Susan Haigney

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

Datwyler, a provider of elastomer components, launched the NeoFlex Prefilled Syringe 10mL and NeoFlex Cartridge Wearable 10mL at CPHI Milan on Oct. 8, 2024. The new coated plungers are designed for large-volume injectables and are part of the company’s NeoFlex line, which includes the 0.5, 1, and 2.25 mL prefilled syringes, along with the 3 mL cartridge plungers.

According to the company, the desire for at-home care for chronic illnesses has increased the use of auto- and wearable injectors so that patients can self-administer treatments for conditions such as autoimmune diseases, neurological diseases, and cardiovascular diseases. These treatments are often large volume subcutaneous biopharmaceuticals (LVSCs), which are high-concentration and higher-viscosity formulas sensitive to impurities.

Use of auto- and wearable injectors is on the rise, driven by the embrace of at-home care for chronic diseases. These devices support the self-administered treatment of certain cancers as well as autoimmune, neurological, and cardiovascular diseases with LVSCs. Often, the injectables that must be administered are high-concentration, and higher-viscosity formulas that are sensitive to impurities. These drugs are expensive to manufacture and distribute, requiring the utmost attention to every component to uphold patient safety and prevent instances of contamination that can lead to recalls.

“If you’ve seen a loved one battle cancer, you know that time is precious—and so is the patient’s power to control how they spend it,” said Dirk Borghs, chief executive officer of Datwyler Healthcare Solutions, in a press release (1). “Auto- and wearable injectors stand to give millions of patients more power over their time in treatment. That represents a monumental shift in healthcare but it all rests on the quality and performance of these devices. Every component matters.”

The new additions to the NeoFlex line, like the current offerings, are covered in a non-fluorosurfactant grade fluoropolymer coating to prevent rubber particulates from shedding and to minimize degradation from extractables and leachables. “NeoFlex plungers are manufactured at Datwyler’s FirstLine facilities to ensure highest level of quality assurance and risk mitigation with cleanroom environments, automated production cells, and 100% camera inspection,” the company stated in the press release.

Because the plungers are naturally lubricious, silicone is unnecessary for smooth operation inside the syringe or cartridge barrels, and compatibility with complex formulations is supported, which offers effective delivery of a highly sensitive, highly viscous biologic.

Highly viscous products require certain processing techniques, such as pump choice, to minimize costs and ensure quality. “Datwyler worked closely with leading pharmaceutical companies and system integrators to design the new NeoFlex plungers for superior machinability when filling larger cartridges with minimal headspace and controlled plunger compression. This collaboration is essential to support effective commercialization,” the company stated.

Datwyler can be found at Booth 20B48 at CPHI Worldwide in Milan, Italy, which is being held from Oct. 8-10, 2024.

1. Datwyler. Datwyler Launches NeoFlex Plungers for Large Volume Biologics in Auto- and Wearable Injectors. Press Release. Oct. 8, 2024.

Articles

The company has expanded its NeoFlex coated plungers with new sizes for large-volume auto-injectors and wearable devices. 

Datwyler Launches NeoFlex Plungers at CPHI Milan 2024

CPHI Milan 2024: Flavonoids in Pharmaceuticals

 sat down with Álvaro Nocete Díaz, Pharma Division Manager at HTBA, about the benefits of flavonoids and their use in the pharmaceutical industry. Nocete Díaz discusses how the flavonoid industry has developed, its future, and how to ensure quality when using flavonoids in pharmaceuticals.

“When you think about flavonoids, and again being phytochemicals, it is very important to think about the main source, which is normally a fruit, a vegetable, or an herb,” says Nocete Díaz. “So, the first stage in developing a flavonoid as an ingredient, either for the pharma or nutraceutical industry, will be to have a very strong and robust supply chain of those materials, because they come from crops, right? Then it is also very important to control the quality assurance.”

Nocete Díaz points to product standardization, identification, and quantification as important factors for quality assurance for flavonoids in pharmaceuticals. “[D]eveloping a method of analysis for those products is also very important when moving from the first stage of the natural source to a pure natural or active ingredient, which can be used in the pharmaceutical industry. [It is] also very important to consider the regulatory work that needs to be done, both from the agencies and from the industry, to control all [these aspects of quality],” Nocete Díaz says.

Click the above video to watch the full interview.

 is being held from Oct. 8–10, 2024 in Milan, Italy.

Videos

Pharmaceutical Technology® Europe sat down with Álvaro Nocete Díaz, Pharma Division Manager at HTBA, about the benefits of flavonoids and their use in the pharmaceutical industry. 

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). 

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.”

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.

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.”

