Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modal­i­ty So­lu­tions is an ISO:9001-reg­is­tered bio­phar­ma­ceu­ti­cal cold chain en­gi­neer­ing firm with unique trans­port sim­u­la­tion ca­pa­bil­i­ties that sup­port ac­cel­er­at­ed reg­u­la­to­ry ap­proval for bi­o­log­ics and ad­vanced ther­a­peu­tic med­i­c­i­nal prod­ucts (ATMP). Our ex­per­tise com­bines tra­di­tion­al val­i­da­tion en­gi­neer­ing ap­proach­es with reg­u­la­to­ry knowl­edge in­to a method­ol­o­gy tai­lored for the life sci­ences in­dus­try. We pro­vide in­sight and ex­e­cu­tion for the chal­lenges faced in your cold chain lo­gis­tics net­work.

Trans­port Sim­u­la­tion Sup­ports Ap­proval Time­lines in Ex­pe­dit­ed Pro­grams

Your cold chain process val­i­da­tion is one com­po­nent con­sid­ered in the FDA ex­pe­dit­ed pro­gram sub­mis­sion and ap­proval process. A ro­bust, risk-based qual­i­ty as­sess­ment of a drug prod­uct re­quires ship­ping stud­ies to en­sure chem­i­cal and phys­i­cal sta­bil­i­ty of your ther­a­py dur­ing trans­port¹. Ex­pe­dit­ed pro­grams are in­tend­ed to speed up the avail­abil­i­ty of new ther­a­pies. This flex­i­bil­i­ty can com­press ap­prox­i­mate­ly eight years of tra­di­tion­al de­vel­op­ment and val­i­da­tion ac­tiv­i­ties in­to rough­ly 18 months. Each clin­i­cal phase is con­densed, and val­i­da­tion da­ta are re­viewed on a rolling sub­mis­sion ba­sis to fol­low an ac­cel­er­at­ed time­line.

Trans­port sim­u­la­tion val­i­dates your cold chain sup­ply chain in a cost-ef­fec­tive, re­li­able, and ex­pe­di­tious way to keep your de­vel­op­ment pro­gram on an ac­cel­er­at­ed ap­proval time­line. More im­por­tant­ly, trans­port sim­u­la­tion chal­lenges drug prod­uct phys­i­cal and chem­i­cal sta­bil­i­ty in a way that re­al-world ship­ping stud­ies can nev­er do.

Trans­port sim­u­la­tion test­ing re­quires on­ly three days to test your ther­a­py for most mul­ti­modal trans­port lanes from the point of man­u­fac­ture to the whole­saler, spe­cial­ty phar­ma­cy, or di­rect to pa­tient de­liv­ery mod­els. The da­ta pro­vid­ed by the sim­u­la­tion test­ing, cou­pled with post-test­ing an­a­lyt­i­cal re­sults are ro­bust and re­li­able.

Most im­por­tant­ly, this ap­proach gives you some­thing re­al-world ship­ping stud­ies can nev­er guar­an­tee – test­ing at the edges of your op­er­at­ing space for all five ma­jor en­vi­ron­men­tal haz­ards in the cold chain. Trans­port sim­u­la­tion pro­vides a clear pic­ture of whether the worst-case con­di­tions af­fect your drug for­mu­la­tion’s phys­i­cal and chem­i­cal in­tegri­ty based on the drug for­mu­la­tion’s sta­bil­i­ty pro­file.

Re­al-Time Con­cur­rent Haz­ard Test­ing As­sures Val­i­dat­ing Across the En­tire Op­er­at­ing Space

The on­ly way to ap­pro­pri­ate­ly chal­lenge your ther­a­py is by us­ing con­cur­rent en­vi­ron­men­tal haz­ards with non-ac­cel­er­at­ed pro­files that sim­u­late sea­son­al con­di­tions. Trans­port sim­u­la­tion test­ing is the on­ly re­li­able way to eval­u­ate drug prod­uct qual­i­ty with test­ing at the edges of your op­er­at­ing space with worst-case ex­po­sures to the five ma­jor con­cur­rent trans­port en­vi­ron­men­tal haz­ards. Re­al-world ship­ping stud­ies alone can­not guar­an­tee that these haz­ards will stress your drug prod­uct ther­a­py at all, let alone all haz­ards at worst-case in­ten­si­ty con­cur­rent­ly.²

