Behind the Headlines Episode 27

Ask the Expert

Small Molecules, APIs, and Excipients—Trends, Challenges, and Opportunities

Drug Digest September 2025

Artificial intelligence, machine learning, and novel instruments are helping drug developers.

Enhancing Bioanalysis and Drug Development with Advanced Tools and Technologies

J.P. Morgan Report Lists Biologics, Obesity, China

Top Trends Reshaping Pharma R&D

Susan J. Schniepp is a fellow at Regulatory Compliance Associates, Inc. and a member of Pharmaceutical Technology's Editorial Advisory Board.

Question mark background | Image Credit: © Leigh-Prather - © Leigh Prather - stock.adobe.com

Q: I am working on making our quality control test laboratory methods more sustainable and environmentally friendly. Do I need to let the regulatory authorities know I am undertaking this initiative?

A: This is a great initiative. Focusing on methods that minimize waste and eliminate the use of hazardous substances is in line with current industry and regulatory trends. Global regulatory authorities have long-term initiatives to encourage quality control (QC) laboratories to adopt sustainable methods within their companies. For example, the 

) has an initiative to remove the rabbit pyrogen test from the Ph. Eur. by 2026.

While you don’t need to inform the regulatory authorities of the initiative during the feasibility phase of exploring alternative methods utilizing sustainable technology, you will need to inform them of your intent to implement these methods when you are ready to use them as your primary methods for evaluating excipients for manufacturing and for releasing the final product for patient use.

One strategy for implementing sustainable testing for monographed items is to submit your test procedure along with the appropriate validation and comparability results to the compendial authorities showing the new method to be equivalent or better than the current existing test method(s). If the compendial authorities adopt the new procedure as part of the official monograph, and, assuming you have indicated in your filing that you follow the current compendia(s), you can just implement the change, noting the adoption of the new compendial procedure in the annual report per Appendix B in FDA’s 

Guidance for Industry, CMC Postapproval Manufacturing Changes To Be Documented in Annual Reports

, which states “Any change made to comply with the official compendium, except relaxation of an acceptance criterion or deletion of a test (see 21 

The drawback to this approach is the unknown amount of time it may take the proposed change to work its way through the monograph revision process and become officially adopted. This approach could take years, and there is no guarantee that it will be successful because the global pharmacopoeias are not harmonized.

The filing requirements when implementing new test method changes to proprietary items can also be accomplished in an annual report, if you submit it as an alternate procedure according to the aforementioned document, according to the FDA guidance, which says, “For drug substance and drug product, the addition or revision of an alternative analytical procedure that provides the same or increased assurance of the identity, strength, quality, purity, or potency of the material being tested as the analytical procedure described in the approved application or deletion of an alternative analytical procedure. The appropriate validation and comparability results against the original procedure will still need to accompany the annual report” (1).

Sustainable product safety tests are straightforward to conduct, but, before implementing them, the company must make sure they are sufficiently validated and yield comparable results to the original method, in addition to notifying the relevant regulatory bodies.

Guidance for Industry, CMC Postapproval Manufacturing Changes to Be Documented in Annual Reports

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates.

When referring to this article, please cite it as Schniepp, S.J. Going Green: Updating Your Filings.

Articles

The implementation of new quality control methods must be reported to regulators, says Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates. 

Going Green: Updating Your Filings

ROSS FDA-3500 dual shaft mixer | Image Credit: Charles Ross & Son Company

The ROSS line of Dual Shaft Mixers are robust, versatile systems with enough power to batch dispersions, suspensions, and emulsions with viscosities up to several hundred thousand centipoise. The custom-built ROSS FDA-3500 has a maximum working capacity of 3500 gallons, a two-zone stainless-steel dimpled jacket for heating/cooling, a 4-inch pneumatic discharge valve, and an explosion-proof load cell system rated for up to 20,000 lbs.

This multi-agitator system is equipped with independently controlled drives and is designed to efficiently produce good turnover and impart shear to a viscous batch. Powered by a 300 HP TEFC inverter duty motor, the high-speed disperser runs at tip speeds up to 5000 ft. per minute, inducing high shear forces. Meanwhile, the 60 HP Three-Wing Helical Anchor Agitator feeds product towards the disperser blade and ensures that the mixture is constantly in motion. Teflon scrapers on the anchor wipe materials from the vessel wall, enhancing heat transfer from the jacket.

