FDA faults Japan­ese man­u­fac­tur­er with da­ta breach, con­t­a­m­i­nat­ed in­jecta­bles

The FDA has come down hard on a Japan­ese man­u­fac­tur­er, with cGMP fail­ures that in­clude batch dis­crep­an­cies left with­out in­ves­ti­ga­tion, da­ta breach­es left un­ad­dressed and the ma­nip­u­la­tion of con­tact plate mea­sure­ments.

Toy­obo Co. re­ceived a warn­ing let­ter on Aug. 19. If it can­not cor­rect the vi­o­la­tions, the FDA can refuse the im­port of drugs man­u­fac­tured at the Shi­ga site in­to the US. Toy­obo has 15 days to re­spond to the let­ter.

Be­tween 2019 and 2020, for­eign ob­jects were found in batch­es of an in­jectable pro­duced at the site, and Toy­obo didn’t in­ves­ti­gate the root cause of the con­t­a­m­i­na­tion soon enough, nor did it try to as­sess the im­pact the con­t­a­m­i­na­tion could have. While the com­pa­ny has now hired out­side au­di­tors and con­sul­tants to fix up its op­er­a­tion, the in­ves­ti­ga­tion found that the wash­ing and ster­il­iza­tion process couldn’t re­move par­ti­cles on stop­pers and vials, and the root of that prob­lem has still not been ad­dressed, the FDA said.

“Our re­view re­vealed that your in-process qual­i­ty stan­dards, lim­its, cat­e­gories, and trig­gers for in­ves­ti­ga­tions do not suf­fi­cient­ly dif­fer­en­ti­ate in­trin­sic from ex­trin­sic par­tic­u­late con­t­a­m­i­na­tion,” the warn­ing let­ter says.

There were 12 batch­es that had cel­lu­lose and glass fibers, stains, and par­ti­cles on vials, the FDA said.

Among the most egre­gious of­fens­es, the com­pa­ny failed to en­sure the ac­cu­ra­cy and in­tegri­ty of the da­ta, which can lead to fluc­tu­at­ing safe­ty, ef­fi­ca­cy and qual­i­ty of the drugs. Par­ti­cle da­ta was mis­re­port­ed when the lev­els were high­er than alert lev­els, and op­er­a­tors were in­volved in the ma­nip­u­la­tion of da­ta, the let­ter said. The weak­ness­es could have im­pact­ed batch­es dat­ing all the way back to 2016.

“Aware­ness of mi­cro­bial ex­cur­sions in an asep­tic pro­cess­ing op­er­a­tion is es­sen­tial to trig­ger prompt ac­tions that main­tain en­vi­ron­men­tal con­trol. Ad­di­tion­al­ly, time­ly and thor­ough eval­u­a­tion of ac­tion lev­el ex­cur­sions, iden­ti­fy­ing po­ten­tial routes of con­t­a­m­i­na­tion, as well as iden­ti­fy­ing ap­pro­pri­ate fol­low-up mea­sures are nec­es­sary to pre­vent con­t­a­m­i­na­tion risks to the prod­uct,” the FDA said. “Your fail­ure to re­port ac­cu­rate da­ta com­pro­mised the steril­i­ty as­sur­ance of drug prod­ucts re­leased from the fa­cil­i­ty and may have in­creased risks to pa­tients.”

Toy­obo said its em­ploy­ees’ lack of un­der­stand­ing of cGMP and the im­por­tance of da­ta in­tegri­ty, and an in­abil­i­ty to han­dle the pres­sure of de­vi­a­tions are to blame for the slip-ups. The FDA said that in or­der to re­sume op­er­a­tions, the com­pa­ny needs to im­prove staff ac­count­abil­i­ty, and en­act a plan to do so. The com­pa­ny must pro­vide an as­sess­ment of all hu­man in­ter­ac­tion in the con­t­a­m­i­nat­ed area, air qual­i­ty, fa­cil­i­ty lay­out, per­son­nel and ma­te­r­i­al flows and equip­ment place­ment.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; 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.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Proac­tive­ly pre­vent­ing short­ages: New FDA guid­ance spells out which drugs re­quire risk man­age­ment plans

As the majority of drug shortages are still associated with manufacturing-related quality issues, the FDA on Thursday published new draft guidance spelling out how to proactively assess risks to manufacturing processes and supply chains, while understanding the market’s vulnerabilities.

While drug shortages peaked in 2011, the FDA says in its new 18-page draft guidance that the number of new drug shortages “has declined significantly since” that peak, reaching a low in 2015 and 2016, thanks in part to a new law’s enactment, known as FDASIA, which helped the agency better prevent or mitigate drug supply disruptions and shortages, and clarified cGMP requirements.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Paul Hudson, Sanofi CEO (via Getty)

Sanofi's $20B buy­out of Gen­zyme pays off again with Eu­ro­pean OK for first Nie­mann-Pick drug

Sanofi CEO Paul Hudson has made clear his intention to develop new rare disease drugs and broaden his company’s offerings. That effort leaped forward on Friday with the EMA’s signing off on the company’s — and the EU’s — first drug to treat the non-central nervous system manifestations of the rare and debilitating Niemann-Pick disease.

The enzyme replacement therapy, developed to replace patients’ deficient or defective enzyme, known as acid sphingomyelinase, was first developed by Genzyme, which Sanofi acquired for more than $20 billion in 2011. That acquisition has also helped Sanofi pull in sales in the field of MS.

Rob Etherington, Clene CEO

Mary­land of­fers loan to Clene de­spite ALS tri­al bumps

Even after Utah-based Clene failed to hit its primary endpoints for its ALS drug last year, the state of Maryland is putting its money at least behind Clene’s manufacturing facility.

The Maryland Board of Public Works has finalized a $3 million, 60-month loan facility with Clene Nanomedicine. The loan was provided by the state’s Neighborhood BusinessWorks program within the Maryland Department of Housing and Community Development.