Plan­ning a clin­i­cal sup­ply pro­gram? Don’t over­look pri­ma­ry pack­ag­ing.

Im­age cour­tesy of Catal­ent Phar­ma So­lu­tions © 2017 Catal­ent, Inc. All rights re­served



When plan­ning a clin­i­cal tri­al, pri­ma­ry pack­ag­ing — the ma­te­ri­als that come in­to di­rect con­tact with the study drug — may not seem like a big pri­or­i­ty for drug de­vel­op­ment ex­ec­u­tives. And that would be a mis­take.

As we’ll learn, pack­ag­ing and pre­sen­ta­tion is cru­cial to study suc­cess. Drug sta­bil­i­ty, reg­u­la­to­ry strat­e­gy, and pa­tient-cen­tered de­sign are just some of the fac­tors to con­sid­er. In this Deep Dive, we talked with sci­en­tif­ic ex­perts at con­tract de­vel­op­ment and man­u­fac­tur­er Catal­ent and ex­plored these ques­tions:

  • How does pack­ag­ing change from small phase I tri­als to large mul­ti-cen­ter phase III ef­forts?
  • What are the best pack­ag­ing strate­gies to achieve longer sta­bil­i­ty?
  • What are the dif­fer­ences be­tween the US and Eu­rope for ex­piry dates on pack­ag­ing?
  • Can you best source com­para­tor ther­a­pies with­out be­ing charged a for­tune?
  • How can de­vel­op­ers best pack­age for ad­her­ence?

Plan­ning a clin­i­cal sup­ply pro­gram? Keep read­ing for an­swers to these ques­tions and many more.

Ear­ly-stage is the time to be think­ing about pri­ma­ry pack­ag­ing


In phase I, re­searchers are test­ing a new drug or treat­ment in a small group of vol­un­teers for the first time to eval­u­ate its safe­ty, to de­ter­mine a safe dosage range and to iden­ti­fy side ef­fects. The amount of drug prod­uct man­u­fac­tured is rel­a­tive­ly small and easy to con­trol at this point in the prod­uct’s de­vel­op­ment.

Steve McMa­hon, Catal­ent

But when a clin­i­cal tri­al pro­gress­es, the for­mu­la­tion it­self and the dosage form may change as fac­tors like sta­bil­i­ty be­come bet­ter char­ac­ter­ized. As a re­sult, spon­sors may al­so want to con­sid­er the de­sir­able com­mer­cial for­mat in lat­er stage clin­i­cal stud­ies.

Pa­tient and clin­ic needs will al­so change as the drug trav­els from small phase I tri­als to large mul­ti-cen­ter phase III tri­als.

For flex­i­bil­i­ty around dosage it is of­ten best to use a gran­ule dosage form in cap­sules, and the dose can then be ad­just­ed sim­ply by chang­ing the weight or num­ber giv­en.

Catal­ent con­ducts sta­bil­i­ty tri­als of the study drug along­side the clin­i­cal tri­al and will like­ly be test­ing dif­fer­ent pri­ma­ry pack­ag­ing con­fig­u­ra­tions such as sol­id dose tablets or cap­sules in blis­ter packs and bot­tles as part of that process.

Sta­bil­i­ty da­ta will in­flu­ence the pack de­sign, and so the dosage form used at this stage may bear lit­tle re­sem­blance to the fi­nal com­mer­cial form.

Pack­ag­ing is al­so based on the vol­ume of an­tic­i­pat­ed pa­tient re­cruit­ment. Ran­dom­iza­tion of pa­tients to treat­ment types can be strat­i­fied to test dos­ing of pa­tients by gen­der, age, body weight and oth­er fac­tors. From a com­plex­i­ty point of view, the pack de­signs them­selves don’t tend to be com­plex.

Here’s Steve McMa­hon, process leader at Catal­ent:

What does get more com­plex af­ter phase I are fac­tors like ran­dom­iza­tions and la­bel­ing be­cause the cus­tomer and Catal­ent are try­ing to de­vel­op the best dosage form for pa­tients. Strat­i­fied ran­dom­iza­tions may be used when test­ing char­ac­ter­is­tics such as body weight, gen­der, age along­side dosage strength. As a re­sult, the ran­dom­iza­tions tend to be quite com­plex due to the num­ber of vari­ables in­volved.

