Warn­ing let­ter is­sued to New Jer­sey gener­ics man­u­fac­tur­er over qual­i­ty con­trol is­sues

A gener­ics man­u­fac­tur­er has re­ceived a warn­ing let­ter from the FDA over sev­er­al is­sues sur­round­ing su­per­vi­sion and qual­i­ty con­trol.

Bi-Coastal Phar­ma In­ter­na­tion­al’s drug man­u­fac­tur­ing fa­cil­i­ty in Shrews­bury, New Jer­sey ini­tial­ly re­ceived a Form 483 ear­li­er this year. But ac­cord­ing to an­oth­er let­ter dat­ed June 30, the FDA has found some fla­grant is­sues with the com­pa­ny’s re­spons­es.

The let­ter ini­tial­ly stat­ed that Bi-Coastal had failed to es­tab­lish and fol­low writ­ten pro­ce­dures around the han­dling of writ­ten and oral com­plaints for drug prod­ucts.

The FDA found that the com­pa­ny had not in­ves­ti­gat­ed a com­plaint about an ad­verse re­ac­tion af­ter tak­ing Chlor­diazepox­ide Hy­drochlo­ride (HCl) and Cli­dini­um Bro­mide (Br), 5 mg/2.5 mg, which was dis­cov­ered and dis­trib­uted by the com­pa­ny. No in­ves­ti­ga­tion was ini­ti­at­ed to eval­u­ate the man­u­fac­tur­ing and pack­ag­ing of Chlor­diazepox­ide HCl and Cli­dini­um Br, ac­cord­ing to the let­ter. In ad­di­tion, the FDA said Bi-Coastal didn’t at­tempt to ob­tain sam­ples of the drug or more in­for­ma­tion from the com­plainant.

Bi-Coastal said that its CMO was no longer in busi­ness and was un­able to share the com­plaint with the CMO for fur­ther in­ves­ti­ga­tion. How­ev­er, the FDA ar­gues that as the prod­uct own­er, Bi-Coastal is still re­spon­si­ble for en­sur­ing con­trol over out­sourced ac­tiv­i­ties.

While the com­pa­ny said it would re­vise the process for han­dling com­plaints, the FDA found the re­sponse in­ad­e­quate. Reg­u­la­tors al­so ac­cused Bi-Coastal of fail­ing to write down and fol­low pro­ce­dures. No de­tails of its in­ter­im con­trols were sup­plied to the FDA, or an eval­u­a­tion of its agree­ments with the CMOs.

The FDA al­so found that the QA man­ag­er lacked ex­pe­ri­ence and train­ing in qual­i­ty as­sur­ance and the sci­ences, de­spite be­ing re­spon­si­ble for over­see­ing CMOs and batch re­lease. The man­ag­er was al­so “un­aware of GMP sta­bil­i­ty test­ing and process val­i­da­tion re­quire­ments for drug prod­ucts man­u­fac­tured by CMOs.”

In re­sponse, Bi-Coastal said its vice pres­i­dent and gen­er­al man­ag­er will help en­sure prop­er ad­her­ence to pro­ce­dures while it finds a new man­ag­er.

“This re­sponse is in­ad­e­quate. You failed to pro­vide ev­i­dence show­ing this in­di­vid­ual is qual­i­fied to pro­vide over­sight of CGMP ac­tiv­i­ties. In ad­di­tion, you have not pro­vid­ed de­tails as to how you will en­sure the new qual­i­ty as­sur­ance man­ag­er will have the ap­pro­pri­ate com­bi­na­tion of train­ing, ed­u­ca­tion, and ex­pe­ri­ence to per­form the job ad­e­quate­ly,” the let­ter said.

The com­pa­ny had 15 days from June 30 to re­spond to the FDA to fix these is­sues. If the is­sues re­main un­ad­dressed, the FDA may with­hold the is­suance of ex­port cer­tifi­cates, or the ap­proval of new ap­pli­ca­tions or sup­ple­ments un­til the com­pa­ny com­plies.

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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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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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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(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. 

Vlad Coric, Biohaven CEO

Bio­haven touts surge in Nurtec sales ahead of Pfiz­er takeover

Forget buyer’s remorse, Pfizer is likely feeling pretty good about its $11.6 billion Biohaven takeover deal following reports of a 57% sales boost for migraine med Nurtec.

Biohaven reported in Q2 results on Friday that it’s cleared the necessary antitrust hurdles to move forward with the sale of its calcitonin gene-related peptide (CGRP) assets to Pfizer. However, because the company is “focused on workstreams related to the closing” of the deal, it did not host a call with analysts and investors.