The ROSS FDA-3500 dual shaft mixer is equipped with independently controlled drives and is designed to efficiently produce good turnover and impart shear to a viscous batch.

Dual Shaft Mixers with Multi-Agitator System

GEA’s NexGen Press line of tablet presses | Image Credit: © GEA Pharma & Healthcare

GEA Pharma & Healthcare has introduced NexGen Press 45, the latest member of its NexGen Press line of tablet presses. The larger NexGen Press 45 builds on the previous NexGen Press 30 version and offers the same benefits as the smaller generation, including flexibility to adapt to any containment level (up to occupational exposure band 5 [OEB5]), which is attributed to the FAST CHANGEOVER Exchangeable Compression Module (FCO ECM). The new press can also be equipped with the same option packs as the previous version, enabling agile production and making it a system that can be tailored to accommodate a wide range of tableting applications (e.g., multi-unit pellet system, bilayer, poorly flowing products, high yield, microtablets, etc.). Additionally, the system can accommodate different cleaning strategies (wash offline or inline). A further advantage of the NexGen Press range is that every machine is equipped with six compression modes and each benefits from GEA’s unique Air Compensator technology, which effectively reduces common compression issues.

The NexGen Press 45 is the latest member of GEA Pharma & Healthcare’s NexGen Press line of tablet presses.

Next-Generation Tablet Press

Syngene International, a contract research, development, and manufacturing organization (CRDMO), now offers a new protein production platform aimed at rapid protein synthesis. The platform uses a cell line and transposon-based technology that Syngene licensed from ExcellGene, a Switzerland-based service provider specializing in mammalian cell line development. 

Editor’s note: this article was published in the Aug. 1, 2024 issue of 

The new protein synthesis platform, combined with Syngene’s clone selection and development processes, offers significant improvement in efficiency and precision. The platform offers faster preclinical and clinical development and shorter timelines to product launches, shortening time to market. Advantages include up to 10 weeks reduction in time versus traditional cell line development methods; better predictability and protein yields, with high-titer levels of up to 10 g/L achieved; support for a variety of modalities, including monoclonal antibodies, biosimilars, bispecific antibodies, antibody drug conjugates, and other recombinant proteins. In addition, the platform’s versatility facilitates integration with perfusion and fed-batch manufacturing processes.

Syngene’s protein production platform uses a cell line and transposon-based technology licensed from Switzerland-based ExcellGene.

New Protein Production Platform

Felicity Thomas is the former Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

Delving into Biopharmaceutical Development and Manufacturing

In this exclusive Drug Digest video interview, Felicity Thomas, Associate Editorial Director, 

Group, interviews experts from Biosynth and the University of Maryland about biopharmaceutical drug development and manufacturing. During the discussion, Hans de Backer and Peter Timmerman from Biosynth and Anupreet Kaur from the University of Maryland go into detail about the evolution of biopharmaceutical development, highlighting challenges and potential future trends. Additionally, the intricacies of monoclonal antibodies and the complexity of the supply chain are explored.

Post Doctoral Associate, Dr. Robert Brinson Research Group, Institute for Bioscience & Biotechnology Research (IBBR), National Institute for Standards and Technology (NIST), University of Maryland.

Anupreet is a dedicated structural biochemist with more than seven years of experience in structural biology, specializing in protein structural, dynamic and interaction studies. Her strength includes investigating proteins dynamics or conformational exchange using High Resolution Nuclear Magnetic Resonance (NMR) spectroscopy. Anupreet completed her PhD in India and later joined George Washington University as a Post doctoral Research fellow where she did protein engineering to enhance its ligase activity. Currently in IBBR, Anupreet is elucidating the biophysical mechanisms of pharmaceutically relevant excipient-Fab Interactions. Her ultimate aim is to explore the dynamics of monoclonal antibodies at atomic level and characterize the conformational changes in various pharmaceutically relevant formulations using NISTmAb, reference antibody and NIST-Fab with the help of advanced NMR.


