Siddharth Mittal, Biocon CEO

A month af­ter Bio­con was hand­ed a Form 483, doc­u­ments re­veal lack­lus­ter con­di­tions

In Sep­tem­ber, Bio­con got out in front of a Form 483 it was hand­ed by the FDA in a rare out-of-the-coun­try in­spec­tion, in­sist­ing that the hic­cup would not hin­der its plans for the com­mer­cial­iza­tion of in­sulin as­part in the US.

Now, af­ter it’s been re­leased to the pub­lic, that Form 483 high­lights an un­qual­i­fied dis­tri­b­u­tion sys­tem, in­ad­e­quate asep­tic mon­i­tor­ing and leaky drains, among oth­er is­sues at its Malaysia sub­sidiary.

The FDA’s first ob­ser­va­tion is heav­i­ly redact­ed, but through the grey box­es, says that the site’s dis­tri­b­u­tion sys­tem was not qual­i­fied or val­i­dat­ed, nor was it test­ed for qual­i­ty. As for asep­tic be­hav­ior, the com­pa­ny failed to prop­er­ly san­i­tize the en­vi­ron­men­tal mon­i­tor­ing plates of the re­stric­tive ac­cess bar­ri­er. Fail­ure to do so can neg­a­tive­ly im­pact the qual­i­ty of the prod­uct, the FDA said.

Bio­con’s staff failed to prop­er­ly iden­ti­fy each lot and ship­ment of drug re­ceived to en­sure the ad­e­qua­cy of the raw ma­te­r­i­al. Sur­face ma­te­ri­als were al­so left black and dis­col­ored on the side­walls of ves­sels, and wall-mount­ed trans­fer lines were left dirty. Raw ma­te­ri­als were stored at tem­per­a­tures be­tween 20 and 25 de­grees Cel­sius, though the area wasn’t val­i­dat­ed for those tem­per­a­tures.

Leaky drains were left un­re­solved, and the clean­ing process­es were deemed de­fi­cient by the agency.

“The pro­ce­dure fails to el­e­vate re­peat­ed alert lev­el ex­cur­sions that should in­clude a trend in­ves­ti­ga­tion in mit­i­ga­tion of an aber­rant con­di­tion and doc­u­men­ta­tion of cor­rec­tive ac­tion,” the Form 483 reads.

Bio­con is In­dia’s largest bio­phar­ma. It’s cur­rent­ly part­nered with Ada­gio to man­u­fac­ture a mon­o­clon­al an­ti­body that can of­fer pro­tec­tion for up to a full year and serve as a re­place­ment for those who are vac­cine-hes­i­tant.

In a Sep­tem­ber state­ment, the com­pa­ny said: “We are con­fi­dent of ad­dress­ing these ob­ser­va­tions through pro­ce­dur­al en­hance­ments and an ap­pro­pri­ate Cor­rec­tive and Pre­ven­tive Ac­tion Plan, which will be sub­mit­ted to the US FDA in the stip­u­lat­ed time. We do not ex­pect the out­come of this in­spec­tion to im­pact our com­mer­cial­iza­tion plans for in­sulin As­part in the US. Bio­con Bi­o­log­ics re­mains com­mit­ted to glob­al stan­dards of Qual­i­ty and Com­pli­ance.”

Ed­i­tor’s Note: This sto­ry has been up­dat­ed to cor­rect an er­ror. The Form 483 giv­en to Bio­con spec­i­fied ‘raw ma­te­r­i­al’ rather than drug sub­stance. Bio­con re­quest­ed this let­ter be pub­lished along­side this sto­ry: 

With ref­er­ence to the above ar­ti­cle dat­ed Oct 28, 2021, pub­lished by End­points News on the na­ture of ob­ser­va­tions is­sued, at the con­clu­sion  of the USF­DA in­spec­tion at Bio­con Bi­o­log­ics Malaysia fa­cil­i­ty in Sep 2021, we would like to state that this ar­ti­cle con­tains sev­er­al in­ac­cu­rate in­fer­ences drawn from a ‘heav­i­ly redact­ed’ Form 483 and is gross­ly mis­lead­ing.

Fur­ther­more, this ar­ti­cle makes as­sump­tions and ex­trap­o­la­tions which are not just in­ac­cu­rate but al­so ex­ag­ger­at­ed.  “To cite one ex­am­ple, Josh Sul­li­van’s procla­ma­tion that “Bio­con’s staff failed to prop­er­ly iden­ti­fy each lot and ship­ment of drug re­ceived to en­sure the ad­e­qua­cy of the Drug Sub­stance” is in­ac­cu­rate. The ac­tu­al ob­ser­va­tion, as not­ed by the agency, but redact­ed  in the pub­lished Form 483, is re­lat­ed to in­com­ing Raw Ma­te­r­i­al test­ing for a sin­gle in­ert com­po­nent.”

