Susan Haigney

Glass vials for liquid samples. | Image Credit: ©nordroden - stock.adobe.com

Personalized therapies have become a focus of the pharmaceutical industry with the advancement of cell and gene therapies, creating a need for specialized manufacturing processes and infrastructures. This new market of personalized treatments is also increasing the need for small batch sizes.

“Point-of-care production or hub-and-spoke models could become the norm,” David Phasey, Innovation Director at 3P innovation, said in an interview with 

® (1). “The automation of patient and manufacturing data will be key to this. The real question is whether the pharmaceutical industry is ready to adopt and accept this level of automation into a very slow-to-change industry. Can regulations keep up with technology and the opportunities it presents?”

Complexity often comes along with innovation. And the aspects of small-batch manufacturing for personalized medicine are no different. Processing speed, flexibility, and product yield are among these complex challenges.

“Every drop counts for high-value drugs, since even the slightest product loss has significant consequences related to the number of patients treated, as well as economic impacts, and must be avoided,” says Laura Moody, director of Product Management Pharma North America, Syntegon.

The challenges of small-batch manufacturing

Small-batch manufacturing comes with a distinct set of challenges, according to
Dr. Jitendra Amrutkar, Head–Process Technology & Support, ACG Engineering. Small batch means fewer doses and, therefore, a high cost per unit, Amrutkar adds, and these costs can be reduced by using modular systems and single-use technologies. The frequent changeover of products can also hit costs by creating downtime.

“There is clearly a trend toward smaller batch sizes of sterile product,” says Hanns-Christian Mahler, CEO, ten23 health. “This, of course, raises key questions on ‘yield’, as maximizing yield translates directly into the cost-of-goods for a given product. This is particularly important for such costly APIs as biologics.”

The manufacturing facility and processes must be adequately designed for small batches, stresses Mahler. “Specifically, ready-to-use (RTU) containers are convenient to avoid the need for large washing machines or sterilizing tunnels. However, formulation development and stability data are required to allow selection of an RTU container a priori,” he states.

There are also unique complexity considerations with personalized treatments, such as specialized materials and unique regulatory approvals, according to Dr. Amrutkar. “AI [artificial intelligence] and blockchain can help to overcome this issue by improving visibility and coordination,” he offers as a solution to supply chain concerns. For regulatory compliance issues, he recommends using digital records and adaptive pathways.

Automation has been an increasing tool for pharmaceutical manufacturing, but Dr. Amrutkar cautions that traditional automation systems are not suited for small batches. He recommends smart, modular automation and cobots, which offer flexibility.

A variety of process development approaches can help with the challenges of small-batch manufacturing, according to Dr. Amrutkar. He points to modular process design for flexible, scalable setups of products to support faster changeover and reduced downtime. A modular design may also make expansion easier. Virtual testing of processes before they are implemented can be facilitated by digital twins and simulation, Dr. Amrutkar says, which can reduce risk and improve efficiency. Continuous manufacturing can also streamline production by causing fewer interruptions and increasing turnaround times. Lastly, optimal process conditions can be identified by utilizing design of experiments.

“On the process side, suitable processing materials, such as tubing and filters, help to maximize extraction of the product,” Mahler explains. “Pharmaceutical manufacturers must consider ‘flush volumes’ that are required for the setup (e.g., to saturate sterile filters); how much volume other in-process controls (IPCs) require; and how the sampling volume may be reduced. Understanding the scale and batch size capabilities of a facility, including the lowest compounding volume that can be used, are key considerations.”

The evolution of human-centered to fully automated production in aseptic filling is increasing, according to Moody, with the use of “robotics for container transfer, fill/finish operations, and format part exchange within the isolator. A shift to gloveless systems further reduces the need for manual intervention,” she says.

“To avoid product loss, 100% IPC during the filling process ensures that almost every drop of product is filled,” Moody continues. “Moreover, new small- or even micro-batch solutions can support scale-up from manual clinical trial operations to automated production scale.”