Hans received a BSc and MSc in Industrial Engineering and Management Science from the Eindhoven University of Technology in the Netherlands. He spent over seven years at Roland Berger Strategy Consultants, specializing in life sciences. In the four years after that, he spent time in API operations at Aspen Pharmacare, where he built his operational management expertise, first as a Program Manager of a company-wide IT transformation, and later as a Manager of Technical Affairs. In 2019, he joined Pepscan as CEO, which became part of the Biosynth Group after three years, and now Hans is the Head of the Peptide Division at Biosynth.

Peter, Head of Peptide Science at Biosynth, joined the group following the acquisition of Pepscan in 2022, where he had served as CSO since 2012. He drives advancements in protein mimicry for peptide drug discovery programs. Timmerman is the inventor of CLIPS technology and held a chair as a Professor in Protein Mimetic Chemistry at the University of Amsterdam from 2007-2022. He obtained his MSc Chemistry degree from Vrije Universiteit (Amsterdam) and earned his PhD cum laude from the University of Twente. Timmerman has co-authored over 100 scientific papers in peer-reviewed journals.

Drug Digest is a tech talk video series with the 

® editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products.

 Small Molecule APIs, Excipients, and Formulation

Videos

In this exclusive Drug Digest video interview, Felicity Thomas, Associate Editorial Director, Pharmaceutical Technology Group, interviews experts from Biosynth and the University of Maryland about biopharmaceutical drug development and manufacturing.

Drug Digest: Delving into Biopharmaceutical Development and Manufacturing

Thermo’s DNAPac RP HPLC columns | Image Credit: Thermo Fisher Scientific

The Thermo Scientific SurePac Bio 550 SEC MDi columns enable fast separations of adeno-associated virus (AAV) monomers and aggregates. The columns are designed with 3 µm monodisperse particles and inert (MDi) column hardware aimed at providing superior AAV monomer retention and higher resolution of aggregates in cell and gene therapies. 

These columns offer fast run times, optimal separation efficiency, and reliable results with the goal of accelerating time-to-market for novel therapeutics. In addition, Thermo’s DNAPac RP HPLC columns (pictured here) are offered in semi-preparative formats to enable scalability in the development of DNA/RNA oligonucleotides. The DNAPac RP semi-preparative columns are designed so that laboratories can navigate the expanding field of oligonucleotide therapies and precision medicine. The DNAPac RP semi-preparative column utilizes unique chemistry for enhanced performance across wide ranges of pH, temperature, and mobile-phase compositions, offering precise separations and sample purification.

These columns offer fast run times, optimal separation efficiency, and reliable results.

Separation and Purification Columns

Feliza Mirasol is the science editor for 

A new biotech company, Third Arc Bio, which specializes in the development of multifunctional antibodies that are optimized for T cell engagement across solid tumors and inflammatory and immunology (I&I) diseases, has raised $165 million in oversubscribed Series A financing. The company plans to use the funds to advance its drug development programs in clinical studies that address significant unmet needs in oncology and autoimmunity, Third Arc Bio announced in a July 23, 2024 company press release.

Since its initial launch in 2022 with seed financing from Omega Funds, the company has advanced multiple programs that are anticipated to enter the clinic starting in early 2025. The company’s leadership team has collectively brought 19 drugs to market from the discovery and development phases.

“With a powerful discovery engine and a stellar development team, the company is well-positioned to deliver best-in-class therapies and regimens,” said Peter Lebowitz, MD, PhD, CEO of Third Arc Bio, in the press release. “We are grateful for the strong support from Omega Funds and our investor syndicate, who believe in the value of our precise and targeted approach to modulating the immune response with advanced biologics.”

Third Arc Bio’s leadership team consists of:

Peter F. Lebowitz, MD, PhD, who joined as Third Arc Bio’s CEO in January 2024. Lebowitz has extensive drug development experience in his prior role as global head of Oncology R&D at Johnson & Johnson, which achieved 13 major new drug approvals with first and best-in-class medicines, according to the press release. Prior to Johnson & Johnson, Lebowitz also served in multiple leadership roles at GSK, including vice-president, global head of Oncology Early Clinical Development, and vice-president, medical development leader in Late Development at GSK. In those roles, he filed 10 investigational new drug applications (INDs) and played a crucial role in the global registration of two oncology medicines.

