Qual­i­ty met­rics for phar­ma man­u­fac­tur­ing is back in a big way, with FDA pledg­ing to 'ob­jec­tive­ly rate' firms

Af­ter the FDA sig­naled an in­ter­est last month in re­turn­ing to its hot­ly-con­test­ed qual­i­ty met­rics pro­gram for phar­ma man­u­fac­tur­ers, the agency this week out­lined what it wants to do while pledg­ing a pub­lic work­shop in May and an ad­comm lat­er this year.

While the nit­ty grit­ty on these met­rics may be more than a year from flesh­ing out, a new white pa­per out­lines the FDA’s ten­ta­tive plans, ex­plain­ing how trans­par­ent “Qual­i­ty Man­age­ment Ma­tu­ri­ty” rat­ings could em­pow­er man­u­fac­tur­ers to iden­ti­fy ways to im­prove the ef­fec­tive­ness of their qual­i­ty sys­tems.

“There must be clear in­cen­tives for in­dus­try to achieve high­er QMM,” FDA said.

But CDER al­so ac­knowl­edges that these QMM as­sess­ments and rat­ings need to be part of the cen­ter’s sur­veil­lance func­tions, and sep­a­rate from de­ter­min­ing com­pli­ance with reg­u­la­to­ry stan­dards.

“The scope and im­pli­ca­tion of a QMM as­sess­ment must be dis­tinct from one de­ter­min­ing CGMP com­pli­ance (i.e., look­ing for be­hav­iors and in­di­ca­tors above meet­ing min­i­mum reg­u­la­to­ry re­quire­ments). Be­tween on-site QMM as­sess­ments, in­for­ma­tion such as qual­i­ty met­rics could be more rou­tine­ly sub­mit­ted to FDA to bol­ster and sup­port on­go­ing con­fi­dence in the QMM rat­ing of the site,” FDA said.

Stake­hold­ers at a 2020 Duke-Mar­go­lis work­shop “large­ly agreed,” ac­cord­ing to the FDA, that the need to de­vel­op and im­ple­ment qual­i­ty rat­ings is dri­ven by the de­sire to dif­fer­en­ti­ate prod­ucts for pur­chasers by an at­tribute oth­er than price.

“QMM rat­ings based on man­u­fac­tur­ing sites are of lim­it­ed val­ue if pur­chasers do not have in­sight in­to the spe­cif­ic fa­cil­i­ties man­u­fac­tur­ing the drugs or com­po­nents they in­tend to pur­chase, es­pe­cial­ly as re­lat­ed to API man­u­fac­tur­ing,” FDA said. “It will be nec­es­sary for pur­chasers to have sup­ply chain in­for­ma­tion to use QMM site rat­ings in drug pur­chas­ing de­ci­sions.”

But the FDA al­so rec­og­nizes the many con­cerns com­ing from all cor­ners.

The phar­ma in­dus­try pre­vi­ous­ly ques­tioned the val­ue and util­i­ty of the met­rics da­ta, and the in­creased bur­den of col­lect­ing and sub­mit­ting it, while FDA said health care pro­fes­sion­als in­di­cat­ed con­cerns about li­a­bil­i­ty and risk as­so­ci­at­ed with us­ing QMM rat­ings in de­ci­sion-mak­ing re­lat­ed to pa­tient care, par­tic­u­lar­ly if there were “is­sues stem­ming from pro­vid­ing a drug from a low­er-rat­ed fa­cil­i­ty.”

While not­ing that one of its end goals for the FDA is for “top-rat­ed man­u­fac­tur­ers in the US, both large and small,” to gain “a com­pet­i­tive ad­van­tage, po­ten­tial­ly en­abling them to grow mar­ket share and in­crease their work­force,” the agency al­so ac­knowl­edged the un­in­tend­ed risk that pur­chasers may use QMM rat­ings to buy drugs from low­er-rat­ed sites for low­er prices to re­al­ize short-term cost sav­ings.

De­vel­op­ing QMM rat­ings based on man­u­fac­tur­ing site rather than prod­uct al­so re­moves health care pro­fes­sion­als one step from a de­ci­sion-mak­ing process in­formed by QMM, as most health pro­fes­sion­als have “lit­tle or no sup­ply chain site in­sight, es­pe­cial­ly as com­pared to pur­chasers,” FDA said.

The agency’s fo­cus on qual­i­ty met­rics be­gan al­most a decade ago, with the agency seek­ing ideas from stake­hold­ers as to be more proac­tive around drug short­ages, the ma­jor­i­ty of which are caused by man­u­fac­tur­ing is­sues or qual­i­ty prob­lems.

“It be­came clear that those in the in­dus­try with an ear­ly warn­ing sys­tem for avail­abil­i­ty risks use qual­i­ty met­rics,” the FDA said. “As a re­sult, the FDA rec­og­nized a ‘blind spot’ in reg­u­la­to­ry busi­ness process­es (e.g., in­spec­tions, prod­uct qual­i­ty de­fect re­ports): near­ly all were re­ac­tive, fo­cused on de­tect­ing neg­a­tive out­comes.”

A few years lat­er, the FDA of­fered up and then heav­i­ly re­vised a draft guid­ance (fol­low­ing in­dus­try cri­tiques) on how to sub­mit met­rics da­ta, in­clud­ing qual­i­ty-re­lat­ed com­plaints. Even­tu­al­ly, the guid­ance spawned two FDA pi­lot projects in 2018 with phar­ma­ceu­ti­cal man­u­fac­tur­ers to in­form the cri­te­ria used to ob­jec­tive­ly mea­sure a man­u­fac­tur­ing site’s QMM, but nei­ther amount­ed to much more un­til re­cent­ly.