Most of­ten, sup­plies are sent to the clin­i­cal site rather than di­rect­ly to pa­tients, and la­bel­ing might be more com­plex be­cause la­bels will in­clude a unique num­ber that links back to the ran­dom­iza­tion and how a pa­tient is be­ing dosed, McMa­hon said. Clin­i­cal sites usu­al­ly man­age in­ven­to­ry in-house due to short­er turn-around times, and so their abil­i­ty to store items might al­so come in­to play.

More be­comes known about the study drug as the tri­al pro­gress­es to phase II tri­als, where the drug is giv­en to a larg­er group of pa­tients to test for the right dosage and fur­ther eval­u­ate its safe­ty.

Based on sta­bil­i­ty da­ta and oth­er feed­back, pack de­sign and ma­te­ri­als may change to a more ap­pro­pri­ate dosage form, such as tablets, ex­tend­ed-re­lease cap­sules, in­fu­sions or in­jec­tions.

“If a long ex­piry date is not pos­si­ble, then you might try and sim­pli­fy the pack de­sign,” he said, not­ing that in phase II, more sta­bil­i­ty da­ta will be col­lect­ed in a rolling sta­bil­i­ty tri­al, in which case ex­piry dates are ex­tend­ed as more da­ta are cap­tured.

“There are lots of dif­fer­ent fac­tors that we’ll start with, de­pend­ing on the ex­piry date,” McMa­hon said.  “All the time you have to be mind­ful about what the cus­tomer wants to do in phase III and what is re­quired when you com­mer­cial­ize the prod­uct.”

Some pack­ag­ing pro­tects sta­bil­i­ty bet­ter


One of the best forms of pri­ma­ry pack­ag­ing to pro­tect the prod­uct and im­prove the sta­bil­i­ty of a prod­uct is cold form blis­ter pack­ets. Ma­te­ri­als used have a polyvinyl chlo­ride (PVC) or polyvinyli­dene chlo­ride (PVDC) seal, which is dense and re­sis­tant to tem­per­a­ture and hu­mid­i­ty.

“The good thing about blis­ter­ing is that on­ly one tablet is popped at a time, so the sta­bil­i­ty of the rest of the drug prod­uct is main­tained,” McMa­hon stressed. “Where­as, when us­ing a bot­tle, once the bot­tle is opened, the en­tire pack is ex­posed to hu­mid­i­ty.”

Cold form blis­ter pack­ets (Shut­ter­stock)

Stor­age con­di­tions need to be con­sid­ered in the dosage form and pack de­sign he said, not­ing that a site could be stor­ing a prod­uct at -80˚C while the tri­al is on­go­ing, but the prod­uct might be dis­trib­uted at -20˚C.

These types of de­ci­sions sur­round­ing the dosage form can al­so af­fect turn-around times for tri­al sites.

“For ex­am­ple, Catal­ent had a cus­tomer for a rel­a­tive­ly large-scale phase II tri­al, and were do­ing pack­ag­ing runs about every three months. Catal­ent did the ini­tial pri­ma­ry pack­ag­ing and then sec­ondary pack­ag­ing. Then every three months the cus­tomer re­ceived more sta­bil­i­ty da­ta and Catal­ent was re­quired to re-la­bel pack­aged sup­plies with new ex­piry dates.”

“From a cus­tomer point of view this was cost­ing them more mon­ey.”

He ex­plains that the prac­tice of putting ex­piry dates on clin­i­cal tri­al pack­ag­ing is re­quired in some ju­ris­dic­tions. In the U.S., ex­piry dates are not com­pul­so­ry on pack­ag­ing for clin­i­cal tri­als be­cause they can be con­trolled by in­ter­ac­tive tech­nol­o­gy [IRT]. Ex­piry date in­for­ma­tion is al­so sent to the site.

The tri­al med­ica­tion is man­aged through an au­to­mat­ed pre-de­ter­mined or­der sys­tem based on ini­tial or­der and re­sup­ply pa­ra­me­ters in the IRT sys­tem. Since the IRT man­ages ex­piry dates, it makes the whole sup­ply chain a lot smoother. It al­so helps con­trol costs due to less risk of over pro­duc­ing pa­tient kits which may ex­pire be­fore they can be dis­pensed.