Isolators and restricted access barrier systems can provide high contamination control and cost-efficiency for small-batch manufacturing by ensuring sterility in aseptic environments, says Dr. Amrutkar. To minimize product loss and ensure dosing accuracy, he points to micro fillers that can provide precision filling for low-volume, high-value biologics. Digital management of manufacturing and batch records can be achieved through manufacturing execution systems and electronic batch records. “They improve traceability, compliance, and data integrity, which is especially important for personalized medicine,” Dr. Amrutkar says. In addition, “ACG’s capsule filling and inspection systems are high-precision systems tailored for clinical and personalized applications. They are tailored for low-volume needs with integrated inspection to ensure quality assurance,” Amrutkar offers.

Flexible filling platforms are available for small- and micro-batch operations. Syntegon offers platforms that can process between 120 and 500 containers per hour and batches up to 3600 containers per hour. The company’s Versynta microBatch platform is a fully automated gloveless production cell with integrated air handling that was developed in partnership with Vetter, according to Moody.

ten23 uses ready-to-use (RTU) containers to operate at different sterile filling scales. In July 2025, the company announced it had joined the “Alliance for RTU” partnership, which intends to advance knowledge around sterile manufacture of RTU containers. The company’s role will be to contribute its own experience in development, sterile fill/finish, and testing of sterile drug products using RTU containers (2).

When it comes to fill/finish of small batches, scale related to unit operations needs to be appropriate, says Mahler, who says manufacturers should consider the following questions. “How do you mix and homogenize 1 liter of material for a commercial product? Is that in place? Which disposables do you use, and how can you minimize residual volumes on the line? Where and why do you pull samples for in-process testing or extended characterization, and how can these volumes be reduced?”

He adds, “One great example is the choice of adequate sterile filters: some filter materials tend to adsorb critical components of a biologics formulation and may require 1 or more liters of flush volume. Other filters will be saturated with 10 mL. That can be a huge cost driver, or saver.”

Targeted solutions can address challenges associated with the fill/finish of small batches, says Dr. Amrutkar. For sterility assurance, isolators and automated aseptic systems are key for managing contamination risk, he says.

Safeguarding the aseptic environment is key in fill/finish of small batches of biopharmaceutical products, Moody agrees. “Humans pose the greatest risk for product contamination, so operator intervention must be reduced to an absolute minimum or even completely avoided to reduce this risk,” she says. Annex 1 of the European Union’s good manufacturing practice guidelines (3) recommends the use of these barrier technologies.

Precision filling technologies and single-use systems can combat product loss. Adopting a risk-based digital validation approach can streamline repeated validation.

Fill/finish systems that are traditionally used in pharmaceutical manufacturing are often too large for filling small batches of product. Scaling down to miniaturized, single-use equipment can combat this, according to Amrutkar.

Small batches of products may require different container formats that complicate the setup of machines. “Implementing modular lines and quick-change tools can help simplify the process, increase flexibility and adaptability, and help eliminate bottlenecks,” Amrutkar says.

Small-batch manufacturing should be performed holistically with development, manufacturing, and testing approaches integrated, says Mahler, and the combination of formulation and primary packing should be done ‘wisely.’

“Think about potential failure modes and assess your process in development labs, assessing the choice of materials, failure modes and acceptable ranges for your operating parameters, to ensure there is no (relevant) impact on your product’s critical quality attributes,” Mahler concludes.

Haigney, S. New Modalities in Biopharmaceutical Development Transform Industry. 

Lavery, P. ten23 health Joins Gerresheimer, SCHOTT, Stevanato Group in ‘Alliance for RTU’. 

EC. Annex 1: Manufacture of Sterile Medicinal Products. 

®
Vol. 49, No. 6
July/August 2025
Pages: 16–17

When referring to this article, please cite it as Haigney, S. Flexibility Provides Solutions to Small-Batch Manufacturing Challenges. 

