Susan Haigney

Communication between the manufacturing plant and retail stores. | Image Credit: © Cagkan - © Cagkan - stock.adobe.com

The contract development and manufacturing organization (CDMO), Enzene, will be launching its new fully-connected continuous manufacturing platform for biologics at the CPHI Milan show, being held from Oct. 8–10, 2024 in Milan, Italy. The EnzeneX 2.0 is a patented platform that provides uninterrupted processing from perfusion to final drug substance.

The technology uses high titer clones to improve productivity and target protein concentrations, streamline production, and mitigate risks associated with batch-to-batch transfers. The platform also boosts cell productivity by leveraging optimized cell media. Process analytical technology is used to enable real-time monitoring and control quality.

“Enzene continues to lead the industry in launching innovative approaches to maximize product yield while minimizing COGS [cost of goods]. Our latest innovation in fully connected continuous manufacturing can be tailored for a broad range of modalities and media formulations to boost cell productivity and efficiency,” said Himanshu Gadgil, CEO of Enzene, in a press release. “Lower operational costs and higher productivity can enable up to 50% reductions in overall production cost per gram, and we are on target to achieve a game-changing benchmark by 2025. We expect that our FCCM [fully connected continuous manufacturing] will be able to deliver 40 kilograms per thousand-liter batch at $40-per-gram.”

EnzeneX 2.0 can also reduce equipment footprint compared to fed-batch systems, according to the company. It can handle clinical-phase current good manufacturing practice supply from 30-L scale. The modular design has variable bioreactor capacity and can take on scale-on and scale-out expansion.

Enzene is launching a new facility in Hopewell, NJ, to be operational in early 2025, that the company said will provide a fully connected service. “Enzene Biosciences is thrilled to establish our manufacturing operations in New Jersey, as it allows us to extend our local manufacturing capabilities to our valued North American clients,” said Gadgil at the time of the facility announcement (2). “We are excited to provide them with access to our cutting-edge continuous manufacturing platform, which enables streamlined and efficient production processes. New Jersey’s highly skilled workforce, state-of-the-art infrastructure, and renowned academic institutions make it an ideal location for Enzene, ensuring that we can deliver exceptional services and support to our clients in the [United States].”

® spoke with Gadgil in June 2024 about the benefits of continuous manufacturing of biologics. Gadgil talked about the impact on a company’s cost of goods, and stated, “For example, in a 1500-square-foot cleanroom, we can manufacture in a month currently around 10 kilograms of mAbs [monoclonal antibodies], and we are enhancing that platform where we should be able to manufacture on 40 kilograms of mAbs.” Gadgil continued, “So, one of the biggest advantages of continuous manufacturing is cost of goods, because the operational cost is much lower than the conventional manufacturing, [because] the footprint is more compact, and at the same time, the productivity is also very high.” He also said, “Because when you do perfusion, you get significantly higher cell densities almost five to 10 times higher cell densities than the conventional fed batch” (3).

Enzene can be found at CPHI Milan at stand 5D63, Hall 5.

1. Enzene. Enzene Launches EnzeneX 2.0. Press Release. Oct. 4, 2024.
2. Choose New Jersey. Enzene Biosciences Expanding to New Jersey with $50M Investment in Bio Manufacturing Plant. June 15, 2023.
3. Haigney, S. Continuous Manufacturing and Cost of Goods (BIO 2024). 

Articles

The CDMO will be launching its EnzeneX 2.0 continuous manufacturing for biologics technology during CPHI Milan, which is being held Oct. 8–10, 2024 in Milan, Italy.

Enzene to Launch Continuous Manufacturing Technology at CPHI Milan 2024

AAPS PharmSci 360 2024: Drug Delivery in Early Development

As a preview of what’s to come at this year’s AAPS PharmSci 360, being held Oct. 20–23, 2024 in Salt Lake City, UT, 

® sat down with Erica Schlesinger, vice president of Technical Development at Serán Bioscience, to talk about her prologue for AAPS PharmSci 360 2024 and what drives the choice of delivery method for new modalities.

“[A]s biologics have emerged as one of the more common therapeutic areas, we've really been looking at how we can improve the patient experience and make these more widely applicable and safer to administer. And a lot of that focus is on how to convert from IV [intravenous] formulations to subcutaneous formulations and subcutaneous administration. And you know, in order to do that, we need to be able to deliver more drug in smaller volumes or more drug in systems that don't need to be administered through IV,” says Schlesinger in the interview. “I think the other area that's been a huge focus area in the past couple years has really been looking at how we can deliver biomolecules and other low-permeability pharmaceuticals systemically through the oral delivery route by leveraging permeation enhancers.”