But in Eu­rope, even if an IRT is used, the clin­i­cal tri­al pack­ag­ing still needs to be la­beled with ex­piry dates, he not­ed.

“It’s im­por­tant to have strict stan­dard op­er­at­ing pro­ce­dures of how to do these things, and Catal­ent has ex­ten­sive ex­pe­ri­ence in do­ing mul­ti-pack de­signs and la­bel­ing,” McMa­hon stressed.

“Even though it can be com­plex, we will pro­duce batch doc­u­ments that de­tail ex­act­ly what we need to do to for qual­i­ty re­views in­ter­nal­ly and for the client, and af­ter ex­e­cu­tion of that pro­duc­tion run, it gets re­viewed again. The con­trols in place for clin­i­cal tri­als are more re­stric­tive than in com­mer­cial drug man­u­fac­tur­ing, be­cause the con­trols in­clude man­age­ment of blind­ed ma­te­ri­als.”

By the time a drug gets to phase III tri­als, where it will be giv­en to larg­er groups of pa­tients of­ten mul­ti-coun­try or glob­al to con­firm its ef­fec­tive­ness, a sig­nif­i­cant in­crease in pro­duc­tion is quite com­mon.

Com­pa­nies will al­so start run­ning mul­ti-cen­ter stud­ies in mul­ti­ple coun­tries, and pro­duc­tion could shift from 250 units at phase I to two mil­lion units or more at phase III.

En­sur­ing pa­tient com­pli­ance


Pack­ag­ing and la­bel­ing in phase III are de­vel­oped with reg­u­la­to­ry and le­gal re­quire­ments, pa­tient and spon­sor needs as well as com­mer­cial re­quire­ments in mind, and the study may be ran­dom­ized and blind­ed against a place­bo or more like­ly a mar­ket lead­ing com­para­tor. Clin­i­cal tri­al pack­ag­ing will of­ten move to wal­lets or cards with blis­ter packs or in­di­vid­ual bot­tles that are sent to the clin­i­cal sites, which then dis­trib­ute them to pa­tients who gen­er­al­ly self-ad­min­is­ter at home.

In phase I, the drug is ad­min­is­tered at a spe­cial­ized Phase I clin­i­cal site that has dis­pens­ing phar­ma­cists with GMP train­ing who can make-up dose cap­sules  or dis­pense tablets from a bot­tle. This trans­lates in­to strict pa­tient com­pli­ance. But when pa­tients start tak­ing the study drug at home, this is when com­pli­ance can start to slip. One so­lu­tion is to use pack­ag­ing de­signs that make it eas­i­er for the pa­tient to com­ply with the pro­to­col dos­ing sched­ule, such as sun and moon sym­bols on blis­ter cards to in­di­cate AM vs. PM dos­es.

shut­ter­stock

“One of the big things that put pa­tients off tak­ing med­ica­tion is non- pa­tient cen­tric pack­ag­ing and la­bel­ing,” McMa­hon stressed. “If they don’t un­der­stand the pack or the la­bel­ing or it’s cum­ber­some, they may not take the drug.”

Why out­source clin­i­cal sup­plies?


McMa­hon said that most phar­ma­ceu­ti­cal com­pa­nies are geared up for mass man­u­fac­tur­ing, and they don’t re­al­ly have the scale and ca­pa­bil­i­ty to do small­er scale clin­i­cal runs.

Some com­pa­nies have sep­a­rate units for clin­i­cal tri­als, but that of­ten ends up cost­ing more in the long run to keep such a unit up and run­ning.

“It’s ben­e­fi­cial for big phar­ma­ceu­ti­cal com­pa­nies to use in­te­grat­ed providers like Catal­ent be­cause we’ve got the ex­pe­ri­ence and ex­per­tise of do­ing clin­i­cal tri­als, and we have the equip­ment to han­dle most pack­ag­ing de­signs and clin­i­cal tri­al pack­ag­ing. Some cus­tomers might have a high po­ten­cy or con­trolled drug and their fa­cil­i­ty might not be set up for that.”

