Digital Transformation in Pharma Manufacturing

Patent Cliff Deals, Tariff Pressures, and the In Vivo Cell Therapy Bet

Behind the Headlines, Episode 23

ICH Q12 and Post-Approval Changes

Speed, Flexibility Top Large-Molecule Manufacturing Trends

Drug Digest July 2025

Key Insights from Industry Survey Results

Bio/Pharma's Tariff Response

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

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

The World Health Organization (WHO) issued a medical product alert on June 19, 2024 addressing three falsified batches of the type 2 diabetes and obesity drug Ozempic, the increasingly popular brand name of a semaglutide class of medicines. WHO said the falsified semaglutides were detected in Brazil and the United Kingdom in October 2023, and in the United States in December 2023 (1).

Worldwide reports of falsified semaglutide products have been circulating since 2022 and have been observed by WHO’s Global Surveillance and Monitoring System, but WHO said confirmation of some of these reports—specifically the three batches identified—have now resulted in this first official notice being issued.

Because of their high cost, semaglutides are not currently recommended by WHO for diabetes management. These drugs’ tendency to suppress appetite has led to them being prescribed as weight loss medications in some countries (1).

“WHO advises healthcare professionals, regulatory authorities, and the public be aware of these falsified batches of medicines,” Yukiko Nakatani, MD, PhD, WHO assistant director-general for access to medicines and health products, said in a WHO press release (1). “We call on stakeholders to stop any usage of suspicious medicines and report to relevant authorities.”

According to the medical product alert, the falsified products misrepresent their identities and sources in several ways, which expose that they were not manufactured by Novo Nordisk. For one, batch number LP6F832 is not recognized; two, the combination of batch number NAR0074 and serial number 430834149057 does not correspond to legitimate manufacturing records; and three, the product with batch number MP53511 is falsified, even though the batch number is genuine (2).

These pieces of evidence are similar to those cautioned by the European Medicines Agency in October 2023, when the agency said that pre-filled, 1-mg solution pens labeled as Ozempic, and found at wholesalers throughout the UK and European Union, contained genuine information from Ozempic packs—such as batch numbers, 2D barcodes, and unique serial numbers—but that the serial numbers came up as inactive when scanned (3).

In this latest round of falsified products, WHO provided an 

 of batch number labels that should not be sold, distributed, or used.

Using falsified Ozempic could result not only in the ineffective treatment of patients, but also contamination with harmful substances, the interactions of unknown or substituted ingredients, or serious and potentially life-threatening health risks because of the subcutaneous nature of the injection (2).

Other telltale signs of a falsified product include a scale extending out from the pen while setting the dose, a poor-quality label with poor adhesion, or spelling mistakes on the box, according to WHO (2).

Legitimate injectable semaglutides should always be stored in a refrigerator, and packaging and expiration dates should be checked by the consumer (1). A notification of a falsified medicine can be emailed to WHO at 

WHO. WHO Issues Warning on Falsified Medicines Used for Diabetes Treatment and Weight Loss. Press Release. June 20, 2024.

WHO. Medical Product Alert N°2/2024: Falsified OZEMPIC (Semaglutide). Press Release. June 19, 2024.

Articles

This alert follows a similar one from the European Medicines Agency in October 2023 amid a rise in demand for the diabetes medication that, in turn, created a shortage.

WHO Warns About Falsified Ozempic Batches

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The United States Pharmacopeia (USP) announced on June 13, 2024 that it is collaborating with the African Union Development Agency (AUDA –NEPAD), the Africa Centres for Disease Control and Prevention (Africa CDC), the Association of African Universities (AAU), and the Federation of African Pharmaceutical Manufacturers Associations (FAPMA) to advance access to medicines and vaccines. USP grant-free access to the 

United States Pharmacopeia–National Formulary

) and USP’s education training library to all stakeholders in Africa, including regulatory authorities, laboratories, academic institutions, and manufacturers.

The new initiative will support African-led efforts, such as CDC’s New Public Health Order and AUDA-NEPAD's Pharmaceutical Manufacturing Plan for Africa, to increase the production of medical products. The initiative also builds on USP’s efforts to expand access to medicines in Africa through the organization’s direct investment, along with donors such as the US Agency for International Development. These efforts have included capacity building with 39 African manufacturers and 33 African regional and national regulatory authorities.

