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.”

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

(Credit: Shutterstock)

Cracks in the fa­cade: Is phar­ma's pan­dem­ic ‘feel good fac­tor’ wan­ing?

The discordant effects of the Covid-19 pandemic on pharma reputation continues. While the overall industry still retains a respectable halo from its Covid-19 quick response and leadership, a new patient group study reveals a different story emerging in the details.

On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,600+ biopharma pros reading Endpoints daily — and it's free.

Belén Garijo, Merck KGaA CEO (Kevin Wolf/AP Images for EMD Serono)

Mer­ck KGaA pumps €440M in­to ex­pand­ing and con­struct­ing Irish man­u­fac­tur­ing fa­cil­i­ties

The area of Ireland famous for Blarney Castle and its cliffsides along the Atlantic Ocean is seeing Merck KGaA expand its commitment there.

The German drug manufacturer is expanding its membrane and filtration manufacturing capabilities in Ireland. The company will invest approximately €440 million ($470 million) to increase membrane manufacturing capacity in Carrigtwohill, Ireland, and build a new manufacturing facility at Blarney Business Park, in County Cork, Ireland.

Phillip Gomez, SIGA CEO

UP­DAT­ED: On the back of SIGA Tech­nolo­gies' win with the FDA, the mon­key­pox virus sees the com­pa­ny spring­ing to fur­ther ac­tion

As the cases of monkeypox now sit at well over 100 worldwide and have spread to multiple continents, the orders for any type of vaccine against monkeypox are seeing nations and medical bodies looking to get their hands on anything and everything. And now SIGA Technologies seems to be getting in on the action.

According to Euronews, SIGA Technologies, a pharmaceutical company that is focused on providing medical countermeasures to biological and chemical attacks, is now in talks with several European authorities looking to stockpile its antiviral that can counter monkeypox. The drug known as tecovirimat or Tpoxx was approved by the FDA in 2018 as a vaccine for smallpox but was approved by the European Medicines Agency to also act against monkeypox, cowpox and complications from immunization with vaccinia.

Co­pay coupons gone wrong, again: Pfiz­er pays al­most $300K to set­tle com­plaints in four states

Pfizer has agreed to pay $290,000 to settle allegations of questionable copay coupon practices in Arizona, Colorado, Kansas, and Vermont from 2014 to 2018.

While the company has not admitted any wrongdoing as part of the settlement, Pfizer has agreed to issue restitution checks to about 5,000 consumers.

A Pfizer spokesperson said the company has “enhanced its co-pay coupons to alleviate the concerns raised by states and agreed to a $30,000 payment to each.”

Delaware court rules against Gilead and Astel­las in years-long patent case

A judge in Delaware has ruled against Astellas Pharma and Gilead in a long-running patent case over Pfizer-onwed Hospira’s generic version of Lexiscan.

The case kicked off in 2018, after Hospira submitted an Abbreviated New Drug Application (ANDA) for approval to market a generic version of Gilead’s Lexiscan. The drug is used in myocardial perfusion imaging (MPI), a type of nuclear stress test.

Taye Diggs (courtesy Idorsia)

Idor­sia inks an­oth­er celebri­ty en­dors­er deal with ac­tor and dad Taye Dig­gs as Qu­viviq in­som­nia am­bas­sador

Idorsia’s latest Quviviq insomnia campaign details the relatable dad story of a well-known celebrity — actor and Broadway star Taye Diggs.

Diggs stopped sleeping well after the birth of his son, now more than 10 years ago. Switching mom-and-dad nightly shifts to take care of a baby interrupted his sleep patterns and led to insomnia.

“When you’re lucky enough to be living out your dream and doing what you want, but because of something as simple as a lack of sleep, you’re unable to do that, it felt absolutely — it was treacherous,” he says in an interview-style video on the Quviviq website.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,600+ biopharma pros reading Endpoints daily — and it's free.

Rep. Katie Porter (D-CA) (Michael Brochstein/Sipa USA/Sipa via AP Images)

House Dems to Sen­ate lead­er­ship: Quick­ly move a rec­on­cil­i­a­tion bill with drug price ne­go­ti­a­tion re­forms

Twenty House Democrats, including Reps. Katie Porter of California and Susan Wild of Pennsylvania, are calling on Senate leaders to move quickly with a reconciliation bill (meaning they only need a simple majority for passage) with prescription drug pricing reforms, and to include adding new authority for Medicare to negotiate drug prices.

They also called on the Senate to specifically follow suit with the House passage of a $35 per month insulin cap (as Senate Majority Leader Chuck Schumer’s deadline for a vote on that provision has come and gone), and to cap Medicare Part D costs at $2,000 per year for seniors.

Bris­tol My­ers Squibb sues No­var­tis for roy­al­ties sur­round­ing the use of trans­genic mice

Two Big Pharma companies are going to the mat over genetically modified mice in a licensing dispute.

Bristol Myers Squibb is suing Novartis in New York over a dispute concerning an evaluation, research and commercialization agreement stretching back to the late ’90s initially inked between Novartis and BMS’ predecessor Medarex. The deal in question allowed Novartis to use Medarex’s patented transgenic mice to develop therapeutic drugs. Novartis agreed to pay Medarex – and subsequently BMS – a royalty on sales of drugs it developed using the mice.