There are sev­er­al fac­tors that bio­phar­ma­ceu­ti­cal com­pa­nies should take in­to ac­count when vet­ting a drug de­liv­ery so­lu­tion provider such as Catal­ent or con­tract man­u­fac­tur­er (CMO) for out­sourc­ing pri­ma­ry pack­ag­ing. Some of these ven­dor con­sid­er­a­tions in­clude:

  1. The abil­i­ty of a ven­dor to ex­pand pack­ag­ing ca­pac­i­ty on short no­tice.  This may be due to con­straints on stor­age, la­bor or equip­ment ca­pac­i­ty at the cus­tomer’s own sites;
  2. Tak­ing ad­van­tage of a ven­dors ex­pe­ri­ence/spe­cial­ty in a par­tic­u­lar pack­ag­ing field such as blis­ter pack­ag­ing of sol­id dose forms;
  3. Re­duced risk to drug de­vel­op­ment time­lines due to ven­dor’s’s ex­pe­ri­ence in pack­ag­ing and dis­tri­b­u­tion;
  4. Ma­jor cost sav­ings in not hav­ing to in­cur cap­i­tal ex­pen­di­ture on spe­cial­ized equip­ment, re­cruit­ment and train­ing of staff;
  5. Ven­dors can help re­duce drug de­vel­op­ment time with dif­fer­ent pack­ag­ing strate­gies;
  6. A ven­dor’s ge­o­graph­i­cal pres­ence of pack­ag­ing and dis­tri­b­u­tion cen­ters can pro­vide lo­gis­ti­cal sav­ings;
  7. The ven­dor will usu­al­ly have more flex­i­ble pro­duc­tion time­lines with the ca­pa­bil­i­ty to man­age mile­stones on a project crit­i­cal path; and
  8. Some ven­dors have the nec­es­sary ex­pe­ri­ence and con­tacts to pro­cure com­para­tor prod­ucts from mul­ti­ple sources.

McMa­hon said the qual­i­ty unit and the Qual­i­fied Per­son (in Eu­rope) at a com­pa­ny will be able to ad­vise if a planned pack­ag­ing process or pack de­sign is com­pli­ant with Reg­u­la­to­ry Au­thor­i­ties such as the FDA, MHRA good man­u­fac­tur­ing prac­tices reg­u­la­tions or coun­try spe­cif­ic re­quire­ments.

The cus­tomer qual­i­ty unit would al­so typ­i­cal­ly au­dit and ap­prove the CMO be­fore plac­ing work.

The CMO’s pack­ag­ing de­sign group can al­so con­fi­den­tial­ly lever­age their col­lec­tive ex­pe­ri­ence across a va­ri­ety of projects to help cur­rent cus­tomers de­vise their op­ti­mal pack­ag­ing so­lu­tion. .  This guid­ance can take the form of best prac­tices or lessons learned that the cus­tomer may not have been aware of on their own.

The CMO can pro­vide feed­back on whether the pack de­sign is suit­able for pack­ag­ing and dis­tri­b­u­tion to clin­i­cal sites and pa­tients across the world. It can al­so in­form on whether the pack is the cor­rect size to match the var­i­ous phas­es of the pro­to­col and the dis­pens­ing vis­its.

Costs can al­so be man­aged by con­sult­ing with the CMO, be­cause the com­po­nents used to make a pack de­sign can in­crease or de­crease in cost but can al­so add val­ue to a pa­tient through ease of use. This would give in­creased prob­a­bil­i­ty of pa­tient com­pli­ance to the tri­al.

In­ves­ti­ga­tor and clin­i­cal staff, as well as the pa­tient can al­so pro­vide valu­able feed­back on the pack de­sign, par­tic­u­lar­ly about whether the prod­uct is easy to dose and if la­bel­ing in­struc­tions are eas­i­ly fol­lowed.

“We have a pa­tient-cen­tric ini­tia­tive at Catal­ent with the aim of putting the pa­tient first.  Part of this ini­tia­tive re­sult­ed in some of our pre-pro­duc­tion peo­ple vis­it­ing a clin­i­cal site to get feed­back,” McMa­hon said, not­ing that staff are of­ten sur­prised how small the clin­i­cal site can be and why stor­age might be a prob­lem. Al­ter­na­tive­ly, a doc­tor or a nurse in a large hos­pi­tal will want pack­ag­ing that stands out and very clear la­belling be­cause they could be run­ning mul­ti­ple tri­als, and they need to be able to iden­ti­fy the right clin­i­cal sup­plies quick­ly.