“Africa’s over-reliance on pharmaceutical imports created unacceptable supply chain vulnerabilities and delays during the COVID-19 pandemic,” said Jean Kaseya, MD, director-general of Africa CDC, in a USP press release (1). “We are committed to working with partners [such as] USP to build African manufacturing capacity to ensure that never happens again.”

“Development and growth of the pharmaceutical and vaccine manufacturing sector in Africa is critical to building sustainable and equitable access to health products in Africa,” said Symerre Grey Johnson, director for Human Capital and Institutional Development of AUDA-NEPAD, in the release. “With the actualization of the African Medicines Agency coupled with the African Free Trade Agreement and high-level commitments made by the African Union and numerous heads of states, the enabling conditions are primed for this sector to grow.”

“The growth of pharmaceutical manufacturing in Africa hinges on a dynamic and robust workforce,” said Olusola Oyewole, PhD, secretary-general of the Association of African Universities (AAU), in the release. “The development of a well-trained human resource pool with access to essential resources, such as those provided by USP, is crucial for educating tomorrow’s workforce, and transforming the continent’s pharmaceutical ecosystem.”

“Quality, including the adoption and scale up of accepted quality standards, must be at the heart of Africa’s expanding pharmaceutical sector,” said Emmanuel Mujuru, chairperson of FAPMA, in the release. “These resources will help African manufacturers move ever closer toward a thriving, quality-focused African pharmaceutical industry.”

The collaboration was announced at the inaugural meeting of USP’s Africa Regional Chapter. The Africa Regional Chapter brings together perspectives and expertise to identify priority issues. USP’s regional chapters will provide a forum for stakeholders to collaborate to advance pharmaceutical manufacturing and other priorities. There are more than 5000 quality standards in the 

for both chemical and biologic drugs, APIs, and excipients, therefore providing a comprehensive source for quality standards.

USP. African Institutions and USP Announce Free Access to Resources to Support Production of Quality Medical Products in Africa. Press Release. June 13, 2024.

A new initiative will advance access to quality medicines and vaccines in Africa.

USP and African Institutions Provide Free Access to Pharma Production Resources

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Bora Pharmaceuticals is expanding its North American footprint by agreeing to purchase an 87,000-square-foot sterile manufacturing facility previously owned by Emergent BioSolutions in Baltimore, Md. The sale, at a price of approximately $30 million, was announced by both companies on June 20, 2024 (1,2).

Founded in 2007 in Taiwan, Bora acquired Minnesota-based generics manufacturer Upsher-Smith Laboratories earlier in 2024, making the purchase of the Emergent property a second step in its US footprint (1).

The Baltimore location will be Bora’s first sterile manufacturing facility, offering non-viral, aseptic fill/finish services on four fill lines, which the company says include lyophilization, vials filling, and pre-filled syringe filling (1). About 350 current Emergent employees are expected to join Bora in the transaction (2).

Bora said the acquisition complements its development and manufacturing arm for biologics developers, Bora Biologics, which offers cell line, process, and formulation development, analytical services, and clinical current good manufacturing practice manufacturing (3).

The sterile injectable market is forecast to reach the neighborhood of $1 trillion by 2030 with a six-year compound annual growth rate of 10.17%, Bora said, citing a report by Research and Markets (4).

Executives from both Bora and Emergent applauded the move in their organizations’ respective press releases, which each referred to the area of the campus as Baltimore-Camden.

“This transaction not only demonstrates our commitment to our growth strategy and plans for expansion in North America, but also enables us to expand our offering for our biologics customers,” said Bobby Sheng, chairman and CEO of Bora Group, in the press release. “We look forward to working with the hugely talented team at the facility and supporting new and existing customers as we grow and develop the facility.”

“The decision to sell our Camden manufacturing facility is aligned with our multi-year plan to create a customer-focused, leaner, and more flexible organization, while we improve overall profitability and raise capital to reduce our debt,” Joe Papa, Emergent president and CEO, said in the release. “We are grateful to our dedicated colleagues who have embodied Emergent’s mission to protect and enhance life by delivering on our customers’ commitments. We are working to ensure a smooth transition to Bora, especially for our Camden team and valued customers, over the coming weeks and months."

