Sunil Eappen, Brigham and Women's Hospital interim president and CMO

Brigham and Wom­en's gets FDA warn­ing let­ter af­ter PET op­er­a­tion vi­o­la­tions

A drug man­u­fac­tur­ing fa­cil­i­ty at one of Boston’s top hos­pi­tals has re­ceived a warn­ing let­ter from the FDA af­ter its man­u­fac­tur­ing prac­tices for positron emis­sion to­mog­ra­phy drugs were not found to be up to reg­u­la­to­ry code.

The FDA ad­dressed Brigham and Women’s Hos­pi­tal in a let­ter dat­ed April 11. The let­ter is ad­dressed to Sunil Eap­pen, the in­ter­im pres­i­dent and CMO at the hos­pi­tal.

Fa­cil­i­ties were not ad­e­quate­ly pre­pared to pre­vent the con­t­a­m­i­na­tion that could lead to side ef­fects in the prod­ucts, the let­ter said. The hos­pi­tal al­so did not en­sure that the equip­ment is suit­able for asep­tic op­er­a­tions. “Wa­ter in­fil­tra­tions” that oc­curred be­tween Ju­ly and Oc­to­ber 2020 were in close prox­im­i­ty to equip­ment used in the PET asep­tic pro­duc­tion op­er­a­tion, in­clud­ing hot cells, bi­o­log­i­cal safe­ty cab­i­net, and the lam­i­nar flow hood. An over­head wa­ter pipe was ac­tive­ly leak­ing on­to the floor in the same room in which raw ma­te­ri­als were stored too, and there were fun­gal species found in the ISO 5 clas­si­fied cells.

“Your in­ves­ti­ga­tion states that the wa­ter in­fil­tra­tions were due to mul­ti­ple fail­ures as­so­ci­at­ed with the me­chan­i­cal suite above your man­u­fac­tur­ing area and with the roof pen­e­tra­tions lead­ing in­to the plenum spaces above your clean­room ar­eas,” the FDA said. “No­tably, the EM da­ta in­di­cates that the wa­ter in­fil­tra­tion prob­lem pre­ced­ed the date of de­tec­tion and man­i­fest­ed as a loss of en­vi­ron­men­tal con­trol in your asep­tic pro­duc­tion fa­cil­i­ty. The fail­ure to ap­pro­pri­ate­ly de­sign and main­tain the fa­cil­i­ty led to a lack of con­trol and sub­ject­ed drug prod­ucts to the risk of con­t­a­m­i­na­tion.”

Sev­er­al fun­gal or­gan­isms were al­so found in the air qual­i­ty of crit­i­cal ar­eas of man­u­fac­tur­ing that should not be con­t­a­m­i­nat­ed, the let­ter said. Fludeoxyglu­cose for in­jec­tion, which is used to help di­ag­nose can­cer, heart dis­ease and epilep­sy, and am­mo­nia for in­jec­tion, used for PET imag­ing, were both pro­duced in the area. The team at BWH al­so ac­knowl­edged that there was not enough con­tact time for spo­ri­ci­dal dis­in­fec­tant used in the area of bi­o­log­i­cal safe­ty cab­i­nets and hot cells.

The FDA deemed BWH’s re­sponse from a pre­vi­ous Form 483 in­ad­e­quate be­cause, while it in­di­cat­ed that it would con­tin­ue PET drug man­u­fac­tur­ing while mak­ing the nec­es­sary changes, it didn’t pro­vide a suf­fi­cient plan for im­prove­ment.

“Fur­ther­more, you did not ex­plain what ad­di­tion­al steps you would take to pre­vent con­t­a­m­i­na­tion while you con­tin­ue man­u­fac­tur­ing dur­ing re­me­di­a­tions,” the FDA said. “Your re­sponse al­so failed to suf­fi­cient­ly ad­dress your ISO 5 de­con­t­a­m­i­na­tion pro­gram to im­prove its ro­bust­ness such as as­sess­ing the po­ten­tial for in­creas­ing dis­in­fec­tion fre­quen­cy, en­sur­ing more com­pre­hen­sive ap­pli­ca­tion of dis­in­fec­tants to all sur­faces in crit­i­cal en­vi­ron­ments and sur­round­ing en­vi­ron­ments, and oth­er steps that would en­sure more ef­fec­tive dis­in­fec­tion.”

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.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; 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.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).