Trans­port sim­u­la­tion is able to pre­dict drug prod­uct sta­bil­i­ty by ex­pos­ing your ther­a­py to the haz­ards of dis­tri­b­u­tion (such as tem­per­a­ture, pres­sure, shock, vi­bra­tion, and hu­mid­i­ty) across the en­tire op­er­at­ing space, the qual­i­ty of the drug prod­uct for all trans­port modes and sea­son­al vari­a­tions. Ear­ly drug prod­uct trans­port sim­u­la­tion test­ing al­lows spon­sors to make changes to for­mu­la­tions, if nec­es­sary, and cre­ate a more sta­ble drug prod­uct with less sen­si­tiv­i­ty to en­vi­ron­men­tal haz­ards.

Re­al-world ship­ments can­not guar­an­tee test­ing across the en­tire op­er­at­ing space, can­not be as­sured prop­er con­trol of test­ing pa­ra­me­ters, and can­not be used af­ter­ward for root cause analy­sis or op­ti­miza­tion if drug prod­uct for­mu­la­tion sta­bil­i­ty is­sues are un­cov­ered. Hav­ing re­li­able and re­peat­able trans­port sim­u­la­tion tech­nol­o­gy and test­ing tech­niques will max­i­mize your chances of reg­u­la­to­ry ap­proval and en­sure your time­line com­mit­ments.

Trans­port Sim­u­la­tion Test­ing Has Been Ac­cept­ed by Reg­u­la­tors for Over a Decade

Trans­port sim­u­la­tion was first used in sub­mis­sions in the ear­ly 2000s to show drug prod­uct ro­bust­ness dur­ing trans­port for mon­o­clon­al an­ti­bod­ies. Ear­ly sim­u­la­tion test­ing on­ly ex­posed drug prod­ucts for sea­son­al tem­per­a­ture ranges and not atyp­i­cal highs and lows, mul­ti­modal trans­port vi­bra­tion, and shock events were test­ed sep­a­rate­ly. Since the ear­ly use of trans­port sim­u­la­tion, the tech­nol­o­gy has im­proved to in­clude con­cur­rent test­ing and added hu­mid­i­ty and at­mos­pher­ic pres­sure test­ing as well.

Sim­u­la­tion tech­nol­o­gy has got­ten bet­ter and is in wide­spread use across the bio­phar­ma­ceu­ti­cal in­dus­try. Modal­i­ty So­lu­tions has a pro­pri­etary trans­port sim­u­la­tion lab­o­ra­to­ry with the unique abil­i­ty to si­mul­ta­ne­ous­ly test any drug prod­uct for­mu­la­tion for five en­vi­ron­men­tal haz­ards com­mon­ly af­fect­ing pro­tein-based for­mu­la­tions: tem­per­a­ture, shock, vi­bra­tion, hu­mid­i­ty, and pres­sure. We have been us­ing trans­port sim­u­la­tion test­ing to fa­cil­i­tate over 70 suc­cess­ful reg­u­la­to­ry sub­mis­sions over the last sev­en years.

More than 30 coun­tries have adopt­ed or amend­ed Good Dis­tri­b­u­tion Prac­tices for phar­ma­ceu­ti­cals in the past decade.³ While the specifics vary, they all ad­vise some de­gree of en­vi­ron­men­tal or con­di­tion test­ing, mon­i­tor­ing, and track­ing to en­sure ther­a­peu­tics and di­ag­nos­tics are han­dled in a way that en­sures their safe­ty and ef­fi­ca­cy.

