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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

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Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

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I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

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Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

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The campaign and website debut Thursday — just three weeks after Tarsus filed for FDA approval for a drug that treats the disease.

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Work taking place in the clean rooms at Vor (Credit: Vor)

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While it is not uncommon for a biotech to go down the route of having the product manufactured by a contract organization, one small biotech is looking to keep its card close to its chest.

Vor Biopharma has started manufacturing operations at an in-house facility at its HQ in Cambridge, MA after beginning construction last summer.

According to the biotech, the facility aims to develop Vor’s hematopoietic stem cells (eHSCs) and CAR-T therapies for patients with blood cancers. The site will initially manufacture a clinical supply of its candidate VCAR33allo to support its IND, which is slated to be submitted in the first half of next year. It also plans to transfer the production of VOR33 to the facility. Vor is getting to work quickly as engineering runs for VCAR33allo has started this week.

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Avastin has attracted quite the crowd of biosimilars in recent years, and one more pharma company has elbowed its way in.

Regulators on Wednesday approved Celltrion’s biosimilar Vegzelma in six cancer types, including metastatic colorectal cancer; recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC); recurrent glioblastoma; metastatic renal cell carcinoma; persistent, recurrent, or metastatic cervical cancer; and epithelial ovarian, fallopian tube or primary peritoneal cancer.

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Medicines for Europe, a group that represents the generic industry on the continent, sent a letter addressed to energy ministers and commissioners concerning inflation and the costs of energy on the supply of generic medicines.

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But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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