At least four bio­phar­ma com­pa­nies have bro­ken ground over the past four weeks, af­ter Pres­i­dent Don­ald Trump said drug­mak­ers would be ex­empt from his 100% tar­iff threat if they have done so.

Last month, Trump said in a Truth So­cial post that phar­ma com­pa­nies build­ing man­u­fac­tur­ing sites in the US would face no tar­iffs. He de­fined "build­ing" as "break­ing ground" or "un­der con­struc­tion." Yet, con­fu­sion re­mains over those terms, Mol­lie Sitkows­ki, a trade com­pli­ance part­ner at US law firm Fae­gre Drinker told End­points News.

There’s lit­tle de­tail on what con­sti­tutes break­ing ground and whether a drug­mak­er would be ex­empt from tar­iffs glob­al­ly or on­ly at the fa­cil­i­ty un­der con­struc­tion, she said.

As new­ly-launched drugs con­sis­tent­ly fetch list prices that ex­ceed $1 mil­lion or more, a new ICER re­port re­leased Thurs­day finds that even the net prices — once pay­er dis­counts are con­sid­ered — are out­pac­ing in­fla­tion and GDP growth.

The non­prof­it drug pric­ing watch­dog’s re­port looked at launch prices for every new drug and bi­o­log­ic ap­proved be­tween 2022 and 2024. It found a 24% in­crease (from $249,257 to $308,749) in the in­fla­tion-ad­just­ed me­di­an an­nu­al list price of new­ly-launched drugs, and an in­crease of 51% — $182,271 in 2022 to $274,795 in 2024 — for in­fla­tion-ad­just­ed me­di­an an­nu­al net prices.

Gene and cell ther­a­pies, or­phan drugs, first-in-class drugs, and on­col­o­gy and en­docrine/meta­bol­ic drugs "were all as­so­ci­at­ed with high­er launch prices," the re­port says.

Mer­ck KGaA is end­ing its API pro­duc­tion work in Ark­low, Ire­land, and is propos­ing to shut down its fac­to­ry at the end of 2028, a com­pa­ny spokesper­son told End­points News.

The com­pa­ny made the de­ci­sion af­ter a “strate­gic port­fo­lio re­view” found “de­clin­ing vol­umes and low prof­itabil­i­ty,” the spokesper­son said.

The Ark­low site man­u­fac­tures com­mer­cial and late-stage APIs and ad­vanced in­ter­me­di­ates, in­clud­ing the start­ing ma­te­ri­als for an­ti­de­pres­sants, an­ti­his­t­a­mines and an­ti­fun­gal treat­ments, ac­cord­ing to a com­pa­ny fact sheet.

Mer­ck KGaA is con­sid­er­ing a pro­pos­al to cease op­er­a­tions "af­ter a thor­ough eval­u­a­tion and re­view of mul­ti­ple al­ter­nate op­tions and in align­ment with our busi­ness strat­e­gy,” the spokesper­son said. The pro­pos­al is sub­ject to a 30-day con­sul­ta­tion with em­ploy­ees, which will be­gin right away.

One of the more em­bar­rass­ing po­ten­tial mo­ments for a bio­phar­ma com­pa­ny comes when it re­ceives a refuse-to-file (RTF) let­ter from the FDA. The let­ter does­n't sig­nal any­thing to the pub­lic on whether the new drug ap­pli­ca­tion may be ap­prov­able, but in­stead says that the min­i­mum of what's re­quired has­n't been sub­mit­ted cor­rect­ly.

To help in­dus­try get few­er RTF let­ters, the agency on Thurs­day of­fered a se­ries of check­lists for new drug and gener­ic drug sub­mis­sions. The FDA said it's sent out more than 200 RTFs over the last decade which, on av­er­age, can de­lay ap­pli­ca­tions by more than 400 days.

"RTF is an im­por­tant reg­u­la­to­ry tool to help avoid un­nec­es­sary re­view of in­com­plete ap­pli­ca­tions or cer­tain ap­pli­ca­tions that are sub­mit­ted as an NDA but should have been sub­mit­ted as an ab­bre­vi­at­ed new drug ap­pli­ca­tion," the agency ex­plained in an up­dat­ed man­u­al for NDAs and sN­DA.