Make pri­ma­ry pack­ag­ing de­ci­sions ear­ly


To ac­cel­er­ate drug de­vel­op­ment, com­pa­nies need to con­sid­er clin­i­cal tri­al pack­ag­ing strate­gies as ear­ly as pos­si­ble in the de­vel­op­ment process.

“There are sev­er­al fac­tors that need to be con­sid­ered from the cus­tomer’s point of view, such as whether they have the ca­pac­i­ty and re­sources for the pack­ag­ing for a tri­al. If the an­swer is no, then the cus­tomer has to start think­ing about out­sourc­ing straight­away,” he said.

Some cus­tomers will have ca­pac­i­ty for a phase I tri­al or a small phase II tri­al, but then a CMO will be need­ed to han­dle Phase III. For a smooth tran­si­tion, com­pa­nies need to plan for this ear­ly to leave room for au­dit­ing the CMO to make sure they have the nec­es­sary qual­i­ty stan­dards.  For­mal agree­ments al­so need to be put in place and dis­clo­sure that out­sourc­ing is go­ing to oc­cur should be in­clud­ed in any tri­al doc­u­men­ta­tion.

“That is not a quick turn­around, and it could take up to six months to pre­pare, which is a long time dur­ing that crit­i­cal stage,” McMa­hon ad­vised.

Com­pa­nies should al­so con­sid­er the CMO’s pack­ag­ing and dis­tri­b­u­tion net­work. “For ex­am­ple, what if a tri­al needs to be con­duct­ed in Aus­tralia, what are you go­ing to do? Does the cus­tomer re­quire tri­al ma­te­r­i­al to be shipped from the UK? If it’s a tem­per­a­ture-sen­si­tive prod­uct, I don’t think that’s nec­es­sar­i­ly a good idea. Work­ing with a CMO with an ex­ten­sive dis­tri­b­u­tion net­work and the right ex­per­tise can give you oth­er op­tions that may be more ad­vis­able.”

He said that Catal­ent has glob­al man­u­fac­tur­ing ca­pa­bil­i­ty across six con­ti­nents, and can seam­less­ly switch gears to meet clin­i­cal tri­al needs, so ship­ping to re­mote re­gions in Aus­tralia wouldn’t be a prob­lem.

An­oth­er chal­lenge for drug com­pa­nies can be sourc­ing a com­para­tor prod­uct, be­cause in­no­va­tor com­pa­nies may put up road blocks to sourc­ing their ma­te­r­i­al un­til they are as­sured the prod­uct will be used with­in an ap­pro­pri­ate set­ting and not sub­ject to par­al­lel trade as they are legal­ly re­spon­si­ble for that drug.

“This can ei­ther be a high mark up on the orig­i­nal cost of the drug, quan­ti­ty or lot lim­its, an ex­treme­ly long lead time on it or dif­fi­cul­ty in ob­tain­ing the nec­es­sary pa­per­work,” McMa­hon said.  Catal­ent has a spe­cial­ized team with well-es­tab­lished re­la­tion­ships with in­no­va­tors (pre­ferred route) and whole­salers to ex­pe­dite the sourc­ing and pur­chas­ing of com­para­tors.

The com­plex­i­ty of some study de­signs in clin­i­cal tri­al pack­ag­ing can al­so cre­ate chal­lenges, and the dif­fer­ent types of clin­i­cal sup­ply mod­els that a cus­tomer may fol­low can have a ma­jor im­pact on the pack­ag­ing strat­e­gy.

The tra­di­tion­al clin­i­cal sup­ply mod­el, called sup­ply-led pack­ag­ing, is a cen­tral­ized stock-based ap­proach that us­es dis­crete pri­ma­ry and sec­ondary pack­ag­ing runs to bulk-ship fin­ished pa­tient kits to clin­i­cal sites and de­pots based on es­ti­mat­ed de­mand.

Un­der this mod­el, pri­ma­ry and sec­ondary pack­ag­ing is un­der­tak­en at cen­tral­ized GMP pack­ag­ing fa­cil­i­ties where stock is built up well in ad­vance of ac­tu­al need. This mod­el can cause an un­der- or over sup­ply due to vari­a­tions in pa­tient re­cruit­ment rates, which can end up be­ing quite waste­ful or car­ry a greater risk of sup­ply not meet­ing de­mand.