Click the above video to watch the full interview.

prologue presentation can be accessed from the AAPS PharmSci 360 website

. She will also be moderating the presentation, 

Assessment of Permeability: Bridging Traditional and Novel Compounds in Discovery

, at AAPS PharmSci 360, on Monday, Oct. 21, 2024 in Salt Lake City, UT.

Videos

Pharmaceutical Technology sat down with Erica Schlesinger, vice president of technical development at Serán Bioscience, to talk about her upcoming presentation at AAPS PharmSci 360 2024, “High Dose Subcutaneous Delivery of Protein Therapeutics.”

Ashland, an additives and specialty ingredients company, will be showcasing its oral solid dose (OSD) ingredients at two tradeshow events in October 2024: CPHI Milan and AAPS PharmSci 360. Specifically, the company will be highlighting its new low-substituted hydroxypropyl cellulose (hpc) and its improved polyplasdoneLN superdisintegrant.

The company’s new low-substituted hpc, klucel ls, an OSD excipient, is a multifunctional binder and disintegrant for the formulation of smaller tablets. According to the company, klucel ls “offers quick disintegration and rapid dissolution, anti-capping effect, ease of adoption (as a monographed ingredient), and enhanced stability (non-ionic and low nitrite levels). It is also biodegradable (as a non-microplastic disintegrant)” (1).

Klucel ls adheres to low-substituted hpc monograph requirements and “has fewer hydroxypropoxy groups on the cellulose backbone. This lower substitution results in physical chemical properties that differ from traditional klucel grades, including insolubility in water (as klucel ls low-substituted hpc absorbs water and substantially swells in volume enabling rapid tablet disintegration—unlike klucel, which is soluble in water and used primarily as a binder in oral solid dosage forms),” the company stated in the press release. The excipient is one in a series of future low-substituted products the company has planned.

“As a company rooted in science and innovation, the drive to find ingenious solutions applied to chemistry is in our DNA,” said Deneen Law, global strategic marketing director—Klucel, Ashland, in the press release. “We thrive on developing solutions to complex problems through a collaborative approach that offers the features and benefits our customers require, with the dependability and quality they demand. The removal of single-source global supply for low-substituted hpc and the production of consistent, high-quality products are just a few reasons why Ashland’s customer-centric approach is driving success across diverse industries.”

“Klucel hpc formed the basis of a new generation of oral pharmaceutical dosage forms, and the scientists at Ashland continue to innovate and develop new hpc products to meet the needs of the pharmaceutical industry. While klucel ls low-substituted hpc is part of the klucel brand family, it is not the same as klucel hpc,” Law concluded.

The klucel hpc for pharmaceuticals portfolio includes:

binders: klucel ef hpc; klucel elf hpc; klucel exf hpc; klucel exf ultra hpc

multifunctional binder and disintegrant: klucel ls low-substituted hpc

CR polymers: klucel gxf hpc; klucel hf hpc; klucel hxf hpc; klucel lf hpc; kucel lxf hpc; klucel mxf hpc; klucel xtend hpc.

At the tradeshows, Ashland will also be reintroducing its high-purity crospovidone, polyplasdone LN superdisintegrant, which has nitrite levels at no more than 100 parts per billion to minimize the risk of N-nitrosamine forming in OSD formulations that contain crospovidone.

“We are thrilled to lead the industry with this significant advancement, our commitment to quality and safety is at the forefront of everything we do,” said Alejandra Alvarez, global strategic marketing director—Vinyl Pyrrolidone and Derivatives, Ashland, in the press release. “By providing detailed nitrite specifications, we are empowering our customers to make informed decisions and enhance their own quality control measures.”

Ashland may be found at CPHI Milan, in Milan, Italy, from Oct. 8–10 at booth 6D20 and at AAPS PharmSci 360 at booth 1903 in Salt Lake City, Utah, from Oct. 20–23.

1. Ashland. Ashland to Showcase New Pharmaceutical Oral Solid Dose Excipients at CPHI and AAPS. 

The company will be introducing its new low-substituted hydroxypropyl cellulose and its improved polyplasdone LN superdisintegrant at the October 2024 events.

