Janet Woodcock, acting FDA commissioner (Bill Clark/CQ Roll Call via AP Images)

UP­DAT­ED: FDA’s do­mes­tic bio­phar­ma in­spec­tions re­turn to nor­mal as agency faces back­log of 8,000+

For the first time since March 2020, the FDA’s in­spec­tions of US-based bio­phar­ma sites have re­turned to nor­mal, FDA act­ing com­mis­sion­er Janet Wood­cock said Mon­day at a small busi­ness reg­u­la­to­ry event.

“I’m pleased to say that as of this month, we’ve be­gun tran­si­tion­ing back to stan­dard op­er­a­tions for do­mes­tic in­spec­tions while con­tin­u­ing to pri­or­i­tize mis­sion-crit­i­cal work for for­eign in­spec­tions,” Wood­cock said.

The re­turn to nor­mal­cy will be wel­comed by in­dus­try, which has grap­pled with a grow­ing back­log of most­ly sur­veil­lance in­spec­tions, al­though some of those de­layed in­spec­tions have al­so de­layed the ap­proval of new drugs.

Ac­cord­ing to a re­port from FDA in May, an es­ti­mat­ed 68 ap­pli­ca­tions (in­clud­ing 48 for hu­man drugs) have been de­layed due to FDA’s in­abil­i­ty to con­duct pre-ap­proval, pre-mar­ket, or pre-li­cense in­spec­tions as of March.

The agency said it post­poned near­ly 8,000 non-mis­sion-crit­i­cal sur­veil­lance in­spec­tions in 2020 due to the pan­dem­ic. Sur­veil­lance in­spec­tions are rou­tine in­spec­tions that mon­i­tor con­for­mance to FDA re­quire­ments to iden­ti­fy qual­i­ty prob­lems and ad­verse trends, but un­like oth­ers, they’re planned in ad­vance by ap­ply­ing es­tab­lished risk fac­tors and statu­to­ry in­spec­tion fre­quen­cy man­dates.

“FDA es­ti­mates that rough­ly 14% of the 15,514 do­mes­tic sur­veil­lance in­spec­tions still to be con­duct­ed in FY21 will be achiev­able in the Base-Case sce­nario,” the re­port says, not­ing that about 3,229 of those 15,000+ in­spec­tions are re­lat­ed to hu­man and an­i­mal drugs, while the rest are re­lat­ed to hu­man and an­i­mal food.

And in terms of for-cause in­spec­tions, mean­ing in­spec­tions where there are con­sumer com­plaints or re­ports of ad­verse events, the FDA had to skip 8 of those in­spec­tions in FY 2020.

As far as how the agency is work­ing around the ris­ing cas­es of Covid-19 in cer­tain hotspots across the coun­try, FDA re­vealed ear­li­er this month that it de­vel­oped a rat­ing sys­tem to as­sist in de­ter­min­ing when and where it’s safest to con­duct do­mes­tic in­spec­tions.

The rat­ing sys­tem, which FDA said it may sus­pend through Sep­tem­ber as it re­sumes stan­dard op­er­a­tions, us­es re­al-time da­ta to qual­i­ta­tive­ly as­sess the num­ber of Covid-19 cas­es in a lo­cal area based on state and na­tion­al da­ta. FDA shared that da­ta with state agen­cies that car­ry out in­spec­tions of FDA-reg­u­lat­ed en­ti­ties on the agency’s be­half un­der con­tract.

FDA al­so pre­vi­ous­ly said that for the fore­see­able fu­ture, pri­or­i­tized do­mes­tic in­spec­tions will be pre-an­nounced to FDA-reg­u­lat­ed busi­ness­es. Wood­cock did not an­nounce any change to that pol­i­cy.

On the for­eign in­spec­tion side, where Con­gress has been par­tic­u­lar­ly point­ed with the agency, FDA’s As­so­ci­ate Com­mis­sion­er for Reg­u­la­to­ry Af­fairs Ju­dith McMeekin told an Al­liance for a Stronger FDA we­bi­nar last week that the agency has strug­gled.

“We have suc­cess­ful­ly con­duct­ed about 30 for­eign in­spec­tions that were mis­sion crit­i­cal. Go­ing and con­duct­ing these for­eign in­spec­tions dur­ing the pan­dem­ic, it hasn’t been with­out tremen­dous ef­forts to mit­i­gate risk to our in­ves­ti­ga­tors,” she said. “You have to re­mem­ber, there were many months be­fore we had a vac­cine and so our in­ves­ti­ga­tors were go­ing out, trav­el­ing to for­eign coun­tries. And then en­tailed in a tremen­dous for­ti­tude on be­half of our in­ves­ti­ga­tors, many had to quar­an­tine up­on ar­rival in a coun­try for 10 to 14 days and mil­i­tary hous­ing or in their ho­tel room. Some cas­es they were not able to re­al­ly move around freely.”

McMeekin al­so touched on how the agency was able to rapid­ly in­spect fa­cil­i­ties ahead of the Covid-19 vac­cine EUAs:

“Our in­ves­ti­ga­tors con­duct­ed about 26 clin­i­cal re­search fa­cil­i­ty in­spec­tions be­fore the ad­vi­so­ry com­mit­tee meet­ings and be­fore we had au­tho­rized vac­cines. So, in just four weeks, we com­plet­ed all of those in­spec­tions with a team of more than 50 in­ves­ti­ga­tors. So, how did we do this? We col­lab­o­rat­ed with our cen­ters. We col­lab­o­rate with the cen­ters for bi­o­log­ics, we planned out the in­spec­tions and the time­lines in ad­vance of the in­spec­tion as­sign­ments … We gen­er­al­ly send in one in­ves­ti­ga­tor to the fa­cil­i­ty for clin­i­cal re­search in­spec­tions. In these cas­es, we send in two so that we could en­sure the ac­cu­ra­cy, re­li­a­bil­i­ty and the da­ta in the short­est amount of time. So, we al­so im­ple­ment­ed use of portable pro­jec­tors to re­view the doc­u­ments in a so­cial­ly dis­tant man­ner.”