Articles

Advancements in cell and gene therapies have driven the pharmaceutical industry towards personalized treatments, necessitating specialized manufacturing processes and infrastructures. Small-batch manufacturing presents challenges such as high costs, processing speed, and product yield. Modular systems, single-use technologies, and automation are proposed solutions to these challenges. The use of AI, blockchain, and digital records can enhance regulatory compliance and supply chain coordination. Flexible filling platforms, precision filling technologies, and modular lines are essential for efficient small-batch production, ensuring sterility and minimizing product loss.

Modular process design, single-use technologies, and flexible filling lines are some of the ways manufacturers can combat challenges involved in small-batch manufacturing.

Flexibility Provides Solutions to Small-Batch Manufacturing Challenges

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

GSK announced on July 28, 2025, that it has entered into agreements with Hengrui Pharma to develop treatments for respiratory, immunology, and inflammation conditions, and new therapies for GSK’s oncology pipeline. The agreement includes a license for a potential best-in-class PDE3/4 inhibitor for the treatment of chronic obstructive pulmonary disease (COPD) and 11 programs that Hengrui Pharma will develop, and GSK will option, following Phase I completion.

New COPD maintenance treatment part of the agreement

The exclusive worldwide license (excluding mainland China, Hong Kong, Macau, and Taiwan) for Hengrui’s COPD treatment, HRS-9821, gives GSK the potential to add a convenient dry-powder formulation to the company’s inhaled medicine portfolio. HRS-9821, according to GSK, is in development as an add-on maintenance treatment for COPD and has demonstrated potent PDE3 and PDE4 inhibition in early clinical and preclinical studies. The license to HRS-9821 is dependent on applicable regulatory agency clearances under the Hart-Scott-Rodino Act in the United States.

“The addition of HRS-9821 supports GSK’s ambition to treat patients across the widest spectrum of COPD by including those who face continued dyspnea (shortness of breath) or who are unlikely to receive inhaled corticosteroids or biologics, based on their disease profile,” the company stated in a press release (1).

Other potential treatments in development

The other 11 programs included in the collaboration will have their development led by Hengrui Pharma to completion of Phase I trials, including patients outside of China. GSK will then have the option to further develop and commercialize the programs worldwide (excluding mainland China, Hong Kong, Macau, and Taiwan) and certain program substitution rights.

"We're delighted to announce these exciting agreements with Hengrui Pharma which complement our already-extensive pipeline,” Tony Wood, chief scientific officer, GSK said in the press release. “This deal reflects our strategic investment in programs that address validated targets, increasing the likelihood of success, and with the option to advance those assets with the greatest potential for patient impact.”

"This strategic collaboration with GSK marks yet another significant milestone in Hengrui’s globalization journey and our mission to innovate and deliver higher-quality, cutting-edge therapies for patients worldwide,” Frank Jiang, executive vice president and chief strategy officer of Hengrui Pharma, said in the release. “GSK brings additional R&D expertise, a robust global clinical network, and broad regulatory capabilities that will accelerate our PDE3/4 inhibitor as well as an array of other innovative therapy programs to overseas markets, potentially delivering breakthrough treatments to patients globally."

Upfront fees totaling $500 million across the agreements will be paid by GSK to Hengrui Pharma as part of the deal. If all programs are optioned by GSK and all milestones are achieved, Hengrui Pharma could potentially receive up to approximately $12 billion as part of the collaboration.

In other recent GSK news, on July 17, 2025, FDA approved the company’s prefilled syringe version of Shingrix recombinant zoster vaccine used to prevent shingles (2). The previous formulation required clinicians to combine a lyophilized antigen with a liquid adjuvant. The version features easier preparation and reduces risk of handling errors.

“The prefilled syringe presentation of GSK’s shingles vaccine is good news, providing a convenient method of administration,” Brigid Groves, vice president of professional affairs at the American Pharmacists Association, said at the time in a press release (2). “FDA approval is a positive step toward driving prevention of this painful disease, and as a practicing pharmacist I welcome the availability of this new presentation.”

