Why it Works: Man­u­fac­tur­ing a Vac­cine in a Mul­ti-Prod­uct Fa­cil­i­ty.

COVID-19 launched the phar­ma­ceu­ti­cal in­dus­try to the front­line in the bat­tle against the fast-spread­ing glob­al pan­dem­ic. The goal: dis­trib­ute a safe, ef­fec­tive vac­cine as quick­ly as pos­si­ble. Ma­jor play­ers in the vac­cine mar­ket need­ed to part­ner with con­tract de­vel­op­ment and man­u­fac­tur­ing or­ga­ni­za­tions (CD­MOs) to achieve the goal of mass vac­cine quan­ti­ties un­der ex­pe­dit­ed time­lines. With CD­MOs step­ping up to play a crit­i­cal role in the vac­cine man­u­fac­tur­ing process, mul­ti-prod­uct CD­MO fa­cil­i­ties took the spot­light. Part­ner­ships quick­ly formed as the race to save lives and fight a pan­dem­ic was on.

In 2020, the U.S. De­part­ment of Health and Hu­man Ser­vices and the U.S. De­part­ment of De­fense called up­on CD­MOs to sup­port the ex­pan­sion of the Unit­ed States’ ca­pac­i­ty for man­u­fac­tur­ing and dis­trib­ut­ing vac­cines or ther­a­peu­tics re­lat­ed to the COVID-19 pan­dem­ic. One ex­am­ple is through a pub­lic-pri­vate part­ner­ship where the fed­er­al gov­ern­ment re­served fill/fin­ish ca­pac­i­ty on a CD­MO’s com­mer­cial fill­ing line for use by fed­er­al part­ners that are de­vel­op­ing COVID-19 vac­cines or ther­a­peu­tic treat­ments. That com­pa­ny’s ca­pac­i­ty not on­ly sup­port­ed the U.S. gov­ern­ment’s Op­er­a­tion Warp Speed ef­forts and the COVID-19 pan­dem­ic re­sponse but al­so sup­ports an in­crease in U.S. pre­pared­ness for fu­ture pub­lic health emer­gen­cies.

Now more than ever flex­i­bil­i­ty is key to suc­cess in the phar­ma­ceu­ti­cal man­u­fac­tur­ing in­dus­try, specif­i­cal­ly for CD­MOs that serve a va­ri­ety of clients and prod­ucts. Com­bine height­ened aware­ness with el­e­vat­ed de­mand and re­duced time­lines, and the de­mand of CD­MO ca­pac­i­ty, qual­i­ty, and mod­ern equip­ment have in­creased ex­po­nen­tial­ly since the start of 2020. CD­MOs must be equipped to op­er­ate in a fast-paced en­vi­ron­ment with­out sac­ri­fic­ing qual­i­ty. The phar­ma­ceu­ti­cal man­u­fac­tur­ing in­dus­try is con­sis­tent­ly chal­lenged to be more cost-ef­fec­tive and to re­duce time­lines to get prod­ucts to mar­ket faster. Or­ga­ni­za­tions that can meet these de­mands and up­hold strong re­la­tion­ships with part­ners and ven­dors will find suc­cess.

Though tak­ing on ad­di­tion­al ac­cel­er­at­ed pro­duc­tion while meet­ing ex­ist­ing con­tracts may sound daunt­ing, a well-equipped CD­MO pre­pared with the right tech­nol­o­gy and team can com­pe­tent­ly and ef­fec­tive­ly rise to the chal­lenge. Ad­vanced tech­nol­o­gy, flex­i­ble equip­ment and ag­ile team mem­bers are defin­ing fac­tors need­ed for those se­lect­ed for the mass man­u­fac­ture of a vac­cine, un­der time-sen­si­tive cir­cum­stances, and in fa­cil­i­ties al­ready pro­duc­ing mul­ti­ple prod­ucts. The fol­low­ing fac­tors are vi­tal in an ever-chang­ing land­scape.

Adapt­abil­i­ty is Key

Meet­ing the de­mands of mul­ti­ple clients, prod­ucts, and batch sizes takes in­cred­i­ble flex­i­bil­i­ty. When con­sid­er­ing the biggest as­set to in­creased flex­i­bil­i­ty or ca­pa­bil­i­ties, build­ing a new state-of-the-art fa­cil­i­ty or ex­pand­ing up­on cur­rent fa­cil­i­ties like­ly comes to mind.

