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

Feliza Mirasol is the science editor for 

FDA's Center for Biologics Evaluation and Research (CBER) has issued a new draft guidance, 

Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products 

(1). The document was issued in April 2024.

According to FDA in an April 30, 2024 notice in the 

 (2), “Allogeneic cells of human origin may be expanded in culture to manufacture medical products consisting of live cells, inactivated cells, cell lysates, or other cell-based materials such as cell-derived particles.” Thus, the draft guidance provides recommendations to help sponsors of allogeneic cell-based medical products determine what cell safety testing is appropriate to support an investigational new drug application (IND) or a biologics license application (BLA).

The agency notes that cell safety testing should be based on a risk analysis that considers the expansion potential of the cells in addition to the reagents that are used to expand these cells in culture as well as the number of individuals capable of treatment with the cell-based medical product.

Allogeneic cell-based products that are regulated by CBER’s Office of Therapeutic Products are subject to this new guidance. It applies to cultured allogeneic cells—including cell banks—that serve as sources of intended constituents for the final drug product. The guidance also applies to combination products that contain an allogeneic cell or cell-based biologic component in combination with a drug and/or device.

“The recommendations in this guidance also apply to genetically modified allogeneic cells that have been transduced with viral and/or plasmid vectors, and cells that have undergone genome editing. This guidance does not apply to cell substrates that are used during manufacturing of non-cell-based products such as viruses, gene therapy vectors, or recombinant proteins,” the draft guidance document states (1). However, the document emphasizes that recommendations for feeder or other cells used as reagents during manufacturing are beyond the scope of this particular guidance.

FDA is accepting comments on the draft guidance either electronically or in writing until the deadline of July 29, 2024, after which time it will begin work on the final version of the guidance (2).

FDA has stated that this new draft guidance is intended to supplement two other final industry guidance documents, 

Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs)

Draft Guidance for Industry, Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products

Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products; Draft Guidance for Industry; Availability

Guidance for Industry, Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

. Guidance for FDA Reviewers and Sponsors, Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs)

Articles

In the new draft guidance, FDA provides recommendations on cell safety testing of human-sourced allogeneic cells for sponsor companies.

New FDA Draft Guidance Issued for Sponsors of Allogeneic Cell-Based Medical Products.

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

Adare Pharma Solutions, a global contract development and manufacturing organization (CDMO) focused on oral dosage forms, has announced plans to expand its high potency handling capabilities in the United States and Europe. This expansion will include a second high potency suite to Adare’s facility in Philadelphia, upgrades to R&D suites in its Ohio facility, and high potency upgrades to its facility in Milan, Italy.

Adare’s 128,000 sq ft Orthodox Street facility in Philadelphia will receive a second high potency suite, which will add encapsulation, blending, high-shear granulation, and other manufacturing processes. These processes will bolster the site’s existing potent suite, which provides bin blending, roller compaction, milling, and tablet compression. Construction is set to complete by Q4 of 2024.

Work has already begun on the company’s 179,000 sq ft Vandalia facility in Ohio and is also scheduled to complete by Q4 of 2024. The Ohio facility is receiving upgrades to several of its R&D-to-clinical stage production suites to provide high potency handling. Capabilities will include microencapsulation, dry roller compaction, and fluid bed processing.

The expansion to Adare’s 220,000 sq ft Pessano facility in Milan, Italy will add high potency upgrades to its formulation and analytical laboratories, which include bin blending, fluid bed processing, compression, encapsulation, and pan-coating capabilities. Additionally, the facility recently announced plans to add packaging capabilities and more warehouse capacity (2). A two-story, 2800 square-meter extension is underway to accommodate a new packaging line in a specially built packaging hall, which is projected to be installed by Q4 2024. The expansion also contains a 1000 square-meter warehouse with capacity for 900 pallets and space for a second future packaging line.

A week after its packaging and warehouse expansions were announced, Adare revealed further expansions to the Milan site, adding a high-shear mixer granulator to its existing fluid bed capabilities (3). The granulator, an IMA 600-L Roto Mix high-shear mixer with IMILL and Hydrowash, provides wet granulation with either aqueous or organic-based solutions. The mixer’s design allows for lower changeover times and lower water and energy consumption as compared to traditional machine clean-down routines. These expansions, as well as the high potency upgrades, are expected to be operational by the end of 2024.