Sanjaya Singh, PhD, is founder and chief scientific officer of Third Arc Bio and has more than 25 years of experience in biotherapeutics. He has co-invented multiple immunology and immuno-oncology compounds, including risankizumab (Skyrizi). Singh’s prior roles include global head of Janssen Biotherapeutics, Johnson & Johnson, as well as at Boehringer Ingelheim, Biotherapeutics Discovery, and Tanox (acquired by Genentech). He is co-founder and scientific advisory board member of Aliada Therapeutics.

Joe Erhardt, PhD, chief operating officer, Third Arc Bio, has served for more than 20 years in roles ranging from early discovery through to late clinical development. He most recently served as vice-president, global head of Oncology Discovery and External Innovation, Johnson & Johnson. In his prior roles, Erhardt had operational oversight of expansive portfolios as well as licensing and collaboration for oncology discovery and early development. He has delivered a significant number of internal and external candidates in discovery and clinical pipelines across different modalities, including T cell redirection, T cell co-stimulation, antibody drug conjugates, and targeted radiotherapy.

“The Third Arc Bio team has an outstanding track record of developing impactful medicines, including multiple approved drugs that have redefined standard-of-care in oncology and I&I,” said Arjun Goyal, MD, co-founder and managing director of Vida Ventures, which led the Series A financing, in the press release. “We are tremendously excited to lead this round alongside a high-caliber syndicate of life science and strategic investors at a pivotal time for the company’s growth. With Third Arc’s leading portfolio of best-in-class biologics, multiple INDs planned for 2025, and an extraordinary team of drug developers, the company is poised to create bold new treatments leveraging T cell biology for patients globally.”

Engineered T cells are emerging as highly effective treatments, particularly for hematological cancers. This is evidenced by the hundreds of clinical programs that are underway to expand the efficacy, safety, and applications of this modality, otherwise known as a “living drug” (1).

1. Kirouac, D.C.; Zmurchok, C.; Morris, D. Making Drugs from T cells: The Quantitative Pharmacology of Engineered T Cell Therapeutics. 

With the Series A funding, the new biotech company will advance the development of enhanced biologics for treating solid tumors and inflammatory and immunology diseases.

Third Arc Bio to Advance Biologic Drug Development Programs on $165 Million Funding 

STADA and Alvotech have launched Uzpruvo in Europe, marking the first approved biosimilar to Stelara (ustekinumab) in the European market, according to a July 22, 2024 company press release. Uzpruvo is now available across a majority of European countries, including the largest markets in the region where pricing and reimbursement approvals have been secured to ease the biosimilar’s market entry. 

This launch follows close on the heels of the expiry of exclusivity rights related to the European reference molecule patent. The availability of a biosimilar ustekinumab offers expanded access to patients, physicians, and payers for a therapy to treat certain indications in the gastroenterology, dermatology, and rheumatology disease areas. The companies expect to conduct additional launches in other European countries over the coming months following national price approvals and utilizing a fully European supply chain, according to the press release.

“Launching Uzpruvo at the earliest opportunity in Europe’s largest pharmaceutical markets promotes access by creating competition,” stated Peter Goldschmidt, STADA’s CEO, in the release. “This opportunity to improve patient access through wider usage of a life-changing biological treatment emphasizes STADA’s purpose of Caring for People’s Health as a Trusted Partner.”

The European Commission approved Uzpruvo in January 2024, making the product the first ustekinumab biosimilar to be approved in Europe with equivalent efficacy, safety, pharmacokinetics, and immunogenicity to the reference biologic, Stelara (1). Uzpruvo is indicated for treating Crohn’s disease and psoriatic arthritis in adults and for treating plaque psoriasis in adults and children aged from six years. Uzpruvo is not currently approved to treat ulcerative colitis, however, because the originator biologic still holds exclusivity in this indication.