GSK. GSK and Hengrui Pharma Enter Agreements to Develop Up to 12 Innovative Medicines Across Respiratory, Immunology & Inflammation, and Oncology. Press Release. July 28, 2025. 

https://www.gsk.com/en-gb/media/press-releases/gsk-and-hengrui-pharma-enter-agreements/

US FDA Approves GSK’s Shingrix in a Prefilled Syringe Presentation. Press Release

GSK has partnered with Hengrui Pharma to develop treatments for respiratory, immunology, inflammation, and oncology conditions. The collaboration includes a license for a potential best-in-class PDE3/4 inhibitor for COPD and 11 programs that Hengrui will develop through Phase I, with GSK having the option to further develop them. The agreement involves upfront fees of $500 million, with potential earnings for Hengrui up to $12 billion. Additionally, GSK's Shingrix vaccine received FDA approval for a prefilled syringe version, simplifying administration and reducing handling errors.

The two companies have entered into an agreement to develop respiratory, immunology, inflammation, and cancer therapies.

GSK and Hengrui Pharma Collaborate on Drug Development

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The European Medicines Agency (EMA) announced on July 25, 2025 that its Committee for Medicinal Products for Human Use (CHMP) has approved a change in the existing gas propellant used in budesonide/glycopyrronium/formoterol fumarate (BGF, Trixeo Aerosphere and Riltrava Aerosphere) (1,2). The propellant may be replaced with a low global warming potential (GWP) gas alternative that has a 1000-fold reduction in GWP, 99.9% lower than currently used. BGF will be the first inhaled drug in the European Union to use the new low GWP propellant, according to EMA.

The new formulation is the first pMDI to use the low global warming potential (GWP) gas alternative.

New propellant has a 1000-fold reduction in GWP.

High GWP propellants, such as hydrofluorocarbon gases, are being phased out to comply with the EU regulation regarding 

fluorinated greenhouse gases (EU Regulation 2024/573)

BGF is used as a fixed-dose triple-combination maintenance therapy for adults with moderate-to-severe chronic obstructive pulmonary disease (COPD). The usual dose is two inhalations twice daily using a pressurized metered-dose inhaler (pMDI). The propellant used in pMDIs is a liquified compressed gas that generates an aerosol cloud to deliver the API to the patient through inhalation. These propellants that are typically high GWP, such as hydrofluorocarbon gases, are being phased out to comply with the EU regulation regarding 

New formulation is therapeutically equivalent to existing formulation

AstraZeneca AB, the drug’s marketing authorization holder, focused on a lower GWP propellant for the reformulation, which uses the same API and dose characterized in guideline requirements (4). CHMP’s positive opinion was based on results from the next-generation propellant clinical development program, according to AstraZeneca (2). The new formulation of BGF was found to be therapeutically equivalent to the current product, according to EMA (1). The company plans to transition more of its pMDI portfolio to the new propellant by 2030.

“Respiratory medicines delivered by pressurized metered-dose inhalers are essential for millions of people living with respiratory diseases in Europe, including specific vulnerable populations such as children and the elderly,” Frederik Trinkmann, professor and senior pulmonologist at the Thoracic Clinic at Heidelberg University Hospital, Germany, said in the press release (2). “The transition of Trixeo to the propellant with near-zero Global Warming Potential ensures clinicians’ treatment decisions can focus on clinical needs while also supporting environmental goals.” 

“The CHMP positive opinion of Trixeo Aerosphere with the next-generation propellant allows us to address the needs of both patients and the planet and is a significant milestone in our commitment to delivering innovations for sustainable healthcare in the EU,” Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit, AstraZeneca, said in the release. “Starting with Trixeo, the transition to the near-zero Global Warming Potential propellant across our pressurized metered-dose inhaled respiratory medicines is an important step towards achieving our Ambition Zero Carbon strategy.”