“We have seen demand for high potency handling and packaging continue to increase, with around half of solid dose drugs in development being highly potent,” said Tom Sellig, CEO of Adare Pharma Solutions, in a company press release (1). “This proactive investment across our global network of sites will ensure we continue to provide customers with the oral dose capabilities and capacity they will need both now and in the future.”

Adare Pharma Solutions, Adare Expands Global High Potency Handling and Packaging Capabilities. Press Release, May 1, 2024.

Adare Pharma Solutions, Adare Pharma Solutions to Expand Packaging and Warehousing Capabilities in Europe. 

Adare Pharma Solutions, Adare Pharma Solutions Expanding Oral Dose Capabilities in Europe. 

The CDMO plans to expand and upgrade its Philadelphia, Ohio, and Milan facilities to meet the continued growth in demand for high potency handling capabilities.

Adare Expands High Potency Handling Capabilities in US and Europe

ROSS Model VCB-20 | Image Credit: ©Charles Ross & Son Company

ROSS V Cone Blenders utilize diffusion as the main mechanism for mixing. As the V-shaped vessel rotates on its horizontal axis, batch materials cascade down, distributing particles over a freshly exposed surface. Operating at speeds of 5 to 25 revolutions per minute, the ROSS line of tumble blenders can mix dry solid blends (including high density powders), low-viscosity slurries, friable materials, and formulations containing trace components and ingredients that are dissimilar in size, shape, and density.

The pictured ROSS Model VCB-20 includes two pneumatic cylinders affixed to the V cone body to disconnect and connect fiber drums for charging and discharging. The blender’s butterfly valve is operated by optional pneumatic control. A high-speed intensifier bar is installed along the mixer’s axis of rotation to reduce agglomerates, and nozzles can be attached to it for continuous liquid additions during mixing. The model also includes carbon steel legs with 40” clearance beneath the discharge valve to the floor, and safety guardrails at the front and rear of the mixer.

Charles Ross & Son's ROSS V Cone Blenders utilize diffusion as the main mechanism for mixing.

V-Shaped Cone Tumble Blender

Pharmafill TC4 tabletop tablet counter | Image Credit: ©Deitz

Deitz’s Pharmafill TC4 tabletop tablet counter includes an automatic feeder control system to ensure a consistent volume of tablets is fed onto a rotating disc for feeding to the counting sensor. The automatic feeding system features a proximity sensor assembly that automatically stops the flow of tablets from the hopper if the flow rate exceeds the pace of the operator filling the bottles. When ready for additional tablets, the system automatically restarts the vibratory feeder and restores product flow at the preset rate.

The TC4 is suitable for counting and filling capsules, gelcaps, pills, softgels, and other opaque, translucent, and transparent oral solid dosage forms. The compact electronic tablet counter achieves filling rates of up to 2000 tablets per minute, filling bottles up to 10 inches in height. The semi-automated pill counting machine comes with a two-year warranty and arrives ready to plug in to common 110 VAC electrical services.

Deitz’s Pharmafill TC4 tabletop tablet counter is suitable for counting and filling capsules, gelcaps, pills, softgels, and other opaque, translucent, and transparent oral solid dosage forms.

Electronic Tablet Counter with Automated Feed Control

Rees Scientific 

to discuss Rees Scientific's evolution in the market. Learn more about: 

How real-time monitoring of critical environment conditions allows Rees to ensure customers that their products are stored and handled under optimal conditions.

The ease of integration for their monitoring systems into any existing infrastructure.

The importance of temperature mapping and how that helps to protect the efficacy of a product.

Videos

Josh Hirshenhorn (Sales Representative, Rees Scientific) explains current challenges faced by pharmaceutical and biotech companies and how Rees' continuous monitoring systems offer solutions. 

The Impact of Rees Scientific’s Continuous Monitoring Systems in Pharmaceutical and Biotech Companies 

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

As CPHI North America, held at the Pennsylvania Convention Centre (May 7-9, 2024) approaches, experts predict that US-based contract development and manufacturing organizations (CDMOs), especially small to mid-sized, should invest throughout 2024 if they wish to maximize on the rise in contract services funding predicted for 2025. Other key trends for 2024 include exploring pilot-scale manufacturing of new technologies, improving supply chain resilience, and ‘friend shoring’.