“With comparable safety, efficacy, and immunogenicity, Uzpruvo gives clinicians an opportunity for a seamless and simple switch for their patients, who can benefit from a thinner needle and latex-free syringe,” commented Bryan Kim, STADA’s Global Specialty head, in the press release.

Uzpruvo is offered in a pre-filled syringe that has a thinner needle than the reference biologic. The biosimilar is also latex-free to minimize the risk of allergic reactions. According to the companies, Uzpruvo was developed and is manufactured and packaged wholly within Europe. It has a shelf life of 36 months.

Ustekinumab is the second immunology biosimilar to reach the market through the STADA and Alvotech partnership. In December 2022 the companies launched Hukyndra a high-concentration, citrate-free adalimumab therapy, a biosimilar to Humira, on the European market (2).

Meanwhile, in June 2024, the partners expanded their collaboration by entering into a development, manufacturing, and marketing alliance for a proposed biosimilar candidate to Prolia/Xgeva (denosumab), a human monoclonal Immunoglobulin G2 antibody for treating osteoporosis in women and bone loss in men (3,4). Under this agreement, Alvotech is responsible for the development and manufacturing of biosimilars within the partnership at its Reykjavik, Iceland, facility.

Union Register of Medicinal Products for Human Use

 (accessed July 29, 2024).
2. Alvotech. Alvotech and STADA Broaden Access to Hukyndra Adalimumab Biosimilar in Europe. Press Release, Dec. 7, 2022.
3. Alvotech. Alvotech and STADA Add to Strategic Alliance Through Denosumab Partnership. Press Release, June 11, 2024.
4. EMA. 

STADA and Alvotech have launched Uzpruvo in Europe, making it the first approved biosimilar to Stelara (ustekinumab) in the European market.

First Approved Stelara Biosimilar Launched in Europe by STADA and Alvotech

Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - © Artur - stock.adobe.com

The US Pharmacopeia (USP) announced on July 26, 2024 that its Microbiology Expert Committee has approved the inclusion of Chapter <86> Bacterial Endotoxins Test Using Recombinant Reagents into the

 United States Pharmacopeia–National Formulary (USP–NF). 

The chapter permits the use of non-animal-derived reagents for endotoxin testing; the finalized chapter will be published for early adoption in November 2024 before becoming official in May 2025. The new chapter is part of USP’s commitment to expanding the use of animal-free methods and materials.

Endotoxins may cause irreversible side effects and even death in severe cases at sufficient concentrations in the bloodstream (1). Bacterial endotoxins are found in the outer cell membrane of Gram-negative organisms and are known to be one of the most potent toxins. “These toxins are harmless outside of the body and in the alimentary canal. They are extremely potent, however, once introduced in the bloodstream or intrathecally,” Allen L. Burgenson, Testing Solutions, Lonza Pharma & Biotech, said (1).

“Bacterial endotoxins (also referred to as pyrogens) have the capacity to induce a high fever,” said John Dubczak, general manager, Microbial Solutions, Charles River Laboratories (1). “A large enough dose of endotoxin can lead to lung and kidney failure, intravascular coagulation, and a systemic inflammatory response that can lead to septic shock and death.”

Therefore, endotoxin testing is an important part of the quality and safety steps taken in the manufacture of certain sterile pharmaceutical products. Techniques for bacterial endotoxin testing using non-animal derived reagents are provided in the new chapter. Specifically, the new chapter discusses methods using both recombinant cascade (rCR) and recombinant Factor C (rFC) reagents. It also gives information on how to incorporate the methods into quality testing.These new techniques are in addition to those found in Chapter <85> Bacterial Endotoxins.

“Chapter <86>is intended to provide manufacturers with the information needed to use non-animal derived reagents. Manufacturers that currently use limulus amebocyte lysate (LAL) for endotoxin testing can continue to do so and Chapter <86> has no impact on them,” USP said in a press release (2).