“Feed­back from the par­tic­i­pants in the pi­lot pro­grams is now help­ing de­ter­mine best prac­tices for con­duct­ing the as­sess­ments, the as­sess­ment tool, and as­so­ci­at­ed lo­gis­tics,” the FDA said.

“The fact that they’re [FDA] con­tin­u­ing to look at this is promis­ing,” Michael Ganio, se­nior di­rec­tor at the Amer­i­can So­ci­ety of Health-Sys­tem Phar­ma­cists, pre­vi­ous­ly told End­points News. “And we know they rec­og­nize the im­por­tance of qual­i­ty in drugs in the sup­ply chain … it makes sense to give some sort of in­cen­tive or mea­sure­ment so pur­chasers have more in­for­ma­tion on whether they’re re­ward­ing more re­li­able prod­uct man­u­fac­tur­ers.”

Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

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Paul Perreault, CSL Behring CEO

CSL lands FDA ap­proval for he­mo­phil­ia B gene ther­a­py, sets $3.5M list price

The FDA has approved the world’s first gene therapy for hemophilia B, ushering into the market a treatment that’s historic in both what it promises to do and how much it will cost.

CSL will be marketing the drug, Hemgenix, at a list price of $3.5 million — which sets a new record for the most expensive single-use gene therapy in the US.

In a statement provided to Endpoints News, the Australian company noted that the current costs of treating people with moderate to severe hemophilia B can be significant over a lifetime. By some estimates, healthcare systems could spend more than $20 million per person.

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MIT re­searchers re­veal DNA "Paste" tech be­hind lat­est gene edit­ing start­up

MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.

In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.

Elon Musk (GDA via AP Images)

Biggest drug com­pa­nies halt­ed Twit­ter ad buys af­ter Lil­ly in­sulin spoof

Almost all of the drug industry’s biggest advertisers cut their spending on Twitter to zero or near-zero over the last two weeks amid worries about impersonation of their brands by pranksters and the future of the social media company.

Among 18 of the biggest pharmaceutical advertisers in the US market, 12 cut their Twitter ad spending to nothing for the week beginning Nov. 14, according to Pathmatics, which tracks data on prescription drug ad spending as well as general corporate advertising. The list of drugmakers cutting spending to zero includes Merck, AstraZeneca, Eli Lilly, Novartis, Pfizer and others.

FDA preps for DMD drug gener­ics as Sarep­ta has yet to fin­ish its con­fir­ma­to­ry tri­al

The FDA typically releases guidance to help generic drug manufacturers develop new copycats of small molecule drugs, oftentimes in preparation for a brand name product’s patents or exclusivity to expire.

This week, FDA released such bioequivalence guidance for any generic drugmakers looking to take on Sarepta’s Duchenne muscular dystrophy (DMD) drug Exondys 51 (eteplirsen), even though the drug’s sponsor has yet to convert the accelerated approval to a full approval, showing clinical benefit.

Rob Davis, Merck CEO

Up­dat­ed: No Seagen here: 'Do more' means a small $1.35B pur­chase of Ima­go for Mer­ck

Merck is making an acquisition, the Big Pharma announced before Monday’s opening bell. No, Seagen is not entering the fold, as had been speculated for quarters.

Folding under Merck’s wings will be Pfizer-backed Imago BioSciences. For nearly a year, Merck CEO Rob Davis has been saying the pharma giant needs to “do more” on the business development front after its 2021 $11.5 billion acquisition of Acceleron.

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Fu­ji­film to build $188M man­u­fac­tur­ing plant in North Car­oli­na’s re­search tri­an­gle

As the Japanese conglomerate Fujifilm continues to invest heavily in its CDMO arm, one of its manufacturing divisions is teeing up a major investment.

Fujifilm Irvine Scientific announced on Tuesday that parent Fujifilm is making a $188 million investment to build a cell culture media manufacturing site in the Research Triangle Park in North Carolina. The new site will mark Fujifilm Irvine’s fifth manufacturing site globally and its second in the US.

Sus­pend­ed Cal­i­for­nia cell ther­a­py man­u­fac­tur­ing site hit with FDA warn­ing let­ter over ma­jor qual­i­ty con­cerns

A cell therapy outfit in California that manufactures a human umbilical cord derived cellular product and exosome products is facing a warning from the FDA over several major observations related to quality.

The FDA notes the site’s “deficient donor screening practices, inadequate aseptic practices, unvalidated manufacturing,” and the “risk that your products may be contaminated with microorganisms or have other serious product quality defects.”

Days af­ter re­port­ing PhI­II fail­ure, GSK pulls BC­MA drug from US mar­ket — but it's not giv­ing up en­tire­ly yet

GSK is pulling its BCMA-targeting drug from the US market, ending a short, two-year run for a high-profile product that, among other things, was hailed for marking the pharma giant’s return to oncology.

The company is initiating the process for withdrawal at the request of the FDA, which in turn was based on the negative readout of a confirmatory Phase III trial earlier this month. In that trial, GSK’s Blenrep failed to extend progression-free survival over standard of care for patients with multiple myeloma who have received at least two prior lines of therapy.

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