CPHI expert, Brian Scanlan, operating partner–Life Science Edgewater Capital Partners, sees 2024 as a “holding pattern year”, where funding gradually returns to biotech, as reported in a CPHI press release. He stated that he is already seeing this begin to filter through toward the outsourcing community. But if US-based smaller and medium-sized contract research organizations (CROs) and CDMOs want to benefit from a likely 2025 resurgence, they cannot just wait for the market to return. “They need to be focusing now on operational efficiencies and commercial effectiveness,” Scanlan stated. “This means investing in manufacturing process improvements, like continuous and titer reductions, as well as other areas of the business that could bring overall efficiencies, from enhancing quality management to areas like AI [artificial intelligence] to enhance/accelerate process development and quality trend analysis” (1).

Scalan emphasized that these companies should take every opportunity to invest. “Any area that drives more efficiency in CDMO operations, even streamlining and enhancing effectiveness in new business development using AI enabled tools [is worth pursuing]. So, this will be a year of seeking productivity excellence and cost containment to prepare for a potentially bigger resurgence in outsourcing in 2025,” Scalan said. CPHI North America plans to cover at least one of these potential applications—making use of generative AI to analyze upcoming requirements for pharmaceutical drug manufacturers and distributors as the Drug Supply Chain Security Act comes into effect in November 2024.

“What you are seeing in the USA—and in some ways it’s not a new trend—is a much more considered approach to sourcing,” added Bikash Chatterjee, president and chief science officer at Pharmatech Associates, in the press release (1). “Companies are looking to ensure they have alternative supply and potentially also in different geographic locations from their primary options ... What’s driving this? Well, we have seen a whitepaper come out from HHS [Health and Human Services] earlier this month on preventing drug shortages, and in the next few years we could see companies even scored on their supply chain resilience. So, we might be entering a period when companies are willing to pay more for extra resilience in their networks.”

Chatterjee added that in the next six months many companies will be looking to prepare for 2025, focusing on highly detailed planning for supply chain resilience, as well as a greater short-term focus on ‘near’ or ‘friend shoring’ options (instead of domestic US sites). These countries are currently better prepared, he said, to pick up resources and build ingredients and starting materials networks. More and more North American manufacturers are diversifying their sourcing of ingredients, looking not just to India as an alternative to Chinese suppliers, but also exploring options worldwide, including within Europe and South America.

At CPHI North America, where an anticipated 4000 attendees and 300 companies are planning to attend, these shifting trends will be present. This year’s event is focused on “empowering the North American ecosystem with the new insight and next-generation manufacturing approaches” (1) that it will need to “retool” before the 2025 outsourcing surge. The event will see 58 sessions, with notable keynotes on “Sustainability: Accelerating the Path to Net Zero” and “the Importance of Excipient Grade in Pharmaceutical Drug Development.”

Sarah Griffin, event manager, Pharma Brand US at Informa Markets, emphasized that it is critical for companies to use this event to plan their activity in 2025. "CPHI North America is at the heart of pharma in the US,” she added (1). “It's not just about staying informed and connecting with existing contacts; it's about actively engaging in the collaborative ecosystem that sustains success in the pharmaceutical industry.Participating companies can access invaluable resources, forge vital strategic partnerships, and, most importantly, establish the networks and technologies needed to maximize revenue potential in 2025 and beyond.”

Informa Markets. CPHI North America Experts ‘Mid-Sized Domestic CDMOs Need to Invest in Operational Efficiencies to Drive “Real” Reshoring’. Press Release. informamarkets.com, Apr. 30, 2024.

Key areas to invest include manufacturing process improvements, quality management, and AI.

CPHI Experts Report that Small to Mid-sized US CDMOs Must Invest Now to Benefit from 2025 Contract Funding Surge

Lonza's Future

to highlight how Lonza is looking ahead. Learn more about: 

How Lonza is optimizing their network to meet the evolving needs of customers while minimizing environmental impact.

