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.

Spe­cial re­port: Meet 20 ex­tra­or­di­nary women who are su­per­charg­ing bio­phar­ma R&D

Even though many biopharma leaders have come together in recent years to address its gender gap, the consensus is clear: We still have a long way to go.

Companies this year were 2.5 times more likely than last year to have a diversity and inclusion program in place, according to a recent BIO survey, but women are still largely absent from executive roles. Getting women to enter the industry isn’t the problem — studies show that they represent just under half of all biotech employees around the world. But climbing through the ranks can be challenging, as women still report facing stereotypes, and, unfortunately, harassment.

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Op­ti­miz­ing Oral Drug De­liv­ery us­ing Zy­dis® Oral­ly Dis­in­te­grat­ing Tablet Tech­nol­o­gy to Ad­dress Pa­tient Chal­lenges


Patients prefer oral dosing, but swallowing tablets can be a challenge for many patients.
The Zydis® orally disintegrating tablet (ODT) platform addresses challenges associated with oral dosing, expanding benefits for patients and options for healthcare providers.
A strong growth trajectory is expected for ODTs given therapeutic innovation and continued technology development.

Many patients prefer conventional tablets for the administration of medications, but some geriatric and pediatric patients and those with altered mental status and physical impairments find swallowing tablets to be difficult. Orally disintegrating tablets (ODTs), which dissolve completely without chewing or sucking, offer a patient-friendly dosage form for the administration of small-molecule drugs, peptides and proteins. With the potential for multiple sites of drug absorption, often faster onset action for the active pharmaceutical ingredient (API), and potentially greater bioavailability, ODTs are an attractive option for drug developers considering first-to-market formulations or product line extensions of existing drugs with compatible API. In this report, we look at how innovation in the industry-leading Zydis ODT platform is expanding oral formulation options and bringing benefits to patients.

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Geoffrey Porges (SVB Leerink)

The 2022 wave com­ing? Top an­a­lyst says Big Phar­ma will have more than $1T avail­able to sat­is­fy its grow­ing ap­petite for biotech M&A

All through this year you could practically feel the frustration of the biotech investor class as M&A activity continued to drag behind expectations — or desires. Buyouts of public companies provide the essential juice for keeping stocks lively, and there’s been a notable lack of juice in 2021.

So is all that about to change, big time?

SVB Leerink’s Geoffrey Porges, a longtime student of biotech M&A, thinks so. In a lengthy analysis he put out last week, Porges totted up the cash flow of the major pharmas and determined that there was a good long list of industry buyers who would have around a half trillion dollars of cash to play with in 2022. Leverage that up with added debt and you could get that deal cache to $1.6 trillion.

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Mar­ket­ingRx Matchup: How Ab­b­Vie and Bio­haven ads rank in head-to-head mi­graine chal­lenge

Are you ready to rumble? DTC brands that is. MarketingRx is launching a new monthly feature today called MarketingRx Matchup. We’re pitting two pharma brands’ DTC advertising in the same therapeutic category against each other to find out what consumers and patients really think.

Market research company Leger is handling the polling and analysis each month, and I’ll be writing up the results — along with my own take — inside MRx on the first Tuesday of the month.

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Wendy Lund, Organon chief communications officer

Q&A: Organon chief com­mu­ni­ca­tions of­fi­cer Wendy Lund talks about the Mer­ck spin­off, women’s health and why it mat­ters

One of Wendy Lund’s earliest jobs was head of marketing at Planned Parenthood. As the youngest person on its management team, she introduced them to emerging new technologies, and in return, she learned the importance of fighting for what you believe in.

Now as chief communications officer at Organon, the women’s health company recently spun off by Merck, Lund is keeping that point top of mind. That’s in part because women’s health hasn’t been a spotlight therapy area for Big Pharma in years. Several companies have spun off, sold or at least considered selling women’s health assets to focus on “core” products.

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Mar­ket­ingRx roundup: Pfiz­er re-ups pneu­mo­nia ads as Mer­ck threat looms; Re­al Chem­istry founder CEO Jim Weiss steps back

Every autumn, leaves fall from the trees and people start holiday shopping – and for the last few years Pfizer debuts a new “Know Pneumonia” awareness TV ad. This year the commercial, launched a week ago, features different people who talk about why they got vaccinated against pneumococcal pneumonia. Actors portray a young female firefighter with asthma, a mechanic with heart disease and an older woman with her grandchild. A Pfizer spokesperson declined comment on the latest iteration of the long-running campaign.

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Mer­ck pumps the brakes on two more PhI­II tri­als for its lead an­ti-HIV drug

After trial investigators flagged a drop in immune cell counts that an external committee determined was related to treatment last month, Merck has been pausing HIV-related Phase II and III trials ever since.

On Monday, the biopharma company announced it’s pausing enrollment in two of its Phase III trials evaluating its leading anti-HIV drug candidate, which is the once-monthly, oral islatravir.

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Covid-19 roundup: Plant-based shot proves safe, 71% ef­fi­ca­cious in PhI­II; Bourla ex­pects an­tivi­ral to launch this month

Quebec-based Medicago and its adjuvant partner GlaxoSmithKline said Tuesday that their plant-based Covid-19 vaccine candidate proved to be 71% efficacious against all variants of SARS-CoV-2 in a Phase III trial of more than 24,000 adults in Canada, the US, UK, Mexico, Argentina and Brazil.

In addition to showing 75% efficacy against the Delta variant specifically, the companies also said the vaccine proved to be generally safe, with no serious adverse events reported and reactogenicity generally being mild to moderate. The results mean that a regulatory submission will be filed with Health Canada imminently, they said.

Richard Lerner (Scott Audette/AP Images)

Richard Lern­er, an­ti­body pi­o­neer and long­time pres­i­dent of Scripps Re­search, dies at 83

Richard Lerner, the esteemed biochemist who pioneered a new way to develop monoclonal antibodies and led Scripps Research Institute to prominence, has passed away.

A spokesperson for Scripps told the San Diego Union-Tribune that Lerner died of cancer in his La Jolla home. He was 83 years old.

Among other things, Lerner’s lab was known for devising a new technique for creating antibodies — deployed as cancer treatments as well as in immunology and disease research — one that the New York Times called a “major advance in biotechnology.” It led to companies making mAbs a thousand times faster, more accurately, at a lower cost. That foundational research cemented the discovery of Humira, which went on to become the world’s best-selling treatment.