FDA res­ur­rects pro­pos­al to gauge qual­i­ty met­rics in phar­ma man­u­fac­tur­ing

The FDA is once again re­turn­ing to its hot­ly-con­test­ed qual­i­ty met­rics pro­gram for phar­ma man­u­fac­tur­ers, even as com­pa­nies have ex­pressed ma­jor reser­va­tions.

The agency’s fo­cus on qual­i­ty met­rics be­gan in 2015 and con­tin­ued with a heav­i­ly re­vised 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.

The FDA has main­tained its fo­cus on the top­ic of these vol­un­tary qual­i­ty met­rics even as bio­phar­ma com­pa­nies have ques­tioned the val­ue and util­i­ty of the da­ta and cri­tiqued the in­creased bur­den of col­lect­ing and sub­mit­ting the da­ta.

But the FDA stress­es in a new up­date on its qual­i­ty met­rics pro­gram on Tues­day that ad­di­tion­al da­ta can help both the FDA and the sup­ply chain, which needs to have a bet­ter un­der­stand­ing of which man­u­fac­tur­ers are go­ing above and be­yond the sta­tus quo. Cur­rent GMP com­pli­ance “does not nec­es­sar­i­ly in­di­cate” whether a man­u­fac­tur­er is in­vest­ing in im­prove­ments and striv­ing for con­sis­tent con­trol over its man­u­fac­tur­ing per­for­mance and qual­i­ty, FDA said.

Michael Ganio

“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, 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.”

FDA al­so says it’s con­sid­er­ing changes and seeks feed­back on some as­pects of its qual­i­ty met­rics re­port­ing pro­gram.

“To pro­vide flex­i­bil­i­ty to man­u­fac­tur­ers, FDA would fo­cus less on stan­dard­iza­tion of qual­i­ty met­rics and de­f­i­n­i­tions,” the agency said Tues­day. “In­stead, FDA would iden­ti­fy prac­tice ar­eas that are crit­i­cal to en­sure sus­tain­able prod­uct qual­i­ty and avail­abil­i­ty and would per­mit man­u­fac­tur­ers to se­lect a met­ric(s) from each prac­tice area that are mean­ing­ful and en­able es­tab­lish­ments to iden­ti­fy con­tin­u­al im­prove­ment op­por­tu­ni­ties.”

Rather than set met­ric de­f­i­n­i­tions on how es­tab­lish­ments cal­cu­late par­tic­u­lar met­rics, the FDA said it will al­low re­port­ing es­tab­lish­ments (i.e. API and fin­ished dose man­u­fac­tur­ers, among oth­ers) to se­lect the most ap­pro­pri­ate met­ric(s) from each prac­tice area and in­form FDA how the met­rics were cal­cu­lat­ed.

Based on feed­back from the pi­lot par­tic­i­pants, the agency said it iden­ti­fied four gen­er­al ar­eas as ap­pro­pri­ate for its met­rics pro­gram:

(1) Man­u­fac­tur­ing process per­for­mance

(2) Phar­ma­ceu­ti­cal qual­i­ty sys­tem ef­fec­tive­ness

(3) Lab­o­ra­to­ry per­for­mance

(4) Sup­ply chain ro­bust­ness

Ex­am­ples of qual­i­ty met­rics as­so­ci­at­ed with each of these ar­eas in­clude (for area num­ber 1) a met­ric on the pro­por­tion of lots man­u­fac­tured with­out the oc­cur­rence of a non-con­for­mance, (for area num­ber 2) a mea­sure of the pro­por­tion of re­cur­ring de­vi­a­tion mea­sures, (for area num­ber 3) a mea­sure that in­di­cates a lab’s abil­i­ty to ac­cu­rate­ly per­form tests, and (for area num­ber 4) a mea­sure of the ex­tent to which ship­ments are de­liv­ered to their des­ti­na­tion con­tain­ing the cor­rect quan­ti­ty and ac­cord­ing to the or­der’s sched­ule.

As far as ques­tions for in­dus­try, the FDA wants to know if stake­hold­ers agree that re­port­ing should be ag­gre­gat­ed at an es­tab­lish­ment lev­el, and whether re­port­ing at an es­tab­lish­ment lev­el would help fa­cil­i­tate the sub­mis­sion of qual­i­ty met­rics da­ta by con­tract man­u­fac­tur­ers.

The Phar­ma & Bio­phar­ma Out­sourc­ing As­so­ci­a­tion, which rep­re­sents CD­MOs, told End­points that it’s look­ing in­to this lat­est an­nounce­ment and it ap­pears as though the FDA does want to im­ple­ment qual­i­ty met­rics re­port­ing in some way, shape or form. PBOA said it’s look­ing for­ward to pro­vid­ing a de­tailed re­sponse to the dock­et.

The FDA al­so wants stake­hold­ers’ thoughts on what are the crit­i­cal com­po­nents of “a ro­bust qual­i­ty cul­ture,” and whether any of the ex­am­ples of qual­i­ty met­rics pro­posed by the FDA “would not be an ap­pro­pri­ate mea­sure.”

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.