One of the main endotoxin tests, LAL assay “works via the reaction of the LAL reagent-an aqueous extract of blood cells from the horseshoe crab-with bacterial endotoxins and lipopolysaccharides” (1). While the LAL test is an animal-derived test, and the animal itself is not tested upon, the desire to reduce animal use in testing has influenced the pharma industry, which resulted in the LAL test replacing the previous standard Rabbit Pyrogen Test. The LAL test is an animal-derived test, meaning the animal itself is not tested upon (1). This change prevented the use of hundreds of thousands of rabbits per year. There has also been a commitment to conserve the horseshoe crab. “Work has included sustainability partnerships to enhance the horseshoe crab population along the mid-Atlantic shores,” said Victoria Watson, laboratory manager, Microbiology at Wickham Labs. “Such projects have focused on increasing the survival rate of the horseshoe crab in early stages of life. Eggs are collected, and the crabs are grown in predation-free, controlled environments then released into their natural environment when older and stronger” (1).

Thomas, F. Putting Endotoxins to the Test. 

https://www.pharmtech.com/view/putting-endotoxins-test

USP. Expert Committee Approves Endotoxin Testing Using Non-animal Derived Reagents. Press Release. July 26, 2024.

The US Pharmacopeia’s Microbiology Expert Committee approved the inclusion of a chapter into the United States Pharmacopeia–National Formulary that allows the use of non-animal-derived reagents for endotoxin testing.

USP Permits Use of Non-Animal-Derived Reagents for Endotoxin Testing

Scorpius Holdings, an integrated contract development and manufacturing organization (CDMO), is prepared to launch its first current good manufacturing practice (CGMP) mammalian manufacturing campaign at its manufacturing facility in San Antonio, Texas, in the 2024 third quarter. The launch follows the company's expansion efforts for its biomanufacturing capabilities, especially in the area of mammalian cell culture for advanced biopharmaceuticals, according to a July 24, 2024 press release.

The company previously started up CGMP operations at its microbial manufacturing facilities, and the start of mammalian CGMP manufacturing campaigns signifies a strategic company milestone in its CDMO operations. The San Antonio site hosts a dedicated mammalian cell culture facility with CGMP-compliant controlled cleanrooms that can be tailored to allow for adaptable manufacturing solutions, according to a company press release.

“I am extremely proud of what our team has accomplished in a short period of time. Our manufacturing and quality teams have worked exceptionally hard to get our mammalian facilities operational in less than two years, well ahead of the typical timing for such complex buildouts. Scorpius is now extremely well-positioned to support a wide range of early stage clinical programs," said Jeff Wolf, CEO of Scorpius, in the press release.

The facility’s design includes cleanrooms with mobile equipment, which enables customizable configurations for the specific needs of individual projects. Scorpius has secured bookings for additional CGMP activities in the mammalian facility for 2025, according to Wolf in the press release.

The San Antonio site underwent significant expansion in May 2024 as Scorpius grew its operational footprint. The expansion included new storage space and a testing facility. Warehouse space was increased more than sevenfold, from approximately 3000 ft2 to approximately 22,000 ft2 with the expansion. The warehouse includes specialized storage areas with temperature control between -20 °C and -80 °C for raw materials as well as spaces designated for contained sampling and quality control testing. The facility will also accommodate bulk drug substance storage to ensure that products are stored under optimal conditions throughout the development and production cycles. (1).

The expanded facility will include a robust stability program meant to bolster Scorpius' service offerings by allowing the company to provide in-house stability storage capabilities. The company intends to foster smooth transitions into onsite testing with the enhanced in-house stability storage.

"These new capabilities enable us to offer our clients continuity through their supply chain and meet their needs from process development through drug substance release. This strategic expansion reflects our commitment to excellence and our dedication to supporting our clients’ overall needs," Wolf said in a May 20, 2024 company press release.

1. Scorpius Holdings. Scorpius Holdings Announces Major Expansion in San Antonio with New State-of-the-Art Storage and Testing Facility. Press Release, May 20, 2024.

Scorpius Holdings is set to launch its first CGMP manufacturing campaign at its San Antonio, Texas, facility for mammalian cell culture in the 2024 third quarter.

Featured Content

Behind the Headlines Episode 27

Ask the Expert

Drug Digest September 2025

Enhancing Bioanalysis and Drug Development with Advanced Tools and Technologies

Top Trends Reshaping Pharma R&D