U.S. Phar­ma­copeia Good Stor­age and Dis­tri­b­u­tion Prac­tices for Drug Prod­ucts Chap­ter 1079, ad­vis­es op­er­a­tional and per­for­mance test­ing for prod­ucts, as well as tem­per­a­ture pro­fil­ing stud­ies for trans­porta­tion and ware­hous­es.⁴ ASTM D4169, “Stan­dard Prac­tices for Per­for­mance Test­ing of Ship­ping Con­tain­ers and Sys­tems” ad­dress­es pack­ag­ing dura­bil­i­ty for each ship­ping mode.⁵

Si­mul­ta­ne­ous Test­ing of All Sea­son­al Vari­a­tions and Trans­port Modes is Pos­si­ble All Year-Round

Ex­pe­dit­ed pro­gram ap­proval time­lines and rolling sub­mis­sions ac­cel­er­ate the need for time­ly as­sess­ment of your pro­posed ship­ment lanes with prompt val­i­da­tion da­ta. Sea­son­al trans­port val­i­da­tion for your cold chain lo­gis­tics net­work is not avail­able year-round with re­al-world ship­ping stud­ies alone. Trans­port sim­u­la­tion al­lows all sea­son­al and trans­port modes (i.e., air, ground, and ocean) to be con­duct­ed across 3-4 days of test­ing and gen­er­ate re­sults to in­clude in your sub­mis­sion.

We rec­om­mend con­duct­ing a risk as­sess­ment fol­lowed by com­pil­ing a Val­i­da­tion Mas­ter Plan that doc­u­ments over­all val­i­da­tion strate­gies for the life­cy­cle of your prod­uct in­clud­ing your ap­proach to sea­son­al vari­a­tions. Be­fore test­ing, the risk as­sess­ment can iden­ti­fy which trans­port en­vi­ron­men­tal haz­ards place the ther­a­py at the high­est risk and al­lows the fo­cus on the sim­u­la­tion test­ing on the trans­porta­tion en­vi­ron­men­tal haz­ards (e.g., hot or cold, shock, vi­bra­tion, pres­sure, or hu­mid­i­ty) most rel­e­vant to your drug prod­uct qual­i­ty.

Re­ly­ing on re­al-world ship­ping stud­ies alone can de­lay or force an in­com­plete sub­mis­sion to reg­u­la­tors be­cause sea­son­al vari­a­tion stud­ies can on­ly be con­duct­ed in tight win­dows with no guar­an­tee of suc­cess. Plan­ning a re­al-world ship­ping study and wait­ing for the “dog days” does not mean that the ex­pect­ed ex­treme tem­per­a­tures will be seen dur­ing your des­ig­nat­ed test­ing pe­ri­od. On­ly trans­port sim­u­la­tion test­ing can guar­an­tee that the cold­est tem­per­a­tures of win­ter and the high­est tem­per­a­tures of sum­mer can be ex­pe­ri­enced in a sin­gle pro­to­col in a 3 to 4-day test­ing cy­cle.


² Fleis­chman, M. et al., “Ship­ping-In­duced Ag­gre­ga­tion in Ther­a­peu­tic An­ti­bod­ies: Uti­liza­tion of a Scale-Down Mod­el to As­sess Degra­da­tion in Mon­o­clon­al An­ti­bod­ies,” Jour­nal of Phar­ma­ceu­ti­cal Sci­ences, Vol­ume 106, Is­sue 4, pp.994-1000, April 1, 2017.

³ A Glob­al Re­view of Good Dis­tri­b­u­tion Prac­tices, IQPC,­dia/8378/34072.pdf

⁴ U.S. Phar­ma­copeia Good Stor­age and Dis­tri­b­u­tion Prac­tices for Drug Prod­ucts, chap­ter 1079, http://www.phar­ma­

⁵ Stan­dard Prac­tice for Per­for­mance Test­ing of Ship­ping Con­tain­ers and Sys­tems. ASTM, https://www.doc­u­ment-cen­­dards/show/ASTM-D4169

Gary Hutchin­son is Pres­i­dent of Modal­i­ty So­lu­tions, a bio­phar­ma­ceu­ti­cal cold chain en­gi­neer­ing firm spe­cial­iz­ing in glob­al cold chain val­i­da­tion. He has de­signed life sci­ences sup­ply chain lo­gis­tics and bio­phar­ma­ceu­ti­cal cold chains for the last 20 years. He is a mem­ber of the Forbes Tech­nol­o­gy Coun­cil, speak­er for var­i­ous phar­ma­ceu­ti­cal con­fer­ences and has suc­cess­ful­ly de­vel­oped cold chain trans­port val­i­da­tion da­ta for more than 50 new drug prod­ucts with mul­ti­ple reg­u­la­to­ry agen­cies around the globe in the last 5 years.