Just-in-time la­bel­ing


The just-in-time la­bel­ing mod­el us­es dis­crete pri­ma­ry and sec­ondary pack­ag­ing runs the same as in the tra­di­tion­al mod­el to pro­duce base-la­beled pa­tient kits that are held with­in a cen­tral phys­i­cal in­ven­to­ry to await fi­nal la­bel­ing.

Un­der this sce­nario, pack­ag­ing is ac­com­plished via large-batch runs. This mod­el is ef­fi­cient when the study in­volves ma­te­ri­als that are not like­ly to re­quire ex­piry up­date man­age­ment. Or, it could a good op­tion when the ex­piry date is very short and the prod­uct is on a con­cur­rent sta­bil­i­ty pro­gram, and the most up-to-date ex­piry date can be added at the point of ship­ment.

“A po­ten­tial is­sue is the cus­tomer still has all these bot­tles pro­duced, so you could still be pro­duc­ing too much prod­uct. What does give you the flex­i­bil­i­ty is when re­cruit­ment is even across dif­fer­ent coun­tries.”

How­ev­er, la­bel­ing at the time of ship­ment can re­sult in longer as­so­ci­at­ed lead times and re­sult in po­ten­tial bot­tle necks. In ad­di­tion, more qual­i­ty re­sources are need­ed.

Yet an­oth­er op­tion is mul­ti-lan­guage book­lets that have in­di­vid­ual coun­try-spe­cif­ic in­struc­tions in­side, and then that car­ton can be sent any­where around the world.

De­mand-led sup­ply mod­el


The de­mand-led sup­ply (DLS) mod­el is a dy­nam­ic, con­tin­u­ous GMP ap­proach to sec­ondary pack­ag­ing, la­bel­ing, re­lease and dis­tri­b­u­tion.

Un­der this mod­el, made-to-or­der pa­tient kits are shipped to clin­i­cal sites from re­gion­al fa­cil­i­ties based on ac­tu­al pa­tient de­mand. Sec­ondary pack­ag­ing takes place at a re­gion­al, full-ser­vice pack­ag­ing fa­cil­i­ty where a sup­ply of un­la­beled but unique­ly cod­ed ‘bright stock’ is placed in ad­vance. Ac­cord­ing­ly, the pri­ma­ry pack­ag­ing plan should take in­to con­sid­er­a­tion the lead time re­quired to ship bright stock from the cen­tral pri­ma­ry pack­ag­ing fa­cil­i­ty in­to the re­gion­al pack­ag­ing fa­cil­i­ties. By us­ing bright stock, not on­ly can the ex­act kits need­ed be made-to-or­der, but drug prod­uct can po­ten­tial­ly be pooled for use across mul­ti­ple pro­to­cols which can po­ten­tial re­duce the amount of drug that goes un­used.

Then, based on fore­cast­ed de­mand, this bright stock is dis­trib­uted to re­gion­al GMP fa­cil­i­ties where it awaits fur­ther pro­cess­ing. Sec­ondary pack­ag­ing is com­plet­ed and the fin­ished pa­tient kit is shipped to the in­ves­ti­ga­tor site where it is need­ed with­in a mat­ter of days in re­sponse to on-de­mand or­ders re­ceived via IRT.

The ad­van­tage of this mod­el is that sec­ondary or­ders are ful­filled based on what is ac­tu­al­ly need­ed by the sites, lead­ing to more ef­fi­cient use of stock, sig­nif­i­cant­ly re­duced risk of stock-outs and vir­tu­al­ly elim­i­nat­ing the need to up­date ex­piry la­bel­ing at the in­ves­ti­ga­tor site.

Since la­bel­ing is not com­plet­ed un­til just be­fore the ma­te­r­i­al is sent to the site, ex­piry dates can re­flect the most cur­rent sta­bil­i­ty da­ta avail­able. This trans­lates in­to min­i­mal drug waste and can be a ma­jor cost sav­ings for some prod­ucts.

One fu­ture en­hance­ment for la­bel­ing is 2D bar codes. Some will even have hy­per­links in­side the bar codes that en­able the user to scan them with a smart phone to get coun­try-spe­cif­ic in­struc­tions.

