Challenges in Catalysis Applied to Pharmaceutical Development

2012 Spring Symposium

Alan M. All­geier
DuPont (for­mer­ly Amgen Inc.)

Abstract — In the devel­op­ment of phar­ma­ceu­ti­cals, catal­y­sis plays a crit­i­cal role and its prac­ti­tion­ers must nim­bly assim­i­late knowl­edge of organ­ic chem­istry, sur­face reac­tions, reac­tion engi­neer­ing and prod­uct iso­la­tion. In this pre­sen­ta­tion we explore three themes in catal­y­sis for the phar­ma­ceu­ti­cal indus­try: 1) Enabling New Reac­tiv­i­ty, 2) Qual­i­ty… Above All Else and 3) Speed to Deci­sions… Speed to Mar­ket.

New Reac­tiv­i­ty: Asym­met­ric hydro­formy­la­tion of nor­bornene and uti­liza­tion of keto­lac­tols as alde­hyde sur­ro­gates in reduc­tive ami­na­tion are described as nov­el chemistries demon­strat­ed on clin­i­cal man­u­fac­tur­ing scale. In the lat­ter case, den­si­ty func­tion­al the­o­ry pro­vides insight into the mech­a­nism of the reac­tion.
Qual­i­ty: The use of pre­cious met­al cat­a­lysts engen­ders chal­lenges of remov­ing poten­tial­ly tox­ic met­als to meet qual­i­ty spec­i­fi­ca­tions. The emerg­ing tech­nique of HPLC with ICP/MS detec­tion is a valu­able tool for under­stand­ing the diver­si­ty of resid­ual met­al com­plex­es and iden­ti­fy­ing process options to clear met­al impu­ri­ties. In one such devel­op­ment effort a unique dearom­a­ti­za­tion reac­tion was char­ac­ter­ized and its mech­a­nism elu­ci­dat­ed.

Speed: In con­duct­ing hydro­gena­tion catal­y­sis for phar­ma­ceu­ti­cals cat­a­lyst deac­ti­va­tion is inevitably observed at some stage of devel­op­ment. In one case deac­ti­va­tion was par­tic­u­lar­ly depen­dent upon gas to liq­uid mass trans­fer rates in batch reac­tors. A method for mea­sur­ing the vol­u­met­ric mass trans­fer coef­fi­cient (kLa) is described. Using this infor­ma­tion reduces risk asso­ci­at­ed with scale up from lab­o­ra­to­ry to man­u­fac­tur­ing equip­ment.

Speaker’s Biog­ra­phy — Alan All­geier grew up in the beau­ti­ful coun­try­side of north­west Penn­syl­va­nia. He earned his Ph.D. in Inor­gan­ic Chem­istry in 1997 from North­west­ern Uni­ver­si­ty under the direc­tion of Prof. Chad Mirkin. He com­plet­ed post-doc­tor­al stud­ies in het­ero­ge­neous catal­y­sis at DuPont under Dr. Theodore Koch and con­tin­ued at DuPont work­ing on hydro­gena­tion process­es for nylon monomers and spe­cial­ty chem­i­cals, as well as, homo­ge­neous­ly cat­alyzed olefin hydro­cya­na­tion for spe­cial­ty chem­i­cal appli­ca­tions. In 2004 Dr. All­geier moved to Amgen to estab­lish a com­pe­ten­cy in het­ero­ge­neous catal­y­sis and pres­sure chem­istry in sup­port of drug dis­cov­ery and devel­op­ment. In 2011 he returned to DuPont to lead a lab­o­ra­to­ry in the Sur­face and Par­ti­cle Sci­ence Com­pe­ten­cy. Through his career Dr. All­geier has been a leader in pro­fes­sion­al orga­ni­za­tions includ­ing Arrange­ments Chair, Pro­gram Chair, Trea­sur­er and Chair of the Philadel­phia Catal­y­sis Club, Board mem­ber of the 19th North Amer­i­can Catal­y­sis Soci­ety Meet­ing, and Chair of the Organ­ic Reac­tions Catal­y­sis Soci­ety and its 23rd Con­fer­ence. He is a con­tribut­ing author / inven­tor of six­teen jour­nal arti­cles and four­teen patents or patent appli­ca­tions and served as Guest Edi­tor for Top­ics in Catal­y­sis. His tech­ni­cal inter­ests include cat­alyt­ic reac­tions for hydro­gena­tion, car­bony­la­tion, and cou­pling, as well as, cat­a­lyst deac­ti­va­tion and reac­tor design.