Susanna Palkonen, director of the European Federation of Allergy and Airways Diseases Patients' Associations, added, “COPD is a devastating disease and the third-leading cause of mortality in the world. People living with COPD need access to a treatment which is right for them as well as a healthy environment and clean air. We welcome the positive opinion from the CHMP for the inhaled respiratory medicine containing the next-generation propellant with a significantly reduced carbon footprint.”

EMA. First Reformulation of an Inhaled Medicine with Environmentally Friendly Gas Propellant. Press Release. July 25, 2025. 

https://www.ema.europa.eu/en/news/first-reformulation-inhaled-medicine-environmentally-friendly-gas-propellant

AstraZeneca. Trixeo Aerosphere Receives Positive EU CHMP Opinion as First Inhaled Medicine Using Next-Generation Propellant with Near-Zero Global Warming Potential. Press Release. July 25, 2025. 

https://www.astrazeneca.com/media-centre/press-releases/2025/trixeo-aerosphere-receives-positive-eu-chmp-opinion-first-inhaled-medicine-using-next-generation-propellant-with-near-zero-global-warming-potential.html

EU. EUR-Lex. Regulation (EU) 2024/573 of the European Parliament and of the Council of 7 February 2024 on Fluorinated Greenhouse Gases, Amending Directive (EU) 2019/1937 and Repealing Regulation (EU) No 517/2014. Eur-lex.europa.eu. Feb. 20, 2024 (accessed July 25, 2025). 

https://eur-lex.europa.eu/eli/reg/2024/573/oj/eng

EMA. Guideline on the Requirements for Demonstrating Therapeutic Equivalence Between Orally Inhaled Products (OIP) for Asthma and Chronic Obstructive Pulmonary Disease (COPD) (EMA, July 14, 2025). 

https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-requirements-demonstrating-therapeutic-equivalence-between-orally-inhaled-products-oip-asthma-chronic-obstructive-pulmonary-disease-copd-revision-2_en.pdf

The European Medicines Agency has approved a new low global warming potential (GWP) propellant for the inhaled drug budesonide/glycopyrronium/formoterol fumarate (BGF), marking a significant environmental advancement. This reformulation, which maintains therapeutic equivalence to the existing product, aligns with EU regulations on fluorinated greenhouse gases. AstraZeneca plans to transition more of its pressurized metered-dose inhaler (pMDI) portfolio to this eco-friendly propellant by 2030. This initiative supports sustainable healthcare while addressing the needs of patients with chronic obstructive pulmonary disease (COPD).

The agency has given a positive recommendation for a change in the gas propellant in Trixeo Aerosphere and Riltrava Aerosphere that will have a 1000-fold reduction in global warming potential compared to the current propellant.

EMA Approves Lower GWP Alternative for Inhalation Medicine

TOP NEWS on grunge world map | Image Credit: © Sean K - © Sean K - stock.adobe.com

AstraZeneca announced on July 21, 2025, that it will invest $50 billion in manufacturing and R&D facilities in the United States by 2030. The company expects the investment to support its goal of reaching $80 billion in revenue by 2030, half of which will be generated in the US.

Investment includes a multi-billion-dollar drug substance manufacturing facility in Virginia focused on chronic diseases.

The company will expand R&D capabilities in Maryland and Massachusetts.

The investments are part of AstraZeneca’s plan to reach $80 billion in total revenue by 2030, 50% of which is planned to be generated in the US.

Among the facilities will be a multi-billion-dollar manufacturing facility in Virginia to specialize in treatments for chronic diseases. The facility, set to be the company’s largest single manufacturing investment, will produce AstraZeneca’s weight management and metabolic portfolio (e.g., oral GLP-1, baxdrostat, oral PCSK9), small molecules, peptides, and oligonucleotides.