Emergent added that the transfer of assets, equipment, and workforce is expected to close in the third quarter of 2024.

Bora Pharmaceuticals. Bora Pharmaceuticals Expands North American Footprint with Agreement to Acquire First Sterile Manufacturing Facility. Press Release. June 20, 2024. 

bora-corp.com/bora-to-acquire-first-sterile-manufacturing-facility/

Emergent. Emergent BioSolutions Announces Sale of Baltimore-Camden Manufacturing Site to Bora Pharmaceuticals for $30 Million. Press Release. June 20, 2024. 

investors.emergentbiosolutions.com/news-releases/news-release-details/emergent-biosolutions-announces-sale-baltimore-camden

Bora Pharmaceuticals. Biologics—Bora Pharmaceuticals Premium CMDO. 

Global Sterile Injectable Drugs Market by Molecule Type (Large Molecule, Small Molecule), Drug (Blood Factors, Cytokines, Immunoglobulins), Indication, Distribution - Forecast 2024-2030

researchandmarkets.com/report/sterile-injectable-drugs

The transaction, announced June 20, follows Bora’s purchase of Minnesota-based Upsher-Smith Laboratories earlier in 2024.

Bora Pharmaceuticals Acquires Baltimore Manufacturing Facility from Emergent

John Fowler discuses how Pii supports complex therapeutic programs, from scale-up through commercialization.

Cultural Transformations a Necessity to Support Complex Therapeutics Through Development and Manufacturing

Services necessary to carry out new programs for complex molecules, from scale-up to commercialization.

Lyophilization capabilities that can help ensure quality through processing.

Resources to support efficient secondary pharmaceutical packaging.  

Videos

President and CEO of Pharmaceutics International, Inc. (Pii), John Fowler, reacts to the agility and flexibility needed to support the development and manufacture of today's complex biotherapeutics.

Pharmaceutical researcher making dissolution test | Image Credit: © Kadmy - stock.adobe.com

Dissolution testing plays an important role within the bio/pharma sector, providing critical information for quality control and drug development. In an interview with 

, Shailesh Vengurlekar, senior vice president, quality and regulatory affairs, LGM Pharma, provides more details on the role of dissolution testing, recent innovations in the space, and potential upcoming trends.

What key roles does dissolution testing play, especially regarding quality control?

 Dissolution testing assesses the absorption of a drug after oral consumption through the release of the drug substance from the drug product. The dissolution result of a product lot determines the ability of the lot to dissolve at the specified time (e.g., immediate, extended, or delayed) as intended.

During the formulation and development stage, dissolution data are utilized to assess different formulations and identify one that delivers the drug most effectively based on the dissolution criteria (as mentioned, immediate, extended, or delayed release). Consistent, reproducible dissolution data of a drug product can provide a level of assurance about its quality. Dissolution testing is also utilized to perform any equivalency study during changes or development of new formulations, ensuring continuous demonstration of product quality. FDA expects that new drug applications (NDAs) submitted to the agency contain bioavailability data and 

 dissolution data, which, together with chemistry, manufacturing, and controls (CMC) data, characterize the quality and performance of the drug product. Acceptable bioequivalence data, and comparable 

dissolution and CMC data, are all required for approval of abbreviated new drug applications.

What are some recent innovations in dissolution testing? Can you describe their impact?

To my experience, dissolution equipment is more advanced and continues to evolve to meet user demands—for example, the equipment's ability to autosample, including multiple timepoints. Dissolution media have evolved over the years to mimic physiological conditions; media such as water, acid solution, simulated intestinal fluid, and simulated gastric fluid, including enzyme additions, have been developed and implemented. These tests help predict and simulate the 

 movement of the drug product through the gastrointestinal (GI) tract.

What are some chief concerns in dissolution testing?

Dissolution testing has to be accurate and reliable each and every time it is performed, regardless of when, where, or by whom. Thus, the method should be validated to demonstrate accuracy and precision. Dissolution method validation should be performed similarly to potency and purity method validation, which includes but is not limited to specificity and selectivity, accuracy, precision, linearity, range, and solution stability and robustness (including apparatus functionality: speed, temperature, and media type or volume). Acceptance criteria must be defined prior to performing the validation. Additionally, method validation must be performed in accordance with regulatory guidelines, such as 

] and ICH [International Council for Harmonisation].

