St. Louis-based API man­u­fac­tur­er slammed with FDA warn­ing let­ter over 'per­va­sive mold,' qual­i­ty is­sues

The growth of API man­u­fac­tur­ing in In­dia and Chi­na has led to nu­mer­ous warn­ing let­ters and lots of ques­tion marks around qual­i­ty con­trol and da­ta in­tegri­ty is­sues. But vi­o­la­tions by US-based API man­u­fac­tur­ers can be just as ques­tion­able.

For in­stance, in a warn­ing let­ter dat­ed last week, St. Louis-based API man­u­fac­tur­er Jost Chem­i­cal was cri­tiqued for the way it failed to ad­e­quate­ly re­spond to mold con­t­a­m­i­na­tion, fol­low­ing com­plaints from Au­gust 2018 re­lat­ed to its man­u­fac­ture of potas­si­um sul­fate.

“No­tably, you re­port­ed that ap­prox­i­mate­ly 83 per­cent of your mi­cro­bial prod­uct fail­ures were mold-re­lat­ed fail­ures,” FDA not­ed, ex­plain­ing that the site’s wa­ter sys­tems are not ad­e­quate, es­pe­cial­ly as the site man­u­fac­tures APIs that are used by cus­tomers to pro­duce ster­ile drug prod­ucts.

“Your cur­rent fre­quen­cy of test­ing and wa­ter qual­i­ty stan­dards are in­ad­e­quate to en­sure con­trol over your man­u­fac­tur­ing process­es,” the warn­ing says. “You are re­spon­si­ble for en­sur­ing the wa­ter for equip­ment clean­ing and man­u­fac­tur­ing is of suit­able qual­i­ty and does not po­ten­tial­ly con­tribute to con­t­a­m­i­na­tion of mi­crobes or mi­cro­bial byprod­ucts to API process­es.”

What’s more is that the com­pa­ny did not re­call the APIs af­fect­ed by mold.

“You did not ini­ti­ate a for­mal re­call with FDA no­ti­fi­ca­tion but in­stead in­formed your clients the lots failed to meet spec­i­fi­ca­tions and in­struct­ed them to re­turn or de­stroy the fail­ing lots,” the FDA said. “In ad­di­tion, your retests showed per­va­sive mold in three lots, but you did not ex­pand your in­ves­ti­ga­tion suf­fi­cient­ly to in­clude oth­er po­ten­tial­ly im­pact­ed lots to ful­ly ad­dress the scope of the prob­lem.”

Now, the FDA wants Jost to do a ret­ro­spec­tive re­view of out-of-spec re­sults it ini­ti­at­ed over the last three years to iden­ti­fy in­ves­ti­ga­tions that were not ex­pand­ed to in­clude all po­ten­tial­ly im­pact­ed lots.

And like some of its Chi­nese and In­di­an API coun­ter­parts, the FDA al­so warned Jost for in­suf­fi­cient con­trols over its cGMP da­ta. Not on­ly does Jost lack unique pass­words for lab in­stru­ments used to gen­er­ate an­a­lyt­i­cal da­ta for fin­ished API prod­ucts, but the in­spec­tion found that the site’s an­a­lyt­i­cal sys­tems lacked con­trols to pre­vent users from delet­ing elec­tron­ic da­ta — a ma­jor is­sue.

The site al­so lacks pro­ce­dures gov­ern­ing the re­view of au­dit trails of both pro­duc­tion and lab­o­ra­to­ry equip­ment, and the FDA al­so found its clean­ing val­i­da­tion for non-ded­i­cat­ed man­u­fac­tur­ing equip­ment is in­ad­e­quate, and its mi­cro­bial test pro­ce­dure is in­ad­e­quate.

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.