Fur­ther­more, the ar­ti­cle in its open­ing para gives the im­pres­sion that this was a ‘rare out of coun­try in­spec­tion’ and talks about un­qual­i­fied dis­tri­b­u­tion sys­tem with leaky drains pre­sent­ing a very gloomy pic­ture. None of these words ap­pear in this form in the redact­ed doc­u­ment.State­ments such as these and oth­ers in the ar­ti­cle, when tak­en out of con­text or ex­trap­o­lat­ed can be mis­lead­ing and po­ten­tial­ly cause con­cern to all stake­hold­ers.

By way of back­ground, this  in­spec­tion was sched­uled as  a part of the FDA’s ‘Re­silien­cy Roadmap for FDA In­spec­tion­al Over­sight’ (pub­lished May 2021), where­in the agency laid out their roadmap to­wards pri­or­i­tiz­ing do­mes­tic and for­eign in­spec­tions based on sev­er­al fac­tors in­clud­ing those tied to new prod­uct ap­provals.

In this in­stance, the on-site ‘Pre-Ap­proval In­spec­tion’ (PAI)  was a part of the es­tab­lished PAI process for re­view of  a Bi­o­log­ics Li­cense Ap­pli­ca­tion (BLA)  for In­sulin As­part, for which there is cur­rent­ly no ap­proved biosim­i­lar avail­able to US pa­tients.Bio­con Bi­o­log­ics had proac­tive­ly re­leased a pub­lic state­ment on Sep 25, 2021 on the com­ple­tion of the US FDA in­spec­tion of the Malaysia site and dis­closed the is­suance of a Form 483 which had iden­ti­fied six ob­ser­va­tions span­ning  the Drug Sub­stance, Drug Prod­uct and De­vices fa­cil­i­ties.

We had stat­ed that we are con­fi­dent of ad­dress­ing these ob­ser­va­tions through pro­ce­dur­al im­prove­ments ex­pe­di­tious­ly. We can con­firm that our de­tailed Cor­rec­tive and Pre­ven­tive Ac­tion Plan (CA­PA) has been sub­mit­ted to the USF­DA on Oct 15, 2021. End­points News is a wide­ly read pub­li­ca­tion and we have great re­spect for its con­tent hence it is im­por­tant for your sto­ries not to ex­ag­ger­ate,  but pro­vide a fac­tu­al per­spec­tive.

As a com­pa­ny, we be­lieve in open com­mu­ni­ca­tion and would ap­pre­ci­ate if your teams reach out to us in or­der to make an in­formed nar­ra­tive.  We there­fore re­quest you to ei­ther re­tract this ar­ti­cle or pub­lish this ‘Let­ter to the Ed­i­tor’ and link it to our sto­ry.

Albert Bourla (Photo by Steven Ferdman/Getty Images)

UP­DAT­ED: Pfiz­er fields a CRL for a $295M rare dis­ease play, giv­ing ri­val a big head start

Pfizer won’t be adding a new rare disease drug to the franchise club — for now, anyway.

The pharma giant put out word that their FDA application for the growth hormone therapy somatrogon got the regulatory heave-ho, though they didn’t even hint at a reason for the CRL. Following standard operating procedure, Pfizer said in a terse missive that they would be working with regulators on a followup.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,600+ biopharma pros reading Endpoints daily — and it's free.

Graphic: Alexander Lefterov for Endpoints News

Small biotechs with big drug am­bi­tions threat­en to up­end the tra­di­tion­al drug launch play­book

Of the countless decisions Vlad Coric had to make as Biohaven’s CEO over the past seven years, there was one that felt particularly nerve-wracking: Instead of selling to a Big Pharma, the company decided it would commercialize its migraine drug itself.

“I remember some investors yelling and pounding on the table like, you can’t do this. What are you thinking? You’re going to get crushed by AbbVie,” he recalled.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,600+ biopharma pros reading Endpoints daily — and it's free.

Mar­ket­ingRx roundup: Pfiz­er de­buts Pre­vnar 20 TV ads; Lil­ly gets first FDA 2022 pro­mo slap down let­ter

Pfizer debuted its first TV ad for its Prevnar 20 next-generation pneumococcal pneumonia vaccine. In the 60-second spot, several people (actor portrayals) with their ages listed as 65 or older are shown walking into a clinic as they turn to say they’re getting vaccinated with Prevnar 20 because they’re at risk.