How do the trends of the industry affect dissolution testing? Are there any upcoming trends that professionals should be on the lookout for?

The industry is coming out with more innovative drugs, such as biologics and cell and gene therapy, which are not the traditional oral solid dose, and the current standard dissolution techniques are not suitable for these innovative drugs. New innovative drugs will require the development of innovative and new dissolution approaches and analytical techniques. Some considerations affecting the development of such new techniques are the formulation (e.g., tablet, capsule, or powder), particle size, solubility, hardness, and stability of the drug substance.

What do you see in the future for dissolution testing? Is there one change in particular that could have an impact on analytical testing?

Dissolution testing is an important quality control parameter to assess absorption of a drug, as described above, and thus will continue to be important in the analytical space. However, changes to dissolution techniques, method, and instrument may be necessary for new and innovative drugs developed in the future.

Advances in dissolution testing equipment are helping to meet user demands to a certain degree; however, more innovation in the space may be necessary for novel therapies, such as biologics.

Dissecting Dissolution Testing

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Imfinzi, the brand name of AstraZeneca’s human monoclonal antibody (mAb), durvalumab, was approved by FDA in combination with the chemotherapy drugs carboplatin and paclitaxel, followed by Imfinzi monotherapy, for use in adult patients with mismatch repair deficient (dMMR) primary advanced or recurrent endometrial cancer. AstraZeneca announced the approval in a June 17, 2024 press release (1).

The approval follows the reporting of results of a DUO-E/GOG-3041/ENGOT-EN10 Phase III trial (ClinicalTrials.gov identifier NCT04269200), a randomized, double-blind, and placebo-controlled trial conducted in 22 countries, as published in the 

 (2,3). In this trial of almost 700 patients, the risk of disease progression or death was decreased by 58% in dMMR endometrial cancer patients versus chemotherapy alone, according to AstraZeneca (1).

Endometrial cancer, which originates in the tissue lining of the uterus, is the sixth-most common cancer in women across the world, most commonly affecting women who have experienced menopause, with the average age at diagnosis being over 60 (1). Cases and deaths are expected to increase by 61% and 87%, from 420,400 and 97,700, respectively, in 2022 to 676,300 and 183,100 by 2050.

“With the incidence and mortality of endometrial cancer expected to continue to increase significantly in the coming decades, it is more important than ever that we bring new treatment options to patients at the earliest possible moment in their care,” Shannon N. Westin, professor of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center and principal investigator of the trial, said in the AstraZeneca release. “This approval underlines clear evidence that durvalumab plus chemotherapy followed by durvalumab monotherapy delivers important clinical benefits for patients with mismatch repair deficient endometrial cancer.”

In endometrial cancer patients diagnosed at an early stage of the disease—where it is confined to the uterus—AstraZeneca said the five-year survival rate is between 80% and 90% (1). But at stages III and IV, that rate falls to below 20%, a sense of urgency not lost on Dave Fredrickson, AstraZeneca executive vice president, oncology business unit.

“There have been limited advances in the treatment of endometrial cancer in the last few decades, and continued innovation is critical as the burden of this cancer is expected to grow in the future,” he said. “Immunotherapy in combination with chemotherapy is emerging as a new standard of care in this setting, and the approval of Imfinzi offers an important new option for patients with mismatch repair deficient disease.”

FDA recommends a dose of durvalumab with carboplatin plus paclitaxel every three weeks for six cycles, followed by single-agent durvalumab every four weeks (4).

AstraZeneca. Imfinzi Plus Chemotherapy Approved in the US for Mismatch Repair Deficient Advanced or Recurrent Endometrial Cancer. Press Release. June 17, 2024. 

astrazeneca.com/media-centre/press-releases/2024/imfinzi-approved-in-the-us-for-endometrial-cancer.html

ClinicalTrials.gov. Study Details | Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer (DUO-E). 

, March 5, 2024 (accessed June 20, 2024). 

Westin, S.N.; Moore, K.; Chon, H.S.; et al. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. 