The strive to push the boundaries and develop new solutions that address the evolving needs of the industry.

The commitment to providing customers with consistent supply, exceptional quality, and unparalleled service, no matter the challenge.

Meeta B. Kratz (Global Vice President, Product Management & Marketing, Lonza Capsule and Health Ingredients) talks about Lonza's future and how that works in tandem to meet client needs.

Lonza's Commitment to the Future

Podcast will explore the technical aspects and advantages of messenger RNA (mRNA) as the basis for therapeutics in cancer treatment as well as vaccines. Based off the success of the mRNA-based COVID-19 vaccines, the biopharma industry is responding with enthusiasm and intense focus on the development of mRNA-based therapeutics for diseases. An area of particular challenge is the delivery of the mRNA therapeutic in vivo. Formulation solutions, such as encapsulating the mRNA within a lipid nanoparticle (LNP) structure, has proven effective. Here, Stefaan De Koker, vice-president of Technology and Innovation, etherna, goes into more detail about the benefits and challenges of developing mRNA-based therapeutics for oncology and vaccines, and discusses the practical application of LNPs toward that goal.

Stefaan De Koker, Vice-President Technology and Innovation, etherna

Stefaan De Koker holds a master in Bioengineering and obtained his PhD at the lab for Molecular Immunology at Ghent University. Throughout his career, he has had a keen interest in understanding how activation of the innate immune system shapes the adaptive immune system and in translating this knowledge into improved vaccines and immunotherapies. De Koker became involved early in the messenger RNA (mRNA) therapeutics field and published seminal papers on the mode-of-action of mRNA vaccines, on the usage of mRNA for intratumoral immunomodulation, and on the development of novel delivery vehicles for mRNA therapeutics. In September 2016, De Kokerjoined ethernawhere he leads the Technology and Innovation team. His focus is currently on the design of customized mRNA lipid-based nanoparticles (cLNPs) for extrahepatic delivery, immunomodulation, and gene editing. De Koker has authored more than 60 publications and is co-inventor on more than 15 patent applications.

 presents the Drug Solutions podcast, where the editors will chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products.

Podcasts

In this episode fo the Drug Solutions Podcast, etherna’s vice-president of Technology and Innovation, Stefaan De Koker, discusses the merits and challenges of using mRNA as the foundation for therapeutics in oncology as well as for vaccines.

Drug Solutions Podcast: A Closer Look at mRNA in Oncology and Vaccines

The United Kingdom has launched The Circularity in Primary Pharmaceutical Packaging Accelerator (CiPPPA) initiative to develop and implement strategies for end-of-use recycling of medicinal devices and pharmaceutical packaging. CiPPPA is a collaborative non-profit initiative connecting stakeholders from across the pharmaceutical supply chain. It is managed by a steering committee composed by representatives from within the pharmaceutical and healthcare sector who are committed to creating a future where used packaging from meter dose inhalers (MDIs), blisters, and injectables can be easily recycled.

Currently, the health industry faces a great deal of challenges in regard to recycling primary pharmaceutical packaging (PPP), according to a press release from CiPPPA. Present regulations are strict to uphold the safety, efficacy, and regulatory compliance of each active medicinal product, but they have been unable to consider long-term environmental effects. PPP recycling is also not part of mainstream consumer recycling due to the problematic materials involved, resulting in broader environmental, financial, and regulatory obstacles.

To address these obstacles, CiPPPA has established three action task forces, focused on creating packaging solutions for blisters, inhalers, and injectables. Each task force is led by subject experts who make use of organizational schemes and industry collaboration to drive the initiative forward. The task forces are critical, CiPPPA states, in bolstering collaborative efforts and utilizing member organizations’ expertise and resources to tackle the difficult environmental challenges around pharmaceutical packaging. Leading pharmaceutical companies, global over-the-counter (OTC) brands, and healthcare systems such as the National Health Service are closely involved with the initiative, signaling an “united industry commitment to influencing societal and cross-industry change for the benefit of the environment and the community” (1).