During the next five years, the company also plans on expanding its R&D facility in Gaithersburg, Maryland; building a R&D center in Cambridge, Massachusetts; and expanding R&D for novel medicines. New manufacturing facilities will include cell therapy facilities in Rockville, Maryland and Tarzana, California. The company will expand continuous manufacturing capabilities at its Mount Vernon, Indiana facility and specialty manufacturing at its Coppell, Texas facility. New sites for the supply of clinical trial materials are also planned.

“Today’s announcement underpins our belief in America’s innovation in biopharmaceuticals and our commitment to the millions of patients who need our medicines in America and globally,” Pascal Soriot, chief executive officer, AstraZeneca, said in a press release (1). “It will also support our ambition to reach $80 billion in revenue by 2030. I look forward to partnering with Governor Youngkin and his team to work on our largest single manufacturing investment ever. It reflects the Commonwealth of Virginia’s desire to create highly skilled jobs in science and technology and will strengthen the country’s domestic supply chain for medicines.”

“For decades Americans have been reliant on foreign supply of key pharmaceutical products,” Howard Lutnick, US Secretary of Commerce, said in the press release (1). “President Trump and our nation’s new tariff policies are focused on ending this structural weakness. We are proud that AstraZeneca has made the decision to bring substantial pharmaceutical production to our shores. This historic investment is bringing tens of thousands of jobs to the US and will ensure medicine sold in our country is produced right here.”

Governor Glenn Youngkin, Commonwealth of Virginia, added (1), “I want to thank AstraZeneca for choosing Virginia as the cornerstone for this transformational investment in the United States. This project will set the standard for the latest technological advancements in pharmaceutical manufacturing, creating hundreds of highly skilled jobs and helping further strengthen the nation's domestic supply chain. Advanced manufacturing is at the heart of Virginia's dynamic economy, so I am thrilled that AstraZeneca, one of the world's leading pharmaceutical companies, plans to make their largest global manufacturing investment here in the Commonwealth.”

Building on previous US manufacturing investment

This new investment is in addition to the $3.5 billion US expansion the company announced in November 2024 (2) for an R&D center in Cambridge, Massachusetts; a biologics manufacturing facility in Maryland; and specialty manufacturing capabilities in Texas.

“Our multi-billion-dollar investment reflects the attractiveness of the business environment together with the quality of talent and innovation capabilities here in the United States,” Soriot said in a press release at the time of the announcement (2). “By expanding our R&D and manufacturing footprint, we aim to enhance the development of cutting-edge therapies and support the United States leadership in healthcare innovation.”

AstraZeneca Plans to Invest $50 Billion in America for Medicines Manufacturing and R&D

2. AstraZeneca. AstraZeneca Invests $3.5 Billion in R&D and Manufacturing in the United States. Press Release. Nov. 12, 2024.

The company will build a multi-billion-dollar drug manufacturing center in Virginia that will focus on chronic diseases, as well as facilities in California, Indiana, Maryland, Massachusetts, and Texas.

AstraZeneca to Invest $50 Billion in US Manufacturing and R&D

FDA announced on July 21, 2025 that George Francis Tidmarsh, MD, PhD has been appointed the new director of the agency’s Center for Drug Evaluation and Research (CDER), which is tasked with ensuring the safety and efficacy of drugs in the United States (1). Tidmarsh has more than 30 years of experience in biotechnology, clinical medicine, and regulatory science.

Tidmarsh attended Stanford University where he earned a degree in medicine and a PhD in cancer biology, as well as completing a residency in pediatrics. He also completed two subspecialty programs at Stanford in pediatric oncology and neonatology and is the founding co-director of Stanford’s Master of Translational Research and Applied Medicine (M-TRAM) program. M-TRAM trains students and researchers on how to translate scientific research into real-world application.

