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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

Endpoints Premium

Premium subscription required

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

Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

David Light, Valisure CEO

Val­isure in the hot seat: New Form 483 over a 2021 in­spec­tion as CEO fires back

The notorious drug testing company Valisure, which has made a name for itself by forcing FDA’s hand with some of its safety-related uncoverings, received a letter this week after the FDA uncovered violations at its Connecticut-based testing lab in 2021.

The letter, which was sent on Dec. 5, stated that the FDA is “concerned” that Valisure was not aware of  drug supply chain security requirements.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.

FDA re­view­ers head back to White Oak in 2023, with lead­er­ship look­ing to ap­pease a new Con­gress

Republicans have taken a stand against the pandemic era habit of lax work-from-home schedules. Now that they’ve wrestled control of the House majority, the FDA’s leadership is playing ball, sending many of the agency’s more than 18,000 employees back to their desks early next year.

Whether this exodus back to White Oak in Silver Spring, MD (many staff will still be allowed to work from home for multiple days per week) will mean more defections to industry and elsewhere remains to be seen.

Bags of shred­ded docs: In­di­an drug­mak­er Lupin hand­ed a Form 483 by FDA in­spec­tors

The generics manufacturer Lupin has been given another Form 483 from the FDA this year.

US regulators inspected Lupin’s pharmaceutical manufacturing site in the town of Mandideep, India from Nov. 14 through Nov. 23, with the 14-page report marking 16 observations.

The inspection report stated that the site did not have the appropriate controls over its computer systems to ensure that changes in “master production” or records are only done by authorized personnel, along with written procedures not being established to conduct annual reviews of records associated with drug batches.

Bro­ken promis­es? FDA needs more pow­er to re­move drugs from mar­ket­place, JA­MA analy­sis finds

The FDA is struggling to remove drugs from the marketplace that don’t show effectiveness in late stage trials, new JAMA analyses found, thanks to the persistent tension between speed and confidence in early clinical data.

Congress, regulated industry and patients have urged the FDA to shorten the amount of time that the market has to wait for drugs to become available that may help severe and prevalent diseases – and the FDA has listened, offering up a quick accelerated approval pathway that’s frequently used by new cancer drugs.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.