Drugmakers seek tweaks to ICH guidance on continuous manufacturing

Eli Lil­ly, Gilead, Ther­mo Fish­er and oth­er in­dus­try groups and non­prof­its like BIO and USP are seek­ing some slight changes and more clar­i­ty from the In­ter­na­tion­al Coun­cil of Har­mon­i­sa­tion on its new guid­ance re­lat­ed to con­tin­u­ous man­u­fac­tur­ing.

The guid­ance, known as Q13, fo­cus­es on con­tin­u­ous man­u­fac­tur­ing and its po­ten­tial to low­er man­u­fac­tur­ing costs and re­duce the phys­i­cal foot­print of man­u­fac­tur­ing fa­cil­i­ties com­pared to tra­di­tion­al batch man­u­fac­tur­ing, ac­cord­ing to USP. Con­tin­u­ous man­u­fac­tur­ing al­so may im­prove qual­i­ty con­trol, low­er the vari­abil­i­ty in man­u­fac­tured prod­ucts, and pro­vide en­hanced flex­i­bil­i­ty in pro­duc­tion quan­ti­ty and uti­liza­tion of man­u­fac­tur­ing lines.

But drug­mak­ers have been re­luc­tant to com­plete­ly jump in­to con­tin­u­ous man­u­fac­tur­ing be­cause of the up­front costs and time-con­sum­ing na­ture of al­ter­ing their man­u­fac­tur­ing op­er­a­tions. And some are still try­ing to wrap their heads around how this new ICH guid­ance aligns with FDA’s own draft guid­ance.

USP, which says it wants to help FDA and ICH pro­vide re­sources and train­ing on con­tin­u­ous man­u­fac­tur­ing, al­so seeks more clar­i­ty on how the ICH guid­ance will im­pact that FDA’s draft from 2019, known as ‘Qual­i­ty Con­sid­er­a­tions for Con­tin­u­ous Man­u­fac­tur­ing,’ which de­scribes FDA’s cur­rent think­ing on con­tin­u­ous man­u­fac­tur­ing of small mol­e­cule, sol­id oral drugs.

Oth­ers like BIO are re­quest­ing more spe­cif­ic tweaks. For in­stance, BIO is call­ing on ICH to widen its de­f­i­n­i­tion of a ‘batch,’ as there may be ‘sit­u­a­tions where the defin­ing it by ‘size’ may not al­ways be the most rel­e­vant, e.g., yield/pro­duc­tiv­i­ty or flow rate may not al­ways be con­stant lead­ing to a fair­ly wide range of ‘batch sizes’.’

Gilead, mean­while, al­so calls on ICH to bet­ter de­fine the word ‘fluc­tu­a­tion’ in the Q13 guid­ance, as it’s on­ly used once and on­ly used it’s ‘not very clear the dif­fer­ence be­tween fluc­tu­a­tions and dis­tur­bances. If fluc­tu­a­tions have no im­pact to the process, then the ac­tion of ‘masked by the da­ta analy­sis method used’ should not be an is­sue.’ If it is a ‘large’ fluc­tu­a­tion, it should then be  con­sid­ered a dis­tur­bance, Gilead said.

Eli Lil­ly al­so takes is­sue with an area of the guid­ance that fo­cus­es on how con­tin­u­ous mon­i­tor­ing can help cre­ate ad­di­tion­al op­por­tu­ni­ties for process mon­i­tor­ing and con­trol that as­sure the process is op­er­at­ing in a state of con­trol.

‘Thus, CM does not re­quire com­par­isons to his­tor­i­cal ranges to iden­ti­fy drifts or trends with­in the batch to en­sure the process is op­er­at­ing in a state of con­trol. While this may be a best prac­tice, writ­ten as is, this may be con­sid­ered as a new re­quire­ment,’ Lil­ly said, call­ing on ICH to pull that ref­er­ence.

The ICH draft guid­ance al­so notes that, ‘All in­for­ma­tion for mod­els used as part of com­mer­cial man­u­fac­tur­ing should be main­tained at the man­u­fac­tur­ing site’

But Lil­ly says that ‘All in­for­ma­tion’ is too broad. ‘Could it be more spe­cif­ic (e.g. mod­el de­vel­op­ment, val­i­da­tion and main­tainence)? Please al­so clar­i­fy what ‘main­tained at the man­u­fac­tur­ing site’ means,’ the com­pa­ny adds.

Sensor-based technology for clinical trial data collection represents the latest medical paradigm shift. There are more than 700 clinical studies involving wearable devices currently underway in the United States. A study from Intel IT projects their inclusion in clinical trials will surge to 70% by 2025.

Apps, biosensors and patient-centered technologies increase visibility of comprehensive patient data. Pharma leaders anticipate the benefits of wearables to include better data (58%), faster results (33%) and lower trial costs (10%).

