Gly­col­ic acid, TCA among FDA's pro­posed ad­di­tions to 503B bulk drugs list

Four new bulk sub­stances are up for in­clu­sion on the list of ac­tive phar­ma­ceu­ti­cal in­gre­di­ents that out­sourc­ing fa­cil­i­ties can use in drug com­pound­ing un­der sec­tion 503B of the Fed­er­al Food, Drug, and Cos­met­ic Act, ac­cord­ing to a pro­pos­al from the FDA.

The four sub­stances FDA is propos­ing to in­clude as bulk drug sub­stances are diphenyl­cy­clo­propenone, gly­col­ic acid, squar­ic acid dibutyl es­ter and trichloroacetic acid. An ad­di­tion­al 19 bulk drug sub­stances were con­sid­ered for in­clu­sion in the 503B bulk drug sub­stances list, but FDA is propos­ing not to in­clude these sub­stances, cit­ing a lack of clin­i­cal need for an out­sourc­ing fa­cil­i­ty to com­pound drugs from the 19 sub­stances. This lack of need, said the agency, meant the drugs did not meet the statu­to­ry cri­te­ria for ad­di­tion to the list.

Pa­trizia Cavaz­zoni FDA

“If the pro­pos­al is fi­nal­ized, out­sourc­ing fa­cil­i­ties would be au­tho­rized to use these sub­stances in com­pound­ing as long as they meet the oth­er con­di­tions in sec­tion 503B,” said Pa­trizia Cavaz­zoni, act­ing di­rec­tor of FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search (CDER). “As part of our over­sight ef­forts to help en­sure that Amer­i­cans have ac­cess to com­pound­ed med­i­cines, we are de­vel­op­ing and eval­u­at­ing a list of bulk drug sub­stances that out­sourc­ing fa­cil­i­ties can use in com­pound­ing when it’s been de­ter­mined that there is a clin­i­cal need,” she said.

As part of the rolling re­view process of which bulk drug sub­stances to in­clude on the 503B bulks list, the agency is weigh­ing safe­ty against the need for ac­cess, said Cavaz­zoni: “While com­pound­ed drugs do not un­der­go pre­mar­ket re­view for safe­ty, ef­fec­tive­ness and qual­i­ty, we rec­og­nize they can serve an im­por­tant role for pa­tients whose med­ical needs can­not be met by an FDA-ap­proved drug prod­uct. As we de­vel­op the 503B bulks list, we are bal­anc­ing these goals of pa­tient pro­tec­tion and ac­cess to com­pound­ed drugs for pa­tients who need them, par­tic­u­lar­ly com­pound­ed drugs in­tend­ed for use in health care sys­tems, in­clud­ing use for of­fice stock.”

The agency’s Fed­er­al Reg­is­ter en­try lists the 19 sub­stances not pro­posed for in­clu­sion: di­azepam, dobu­t­a­mine hy­drochlo­ride (HCl), dopamine HCl, ede­tate cal­ci­um dis­odi­um, folic acid, gly­copy­rro­late, hy­drox­yzine HCl, ke­toro­lac tromethamine, la­betalol HCl, man­ni­tol, meto­clo­pramide HCl, mox­i­floxacin HCl, nal­buphine HCl, poli­do­canol, potas­si­um ac­etate, pro­cainamide HCl, sodi­um ni­tro­prus­side, sodi­um thio­sul­fate, and ve­r­a­pamil HCl.

“For each of these pro­pos­als, we are seek­ing com­ments from the pub­lic be­fore mak­ing a fi­nal de­ci­sion. The FDA will con­tin­ue to eval­u­ate oth­er bulk sub­stances for in­clu­sion on this list as part of our con­tin­u­ing ef­forts to help en­sure avail­abil­i­ty for pa­tients who re­quire ac­cess to med­ical­ly nec­es­sary com­pound­ed drug prod­ucts,” Cavaz­zoni said.


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.

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Warren Huff, Reata CEO

Rea­ta sug­gests Friedre­ich's atax­ia pro­gram could be de­layed, send­ing stock plung­ing

Reata Pharmaceuticals $RETA made waves last October when its drug omaveloxolone produced positive trial results in treating a rare neurological disorder, but the candidate’s path forward became much murkier Monday.

In a report of quarterly earnings, the biotech divulged that the FDA is considering delaying omaveloxolone’s NDA pending completion of a second trial. That could push back approval by at least a year given that the target population, individuals with Friedreich’s ataxia, is limited and progression of the hard-to-treat illness is notoriously slow. The Covid-19 pandemic would also hinder Reata’s ability to complete an additional trial.

DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 86,800+ biopharma pros reading Endpoints daily — and it's free.

Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 86,800+ biopharma pros reading Endpoints daily — and it's free.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 86,800+ biopharma pros reading Endpoints daily — and it's free.

Vi­da Ven­tures co-leads Dyne's $115M megaround for next-gen oli­go ther­a­pies aimed square­ly at mus­cles

Dyne Therapeutics started out last April with a modest $50 million to mine targeted muscle disease therapies from its in-house conjugate technology. The biotech has now convinced more investors that it’s got gems on its hands, closing $115 million in fresh financing to push its next-gen oligonucleotide drugs into the clinic.

Vida Ventures and Surveyor Capital led the round, joined by a group of other new backers including Wellington Management Company, Logos Capital and Franklin Templeton.

Eli Lil­ly teams with Pieris on HER2+ tu­mors; Op­di­vo + Yer­voy best chemo in mesothe­lioma

Despite the FDA putting a partial clinical hold on its lead program only a few weeks ago, Boston-based Pieris Pharmaceuticals is plowing forward with a new collaboration.

Pieris will work with Eli Lilly to further advance studies on PRS-343, a 4-1BB/HER2 bispecific for HER2-positive tumors, in combination with the latter’s ramucirumab and paclitaxel for the second-line treatment of patients with HER2-positive gastric cancer in a single-arm, Phase II study.

In­novent and Eli Lil­ly chal­lenge Mer­ck­'s mega-block­buster Keytru­da in non-small cell lung can­cer field

China-based Innovent Biologics and its multinational ally Eli Lilly shared Phase III evidence that their PD-1 inhibitor combo can delay the progression of nonsquamous non-small cell lung cancer.

But the drugmakers will face stiff competition in China from Merck’s Keytruda, the ruling PD-1 which is already approved to treat both squamous and nonsquamous NSCLC and boasts positive overall survival rates.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 86,800+ biopharma pros reading Endpoints daily — and it's free.