“Dr. Tidmarsh is an accomplished physician-scientist and leader whose experience spans the full arc of drug development—from bench to bedside,” said FDA Commissioner Marty Makary. “His appointment to lead CDER brings exceptional scientific, regulatory, and operational expertise to the agency. I look forward to working with him to strengthen our drug review programs, foster innovation, and advance cross-agency initiatives that improve health outcomes for the American public.”

A founder and CEO of multiple biopharmaceutical companies over the years, including La Jolla Pharmaceutical Company and Horizon Pharma, Tidmarsh has been involved with the clinical development of seven FDA-approved drugs from discovery through approval (2). Unlike previous CDER directors, Tidmarsh lacks previous experience in government, but has served as an expert on FDA panels (3).

It is speculated that Tidmarsh may play a role in reassessing FDA’s approach to prescription drug advertising (4). According to Bloomberg, Tidmarsh has expressed concerns about inconsistencies by FDA regarding the regulation “long-standing restrictions on off-label communication by manufacturers and questioned some vaccine makers’ ads during the pandemic” (4). Tidmarsh, according to Bloomberg, has also expressed concerns about fraud in academic science and funds a program supporting investigation of scientific fraud (4).

Tidmarsh has served on advisory boards across academia, government, and industry and has authored 143 scientific publications and patents.

“It is good to see a scientist and physician with phenomenal experience like Dr. Tidmarsh at the helm of CDER,” Aloka Srinivasan, a member of 

®’s Editorial Advisory Board, and principal and managing partner of Raaha LLC, said of the appointment. “Dr. Tidmarsh understands how the pharmaceutical industry operates and the roadblocks to better treatment of many diseases. As a former FDA employee and a member of the pharmaceutical industry, I hope that he is able to change the culture of the office he is heading, and incorporate better understanding of their role, which, other than just approving drugs is to see the bigger picture and understand how the approval of a drug may affect the American public."

Former CDER director retired in January 2025

CDER’s previous director, Patrizia Cavazzoni, resigned in January 2025. She started with FDA as deputy director of operations of CDER and served as acting principal deputy commissioner of Food and Drugs briefly in 2019. In 2021, she was made the director of CDER.

“While I could spend a lot of time enumerating our achievements, I want to highlight our biggest success: our people and our culture,” Cavazzoni said in a letter to her colleagues at the time of her retirement. “As I leave CDER, I can say with confidence that the Center is at its strongest. We have hired and retained record numbers of the best scientists and professionals. We have built a cohort of world-class managers and executives who are solidly at the helm of our organization and will continue to lead CDER. And most important of all, we created a culture that fosters respect for one another, inclusion, accountability, and diversity of thought and life experience. Our culture is what makes us strong and resilient, and it’s the foundation of what we have accomplished and will accomplish in the future” (5).

FDA. Stanford Faculty Member George Tidmarsh, MD, PhD Named Director of Center for Drug Evaluation and Research. Press Release. July 21, 2025. 

https://www.fda.gov/news-events/press-announcements/stanford-faculty-member-george-tidmarsh-md-phd-named-director-center-drug-evaluation-and-research

Joseph, A. FDA Taps Biotech Veteran George Tidmarsh to Lead Drug Center. 

https://www.statnews.com/2025/07/21/george-tidmarsh-fda-marty-makary-drug-center-director/

Samorodnitsky, D. FDA’s CDER Gets New Chief in Biopharma Veteran George Tidmarsh. 

Langreth, R. and Hornblower, S. FDA Appoints Biotech Executive as Top Drug Regulator Under RFK Jr. 

Haigney, S. Cavazzoni Retires as CDER Director. 

https://www.pharmtech.com/view/cavazzoni-retires-as-cder-director

George Francis Tidmarsh, MD, PhD, founding co-director of Stanford’s Master of Translational Research and Applied Medicine program, has been appointed as the new director of the Center for Drug Evaluation and Research.