“Having previously sold thousands of tons of blister pack materials into the UK, and knowing that none of it was getting recycled, I became frustrated at the lack of sustainable solutions for the packs' end-of-life,” said Duncan Flack, Global Sustainability Lead at Honeywell and Chairman of CiPPPA, in the press release (1). “By founding and establishing CiPPPA, we are able to deliver enhanced end-of-life for blister packs and related pharmaceutical packaging such as metered-dose inhalers and injectables. The willingness of leading pharmaceutical companies and global OTC brands to support the initiative has been tremendous, and as CiPPPA continues to grow, so too does our ability to influence societal and cross-industry change.”

“We’re proud to be a founding member of CiPPPA and join forces with partners across the sector to address the sustainable packaging of medicines and vaccines,” said Claire Lund, vice president of Sustainability, GSK (1). “We have ambitious company targets across climate and nature and through collaborative initiatives such as CiPPPA, we believe we can make a positive impact through the increased recycling of packaging, helping to protect the health of both people and the planet.”

CiPPPA. Circularity in Primary Pharmaceutical Packaging Accelerator (CiPPPA) Launched to Take Collaborative Action on Pharmaceutical Packaging. Press Release. Apr. 24, 2024.

The non-profit initiative puts collaboration at the forefront as it tackles the challenges surrounding recycling primary pharmaceutical packaging.

UK Launches Circularity in Primary Pharmaceutical Packaging Accelerator Initiative to Implement Pharmaceutical Packaging Strategies

The European Medicines Association (EMA) and the European Commission’s (EC) Directorate-General for Health and Food Safety (DG SANTE) have signed a working agreement with the Ministry of Food and Drug Safety (MFDS) of the Republic of Korea in order to share confidential information on medical and medicinal products. This partnership will build on the close cooperation fostered between the two regulatory authorities during the COVID-19 pandemic and is intended as a step toward mutual recognition and regulatory harmonization as they work to improve human and animal health. The agreement also builds on the previously established ad-hoc arrangement, which ensured the exchange of medicinal information used for diagnosing, preventing, and treating COVID-19 and related infectious diseases.

The arrangement, which came into effect on Apr. 25, 2024, will allow participants to exchange sensitive information on medicinal products as part of their regulatory and scientific processes. This will include confidential information about the safety, quality, and efficacy of human medicines which have been authorized or are under evaluation, as well as information on inspections, regulatory guidance, and legislation. These types of confidentiality agreements can allow for faster exchanges of information on quickly emerging global issues, such as medicine shortages, quality concerns, and safety questions.These type of confidentiality arrangements, EMA said in a press release, “are the cornerstone of global cooperation” (1). This arrangement between the EU and Korea is valid for an indefinite period and will not need a renewal.

In its International Agreements page, EMA states that it has formalized its working relations with a number of third-country regulators through bilateral confidentiality agreements, which allows the parties to exchange confidential information and provide a framework for regulatory cooperation. “The emphasis,” the agency states, “is on exchange of information concerning regulatory guidance, legislation and non-public information on products, as well as safety information including adverse reactions, good manufacturing practice (GMP) and good clinical practice (GCP) inspection findings” (2).

EMA has listed the countries it has standing confidentiality agreements with, which are: Australia, Brazil, Canada, Japan, Switzerland, the United States, and now the Republic of Korea. It also has this agreement with the European Directorate for the Quality of Medicines and HealthCare (EDQM) of the Council of Europe, and the World Health Organization (WHO). The agency states that it can also establish ad-hoc confidentially arrangements with international regulators to address specific public-health needs; such agreements have a limited scope and duration.

The agency also has signed several mutual recognition agreements on the conformity assessment of regulated products, which covers the mutual recognition of GMP compliance for human and veterinary medicines. These agreements aim to “facilitate market access while protecting consumer safety and encourage greater international harmonization of compliance standards” (2). EMA has signed mutual recognition agreements with Australia, Canada, Japan, New Zealand, Switzerland, and the United States. It has also signed this agreement with Israel, though the agency notes the agreement is on conformity assessment and acceptance of industrial products.

Confidentiality Arrangement between the EU and the Republic of Korea

ema.europa.eu/en/partners-networks/international-activities/international-agreements

The agreement, which will allow participants to share confidential information on medical and medicinal products, builds on the cooperation fostered between the two regulatory authorities during the COVID-19 pandemic.

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