Oth­er Covid-re­lat­ed tran­si­tions

Fol­low­ing Wood­cock’s com­ments, FDA cen­ter di­rec­tors Jeff Shuren (de­vices), Pa­trizia Cavaz­zoni (drugs) and Pe­ter Marks (bi­o­log­ics) al­so of­fered their per­spec­tives on what Covid-re­lat­ed pro­vi­sions may car­ry over to the post-Covid FDA.

Shuren stressed the need for faster guid­ance de­vel­op­ment, not­ing that some Covid-re­lat­ed guid­ance doc­u­ments were de­vel­oped in on­ly days or weeks, and he’d like to see that ex­pe­dit­ed ap­proach car­ry over be­yond the pan­dem­ic. Marks and Cavaz­zoni con­curred, and Cavaz­zoni men­tioned the need to build off FDA’s ac­cu­mu­lat­ed ex­pe­ri­ence with de­cen­tral­ized clin­i­cal tri­als dur­ing Covid-19, and the use of al­ter­na­tive ap­proach­es, such as re­mote eval­u­a­tions, to in­spect man­u­fac­tur­ing and clin­i­cal tri­al fa­cil­i­ties.

As far as when the EUA path­way may close for spon­sors, Shuren said he didn’t think it would hap­pen any time soon, and he not­ed that there will be an “am­ple tran­si­tion pe­ri­od,” as well as guid­ance on that tran­si­tion. Marks said the EUA tran­si­tion pe­ri­od for vac­cines may look com­pli­cat­ed as there might be some pe­di­atric in­di­ca­tions still un­der EUAs for vac­cines that have won full ap­provals. He stressed that the idea is to min­i­mize any­thing that cre­ates con­fu­sion, and de­creas­es trust.

Ed­i­tor’s note: Ar­ti­cle up­dat­ed with com­ments from Dr. McMeekin.

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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Sean Ianchulev, Eyenovia CEO and CMO

Re­cent court de­ci­sion push­es FDA to re­ject and re­clas­si­fy drug-de­vice com­bo, crush­ing shares

Back in April, the FDA lost a crucial court case in which its broad discretion of regulating medical products that might satisfy the legal definitions of either “drug” and/or “medical device” was sharply curtailed.

In addition to the appeals court ruling that Genus Medical Technologies’ contrast agent barium sulfate (aka Vanilla SilQ) should not be considered a drug, as the FDA had initially ruled, but as a medical device, the agency also was forced to spell out which drugs would transition to devices as a result of the ruling.

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Robert Califf (Pablo Martinez Monsivais, AP Images, File)

As buzz on Califf FDA nom heats up, in­dus­try and agency in­sid­ers of­fer a strong nod for the ‘per­fect’ choice

For once in this long, dramatic road to finding a new FDA commissioner, there’s been some continuity. Both CNN and Politico reported this weekend that Rob Califf met with President Biden to discuss the permanent commish role, following earlier news broken by the Washington Post that all signs point to Califf.

Although there may be a few Democrats who continue to grandstand about the dangers of COI (Califf has worked for Verily, sits on the board of Centessa Pharmaceuticals, and has other ties to industry research), with the pandemic ongoing and the need for some kind of continuity at FDA mounting, Califf is likely to meet the same fate as when he first won Senate confirmation in 2016, by a vote of 89-4 — Bernie Sanders and 6 others didn’t vote.

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AstraZeneca CEO Pascal Soriot (Raphael Lafargue/Abaca/Sipa USA)

A com­bo of As­traZeneca's Imfinzi and chemo wins where oth­ers have failed in piv­otal bil­iary tract test

Looking to run with the big dogs in the PD-(L)1 class, AstraZeneca’s Imfinzi has a tall hill to climb to compete in an increasingly bustling market. An aggressive combo strategy for the drug has paid off so far, and now AstraZeneca is adding another notch to its belt.

A combo of Imfinzi (durvalumab) and chemotherapy significantly extended the lives of first-line patients with advanced biliary tract cancer over chemo alone, according to topline results from the Phase III TOPAZ-1 study revealed Monday.

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UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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Sim­mer­ing feud be­tween blue­bird and a ri­val con­tin­ues with al­le­ga­tions of patent fraud

Bluebird bio was hit with a patent infringement lawsuit last week from a Chicago-based biotech it has had an ongoing beef with calling for $2 billion to help cure the “irreparable harm” caused by alleged willful infringement.

Bluebird bio is facing a lawsuit from Errant Gene Therapeutics for violating patent law in two instances, the company says.

The suit alleges that bluebird infringed the rights of EGT’s recombinant vectors used in the gene therapy treatment of rare diseases such as sickle cell disease and beta thalassemia for its drugs Zynteglo and LentiGlobin. EGT has an exclusive license from the Memorial Sloan Kettering Cancer Center to patents titled “vector encoding human global gene and use thereof in treatment of Hemoglobinopathies.”

How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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Just as first Lu­cen­tis biosim­i­lar wins ap­proval, Roche snags an OK for an eas­i­er route of ad­min­is­tra­tion

It’s been a month since the FDA cleared the first biosimilar to Roche’s blockbuster wet age-related macular degeneration (AMD) drug ranibizumab. But the pharma giant isn’t going down without a fight.

Roche’s Genentech got approval on Friday for a new ranibizumab administration route that will allow wet AMD patients to ditch their current monthly injections and opt instead for as few as twice-annual treatments.