FDA Appoints New CDER Director, George Tidmarsh

The European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) have issued recommendations through the 

Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG)

 for securing the supply of anti-D immunoglobulins used to prevent RhD immunization during pregnancy in the European Union. The supply is in trouble because the number of plasma donors has declined. Donors with anti-D immunoglobulins are the only source for manufacturing these drugs, according to EMA, and these treatments are the only option to prevent RhD immunization during pregnancy.

Supply of anti-D immunoglobulins used to prevent RhD immunization during pregnancy is at risk in the EU. The number of immunized donors is limited and there is a decline in existing donors.

EMA’s drug shortages steering group recommends EU Member States to create plans to secure the supply of anti-D immunoglobulins in the EU that include safety, legal, ethical, and regulatory considerations.

Industry is encouraged to invest in manufacturing capacity and development of alternatives to plasma-derived anti-D immunoglobulins.

PhD immunization occurs, according to EMA, when a pregnant person with RhD-negative blood is exposed to RhD-positive blood from the fetus growing in their body. A potentially fatal immune reaction may result from the exposure and impact the health of the fetus as well as after the baby is born (1).

During their assessment, MMSG identified the following key vulnerabilities in the supply chain (2):

The number of immunized donors was limited and there was a decline in existing donors.

There were challenges in the collection, manufacturing, and pooling of small plasma batches.

Global capacity was constrained by a limited number of marketing authorization holders and centers collecting plasma for anti-D immunoglobulins.

There was a dependency on countries outside of the EU for supply of plasma for these products.

Recommendations for regulators, industry, and other stakeholders

MMSG issued recommendations to national regulators, the European Commission, the plasma industry, and research organizations. The new recommendations are for EU Member States to create plans to secure the supply of anti-D immunoglobulins in the EU that include safety, legal, ethical, and regulatory considerations. Reducing unnecessary use through procedures such as non-invasive prenatal screening should be focused on. Alternative treatments should also be researched and developed. Communication campaigns about plasma-derived medicinal products should also be implemented.

The recommendations also state, “Member States, in collaboration with experts, including learned societies, patient organizations, and other relevant stakeholders should develop national guidelines to facilitate prioritization of patients who require these medicines during shortage situations, where necessary. The MSSG may coordinate the development of a Union level prioritization plan to manage critical shortages, coordinated at Union level” (2).

EMA stated in the press release that the EC should identify measures to ensure the supply of these treatments and coordinate with EU Member States (1). “Policy measures set out in the proposed Critical Medicines Act could be leveraged, such as joint procurement of manufacturing services to establish or increase supply of these medicines to the EU,” the agency stated in the release. The recommendations document says the EC should also “facilitate cooperation between key stakeholders, including national competent blood authorities and national competent medicines authorities to ensure coherence across relevant legislative frameworks.”

Industry is also being encouraged to ensure the supply of these treatments in Europe by investing in manufacturing capacity and development of alternatives to plasma-derived anti-D immunoglobulins.

The recommendations (2) state that the plasma industry and research organizations should “collaborate with Member States and the European Commission to identify effective mechanisms to support plasma collection and use. Consider initiatives and tools implemented by regulatory authorities to secure the supply of anti-D immunoglobulins and where needed, provide relevant data necessary for identifying and developing these mechanisms.”

EMA. Strengthening Supply Chain of Anti-D Immunoglobulins. Press Release. July 4, 2025. 

https://www.ema.europa.eu/en/news/strengthening-supply-chain-anti-d-immunoglobulins

EMA. Recommendations of the Executive Steering Group on Shortages and Safety of Medicinal Products to Address Anti-D Immunoglobulin Supply Chain Vulnerabilities. EMA/135603/2025. June 23, 2025. 

https://www.ema.europa.eu/en/documents/other/recommendations-executive-steering-group-shortages-safety-medicinal-products-address-anti-d-immunoglobulin-supply-chain-vulnerabilities_en.pdf

The agency’s Executive Steering Group on Shortages and Safety of Medicinal Products has issued recommendations to address vulnerabilities in the supply chain of anti-D immunoglobulins.