When de­cid­ing on fa­cil­i­ty in­vest­ments, it is vi­tal to con­sid­er the po­ten­tial ob­sta­cles of retro­fit­ted fa­cil­i­ties and tech­nol­o­gy. Retro­fit­ted and out­dat­ed fa­cil­i­ties make it dif­fi­cult to es­tab­lish one-way prod­uct flow, im­ped­ing their flex­i­bil­i­ty and adapt­abil­i­ty. Util­i­ties and in­ter­faces must be pre­pared to meet the de­mands of the lat­est phar­ma­ceu­ti­cal process­es. Re­quire­ments range in com­plex­i­ty from the reg­u­la­tion of vary­ing air pres­sure ca­pac­i­ties to en­sure asep­tic pro­cess­ing, to the HVAC ca­pa­bil­i­ties need­ed to main­tain a ster­ile en­vi­ron­ment. Air-han­dling sys­tems and flows must be de­signed to al­low for the cap­ture of air­borne par­ti­cles. New­er fa­cil­i­ties can be de­signed as such, with the ap­pro­pri­ate peo­ple and prod­uct flows to en­sure prod­uct con­tain­ment through­out the ster­ile man­u­fac­tur­ing process.

Key play­ers in the CD­MO space and es­sen­tial part­ners in pro­duc­ing life-sav­ing vac­cines saw an in­flux in ex­pan­sions due to the dra­mat­ic in­crease in de­mand for vac­cines and ther­a­peu­tics. One ex­am­ple be­ing Grand Riv­er Asep­tic Man­u­fac­tur­ing (GRAM) who em­barked on a phase 2 ex­pan­sion of their large-scale fa­cil­i­ty a year af­ter open­ing the fa­cil­i­ty’s doors, plus re­cent­ly com­plet­ing their new fin­ish­ing cen­ter in un­der one year.

Mod­ern, state-of-the-art fill/fin­ish fa­cil­i­ties pro­vide ac­cess to top-qual­i­ty ster­ile in­jectable drug man­u­fac­tur­ing for all batch sizes while cut­ting down the vari­ables for cross-con­t­a­m­i­na­tion and need­less waste. Mul­ti-prod­uct risk as­sess­ments cre­ate less room for er­ror and re­duces vari­ables of con­t­a­m­i­na­tion. CD­MOs should pro­vide a mul­ti-prod­uct risk as­sess­ment for each fa­cil­i­ty, iden­ti­fy­ing gates for po­ten­tial cross con­t­a­m­i­na­tion and mak­ing sure the CD­MO has pro­ce­dur­al or en­gi­neer­ing con­trols in place to mit­i­gate the po­ten­tial risks. Ef­fi­cient process­es and fa­cil­i­ty de­sign sup­port the pro­duc­tion of life-sav­ing vac­cines or ther­a­peu­tics.

FDA and EU guid­ance and reg­u­la­to­ry re­quire­ments en­cour­age the in­dus­try to mod­ern­ize and keep up with the lat­est safe­ty and qual­i­ty con­trol tech­nol­o­gy. CD­MOs not mod­ern­iz­ing their process­es or fa­cil­i­ties may run the risk of heavy scruti­ny dur­ing au­dits and find them­selves sub­ject to the as­so­ci­at­ed con­se­quences. De­spite these risks, an en­tire­ly new fa­cil­i­ty or ex­pand­ed space isn’t al­ways at­tain­able. This is es­pe­cial­ly true when up­dates are not a vi­able so­lu­tion due to bud­get, space, or time re­stric­tions. In­no­v­a­tive and up-to-date fa­cil­i­ties are es­sen­tial for fu­ture growth and emer­gency pre­pared­ness.

The Pow­er of Flex­i­ble Tech­nol­o­gy

Mod­ern equip­ment and tech­nol­o­gy al­low for greater flex­i­bil­i­ty, prod­uct con­tain­ment, and ca­pa­bil­i­ties. Lean­ing on reg­u­la­to­ry guide­lines, as well as ex­pe­ri­enced con­trac­tors and orig­i­nal equip­ment man­u­fac­tur­ers (OEMs), CD­MOs can con­fi­dent­ly choose the so­lu­tion that best fits cur­rent and fu­ture client needs.

One way to achieve this is to in­vest in ver­sa­tile tech­nol­o­gy like the Var­ioSys sy­ringe and vial filler with SKAN iso­la­tor. The mod­u­lar VaioSys tech­nol­o­gy of­fers unique, flex­i­ble L-flange tech­nol­o­gy. The L-flange hous­es the fill­ing sys­tem that fits in­to the iso­la­tor. Be­cause the L-flange can be re­placed with a new piece of fill­ing tech­nol­o­gy, it al­lows for the use of a vial filler, sy­ringe filler, and asep­tic for­mu­la­tion iso­la­tor—all uti­liz­ing one room and one iso­la­tor.

The unique L-shaped flange en­ables a quick ex­change of pre­cise­ly tai­lored mod­ules, en­sur­ing a uni­ver­sal ster­ile work­ing en­vi­ron­ment for asep­tic, or high­ly ac­tive phar­ma­ceu­ti­cal prod­ucts. This flex­i­bil­i­ty of­fers a huge ad­van­tage when it comes to se­lect­ing a mul­ti-prod­uct fa­cil­i­ty. A cus­tomer who has mul­ti­ple prod­ucts in their port­fo­lio with many dif­fer­ent pre­sen­ta­tions, rang­ing from vial to sy­ringe or car­tridge pre­sen­ta­tion, would be able to fill dif­fer­ent con­fig­u­ra­tions in one clean room.

