FDA-EMA work­shop dis­cuss­es qual­i­ty chal­lenges for PRIME, break­through ther­a­pies

Last No­vem­ber, of­fi­cials from the EMA and FDA met with in­dus­try rep­re­sen­ta­tives in Lon­don to dis­cuss the var­i­ous qual­i­ty chal­lenges that arise when the de­vel­op­ment of in­ves­ti­ga­tion­al prod­ucts is ac­cel­er­at­ed.

The EMA’s launch of its pri­or­i­ty med­i­cines (PRIME) scheme and the FDA’s break­through ther­a­py des­ig­na­tion have en­abled com­pa­nies to speed cer­tain treat­ments to mar­ket, al­though there have been dif­fi­cul­ties in iden­ti­fy­ing pos­si­ble sci­en­tif­ic and reg­u­la­to­ry ap­proach­es to fa­cil­i­tate the type of ro­bust qual­i­ty da­ta pack­ages nec­es­sary to en­sure that pa­tient safe­ty and prod­uct qual­i­ty and ef­fi­ca­cy are not com­pro­mised, ac­cord­ing to a re­port re­leased Wednes­day on the work­shop.

Ramesh Sood

In ad­di­tion to the fo­cus on ear­ly ac­cess ap­proach­es, the work­shop dis­cussed process val­i­da­tion, con­trol strate­gies, good man­u­fac­tur­ing prac­tice (GMP) com­pli­ance, com­pa­ra­bil­i­ty, sta­bil­i­ty and reg­u­la­to­ry tools.

Ramesh Sood, se­nior sci­en­tif­ic ad­vi­sor at the FDA’s Of­fice of New Drugs, dis­cussed the agency’s break­through pro­gram, not­ing the chal­lenges faced by ap­pli­cants col­lect­ing the nec­es­sary man­u­fac­tur­ing da­ta and pro­vid­ing an ad­e­quate man­u­fac­tur­ing con­trol strat­e­gy.

“It be­comes im­por­tant for the Agency re­view­ers to do a risk-ben­e­fit as­sess­ment re­gard­ing [the] risk of less man­u­fac­tur­ing in­for­ma­tion ver­sus pa­tient ben­e­fit,” the work­shop re­port says of Sood’s pre­sen­ta­tion. “This re­quires in­no­v­a­tive risk-mit­i­ga­tion strate­gies to en­sure prod­uct qual­i­ty and re­duce the qual­i­ty-re­lat­ed prod­uct risk to an ac­cept­able lev­el.”

Veroni­ka Jek­er­le

Veroni­ka Jek­er­le of the EMA’s qual­i­ty of­fice al­so dis­cussed the sci­en­tif­ic chal­lenges for PRIME can­di­dates, which in­clude ab­bre­vi­at­ed time­lines that add con­straints to set­ting up com­mer­cial man­u­fac­tur­ing sites.

“An analy­sis ex­am­in­ing sci­en­tif­ic is­sues most com­mon­ly iden­ti­fied by PRIME ap­pli­cants (as in­di­cat­ed by SA [sci­en­tif­ic ad­vice] re­quests) re­vealed the fol­low­ing ar­eas as the most crit­i­cal: start­ing ma­te­ri­als, com­pa­ra­bil­i­ty, process val­i­da­tion, an­a­lyt­i­cal con­trol strat­e­gy, spec­i­fi­ca­tions and sta­bil­i­ty,” the re­port says.

Stu­art Finnie, di­rec­tor of reg­u­la­to­ry CMC at As­traZeneca, al­so pre­sent­ed on a small mol­e­cule prod­uct that earned the FDA’s break­through des­ig­na­tion but ran in­to process val­i­da­tion prob­lems that meant sup­plies of the drug would come four months af­ter ap­proval.

As­traZeneca ap­proached the FDA and dis­cussed de­cou­pling the val­i­da­tion of drug sub­stance and drug prod­uct, and dis­cussed plans to use drug sub­stance man­u­fac­tured in the clin­i­cal fa­cil­i­ty to sup­ply drug prod­uct val­i­da­tion.

