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.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,400+ biopharma pros reading Endpoints daily — and it's free.

Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,400+ biopharma pros reading Endpoints daily — and it's free.

In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

Lan Huang, BeyondSpring CEO

Months af­ter shock­ing in­vestors with lung can­cer win, Be­yond­Spring's lead drug hits road­block at the FDA

BeyondSpring shocked investors in early August after its once-marginal lead drug suddenly showed a lot of promise in a common form of lung cancer. With hopes high, the FDA has now slammed the door on that drug in another indication — does that spell bad news for BeyondSpring’s Cinderella story?

The FDA issued BeyondSpring a complete response letter for its plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia, effectively shutting down the drug’s immediate chances at a marketing approval, the biotech said Wednesday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,400+ biopharma pros reading Endpoints daily — and it's free.

With on­ly burns to show in gene ther­a­py, Astel­las inks deal with AAV spe­cial­ist Dyno in push for a bet­ter cap­sid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.

J&J and Sanofi's mul­ti­ple myelo­ma tit-for-tat con­tin­ues, as sub­cu­ta­neous Darza­lex wins com­bo ap­proval

J&J and Sanofi have gone back and forth in their multiple myeloma tug-of-war. Earlier this year, Sanofi notched an approval of Sarclisa in combination with Amgen’s Kyprolis to try to outflank the big conglomerate, but J&J is clapping back.

Wednesday afternoon, Amgen announced that the subcutaneous version of J&J’s blockbuster Darzalex is also now approved as a combo with Kyprolis and dexamethasone. The green light came through for adults with relapsed or refractory multiple myeloma who had progressed on one to three earlier lines of therapy.

As first Omi­cron case in US crops up, re­searchers won­der: which an­ti­bod­ies, vac­cines will hold up?

As Covid-19 drug and vaccine developers race to figure out which of their products might be hampered by the new variant, the CDC on Wednesday afternoon announced the first confirmed case of the Omicron variant (B.1.1.529) in the US, found in San Francisco.

The unidentified individual was a traveler who returned from South Africa on Nov. 22, 2021, was fully vaccinated, and had mild symptoms that the CDC described as improving. All close contacts have been contacted and have tested negative, the centers said.

FDA ad­comm nar­row­ly votes in fa­vor of Mer­ck­'s an­tivi­ral for out­pa­tient Covid-19

With little explanation for why Merck’s potential Covid-19 antiviral was less effective in reducing Covid hospitalizations and deaths in a full analysis of a Phase III trial versus an interim look, the FDA’s antimicrobial drugs advisory committee on Tuesday voted 13-10 in favor of the pill’s benefits outweighing the risks for adults within 5 days of developing Covid symptoms.

Molnupiravir will likely be authorized by FDA in the coming days for adults with mild or moderate Covid-19. While Pfizer’s antiviral may prove to be more effective, Merck’s pill will be another weapon in the armamentarium of Covid-19 treatments for countries around the world, adding to the mAb treatments already in use in the outpatient space from Regeneron, Eli Lilly and Vir/GlaxoSmithKline.