Strate­gic up­dates in tech­nol­o­gy are what CD­MOs must strive for to ef­fi­cient­ly in­crease fu­ture ca­pac­i­ty, de­liv­er con­sis­tent­ly to clients and up­hold reg­u­la­to­ry guide­lines.

The Val­ue of Ex­pe­ri­ence

In­creas­ing flex­i­bil­i­ty and ca­pac­i­ty with in­no­v­a­tive tech­nol­o­gy is one thing, but it means very lit­tle with­out the cru­cial sup­port of tal­ent­ed and ag­ile team mem­bers. Adapt­abil­i­ty with­in your team is es­sen­tial to suc­cess, and just as crit­i­cal is their ex­per­tise. Every op­er­a­tor and MS&T (Man­u­fac­tur­ing, Sci­ence and Tech­nol­o­gy) spe­cial­ist must be an ex­pert in the equip­ment on hand to keep pro­duc­tion run­ning smooth­ly in a mul­ti-prod­uct fa­cil­i­ty. In­vest­ing in mul­ti­ple pieces of equip­ment and tech­nol­o­gy from the same OEM helps staff un­der­stand all as­pects of the tech­nol­o­gy more ef­fi­cient­ly. Team mem­bers can trans­fer the same lev­el of ex­per­tise from ma­chine to ma­chine, cut­ting down on train­ing and trou­bleshoot­ing be­tween batch­es and ex­pe­dit­ing pro­duc­tion for clients. It al­so cre­ates op­er­a­tors that are in­cred­i­bly skilled when go­ing from one ma­chine to an­oth­er and tran­si­tion­ing be­tween prod­uct batch­es.

In ad­di­tion to ex­pert staff, qual­i­ty re­la­tion­ships with OEMs pro­vide a mul­ti­tude of mu­tu­al ben­e­fits. Strong re­la­tion­ships have proven to re­duce time­lines and adapt new sup­port meth­ods un­der sit­u­a­tions when get­ting prod­ucts to mar­ket quick­ly un­der ex­pe­dit­ed time­lines is crit­i­cal. Strength in re­la­tion­ships has ex­po­nen­tial­ly come to light while the in­dus­try has bat­tled the COVID-19 pan­dem­ic. Con­sis­tent tech­nol­o­gy cou­pled with skilled op­er­a­tors makes for a safe and ef­fi­cient mul­ti-prod­uct CD­MO.

Knowl­edge­able team mem­bers backed by sup­port­ive part­ners is vi­tal to the suc­cess of projects, es­pe­cial­ly those with crit­i­cal dead­lines. While CD­MOs must in­vest in so­phis­ti­cat­ed tech­nol­o­gy to en­force reg­u­la­to­ry guide­lines, ded­i­cat­ing re­sources to the cu­ra­tion of a skilled team is cru­cial for the com­pa­ny’s suc­cess and the job mar­ket in the lo­cal com­mu­ni­ty. Do­ing so im­proves the abil­i­ty to meet new client de­mand as equip­ment, fa­cil­i­ties, and in­dus­try ex­pec­ta­tions con­tin­ue to ex­pand.

Look­ing Ahead

The suc­cess or fail­ure of CD­MOs to adapt to times of cri­sis and un­par­al­leled de­mand will ul­ti­mate­ly de­pend on their abil­i­ty to stay nim­ble. Look­ing to­wards the fu­ture, an­tic­i­pat­ing reg­u­la­to­ry re­quire­ments, and un­der­stand­ing the lat­est equip­ment and tech­nol­o­gy to sup­port the var­ied needs of cur­rent and prospec­tive clients is im­per­a­tive. Ad­vanced dig­i­tal so­lu­tions for mon­i­tor­ing and track­ing prod­ucts and process­es will con­tin­ue im­prov­ing to sup­port con­tain­ment in mul­ti-prod­uct fa­cil­i­ties. Mod­u­lar equip­ment de­signs of the fu­ture will al­low for the ben­e­fits of seg­re­ga­tion with­out the ex­pense of sep­a­rate fill lines, adding flex­i­bil­i­ty and tech­nol­o­gy for easy scale-up.

Ex­pec­ta­tions on these fa­cil­i­ties and vac­cine de­vel­op­ment will stay at the fore­front for years to come. The bat­tle against a pan­dem­ic and race to a vac­cine has ig­nit­ed some of the most un­like­ly re­la­tion­ships in­clud­ing those with the fed­er­al gov­ern­ment, glob­al phar­ma­ceu­ti­cal com­pa­nies, and ster­ile in­jectable CD­MOs. The spir­it of col­lab­o­ra­tion has nev­er been stronger, and the in­dus­try is bet­ter off for it. Emer­gency pre­pared­ness and sup­port that en­sures the phar­ma­ceu­ti­cal in­dus­try is ready to ac­cel­er­ate time­lines when the need aris­es has tak­en a front row seat in vac­cine man­u­fac­tur­ing, and CD­MOs are ready for the chal­lenge.