Phar­ma man­u­fac­tur­ers in In­dia, US lat­est to re­ceive qual­i­ty con­trol hits from the FDA

Two drug man­u­fac­tur­ers on op­po­site sides of the globe are fac­ing the heat from the FDA over sev­er­al qual­i­ty con­trol is­sues.

In­dia-based man­u­fac­tur­er Sun Phar­ma was hit with a Form 483 fol­low­ing an FDA in­spec­tion of its Mo­hali fa­cil­i­ty from Aug. 3-12.

The FDA found fail­ures when re­view­ing un­ex­plained dis­crep­an­cies re­gard­ing whether a batch al­ready had been dis­trib­uted at the lo­ca­tion.

The in­ves­ti­ga­tion found that there were in­stances of back­dat­ing, but Sun’s re­port was not thor­ough enough for the FDA to eval­u­ate the full scope of the of­fense. Sun did not in­ter­view all qual­i­ty as­sur­ance re­view­ers, but it did con­firm back­dat­ing by em­ploy­ees who had de­nied the prac­tice ini­tial­ly. Sun al­so did not have a thor­ough re­view of oth­er work per­formed by the em­ploy­ees, ac­cord­ing to the FDA re­port.

An au­dit to as­sess the back­dat­ing risk was con­duct­ed in Sun’s GMP doc­u­ments, but it did not in­clude spe­cif­ic ac­tions that could iden­ti­fy if back­dat­ing was still on­go­ing or give the ex­tent of the dam­age. Ad­di­tion­al qual­i­ty con­trol em­ploy­ees were not in­ter­viewed when eval­u­at­ing the scope of the back­dat­ing in the QC lab­o­ra­to­ry as well.

The 483 form in­cludes a charge that a for­mer em­ploy­ee al­leged many back­dat­ing cas­es in the qual­i­ty con­trol lab­o­ra­to­ry. Doc­u­ments were pro­vid­ed iden­ti­fy­ing a cur­rent em­ploy­ee who was in­volved in back­dat­ing, but the for­mer em­ploy­ee did not re­spond to re­quests for ad­di­tion­al in­for­ma­tion.

The FDA de­ter­mined that still did not thor­ough­ly jus­ti­fy why there was not enough in­for­ma­tion to ini­ti­ate an in­ves­ti­ga­tion be­cause there were oth­er open in­ves­ti­ga­tions re­lat­ed to back­dat­ing and coun­ter­feit sig­na­tures.

The in­ves­ti­ga­tion al­so found cross-con­t­a­m­i­na­tion in prod­ucts and iden­ti­fied shared-use equip­ment as the like­ly root cause, but no spe­cif­ic source of the con­t­a­m­i­na­tion was de­ter­mined, lead­ing to a re­call of prod­ucts.

The FDA al­so found that sam­pling plans, test pro­ce­dures and lab­o­ra­to­ry con­trol mech­a­nisms were not doc­u­ment­ed, with records show­ing the em­ploy­ee re­spon­si­ble for col­lect­ing sam­ples did not en­ter the build­ings where the sam­ples were doc­u­ment­ed to have been col­lect­ed or that the em­ploy­ee was in a dif­fer­ent build­ing at the time the sam­ple was doc­u­ment­ed to have been col­lect­ed. Those in­ci­dents hap­pened on nu­mer­ous oc­ca­sions.

Writ­ten pro­ce­dures were re­viewed and ap­proved by the qual­i­ty con­trol unit along with lab­o­ra­to­ry records be­ing de­fi­cient and lab­o­ra­to­ry con­trols not in­clud­ing sci­en­tif­i­cal­ly sound test pro­ce­dures. Writ­ten pro­ce­dures were al­so not fol­lowed in the test­ing of com­pounds as well.

Sun has had sim­i­lar pri­or run-ins with the FDA. A Form 483 from an in­spec­tion in May at its plant in Halol, In­dia, showed 10 ob­ser­va­tions rang­ing from qual­i­ty con­trol is­sues to a lack of train­ing. The com­pa­ny has now racked up its 11th 483 since 2016.

