Trou­bled can­cer cen­ter in Con­necti­cut hand­ed Form 483 by FDA, again

The John­son Memo­r­i­al Can­cer Cen­ter in En­field, CT is no stranger to bat­tles with in­spec­tion prob­lems, and it was hit with an­oth­er Form 483 in Oc­to­ber, af­ter a string of trou­bles not­ed by the FDA.

A num­ber of ob­ser­va­tions were made, but per­haps the most glar­ing: staff at­tach­ing wipes to a mop han­dle to try and clean pro­duc­tion equip­ment.

The site was in­spect­ed 10 times be­tween Sept. 20 and Oct. 20 of last year.

Borte­zomib is used to treat adult pa­tients with mul­ti­ple myelo­ma, a can­cer of the bone mar­row, as well as man­tle cell lym­phoma. Mar­ket­ed un­der the name Vel­cade, it was co-de­vel­oped by Mil­len­ni­um Phar­ma­ceu­ti­cals and J&J, and land­ed FDA ap­proval for in­tra­venous in­jec­tion in 2003, then sub­cu­ta­neous­ly in 2012. It was lat­er ap­proved in 2014 for pre­treat­ment of mul­ti­ple myelo­ma pa­tients. One treat­ment cy­cle in­cludes twice-week­ly in­jec­tions for two weeks, fol­lowed by a 10-day rest pe­ri­od. Take­da and Janssen co-pro­mote the drug in Japan.

Poor clean­ing prac­tices were the rea­son for the hold, in par­tic­u­lar, dur­ing the pro­duc­tion process. A tech­ni­cian was ob­served fail­ing to clean the in­ter­nal screen be­tween batch­es and used a stain­less steel mop han­dle out­fit­ted with ster­il­iz­ing wipes to clean the in­te­ri­or of a biore­ac­tor in­stead of the ap­pro­pri­ate mop, which meant that the tech­ni­cian wasn’t able to reach and clean the en­tire in­te­ri­or, in­clud­ing the back and sides.

A phar­ma­cy tech­ni­cian al­so failed to clean the sep­tum of two vials of the drug prod­uct in be­tween ster­ile pro­duc­tion ac­tiv­i­ties, and the high-ef­fi­cien­cy par­tic­u­late air fil­ter — al­so known as a HE­PA — cov­er­age wasn’t ad­e­quate enough, there­by ex­pos­ing ster­ile prod­uct, the FDA said.

Smoke stud­ies, in which man­u­fac­tur­ers must an­a­lyze air pat­tens to en­sure that the qual­i­ty can­not con­t­a­m­i­nate the drug prod­uct, were lack­ing key as­pects in Au­gust 2020, Feb­ru­ary 2021 and Au­gust 2021, the agency said.

It’s not the lo­ca­tion’s first run-in with con­t­a­m­i­na­tion prob­lems. In 2014, the site was hand­ed a Form 483 for fail­ing to pre­vent mi­cro­bial con­t­a­m­i­na­tion and mix-ups. In­ves­ti­ga­tors no­ticed wa­ter stain marks in rooms, and the com­pa­ny failed to eval­u­ate air qual­i­ty, with out­side air pen­e­trat­ing through a room used for gown­ing and prepa­ra­tion be­fore ster­il­iza­tion. HE­PA fil­ters hadn’t been prop­er­ly swapped out and were yel­low at the time of in­spec­tion, and the firm didn’t eval­u­ate the pres­sure be­tween clean rooms, some­thing es­sen­tial to pre­vent­ing con­t­a­m­i­na­tion.

Then in 2015, mold and fun­gus at the site led Con­necti­cut au­thor­i­ties to close the can­cer in­fu­sion cen­ter for months, on top of the man­u­fac­tur­ing op­er­a­tions for more than a year. The build­ing was built in 1998, ac­cord­ing to the Hart­ford Busi­ness Jour­nal, but state in­spec­tors found more than 50 se­ri­ous vi­o­la­tions at the hos­pi­tal and its treat­ment cen­ters, which in­clud­ed staff bla­tant­ly ig­nor­ing prob­lems that in­clud­ed mold and fun­gus. De­spite the in­di­ca­tion that staff was aware of the prob­lems, they weren’t dis­cussed pub­licly, ac­cord­ing to the meet­ing min­utes.

A rep­re­sen­ta­tive from the cen­ter did not re­turn a re­quest for in­for­ma­tion by pub­li­ca­tion time.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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David Light, Valisure CEO

Val­isure in the hot seat: New Form 483 over a 2021 in­spec­tion as CEO fires back

The notorious drug testing company Valisure, which has made a name for itself by forcing FDA’s hand with some of its safety-related uncoverings, received a letter this week after the FDA uncovered violations at its Connecticut-based testing lab in 2021.

The letter, which was sent on Dec. 5, stated that the FDA is “concerned” that Valisure was not aware of  drug supply chain security requirements.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Bags of shred­ded docs: In­di­an drug­mak­er Lupin hand­ed a Form 483 by FDA in­spec­tors

The generics manufacturer Lupin has been given another Form 483 from the FDA this year.

US regulators inspected Lupin’s pharmaceutical manufacturing site in the town of Mandideep, India from Nov. 14 through Nov. 23, with the 14-page report marking 16 observations.

The inspection report stated that the site did not have the appropriate controls over its computer systems to ensure that changes in “master production” or records are only done by authorized personnel, along with written procedures not being established to conduct annual reviews of records associated with drug batches.

Nashville-based CD­MO nets a $65M Se­ries B to ex­pand fa­cil­i­ty and ca­pa­bil­i­ties

Another $65 million is music to the ears of the team at August Bioservices, a contract manufacturer in Nashville.

The company announced the Series B round last week, which will fund equipment in a new building expected to open in 2023, according to CEO Jenn Adams. It was led by Oak HC/FT, the same firm that led August’s Series A round in July 2020.

August Bioservices, a producer of materials such as prefilled syringes, IV bags and vials, was formed back in 2020 after the acquisition of PMI BioPharma Solutions, also based in Nashville. Adams said the goal was to build a business that could “address the scarcity of supply relative to sterile injectable manufacturing based in the US” and provide a broad range of manufacturing services.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.