The de­mand-led mod­el is al­so a good choice when a com­para­tor drug is need­ed and is dif­fi­cult to source, very ex­pen­sive, or in short sup­ply. This mod­el is al­so well suit­ed for or­phan drug prod­ucts and cer­tain spe­cial­ty prod­ucts that are of­ten sub­ject to ex­treme lim­it­ed avail­abil­i­ty and very tight dis­tri­b­u­tion con­trol.

Qual­i­ty and due dili­gence


The ap­proach to good man­u­fac­tur­ing prac­tices should be the same re­gard­less of the phase of a clin­i­cal tri­al.  It is crit­i­cal that qual­i­ty per­son­nel are in­volved in the de­vel­op­ment of a study from the start to en­sure com­pli­ance to GMP at all stages.

The com­plex­i­ty of a study means greater in­volve­ment and un­der­stand­ing of qual­i­ty per­son­nel.  “Com­pli­ance to GMP, the Or­ange Guide, FDA reg­u­la­tions for la­bel­ing and pack­ag­ing pre­vents is­sues from aris­ing,” he said.

“Spend­ing more time up­front in plan­ning, tak­ing care to use es­tab­lished stan­dard op­er­at­ing pro­ce­dures and best prac­tices pro­duces greater ef­fi­cien­cies and re­duced er­rors,” McMa­hon stressed.

And, if the com­plex­i­ty of a study re­quires a de­vi­a­tion from an SOP, then this needs to be doc­u­ment­ed pre-pro­duc­tion ap­pro­pri­ate­ly.

Com­pli­ance en­sures faster ap­provals for la­bel art­work, batch doc­u­men­ta­tion and ul­ti­mate­ly faster avail­abil­i­ty to the pa­tient. That trans­lates in­to few­er de­lays in pro­duc­tion and ul­ti­mate­ly clin­i­cal tri­al da­ta that is ac­cept­ed by reg­u­la­tors.

For in­spect­ing pri­ma­ry pack­ag­ing, Catal­ent us­es cam­eras to in­spect the blis­ter packs af­ter they’ve been filled, or the cam­era can al­so be set up be­fore the packs are sealed as well.

The pri­ma­ry pack­ag­ing ma­te­ri­als them­selves can be chal­leng­ing, be­cause cer­tain ma­te­ri­als are more dif­fi­cult to work with. For cold form blis­ter pack­ing, the ac­tu­al pock­et is formed by pres­sure, and the ma­te­r­i­al ba­si­cal­ly bends in­to a pock­et.

When it comes to high po­ten­cy drug prod­ucts, many CMOs have spe­cial­ized pack­ag­ing suites that are used ex­clu­sive­ly for these types of drugs be­cause they typ­i­cal­ly can’t be pack­aged in nor­mal pri­ma­ry pack­ag­ing rooms. Phar­ma­ceu­ti­cal com­pa­nies that do not typ­i­cal­ly have po­tent and cy­to­tox­ic drugs in their port­fo­lios may find that they do not have the nec­es­sary in­fra­struc­ture in place to pack­age these drugs on their own.

Catal­ent can al­so pro­vide tai­lored so­lu­tions for con­trolled drug ca­pa­bil­i­ties, in­clud­ing man­u­fac­tur­ing, im­port/ex­port and stor­age. Con­trolled drugs are typ­i­cal­ly sub­ject to dif­fer­ent re­quire­ments and what may be con­sid­ered con­trolled in one coun­try may car­ry a dif­fer­ent clas­si­fi­ca­tion in an­oth­er. Hav­ing an ex­pe­ri­enced part­ner with both the nec­es­sary fa­cil­i­ties and ex­per­tise in han­dling con­trolled sub­stances can be very ben­e­fi­cial.

Fi­nal­ly, hav­ing a CMO part­ner like Catal­ent means more flex­i­bil­i­ty when it comes time for scale up and tech­nol­o­gy trans­fer. With more than 8,500 clin­i­cal pack­ag­ing and la­bel­ing prod­ucts un­der its belt, Catal­ent  can pro­vide flex­i­ble so­lu­tions from clin­i­cal sup­ply man­age­ment to tech­nol­o­gy trans­fer to reg­u­la­to­ry dossiers, and  fi­nal­ly to scale up across mul­ti­ple con­ti­nents.