Ashland to Exhibit Excipients at CPHI Milan and AAPS PharmSci 360

On Oct. 1, 2024, the Almac Group, a contract development and manufacturing organization, announced it is investing £11 million (US$14.7 million) to expand its existing analytical laboratories, technology, and resources and create 100 new jobs. Almac, which includesAlmac Sciences and Almac Pharma Services, has locations in Craigavon, United Kingdom; Charnwood, UK; Souderton, Pa. in the United States; Athlone, Ireland; and Dundalk, Ireland.

As part of the expansion, the company is planning new laboratory space at its Craigavon headquarters and upgrades to existing labs across all sites. Specialized instrumentation and techniques have also been added to service lines, including chromatography, spectroscopy, and biologics. Equipment investment to enhance capabilities includes a new spray drying at the Charnwood site. The company also recently added its Raman TRS100 system for faster assay of tablets, capsules, and other dosage forms. Investment in training of staff has also been put into place.

“We have experienced a significant increase in demand for our dedicated analytical solutions and recognize the importance of continually investing, not just in our systems and facilities, but also in our people,” Darren Thomas, vice president Analytical Operations, Almac Sciences, said in a press release. “We are committed to offering a best-in-class service to our global client base and are delighted to continue at pace with significant investment across our UK, EU [European Union], and US facilities in order to strengthen our competitive position in the marketplace.”

Trevor Clarke, vice president Analytical Operations, Almac Pharma Services added: “We are positioned as the partner of choice with significant experience in a wide range of analytical services to meet the varying requirements of our clients’ unique development and commercial programs. As we continue to expand our global analytical capabilities, we remain committed to delivering excellence. This significant investment in innovative technology, skilled talent, and state-of-the-art laboratories underscores our dedication to providing comprehensive analytical solutions for our clients worldwide.”

Almac Group’s Almac Clinical Servicesdivision also invested in enhancing the company’s Singapore cold chain facility back in July 2024, quadrupling the available floorspace and providing 480 additional storage locations (2). The facility operates at temperatures from -25 °C to -15 °C and has dedicated secondary production rooms with frozen conditions.

“The growth of biologics and the complexities surrounding their development and use necessitates continuous improvement. Biologics are highly sensitive to environmental conditions, including temperature, light, pH, and oxygen levels,” Kevin Cheong, Director of Clinical Operations at Almac Clinical Services, said in the press release at the time of the announcement (2). “Even minor deviations can lead to significant changes in the stability efficacy, and safety of these products. This investment will significantly enhance our ability to support our global pharmaceutical sponsors and underscores our dedication to providing the best service offering to clients, ensuring that patients receive the right drugs, at the right time and in the right condition.”

Almac Group. Almac Group Announces £11m Investment to Expand Global Analytical Services. Press Release. Oct. 1, 2024.

Almac Group. Almac Announces Investment in Singapore to Enhance Cold Chain Facility for Global Pharmaceutical Sponsors and Patients. Press Release. July 30, 2024.

The Almac Group is planning a £11 million (US$14.7 million) investment to expand the company’s existing analytical laboratories.

Almac Group Invests in Expansion of Analytical Services

AAPS PharmSci 360 2024: Flex Manufacturing

® sat down with Anna Jenks, director of Pharmaceutical Operations for Merck & Co., Inc. (known as MSD outside of the United States and Canada) in Rahway, NJ, USA to talk about her 

 for the conference and the benefits of utilizing flexible manufacturing.

“Flexible manufacturing really relates to the industry and the needs of the industry,” says Jenks in the interview. “I think, from [a] historical facility standpoint, oftentimes we build fixed facilities that are harder to change. Flexible manufacturing looks at what we need now, but also is looking at what we need in the future, and even recognizing we don't know everything that we need, and we need to be able to change in the future when that need comes.”

At Merck & Co., Inc., Rahway, NJ, USA, Jenks states that they are focused on using flex manufacturing in clinical stage manufacturing but are looking to also apply it to commercial manufacturing.

“The clinical manufacturing has a short-term turnaround,” Jenks says. “Oftentimes, you see many short campaigns that are on days to weeks timeframe[s] and need fast switchover from one to the next, whereas the commercial manufacturing oftentimes has low, longer timeframes. So, you're looking, in a few years, [at] what kind of process train might be needed, and how are those retrofits going to occur. So the needs of flexible manufacturing might be slightly different, but the concepts definitely apply.”

 AAPS PharmSci 360 is being held Oct. 20–23, 2024 in Salt Lake City, UT.

Pharmaceutical Technology sat down with Anna Jenks, director of Pharmaceutical Operations for Merck & Co., Inc. in Rahway, NJ, USA to talk about her prologue presentation for AAPS PharmSci 360 2024.

