Proac­tive­ly pre­vent­ing short­ages: New FDA guid­ance spells out which drugs re­quire risk man­age­ment plans

As the ma­jor­i­ty of drug short­ages are still as­so­ci­at­ed with man­u­fac­tur­ing-re­lat­ed qual­i­ty is­sues, the FDA on Thurs­day pub­lished new draft guid­ance spelling out how to proac­tive­ly as­sess risks to man­u­fac­tur­ing process­es and sup­ply chains, while un­der­stand­ing the mar­ket’s vul­ner­a­bil­i­ties.

While drug short­ages peaked in 2011, the FDA says in its new 18-page draft guid­ance that the num­ber of new drug short­ages “has de­clined sig­nif­i­cant­ly since” that peak, reach­ing a low in 2015 and 2016, thanks in part to a new law’s en­act­ment, known as FDA­SIA, which helped the agency bet­ter pre­vent or mit­i­gate drug sup­ply dis­rup­tions and short­ages, and clar­i­fied cGMP re­quire­ments.

How­ev­er, the FDA ex­plains how this down­ward trend “did not con­tin­ue in sub­se­quent years,” not­ing:

Drug short­ages con­tin­ue to oc­cur and at rough­ly the same lev­els since 2018. Fur­ther, drug short­ages have grown more per­sis­tent (i.e., in­creased length of ac­tive drug short­ages). Many of the rea­sons for drug short­ages are, for ex­am­ple, is­sues re­lat­ed to drug qual­i­ty, dis­rup­tions to sup­ply chain man­u­fac­tur­ing op­er­a­tions (e.g., caused by nat­ur­al dis­as­ter or dis­con­tin­u­a­tion of com­po­nents by sup­pli­ers), lim­i­ta­tions in fore­cast­ing fu­ture de­mand, and mar­ket with­drawals of drug prod­ucts.

In March 2020, with the en­act­ment of the CARES Act, Con­gress added a sec­tion to the law gov­ern­ing the FDA, which took ef­fect in Sep­tem­ber 2020, and that re­quires cer­tain man­u­fac­tur­ers to de­vel­op, main­tain, and im­ple­ment a “re­dun­dan­cy risk man­age­ment plan that iden­ti­fies and eval­u­ates risks to the sup­ply of the drug, as ap­plic­a­ble, for each es­tab­lish­ment in which such drug or ac­tive phar­ma­ceu­ti­cal in­gre­di­ent of such drug is man­u­fac­tured.”

Since at least the pub­li­ca­tion of ICH Q9 in 2006, the phar­ma­ceu­ti­cal in­dus­try has tak­en steps to im­ple­ment qual­i­ty risk man­age­ment prin­ci­ples.

The types of drugs for which the FDA will re­quire risk man­age­ment plans in­clude:

  • Life-sus­tain­ing and life-sup­port­ing drugs and APIs
  • Drugs to pre­vent or treat a de­bil­i­tat­ing dis­ease or con­di­tion, in­clud­ing for emer­gency med­ical care or surgery or that’s crit­i­cal to the pub­lic health dur­ing a pub­lic health emer­gency
  • Any as­so­ci­at­ed med­ical de­vice used for the prepa­ra­tion or ad­min­is­tra­tion of these drugs

For 7 oth­er types of drugs, the FDA draft says that it rec­om­mends, rather than re­quires, RMPs:

  1. Drugs to treat rare dis­eases
  2. Drugs that lack ap­pro­pri­ate al­ter­na­tives
  3. Med­ical coun­ter­mea­sures used in the event of a po­ten­tial pub­lic health emer­gency stem­ming from a ter­ror­ist at­tack with a bi­o­log­i­cal, chem­i­cal, or ra­di­o­log­i­cal/nu­clear ma­te­r­i­al, or a nat­u­ral­ly oc­cur­ring emerg­ing dis­ease and oth­er threat agents (i.e., es­sen­tial to na­tion­al se­cu­ri­ty)
  4. Sole source drugs
  5. Drugs with on­ly one API man­u­fac­tur­er in the prod­uct’s sup­ply chain that has been ap­pro­pri­ate­ly qual­i­fied by the qual­i­ty unit of the fin­ished dosage form (FDF) es­tab­lish­ment
  6. Drugs with on­ly one FDF man­u­fac­tur­er in the prod­uct’s sup­ply chain
  7. Drugs man­u­fac­tured in a fa­cil­i­ty (in­clud­ing pack­ag­ing fa­cil­i­ties and lab­o­ra­to­ries) with an in­spec­tion in the last 5 years that was clas­si­fied as of­fi­cial ac­tion in­di­cat­ed (OAI) and there is no oth­er man­u­fac­tur­ing fa­cil­i­ty that is qual­i­fied in the prod­uct’s sup­ply chain to con­duct that op­er­a­tion

While the agency ac­knowl­edges that short­ages and short­age mit­i­ga­tion ef­forts pose a sig­nif­i­cant fi­nan­cial and re­source bur­den on phar­ma com­pa­nies, among oth­er stake­hold­ers, the FDA said it views RMPs as an im­por­tant mech­a­nism to proac­tive­ly iden­ti­fy, as­sess, and mit­i­gate the risks that might lead to a dis­rup­tion in the sup­ply of drugs.

Ad­di­tion­al­ly, in re­cent years, FDA said it has ob­served a rise in num­ber of cy­ber­at­tacks on drug man­u­fac­tur­ers “and is in­creas­ing­ly con­cerned about the ef­fect of such at­tacks on the drug sup­ply chain.”

In 2017, a cy­ber­at­tack in­volv­ing ran­somware on Mer­ck’s man­u­fac­tur­ing ops led to is­sues that last­ed for more than a month af­ter the at­tack oc­curred.

Vas Narasimhan (Photographer: Jason Alden/Bloomberg via Getty Images)

No­var­tis de­tails plans to axe 8,000 staffers as Narasimhan be­gins sec­ond phase of a glob­al re­org

We now know the number of jobs coming under the axe at Novartis, and it isn’t small.

The pharma giant is confirming a report from Swiss newspaper Tages-Anzeiger that it is chopping 8,000 jobs out of its 108,000 global staffers. A large segment will hit right at company headquarters in Basel, as CEO Vas Narasimhan axes some 1,400 of a little more than 11,000  jobs in Switzerland.

The first phase of the work is almost done, the company says in a statement to Endpoints News. Now it’s on to phase two. In the statement, Novartis says:

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Peter Marks (Jim Lo Scalzo/Pool via AP Images)

FDA's VRB­PAC votes in fa­vor of adapt­ing the Covid-19 vac­cine to the lat­est Omi­cron vari­ant

The FDA’s Vaccine and Related Biological Products Advisory Committee on Tuesday gave the thumbs up — by a vote of 19-2 — that the FDA should require an Omicron-related component in this next season’s booster dose for Covid-19, which both Pfizer/BioNTech and Moderna are hard at work on.

And while neither booster will likely be ready to go with adequate supplies for all American adults by the beginning of the next school year, the situation is still complex and fluid, with CBER Director Peter Marks telling the committee that it’ll take companies at least three months to ready their supplies for this expected next wave.

Aurobindo Pharma co-founders P. V. Ram Prasad Reddy (L) and K. Nityananda Reddy

Au­robindo Phar­ma re­ceives warn­ing let­ter from In­di­a's SEC fol­low­ing more FDA ques­tion marks

Indian-based generics manufacturer Aurobindo Pharma has been in the crosshairs of the FDA for several years now, but the company is also attracting attention from regulators within the subcontinent.

According to the Indian business news site Business Standard, a warning letter was sent to the company from the Securities Exchange Board of India, or SEBI.

The letter is related to disclosures made by the company on an ongoing FDA audit of the company’s Unit-1 API facility in Hyderabad, India as well as observations made by the US regulator between 2019 and 2022.