“Three key el­e­ments lead to the suc­cess of this pro­pos­al,” the re­port says of the As­traZeneca work. “First­ly, the ap­pli­cant pro­vid­ed the Agency with sig­nif­i­cant ev­i­dence of sim­i­lar­i­ty in terms of qual­i­ty, man­u­fac­tur­ing process and qual­i­ty sys­tem be­tween the clin­i­cal cam­paigns and the pro­posed com­mer­cial cam­paign. Sec­ond­ly, dur­ing the site in­spec­tion there was open and close en­gage­ment be­tween the in­spec­tors, re­view­ers, sub­ject mat­ter ex­perts and qual­i­ty de­part­ments en­sur­ing that ques­tions raised were an­swered swift­ly lead­ing to a bal­anced and aligned view on risk as­sess­ment. Fi­nal­ly, and most im­por­tant­ly, it was clear that through­out the in­ter­ac­tions all par­ties were fo­cused on en­sur­ing sup­ply to the pa­tient.”

Oth­er in­dus­try pre­sen­ta­tions in­volved rep­re­sen­ta­tives from Pfiz­er, Am­gen, Cel­gene, MSD (known as Mer­ck in the US), Bio­gen and sev­er­al vac­cine man­u­fac­tur­ers, among oth­ers.

As far as fu­ture joint EMA-FDA ac­tions, the re­port points to the use of mod­els for sta­bil­i­ty and shelf life de­ter­mi­na­tions, in­no­v­a­tive process val­i­da­tion ap­proach­es and al­low­ing launch­es from clin­i­cal man­u­fac­tur­ing sites.

Ned Sharp­less NIH

“In ad­di­tion, the or­ga­niz­ing com­mit­tee pro­pos­es to de­vel­op a ‘Tool­box- guid­ance’ for PRIME prod­ucts, which shall sum­marise the iden­ti­fied sci­en­tif­ic el­e­ments/reg­u­la­to­ry tools that are al­ready avail­able in the EU to ad­dress some of the chal­lenges faced dur­ing the de­vel­op­ment of prod­ucts un­der PRIME and gen­er­a­tion of ro­bust qual­i­ty pack­ages for MAA [mar­ket­ing au­tho­riza­tion ap­pli­ca­tion] re­view,” the re­port says.

Act­ing FDA Com­mis­sion­er Ned Sharp­less added in a state­ment: “We will con­tin­ue to work with our EMA col­leagues and in­dus­try to dis­cuss ways to ad­dress qual­i­ty chal­lenges as­so­ci­at­ed with ex­pe­dit­ed de­vel­op­ment pro­grams to help en­sure pa­tients re­ceive safe, ef­fec­tive drugs.”

Work­shop Re­port


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Mov­ing Out of the Clin­ic with Dig­i­tal Tools: Mo­bile Spirom­e­try Dur­ing COVID-19 & Be­yond

An important technology in assessing lung function, spirometry offers crucial data for the diagnosis and monitoring of pulmonary system diseases, as well as the ongoing measurement of treatment efficacy. But trends in the healthcare industry and new challenges introduced by the COVID-19 pandemic are causing professionals in clinical practice and research to reevaluate spirometry’s deployment methods and best practices.

Paul Hudson (Getty Images)

Sanofi, Glax­o­SmithK­line jump back in­to the PhI­II race for a Covid vac­cine — as the win­ners con­gre­gate be­hind the fin­ish line

Sanofi got out early in the race to develop a vaccine using more of a traditional approach, then derailed late last year as their candidate failed to work in older people. Now, after likely missing the bus for the bulk of the world’s affluent nations, they’re back from that embarrassing collapse with a second attempt using GSK’s adjuvant that may get them back on track — with a potential Q4 launch that the rest of the world will be paying close attention to.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

SCO­TUS de­clines to re­view En­brel biosim­i­lar case, tee­ing up 30+ years of ex­clu­siv­i­ty and $20B more for Am­gen’s block­buster

As the House Oversight Committee is set to grill AbbVie CEO Richard Gonzalez on Tuesday over tactics to block competition for its best-selling drug of all time, another decision on Capitol Hill on Monday opened the door for billions more in Amgen profits over the next eight years.

