FDA hands a warn­ing let­ter to a Lupin sub­sidiary af­ter fail­ing to main­tain clean­li­ness once again

From In­dia to NJ, the core of the FDA’s in­struc­tions to Lupin sub­sidiary Nov­el Lab­o­ra­to­ries were the same: es­tab­lish prop­er clean­ing and process val­i­da­tion guide­lines at your man­u­fac­tur­ing sites. And af­ter fail­ing to do so for the third time in four years, the com­pa­ny has re­ceived a warn­ing let­ter.

Drug residue on tablet press­es and a fail­ure to val­i­date the man­u­fac­tur­ing process af­ter equip­ment changes were just two of the is­sues raised by the FDA af­ter an in­spec­tion of a Nov­el Lab­o­ra­to­ries plant that led to the June 11 let­ter.

The FDA said that Nov­el Lab­o­ra­to­ries’ Som­er­set, NJ plant had vi­o­la­tions of cur­rent good man­u­fac­tur­ing prac­tice reg­u­la­tions such as an in­ad­e­quate clean­ing pro­ce­dure and qual­i­ty con­trol pro­ce­dures. It’s the first vi­o­la­tion at this site, but the third in four years for sites with­in the com­pa­ny’s net­work.

Nov­el Labs is a sub­sidiary of Lupin. Two of the com­pa­ny’s sites in In­dia, one in Goa and an­oth­er in Man­dideep, were is­sued warn­ing let­ters in 2017 and 2019, re­spec­tive­ly, for sim­i­lar cGMP vi­o­la­tions. Those two fa­cil­i­ties made prod­ucts that, at the time, made up more than 40% of Lupin’s sales. The com­pa­ny did not re­spond to a re­quest for com­ment by the time of pub­li­ca­tion Thurs­day.

“This is a big neg­a­tive for the com­pa­ny … The warn­ing let­ter will not on­ly de­lay new ap­provals, thus im­pact­ing US rev­enues, but al­so in­crease re­me­di­a­tion cost that will put pres­sure on mar­gins,” bro­ker­age firm Edel­weiss Se­cu­ri­ties said in re­gards to the pre­vi­ous two let­ters.

“Re­peat­ed vi­o­la­tions at mul­ti­ple sites demon­strate that your com­pa­ny’s cor­po­rate over­sight and con­trol over the man­u­fac­ture of drugs is in­ad­e­quate,” the let­ter stat­ed. “You should fur­ther com­pre­hen­sive­ly as­sess your com­pa­ny’s glob­al man­u­fac­tur­ing op­er­a­tions to en­sure that sys­tems and process­es, and ul­ti­mate­ly, the drug prod­ucts man­u­fac­tured, con­form to FDA re­quire­ments at all your sites.”

The qual­i­ty unit failed to es­tab­lish and fol­low writ­ten pro­ce­dures to en­sure the drug was up to stan­dards. The FDA said the clean­ing pro­to­col didn’t have ad­e­quate over­sight, and the com­pa­ny failed to com­plete the re­quired an­nu­al prod­uct re­view. While the com­pa­ny pre­vi­ous­ly made com­mit­ments to strength­en op­er­a­tions and ac­knowl­edged a need for more qual­i­ty unit over­sight, it failed to pro­vide a com­pre­hen­sive as­sess­ment of all writ­ten pro­ce­dures, the let­ter said.

Nov­el Labs is re­quired to fol­low up with re­spons­es to the FDA for the fol­low­ing:

  • A com­pre­hen­sive as­sess­ment and re­me­di­a­tion plan to en­sure its qual­i­ty con­trol unit is giv­en the au­thor­i­ty and re­sources, in­clud­ing a de­ter­mi­na­tion of whether pro­ce­dures used by the firm are ro­bust and ap­pro­pri­ate.
  • A de­ter­mi­na­tion of whether the com­pa­ny’s qual­i­ty con­trol unit has the ad­e­quate ed­u­ca­tion, train­ing, and ex­pe­ri­ence to per­form its du­ties.
  • Pro­vi­sions for qual­i­ty con­trol unit over­sight through­out op­er­a­tions to eval­u­ate ad­her­ence to ap­pro­pri­ate prac­tices
  • A com­plete and fi­nal re­view of each batch and its re­lat­ed in­for­ma­tion be­fore the qual­i­ty con­trol unit dis­po­si­tion de­ci­sion.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Tillman Gerngross (Adagio)

Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Like the flu vac­cine every year, the FDA could move quick­ly on a vari­ant-tar­get­ed Covid vac­cine

In the same way that the FDA signs off on flu vaccines every year without requiring large clinical trials to measure their efficacy, the FDA may employ a similar strategy in authorizing variant-focused versions of the mRNA vaccines.