The update to Pfizer’s blockbuster Prevnar 13 vaccine was approved in June, and as its name suggests is a vaccine for 20 serotypes — the original 13 plus seven more that cause pneumococcal disease. Pfizer used to spend heavily on TV ads to promote Prevnar 13 in 2018 and 2019 but cut back its TV budgets in the past two fall and winter seasonal spending cycles. Prevnar had been Pfizer’s top-selling drug, notching sales of just under $6 billion in 2020, and was the world’s top-selling vaccine before the Covid-19 vaccines came to market last year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,600+ biopharma pros reading Endpoints daily — and it's free.

Alexander Lefterov/Endpoints News

A new can­cer im­munother­a­py brings cau­tious hope for a field long await­ing the next big break­through

Bob Seibert sat silent across from his daughter at their favorite Spanish restaurant near his home in Charleston County, SC, their paella growing cold as he read through all the places in his body doctors found tumors.

He had texted his wife, a pediatric intensive care nurse, when he got the alert that his online chart was ready. Although he saw immediately it was bad, many of the terms — peritoneal, right iliac — were inscrutable. But she was five hours downstate, at a loud group dinner the night before another daughter’s cheer competition.

Endpoints Premium

Premium subscription required

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

Nabiha Saklayen, Cellino co-founder and CEO (via Cellino)

Backed by Bay­er's Leaps, Boston-based Celli­no lands $80M for cell ther­a­py-in-box

The summer before Cellino CEO and co-founder Nabiha Saklayen started at Harvard, she lost her grandmother following complications to diabetes. Before then, she hadn’t taken a biology class since ninth or tenth grade — the mark of a classic physicist — but it was then she decided she wanted the rest to sit at the intersection of the two for the rest of her career

Combine that with being across the way from the University’s stem cell institute in Cambridge, and you get the birth of Cellino, an autonomous cell therapy manufacturing company that just announced the closing of its Series A.

Roy Baynes, Merck

FDA bats back Mer­ck’s ‘pipeline in a prod­uct,’ de­mands more ef­fi­ca­cy da­ta

Despite some heavy blowback from analysts, Merck execs maintained an upbeat attitude about the market potential of its chronic cough drug gefapixant. But the confidence may be fading somewhat today as Merck puts out news that the FDA is handing back its application with a CRL.

Dubbed by Merck’s development chief Roy Baynes as a “pipeline in a product” with a variety of potential uses, Merck had fielded positive late-stage data demonstrating the drug’s ability to combat chronic cough. The drug dramatically reduced chronic cough in Phase III, but so did placebo, leaving Merck’s research team with a marginal success on the p-value side of the equation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,600+ biopharma pros reading Endpoints daily — and it's free.

Florida Gov. Ron DeSantis (AP Photo/Wilfredo Lee, File)

Opin­ion: Flori­da is so mAb crazy, Ron De­San­tis wants to use mAbs that don't work

Florida Gov. Ron DeSantis is trying so hard to politicize the FDA and demonize the federal government that he entered into an alternate universe on Monday evening in describing a recent FDA action to restrict the use of two monoclonal antibody, or mAb, treatments for Covid-19 that don’t work against Omicron.

Without further ado, let’s break down his statement from last night, line by line, adjective by adjective.

Not cheap­er by the dozen: Bris­tol My­ers be­comes the 12th phar­ma com­pa­ny to re­strict 340B sales

Bristol Myers Squibb recently joined 11 of its peer pharma companies in limiting how many contract pharmacies can access certain drugs discounted by a federal program known as 340B.

Bristol Myers is just the latest in a series of high-profile pharma companies moving in their own direction as the Biden administration’s Health Resources and Services Administration struggles to rein in the drug discount program for the neediest Americans.

Joaquin Duato, J&J CEO (Photo by Charles Sykes/Invision/AP)

New J&J CEO Joaquin Du­a­to promis­es an ag­gres­sive M&A hunt in quest to grow phar­ma sales

Joaquin Duato stepped away from the sideline and directly into the spotlight on Tuesday, delivering his first quarterly review for J&J as its newly-tapped CEO after an 11-year run in senior posts. And he had some mixed financial news to deliver today while laying claim to a string of blockbuster drugs in the making and outlining an appetite for small and medium-sized M&A deals.

Duato also didn’t exactly shun large buyouts when asked about the future of the company’s medtech business — where they look to be in either the top or number 2 position in every segment they’re in — even though the bar for getting those deals done is so much higher.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,600+ biopharma pros reading Endpoints daily — and it's free.