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.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Pfiz­er, Sarep­ta and two oth­ers sug­gest Duchenne drug safe­ty is­sues tied to "class ef­fect"

Since the first experimental Duchenne gene therapy programs came about, the space has proven rife with safety issues and patient deaths in clinical trials. Pfizer and three biotechs now think they’ve found a reason why.

The four companies suggested there may be a “class effect” causing the adverse events in Duchenne gene therapies, they wrote in a new study. They specifically highlighted how side effects in five patients across three trials, who all showed muscle weakness with cardiac involvement, were “strikingly similar.”

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Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

De­spite fed­er­al ef­forts to di­ver­si­fy clin­i­cal tri­als, progress re­mains 'stag­nan­t' — re­port

While calls to diversify clinical trials have grown louder in recent years — gaining support from federal agencies such as the FDA and NIH — progress has largely stalled, according to a new report from the National Academies of Sciences, Engineering and Medicine.

Swaths of patients in racial and ethnic minority groups, as well as LGBTQIA+, pregnant and older adult populations continue to be left out of clinical trials. While some advances have been made in the last 30 years — women now account for roughly half of clinical trial participants — growth in other areas remains stagnant, according to the report, which was mandated by Congress and sponsored by the NIH.

Paul Chaplin, Bavarian Nordic president and CEO

Bavar­i­an Nordic se­cures BAR­DA con­tract for small­pox vac­cine

It seems that smallpox vaccination production is weighing on the mind of the US government. And manufacturer Bavarian Nordic is the latest company to benefit.

Just a few days after Emergent, a company that has made government contracts its lifeblood, acquired the exclusive rights to Tembexa from Chimerix, with a $225 million cash payment and an expected BARDA contract, the agency has offered a contract for smallpox vaccine production.

Frank Pallone (D-NJ), House Energy and Commerce Committee chair (Kevin Dietsch/Pool via AP Images)

House com­mit­tee unan­i­mous­ly ad­vances FDA user fee leg­is­la­tion with ac­cel­er­at­ed ap­proval tweaks

The House Energy and Commerce Committee on Wednesday offered a rare show of bipartisan support for a bill that would provide the FDA with user fees for the next five years.

The committee voted 55-0 to advance the quinquennial user fee bill to the full House floor, which if approved, will allow the FDA to use biopharma funds to hire new reviewers, and hit new marks as outlined in the user fee deals that the FDA and biopharma companies forged over the past several years.

Lina Khan, FTC chair (Saul Loeb/Pool via AP)

New FTC com­mis­sion­er could turn the tide for an in­ves­ti­ga­tion in­to PBMs

The Senate last week voted along party lines, 51-50, with Vice President Kamala Harris casting the tie-breaker, to make President Biden appointee Alvaro Bedoya the deciding vote on a split 2-2 Federal Trade Commission.

The addition of Bedoya to the FTC could not only spell more trouble for biopharma M&A activity, as he may align with his Democrat partners to break the FTC ties, but it may also mean that FTC Chair Lina Khan has what she needs to move forward on a study around the pharma middlemen known as pharmacy benefit managers.

Patty Murray (D-WA) (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

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Pri­cy in­halers re­main ex­pen­sive due to de­vice tweaks that keep com­peti­tors at bay, re­searchers find

New research published in Health Affairs today highlights the way in which the FDA’s inhaler regulations have rewarded incremental adjustments to older products, thereby enabling companies to skirt around cheaper competition.

A DC appeals court clerk and researchers from Harvard and the University of Calgary dug through all the patents and regulatory exclusivities granted to inhalers approved by the FDA between 1986 and 2020, finding that of the 62 inhalers approved, 53 (or 85%) were brand-name products, with a median of 16 years of protection from generic competition.