Bob Nelsen (Lyell)

As bear mar­ket con­tin­ues to beat down biotech, ARCH clos­es a $3B ear­ly-stage fund

One of the biggest names in biotech investing has a whole lot of new money to spend.

ARCH Venture Partners closed its 12th venture fund early Wednesday morning, the firm said, bringing in almost $3 billion to invest in early-stage biotechs. The move comes about a year and a half after ARCH announced its previous fund, for almost $2 billion back in January 2021.

In a statement, ARCH managing director and co-founder Bob Nelsen appeared to brush off concerns about the broader market troubles, alluding to the downturn that’s seen several biotechs downsize and the XBI fall back to almost pre-pandemic levels.

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Lina Gugucheva, NewAmsterdam Pharma CBO

Phar­ma group bets up to $1B-plus on the PhI­II res­ur­rec­tion of a once dead-and-buried LDL drug

Close to 5 years after then-Amgen R&D chief Sean Harper tamped the last spade of dirt on the last broadly focused CETP cholesterol drug — burying their $300 million upfront and the few remaining hopes for the class with it — the therapy has been fully resurrected. And today, the NewAmsterdam Pharma crew that did the Lazarus treatment on obicetrapib is taking another big step on the comeback trail with a €1 billion-plus regional licensing deal, complete with close to $150 million in upfront cash.

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How pre­pared is bio­phar­ma for the cy­ber dooms­day?

One of the largest cyberattacks in history happened on a Friday, Eric Perakslis distinctly remembers.

Perakslis, who was head of Takeda’s R&D Data Sciences Institute and visiting faculty at Harvard Medical School at the time, had spent that morning completing a review on cybersecurity for the British Medical Journal. Moments after he turned it in, he heard back from the editor: “Have you heard what’s going on right now?”

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New Charles River Laboratories High Quality (HQ) Plasmid DNA Centre of Excellence at Bruntwood SciTech’s Alderley Park in Cheshire, United Kingdom. (Charles River)

Charles Riv­er Lab­o­ra­to­ries to start cell and gene ther­a­py man­u­fac­tur­ing at UK site in Sep­tem­ber

While Massachusetts-based Charles River Laboratories has been on an acquisition spree, they are not against planting their flag. The latest move by the company sees them crossing the pond to establish a manufacturing site in the UK.

The company on Tuesday opened its cell and gene therapy manufacturing center at Bruntwood SciTech’s Alderley Park in Cheshire, United Kingdom. The expansion follows Charles River’s acquisition of Cognate BioServices and Cobra Biologics in 2021 for $875 million. Cognate is a plasmid DNA, viral vector and cell therapy CDMO.

Ankit Mahadevia, Spero CEO

Spero’s UTI can­di­date gets the CRL ham­mer as the com­pa­ny falls in­to pen­ny stock sta­tus

Spero Therapeutics has been struggling in the past few years, dealing with FDA holds and staff reductions amidst a rough biotech market, and the latest news from the Massachusetts-based company confirms what it anticipated in May: a CRL.

The company was slapped with the no-go for its NDA, the biotech disclosed Monday. The company was seeking approval for tebipenem HBr oral tablets, intended for the treatment of adult patients with complicated urinary tract infection, or cUTI, including pyelonephritis. The FDA had set a PDUFA date of June 27.

Sanofi to cut in­sulin prices for unin­sured from $99 to $35, match­ing the in­sulin cap com­ing through Con­gress

As the House-passed bill to cap the monthly price of insulin at $35 nationwide makes its way for a Senate vote soon, Sanofi announced Wednesday morning that beginning next month it will cut the monthly price of its insulins for uninsured Americans to $35, down from $99 previously.

The announcement from Sanofi, which allows the uninsured to buy one or multiple Sanofi insulins (Lantus, Insulin Glargine U-100, Toujeo, Admelog, and Apidra) at $35 for a 30-day supply effective July 1, follows House passage (232-193) of the monthly cap in March, with just 12 Republicans voting in favor of the measure.