ibe lorkshop 01/ CR Dos(fge Forllls: Ismes (Ind COlln~"mies (1987) indicated that the state of science and technology at that time did not pennir consistently meaningful rvlVC for ER dosage forill s and encouraged lVJVC as a future objective. Dissolution testing was considered useful only for process control, stability, minor fonnubrion changes, and manufacturing site changes.