Sim­i­lar­ly, a US man­u­fac­tur­er is al­so in the FDA’s crosshairs with an­oth­er Form 483. Re­vance Ther­a­peu­tics’ man­u­fac­tur­ing site in the Bay Area city of Newark, CA , notched three prob­lems ob­ser­va­tions not­ed by the FDA.

An in­spec­tion held in mid-Ju­ly re­port­ed that de­vi­a­tions at the site were not al­ways ini­ti­at­ed ac­cord­ing to de­vi­a­tion re­port­ing and han­dling stan­dards. The FDA al­so found cer­tain op­er­a­tions and clean­ing op­er­a­tions did not con­tain ad­e­quate in­for­ma­tion to en­sure con­sis­tent per­for­mance.

The site al­so did not have its work­ing cell bank stor­age fa­cil­i­ty in­for­ma­tion list­ed.

Man­u­fac­tur­ing is­sues have im­pact­ed Re­vance be­fore, as last year the biotech was hand­ed a CRL for its Botox-based ther­a­py for mod­er­ate-to-se­vere glabel­lar lines. Re­vance said the re­jec­tion came from de­fi­cien­cies at a man­u­fac­tur­ing site. The 483 from that pe­ri­od showed that banks test­ing meth­ods were not suf­fi­cient to track qual­i­ty, and the man­u­fac­tur­ing process was dif­fer­ent from the one orig­i­nal­ly pro­posed for com­mer­cial­iza­tion.

Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

Up­dat­ed: As­traZeneca jumps deep­er in­to cell ther­a­py 2.0 space with $320M biotech M&A

Right from the start, the execs at Neogene had some lofty goals in mind when they decided to try their hand at a cell therapy that could tackle solid tumors.

Its founders have helped hone a new approach that would pack in multiple neoantigen targets to create a personalized TCR treatment that would not just make the leap from blood to solid tumors, but do it with durability. And they managed to make their way rapidly to the clinic, unveiling their first Phase I program for advanced tumors just last May.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Emily Leproust, Twist Bioscience CEO

Twist Bio­science’s 'Fac­to­ry of the Fu­ture' in Ore­gon could de­liv­er with com­pet­i­tive pric­ing, SVB Se­cu­ri­ties says

The synthetic DNA manufacturer Twist Bioscience has given a peek behind the curtain to several analysts into its “Factory of the Future” as well as insight into the cost structure, workflow and technology at the site.

The 110,000-square-foot manufacturing site in the city of Wilsonville, OR, just south of Portland, which was announced back in 2020, will double Twist’s production capacity and bring around 400 jobs to the area.

Digital render of CPI's Medicines Manufacturing Innovation Centre in Glasgow, Scotland (Image:

CPI opens the doors to a new $100M+ man­u­fac­tur­ing fa­cil­i­ty in Scot­land

A manufacturing site that has received interest and investments from large pharma companies and the UK government is opening its doors in Scotland.

The manufacturer CPI (Centre for Process Innovation) has opened a new £88 million ($105 million) “Medicines Manufacturing Innovation Centre” in Glasgow, Scotland, to accelerate the development of manufacturing tech and solve longstanding challenges in medicine development and manufacturing.

Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

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Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and DN­Di aim to elim­i­nate sleep­ing sick­ness in Africa with promis­ing Ph II/III re­sults for new drug

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting:

Lex­i­con slams FDA over hear­ing de­nial fol­low­ing a CRL for its SGLT2 in­hibitor can­di­date

Lexicon Pharmaceutical is not giving up on its Type I diabetes candidate, despite FDA’s repeated rejections. This week the company laid out is argument again for a hearing on sotagliflozin in response to the FDA’s most recent denial.

The issue goes back to March 2019 when the FDA made very clear to Lexicon and its now departed partner Sanofi that it would not approve their application for a potential Type I diabetes drug because it does not appear to be safe.

Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

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Pro­tect­ing its megablock­buster, Janssen chal­lenges Am­gen's Ste­lara biosim­i­lar ahead of planned 2023 launch

Johnson & Johnson unit Janssen on Wednesday sued Amgen over the company’s proposed biosimilar to its megablockbuster Stelara (ustekinumab), after Amgen said it was ready to launch next May or as soon as the FDA signs off on it.

If Amgen carries through with that plan, Janssen told the Delaware district court that the Thousand Oaks, CA-based company will infringe on at least two Janssen patents.