FDA. FDA Approves Durvalumab with Chemotherapy for Mismatch Repair Deficient Primary Advanced or Recurrent Endometrial Cancer. Press Release. June 14, 2024. 

fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-chemotherapy-mismatch-repair-deficient-primary-advanced-or-recurrent

Imfinzi (durvalumab) combined with chemotherapy decreased the risk of disease progression or death by 58% in a 700-patient trial.

AstraZeneca mAb Approved by FDA for Endometrial Cancer Patients

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The German government, in 2022, awarded a contract to WACKER, a contract manufacturer, and CordenPharma, a contract development and manufacturing organization, to produce and supply vaccines to prepare for potential future pandemics (1, 2). On June 19, 2024, WACKER and CordenPharma announced that their joint consortium entered the pandemic-readiness state on June 1, 2024 after the expansion and qualification phase. The consortium now enters the stand-by phase for a minimum of five years.

The two companies have taken measures to be able to produce 80 million vaccine doses a year under a short timeframe. A fee will be paid to the two companies to keep their capacity and expertise available for at least five years; the German government will request specific messenger RNA (mRNA) vaccines should a need develop.

Vaccines will be jointly produced by WACKER and CordenPharma with production occurring mostly in Germany. WACKER will produce plasmid DNA (pDNA), active pDNA, and lipid nanoparticles at its site in Halle, Germany, which was expanded to accommodate production over the past two years to include a new mRNA Competence Center.

CordenPharma will manufacture custom and standard lipids for the consortium at their Frankfurt, Germany and Chenôve, France sites. Aseptic fill/finish and packaging will be done at CordenPharma’s Caponago, Italy facility. To meet demand, the company invested in expansions in new lipid purification capacity and capabilities using supercritical fluid chromatography (SFC) and new compounding and freezing equipment. Both companies have also strengthened production security and supplier networks.

“We have expanded our Halle site into a Competence Center for mRNA production,” said WACKER CEO Christian Hartel, in a press release (3). “WACKER has invested over 100 million Euros in this expansion and created over 100 highly qualified jobs. Our expertise in making mRNA and LNPs [lipid nanoparticles] will contribute to the fight against future pandemics. Together with CordenPharma, we are proud to serve the German government in its pandemic preparedness plans.”

“Obtaining the official confirmation of pandemic readiness by the German government is a major milestone for CordenPharma,” said Michael Quirmbach, CEO of CordenPharma Group, in the release. “I am extremely proud of our teams across the CordenPharma sites involved in establishing and delivering our pandemic readiness plan on schedule. We are now ready, together with our partner WACKER, to manufacture end-to-end mRNA-based vaccines for the German government and other customers.”

At the time the contract was awarded, Hartel commented in a press release (1), “We are happy that our expertise in making mRNA vaccines will contribute to the fight against future pandemics. Together with CordenPharma, our partner, we will produce vaccines for Germany should the need arise.”

“WACKER and CordenPharma jointly cover the entire manufacturing chain for mRNA vaccines, which we will supply to the German government if needed. We are proud to contribute to supply security in Germany,” Quirmbach added (1).

CordenPharma. CordenPharma and WACKER to Produce mRNA Vaccines for Germany When Needed. Press Release. April 11, 2022.

CordenPharma. CordenPharma & WACKER Prepare for mRNA Vaccine Production. Press Release. June 14, 2022.

WACKER. WACKER & CordenPharma Enter Pandemic Readiness on 1 June 2024 After Successful Expansion & Qualification. Press Release. June 19, 2024.

The companies have completed the expansion and qualification phase and now enter a stand-by phase for five years.

CordenPharma and WACKER Consortium Enters Pandemic Readiness

glove hand Concept of FDA approved. Food and drugs administration. Quality medcine, assurance, organization. | Image Credit: © everythingpossible - stock.adobe.com

Thermo Fisher Scientific announced on June 18, 2024 that its Pharmaceutical Product Development (PPD) clinical research business opened a new building at its good manufacturing practice (GMP) laboratory in Middleton, Wisconsin (1).

The 72,000-square-foot facility was touted by the company in a press release as an expansion of its clinical research laboratory, increasing the lab’s analytical capacity in the area of chemistry, manufacturing, and controls (CMC).

Currently, the Wisconsin campus is home to nearly 2300 Thermo Fisher employees, and the expansion makes room for up to 350 additional scientists and lab support professionals, something Leon Wyszkowski, president, analytical services, clinical research, said would be reflected in the company’s services to consumers.

