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.”

UP­DAT­ED: In a fresh dis­ap­point­ment, Am­gen spot­lights a ma­jor safe­ty is­sue with KRAS com­bo

Amgen had hoped that its latest study matching its landmark KRAS G12C drug Lumakras with checkpoint inhibitors would open up its treatment horizons and expand its commercial potential. Instead, the combo spurred safety issues that blunted efficacy and forced the pharma giant to alter course on its treatment strategy, once again disappointing analysts who have been tracking the drug’s faltering sales and limited therapeutic reach.

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Ad­dress­ing the ‘Ca­pac­i­ty Crunch’ with a Scal­able Plat­form Process Ap­proach

The field of gene therapy has been diligently moving forward over the past several decades to bring potentially life-saving treatments to patients with genetic diseases. In addition to two approved adeno-associated viral (AAV) gene therapies, there are more than 250 AAV gene therapies in various clinical trial stages.1 AAV vectors remain the most frequently used vector for delivering therapeutic transgenes to target tissues due to their demonstrated and lasting clinical efficacy and extensive safety track record. As AAV therapies advance through clinical trials and into commercialization, many biotech companies are turning to contract development and manufacturing organizations (CDMOs) to prepare their programs for late-stage clinical and commercial scale manufacturing. Given the scope and scale of the manufacturing needs that will accompany regulatory approvals for these assets, CDMOs continue to expand their capacity to meet the needs of increasing prevalent patient populations. However, despite rapid growth, projected gene therapy manufacturing demands still outpace the collective capacity of the CDMO industry.

A $5B Pfiz­er buy­out? Am­gen, Gilead head­line M&A Thurs­day; Al­ny­lam's AT­TR sweep; An­drew Lo's rare dis­ease quest; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

One of the cool things about adding EndpointsPharma to the daily roster is that my colleagues can now dedicate time to tracking quarterly updates and tuning into calls with Big Pharma companies. Check out their dispatch from the Q2 earnings below.

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Albert Bourla, Pfizer CEO (Laurent Gillieron/Keystone via AP)

Break­ing: Pfiz­er in hot pur­suit of a $5B buy­out of Glob­al Blood Ther­a­peu­tics — re­port

Pfizer CEO Albert Bourla has vowed to leave no stone unturned in the search for new biotech deals, and the BD team is not letting him down.

The Wall Street Journal reported today that Pfizer is in the final stages of acquiring Global Blood Therapeutics for $5 billion. According to the Journal report, though, Pfizer is not the only buyer at the deal table and while the pharma giant may be close to clinching it, there are no guarantees it will continue.

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Bob Bradway, Amgen CEO (Justin Kase Conder/AP Images for Amgen)

UP­DAT­ED: Am­gen chief Brad­way nabs a rare dis­ease play­er in $4B buy­out as the M&A tem­po ac­cel­er­ates

Amgen CEO Bob Bradway is bellying up to the M&A table today, scooping up the newly anointed commercial biotech ChemoCentryx $CCXI and its recently approved rare disease drug for $3.7 billion out of the cash stockpile. The deal comes in at $52 a share — a hefty increase over the $24.11 close yesterday.

Bradway and the Amgen team get a drug called Tavneos (avacopan) in the deal, a complement factor C5a inhibitor OK’d to treat anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis, an autoimmune disease which can be lethal.

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George Yancopoulos, Regeneron president and CSO (Brendan McDermid/Reuters/Alamy)

George Yan­copou­los says he's on the trail of the holy grail: ‘This could rep­re­sent the next break­through for im­munother­a­py’

Two of the most outspoken — and successful — drug developers in biotech say they’ve collected early-stage clinical data that are pointing them down the trail to the holy grail in cancer immunotherapy R&D.

While analysts largely busied themselves today with chronicling the ongoing success of Regeneron’s two big cash cows — Dupixent and Eylea — chief scientist George Yancopoulos and CEO Len Schleifer used the Q2 call to spotlight their early success with a combination of the “homegrown” PSMAxCD28 costimulatory bispecific antibody REGN5678 in combination with their PD-1 checkpoint Libtayo. The presentation comes just weeks after Regeneron completed a deal to gather all rights to the PD-1 that had been in Sanofi’s hands. And the two top execs are unstinting in their praise of the potential of a whole set of costimulatory pipeline projects which they say may finally deliver the long-awaited next-level approach to broadening the immunotherapy field of drugs.

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(AP Photo/Richard Vogel, File)

US de­clares mon­key­pox a na­tion­al health emer­gency, as new drug­mak­ers con­sid­er en­ter­ing vac­cine race

Rising monkeypox cases have put the US on high alert as it announces a national health emergency, which grants the government more power in its response.

The news comes as Bavarian Nordic continues to fill orders for its Jynneos vaccine and other companies – including Moderna – consider jumping into the vaccine race. Meanwhile, the New York Times reports that the US has allowed around 20 million doses of smallpox vaccine in its stockpile to expire.

Sen. Kyrsten Sinema (D-AZ) (Tom Williams/CQ Roll Call via AP Images)

De­moc­rats se­cure sup­port from key sen­a­tor ahead of po­ten­tial drug pric­ing vote

Senate Democrats may have all the votes they need to pass major drug pricing reform, after Sen. Kyrsten Sinema (D-AZ) reportedly pledged her support on Thursday — but will they fit it in before recess?

Sinema said she has agreed to “move forward” with the reconciliation bill with some stipulations, including the removal of a carried tax provision, according to recent reports. The bill is still expected to reduce the deficit by $300 billion, and Sen. Chuck Schumer (D-NY) said that he now anticipates “support from the entire Senate Democratic conference,” the Washington Post reported. 

CDC, NIH, FDA lead­ers call for US-based clin­i­cal tri­al of small­pox drug in treat­ing mon­key­pox

With the rising number of monkeypox cases, leading researchers at the CDC, FDA and NIH are calling on a randomized clinical trial to see if an approved smallpox drug is effective at treating monkeypox.

No monkeypox treatments are approved in the US, so patients looking to get relief for their lesions and other symptoms from the virus must go through a set of hurdles to get the smallpox drug through a government expanded access program. Approved for smallpox in 2018, the drug is marketed as TPOXX by the biotech SIGA. The European Union approved it for monkeypox in addition to smallpox earlier this year and the UK followed suit in July.