As the world braces for more data on the latest variant Omicron, which may reduce vaccine efficacy, top vaccine developers like Moderna and Pfizer-BioNTech have promised they can pull together a new vaccine targeted against a specific Covid variant in about 100 days. Since Omicron emerged last week, Pfizer-BioNTech, Moderna and J&J have all said they’ve begun work on Omicron-specific vaccines, if needed.

Thanks­giv­ing edi­tion: Top 15 End­points sto­ries of 2021; Can you name that vac­cine?; Mer­ck­'s Covid an­tivi­ral dis­ap­points; FDA nom­i­nee's in­dus­try ties; 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.

Happy Thanksgiving to all those who are celebrating it — although, if we are being honest, this week’s abbreviated edition is really for those who are not. Wherever you’re tuning in from, we appreciate your support, hope you find this recap helpful and we wish you a wonderful weekend.

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What were End­points read­ers tun­ing in­to this year? Here’s a look at our 15 most pop­u­lar re­ports of the year (so far)

At the beginning of this year, I laid out a basic objective for Endpoints News as we headed to our 5th anniversary. We’ve long been doing a fine job covering the breaking news in R&D — if I do say so myself — but we needed to expand our horizons on industry coverage, increase the staff and go much, much deeper when the stories demanded it.

In a phrase: broader and deeper.

It’s safe to say, based on our daily web traffic, that you all seemed to like this idea. We’ve doubled the staff — thanks to a growing group of paid subscribers — ramped up the daily report and now publish a regular slate of in-depth articles. And traffic — those clicks you always read about — have gone up in volume too. Monthly sessions are up 43%, to close to 1.5 million. Unique readers are up 63%, to 874,480 in October, after setting a record of close to a million the month before. Page views are running at 3 million-plus a month. And the overall number of subscribers has surged to 124,000.

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Ursula von der Leyen, President of the European Commission

Omi­cron: Re­searchers scram­ble as new coro­n­avirus mu­ta­tion takes flight around the globe — Pfiz­er/BioN­Tech, Mod­er­na vow swift re­sponse

As Americans were waking up for their Black Friday rituals, they were greeted with the news that a new mutation of the Covid-19 virus has appeared and been sequenced — after it caught an international flight to Hong Kong. And two of the leading Covid-19 vaccine developers promised delivery of a new vaccine “within 100 days” if necessary while a third spelled out its 3-prong strategy hours later.

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Nev­er too late: For­bion pitch­es $100M SPAC; Kro­nos Bio re­leas­es ear­ly in­ter­im da­ta on CDK9 in­hibitor

Dutch VC Forbion is hopping on the ever-lengthening SPAC train.

To be led by Jasper Bos, who joined Forbion Growth as a general partner back in May just after the fund closed at $428 million, Forbion European Acquisition will target late-stage opportunities in the life sciences industry in Europe to merge with and bring onto Nasdaq.

Cyril Lesser, senior controller at Forbion, will be the CFO while Bos serves as CEO.

Jeff Albers, Blueprint Medicines CEO

Look­ing past Big Phar­ma ri­vals, Blue­print buys a pre­clin­i­cal biotech for $250M+

J&J’s Rybrevant scored the first approval back in May for a small group of lung cancer patients with a rare EGFR mutation. Despite a swarm of other biopharma companies angling for a piece of that market, Blueprint Medicines is betting nearly $500 million on a candidate it thinks will stand out.

Blueprint is putting down $250 million in cash and another $215 million in biobucks for Lengo Therapeutics and its preclinical non-small cell lung cancer program LNG-451. Though it hasn’t been tested in humans, Blueprint says the candidate was “highly brain-penetrant” in preclinical trials, and has the potential to inhibit all common EGFR exon 20 insertion variants — which are found in just 2% to 3% of NSCLC patients.

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