Crowd gathering at the Westin St. Francis for JPM in 2019 (Endpoints News)

Well, see you in January 2023.

In a surprise about-face, #JPM22 will now be fully virtual after organizers of the popular biotech conference decided to pull the plug on a live event in San Francisco given fears over the Omicron variant and a growing chorus of drugmakers opting out.

The move is no big surprise after reports swirled about some of the industry’s biggest players nixing plans to attend live and pressuring the bank to reconsider the annual meet at the Westin St. Francis. STAT reported Tuesday that Moderna and Amgen, among other large drugmakers, had already pulled out.

Richard Pazdur (via AACR)

There’s no denying that Merck’s Keytruda set a high bar for checkpoint inhibitors in development everywhere. But when it comes to the often redundant development of PD(L)-1 antibodies worldwide, FDA’s top cancer doctors Rick Pazdur and Julia Beaver are calling for more industry coordination.

‘Efforts to corral this enthusiasm should focus on increased international partnerships between sponsors of approved checkpoint inhibitors and those developing novel agents to be used with anti–PD-1 and anti–PD-L1 antibodies rather than developing ‘me too’ drugs,’ Beaver and Pazdur wrote Wednesday in the New England Journal of Medicine.

Unlock this story instantly and join 125,700+ biopharma pros reading Endpoints daily — and it’s free.

The FDA on Wednesday not only approved the first generic versions of the decades-old diabetes insipidus treatment vasopressin, but also simultaneously offered a particularly damning rebuke of a citizen petition attempting to block the generic, while promising to pass along the matter to the Federal Trade Commission.

The response could prove troublesome for the sponsor of the brand name version of the drug, Endo’s Par Sterile Products, which brought in more than $780 million in 2020 for its brand name version of the drug Vasostrict.

Robert Califf (Graeme Sloan/Sipa via AP Images)

As Rob Califf likely makes his return as FDA commissioner next month, his confirmation hearing yesterday offered a peek into some of the larger obstacles he’s going to face in the coming months and years.

The pandemic isn’t going away anytime soon with Omicron, and some vaccines and therapeutics may need to be tweaked or pulled from the market entirely as they prove to be ineffective against the new variant. The FDA, meanwhile, needs to get back on even footing with some longer-term direction.

Unlock this story instantly and join 125,700+ biopharma pros reading Endpoints daily — and it’s free.

A nurse administers a COVID-19 booster shot to Joe Rigdon at a vaccination site in Eastmonte Park, Altamonte Springs. (Photo by Paul Hennessy/SOPA Images/LightRocket via Getty Images)

When Laura Burns went to get her first Covid-19 shot last January, no one had warned her that the vaccines might not work for her.

Burns, the recipient of a double-lung transplant in 2016, knew to be careful about the medicines she took. She consulted with her transplant team when the Pfizer and Moderna shots were authorized and only signed up after being told the vaccines would likely be safe for her, which they were.

Unlock this story instantly and join 125,700+ biopharma pros reading Endpoints daily — and it’s free.

Jay Bradner, President, Novartis Institutes for BioMedical Research

John Carroll: Well, hello everybody. This is John Carroll. I’m the editor of Endpoints News, the editor and founder of Endpoints News. I’m here with Jay Bradner, the president of the Novartis Institutes for BioMedical Research. Jay, we’re going to be talking about ASH in just a second, but you’ve just recently celebrated your sixth anniversary as president of NIBR. And I’m curious, it’s such a significant amount of time for anybody to spend in one career phase. And looking back over the last six years, is everything fundamentally different about the research process and the translational arena that you’re in?

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

For the first time, doctors will have a drug to combat acute graft-versus-host disease — a dangerous side effect of stem cell transplants in which donor cells attack the recipient — before it occurs.

The FDA has approved Bristol Myers Squibb’s Orencia to prevent aGVHD in combination with certain immunosuppressants, the company announced on Wednesday. Adults and kids two years and older can take the drug if they’re undergoing hematopoietic stem cell transplantation from an unrelated recipient.

Karthik Balakrishnan, Nodexus founder and CEO

A new company emerged from stealth this morning in San Francisco Bay, and it’s one focused on research technology.

Nodexus, a bio company that develops automated live cell characterization and isolation technologies, announced its launch this morning with a Series A netting it $30 million.

Even though Nodexus does not develop its own drugs, the Series A was led by major biotech investor RA Capital Management, with participation from California VC fund Section 32 and some previous investors. This comes at the same time Nodexus brings on a new board member: former president at BD Biosciences Bill Rhodes.
https://endpts.com/drugmakers-seek-tweaks-to-ich-guidance-on-continuous-manufacturing/