Colored water in small glass containers on white background | Image Credit: ©Baharlou/Stock.Adobe.com

Materials used in the formulation and manufacture of drug products must meet certain qualifications, as do the companies that manufacture these materials. Contract development and manufacturing organizations (CDMOs), contract testing laboratories (CTLs), and contract manufacturing organizations (CMOs) can assist sponsor companies with the testing of these crucial drug components. Testing may include analytical testing, impurities testing, and qualification services.

According to Iain McGhee, vice-president of Quality at Ascend Advanced Therapies, contract organizations can provide proprietary and sourced analytics and assays as standalone services or included in a complete program. “Regardless of who you work with, CMO/CDMOs should be able to provide suggestions on a range of testing depending on the customer program,” says McGhee. “If they do not offer this in house, they should have validated partners to do this with.”

Contractors can either do the testing or work with other, outside testing facilities to perform testing on raw materials to ensure compliance with specifications and standards. At Andelyn, according to Rajiv Vaidya, head of MS&T, the company uses a two-phased approach to raw material testing. The process is performed in-house as much as possible to keep everything streamlined. “We have a program in place to continuously evaluate and in-source as much material testing as possible,” says Vaidya. “There is a sweet spot to understanding the balance between what should and should not be done in house—it depends not only on speed and cost but what is the best or most excellent provider for any given test, whether outsourced or in-house. We will only in-source a testing method after we’ve confirmed definitively that the methodology and result will be at least equivalent to the CTLs.”

Determining how to test bio/pharmaceutical materials depends on the API, the dosage form, and the stage of the material, according to Mayank Nagar, vice-president and head–Tech Services and New Product Launches, North Americas at Dr. Reddy’s Laboratories, and Himanshu Joshi, director, New Product Launches, North Americas at Dr. Reddy’s Laboratories. Testing may be performed from pre-formulation through packaging and life-cycle management, say Nagar and Joshi.

Contract organizations can provide custom material testing services for a sponsor company’s needs, including identity tests, purity tests, assays, polymorph testing, and compatibility testing, say Nagar and Joshi. “Various physicochemical testing [such as] dissolution, particle size, description, density, LOD are routinely being serviced by CMOs. Additionally, safety, sterility testing, microbiology, and confirmatory testing are other services provided to sponsor companies,” they say.

CDMOs can also provide final product release testing, according to Kim Arsenault, Quality Compliance manager, BIOVECTRA, such as the following:

using high-performance liquid chromatography (HPLC) to provide assay and impurity content utilizing ultraviolet (UV), charged aerosol (CAD), or mass spectrometry (MS) detectors

testing for residual solvents by using gas chromatography (GC)

performing Karl Fischer (KF) titration to test water content

detecting elemental impurities by using inductively coupled plasma with mass spectrometry (ICP–MS) or optical emission spectroscopy (ICP–OES)

microbial limits and bacterial endotoxins testing

performing identity testing using chemical techniques or infrared (IR) spectroscopy

performing enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis biochemical methods

testing for compendial compliance of pH, optical rotation, and loss on drying

performing gravimetry, titrimetry, and colorimetry bench techniques.

Production stage and the grade of materials used matters, according to McGhee. “Ironically, a lower grade of material with impurities can sometimes makes results look better. However, these results will not scale as the grade tightens—we need to know this early on,” he cautions.

Utilizing CMOs and CDMOs to perform the necessary analytical and quality testing of raw materials used in the production of bio/pharmaceutical products can ensure that these medicines are safe and effective for patients. Contract organizations typically have the knowledge, expertise, and equipment to perform the necessary testing.

“Generally, CMOs/CDMOs should be able to perform the tests outlined for characterizing APIs as listed in ICH [International Council for Harmonisation] Q6A, including characterization of physicochemical properties (e.g., pH, melting point/range, IR), particle size determination, polymorphic form, assay and impurity testing (including tests for chirality, identification tests, residual water content, residual solvents, inorganic impurities), and microbial limits (if applicable),” says Joshua Hoerner, general manager and executive vice president, Purisys (part of the Noramco Group). “It is also important to have hyphenated or specialized techniques [such as] LC–MS, GC–MS, LC–CAD/LC–ELSD, and NMR [nuclear magnetic resonance] for investigative or characterization purposes, should a sponsor’s product experience unexpected results during release or stability testing,” he concludes


Vol. 36, No. 9
October 2024
Pages: 31–33

When referring to this article, please cite it as Haigney, S. Contractors Support Material Testing. 

Contract organizations offer assistance for testing raw materials obtained from outside suppliers.

Contractors Support Material Testing

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.