Science laboratory test tubes, laboratory equipment | Image Credit: © BillionPhotos.com - © BillionPhotos.com - stock.adobe.com

On Sept. 26, 2024, FDA announced that the agency has approved Bristol Myers Squibb’s (BMS) Cobenfy (xanomeline and trospium chloride) capsules to treat schizophrenia in adults. The approval is significant because it is the first treatment for schizophrenia that targets cholinergic receptors. The standard treatments target dopamine receptors.

The approval was based on results from two identical studies; both were five-week studies that were randomized, double-blind, placebo-controlled, and multi-centered. Study participants were adults diagnosed with schizophrenia according to DSM-5 criteria.

“The primary efficacy measure was the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at week 5. The PANSS is a 30-item scale that measures symptoms of schizophrenia. Each item is rated by a clinician on a seven-point scale. In both studies, the participants who received Cobenfy experienced a meaningful reduction in symptoms from baseline to Week 5 as measured by the PANSS Total Score compared to the placebo group,” FDA stated in the press release (1).

According to FDA, symptoms of schizophrenia include “hallucinations, difficulty controlling one’s thoughts, and being suspicious of others.” Patients may also have cognitive problems and difficulty with social interactions. Schizophrenia impacts approximately 1% of Americans and is one of the 

 of disability worldwide (2). Schizophrenia also poses a greater risk of death at a young age.

“Schizophrenia is a leading cause of disability worldwide. It is a severe, chronic mental illness that is often damaging to a person’s quality of life,” said Tiffany Farchione, MD, director of the Division of Psychiatry, Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a press release. “This drug takes the first new approach to schizophrenia treatment in decades. This approval offers a new alternative to the antipsychotic medications people with schizophrenia have previously been prescribed.”

“Today’s landmark approval of our first-in-class treatment for schizophrenia marks an important milestone for the community, where after more than 30 years, there is now an entirely new pharmacological approach for schizophrenia—one that has the potential to change the treatment paradigm,” said Chris Boerner, PhD, board chair and chief executive officer at BMS, in a company press release (3). “As we reenter the field of neuropsychiatry, we are dedicated to changing the conversation around serious mental illness, beginning with today’s approval in schizophrenia.”

“For people living with schizophrenia, it's often difficult to find a treatment that works for them. Having a variety of treatment options gives patients and healthcare providers the tools to help manage this serious condition,” said Gordon Lavigne, chief executive officer of the Schizophrenia & Psychosis Action Alliance, in the BMS press release (3). “People living with schizophrenia want and deserve more. Today's approval provides a new option as people with schizophrenia move forward with proper support to rebuild their lives.”

“Due to its heterogeneous nature, schizophrenia is not a one-size-fits-all condition, and people often find themselves in a cycle of discontinuing and switching therapies,” said Rishi Kakar, MD, chief scientific officer and medical director at Segal Trials and investigator in the EMERGENT program, in the press release (3). “The approval of C[obenfy] is a transformative moment in the treatment of schizophrenia because, historically, medicines approved to treat schizophrenia have relied on the same primary pathways in the brain. By leveraging a novel pathway, C[obenfy] offers a new option to manage this challenging condition.”

Cobenfy, however, may cause urinary retention, and should not be prescribed to patients with urinary retention, according to FDA. There is also the possibility of increased heart rate, decreased gastric movement, or angioedema (swelling) of the face and lips. Liver damage is also a risk and, therefore, the drug is not recommended for patients with liver impairment. Patients with moderate to severe renal impairment should also avoid the drug as it is substantially excreted by the kidneys.

Common side effects include nausea, indigestion, constipation, vomiting, hypertension, abdominal pain, diarrhea, increased heartbeat, dizziness, and gastroesophageal reflux disease.

FDA Approves Drug with New Mechanism of Action for Treatment of Schizophrenia.

 Press Release. Sept. 26, 2024.
2. NIMH. Schizophrenia. NIMH.NIH.gov (accessed Sept. 27, 2024). 

https://www.nimh.nih.gov/health/statistics/schizophrenia


3. BMS. US Food and Drug Administration Approves Bristol Myers Squibb’s COBENFY (xanomeline and trospium chloride), a First-In-Class Muscarinic Agonist for the Treatment of Schizophrenia in Adults. Press Release. Sept. 26, 2024.

The new mechanism of action targets cholinergic receptors instead of the standard dopamine receptors.