The Supreme Court on Monday denied Novartis subsidiary Sandoz’s petition to review a Federal Circuit’s July 2020 decision concerning its biosimilar Erelzi (etanercept-szzs), which FDA approved in 2016 as a biosimilar to Amgen’s Enbrel (etanercept). Samsung’s Enbrel biosimilar Eticovo also won approval in 2019 and remains sidelined.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Biolyse, an Ontario-based manufacturer of sterile injectables, forged a deal with Bolivia last week to manufacture up to 50 million J&J Covid-19 vaccine doses, the agreement kicked off what will prove to be a test case for how difficult the system of compulsory licenses is to navigate.

The first problem: When Biolyse asked J&J, via a March letter, to license its Covid-19 vaccine, manufacture it in Canada and pay 5% royalties on shipments to needy, low-income countries, J&J rejected the offer, refusing to negotiate. J&J also did not respond to a request for comment.

Tim Mayleben (L) and Sheldon Koenig (Esperion)

On the heels of a sting­ing Q1 set­back, Es­pe­ri­on's long­time cham­pi­on is ex­it­ing the helm and turn­ing the wheel over to a mar­ket­ing pro

Just days after getting stung by criticism from a badly disappointed group of analysts, there’s a big change happening today at the helm of Esperion $ESPR.

Longtime CEO Tim Mayleben, who championed the company for 9 years from early clinical through a lengthy late-stage drive to successfully get their cholesterol drug approved for a significant niche of patients in the US, is out of the C suite, effective immediately. Sheldon Koenig — hired at the end of 2020 with a resume replete with Big Pharma CV sales experience —  is stepping into his place, promising to right a badly listing commercial ship that’s been battered by market forces.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis' En­tresto takes its 2nd fail­ure of the week­end at ACC, show­ing no ben­e­fit in most dire heart fail­ure pa­tients

Novartis’ Entresto started the ACC weekend off rough with a trial flop in heart attack patients, slowing the drug’s push into earlier patients. Now, an NIH-sponsored study is casting doubt on Entresto’s use in the most severe heart failure patients, another black mark on the increasingly controversial drug’s record.

Entresto, a combination of sacubitril and valsartan, could not beat out valsartan alone in an outcomes head-to-head for severe heart failure patients with a reduced ejection fraction (HFrEF), according to data presented Monday at the virtual American College of Cardiology meeting.

Matt Gline (L) and Vivek Ramaswamy

In­sid­er ac­count of Roivan­t's SPAC deal — and that $7.3B val­u­a­tion — re­veals a few se­crets as Matt Gline po­si­tions the com­pa­ny as the new ‘Big Phar­ma’

It was Oct. 7, 2020, and Matt Gline wasn’t wasting any time.

The CEO of Roivant had word that KKR vet Jim Momtazee’s SPAC had priced late the night before, triggering a green light for anyone interested in pursuing a big check for future operations and riding the financial instrument to Nasdaq. So he wrote a quick email congratulating Momtazee, whom he knew, for the launch.

Oh, and maybe Momtazee would like to schedule something with Gline and his executive chairman, Roivant founder Vivek Ramaswamy, to chat about Roivant and its business?

Endpoints Premium

Premium subscription required

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

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

John­son & John­son do­nates Ebo­la vac­cine amid new out­break; Ji Xing promis­es more than $127M for Mile­stone's nasal spray for rapid heart rate

As Johnson & Johnson continues to roll out its Covid-19 shot, the company is also focused on another vaccine.

J&J is donating up to 200,000 doses of its Ebola vaccine regimen developed with Bavarian Nordic to help health authorities deal with a new outbreak in Sierra Leone. The regimen, Zabdeno and Mvabea, was granted prequalification by the WHO in April, which will help accelerate its registration in countries where Ebola is a threat.