“As research in biopharmaceutical therapies continues to rapidly expand, we are excited to expand our overall capacity and capabilities in laboratory services to help our customers deliver therapies that meet the highest quality and safety standards for patients,” Wyszkowski said in the press release. “We will continue to support and empower our customers as they continue to discover, develop, and deliver new groundbreaking therapies. This $58 million investment to expand the site is a testament to our dedication in supporting Thermo Fisher’s mission of making the world healthier, cleaner, and safer.”

In the press release, Thermo Fisher specified that the new space at the Wisconsin site adds a dedicated liquid chromatography–mass spectrometry (LC–MS) and protein characterization space, two molecular suites with pre- and post-amplification labs, and two other labs for general use. Small molecules and biologics are the focus at the GMP lab, across all phases of drug development, according to Thermo Fisher—including biopharmaceuticals, device testing, cell and gene therapy, and MS analysis (1).

The capabilities of the GMP site had previously been expanded in February 2024 with the addition of mycoplasma and supplementary biosafety testing services, in an effort to ensure contaminants are stripped out of biopharmaceutical products (2).

While Thermo Fisher maintains clinical research laboratories in other US states, such as Kentucky and Virginia, as well as in countries including Belgium, China, Ireland, and Singapore, the new enhancements in Wisconsin have been significant enough to draw the attention of Wisconsin Governor Tony Evers.

“As Wisconsin’s biohealth sector continues to grow, so will our workforce, our economic momentum, and our opportunities to build a healthier, stronger state for all,” Evers said in the June 18 press release. “This new state-of-the-art facility will not only further advance our state’s biosafety testing capabilities and create hundreds of jobs, but it will also help protect consumers and improve patient health outcomes across the state.”

Thermo Fisher Scientific acquired PPD at a price of $17.4 billion in December 2021 (3).

Thermo Fisher Scientific. Thermo Fisher Scientific Expands Clinical Research Laboratory in Wisconsin. Press Release. June 18, 2024. 

newsroom.thermofisher.com/newsroom/press-releases/

Thermo Fisher Scientific. Thermo Fisher Scientific Expands GMP Laboratory Service Offerings with Biosafety Testing Including Mycoplasma Testing. Press Release. Feb. 13, 2024. 

Thermo Fisher Scientific. Thermo Fisher Scientific Completes Acquisition of PPD, Inc. Press Release. Dec. 8, 2021. 

ir.thermofisher.com/investors/news-events/news/

The $58 million investment has resulted in a 72,000-square-foot facility with a dedicated LC–MS space and molecular suites and will bring as many as 350 new jobs onto the campus.

Thermo Fisher Opens New Building at Wisconsin GMP Lab

The European Medicines Agency (EMA) announced on June 14, 2024 that the agency’s Pharmacovigilance Risk Assessment Committee (PRAC) is evaluating potential risks associated with the painkiller metamizole. PRAC is also researching the possible risk of secondary cancers developing in patients who are treated with chimeric antigen receptor (CAR) T-cell medicines.

According to EMA, concerns that measures put in place to minimize the risk of agranulocytosis in the painkiller metamizole might not be adequate. Drugs containing metamizole are authorized in the European Union, varying from country to country, for treating moderate to severe pain and fever. These medicines have a known side effect, agranulocytosis, where a sudden drop in white blood cells occurs. Agranulocytosis is a rare or very rare side effect that may lead to serious, and possibly fatal, infections. There are measures set by EU countries to minimize the risk; however, PRAC is looking into the effectiveness of these measures.

Regarding CAR T-cell medicines, PRAC states that patients receiving these treatments should be monitored for the rest of their lives for secondary cancers. New cancers, different from the original malignancy, may develop after treatment with CAR T-cell medicines.

PRAC came to this conclusion after reviewing data from 38 cases of secondary malignancies of T-cell origin in approximately 42,500 patients. “Tissue samples were tested in half of the cases, revealing the presence of the CAR construct in 7 cases. This suggests that the CAR T-cell medicine was involved in disease development. The secondary malignancies of T-cell origin have been reported within weeks and up to several years following administration of CAR T-cell medicines. Patients treated with these medicines should be monitored life-long for new malignancies,” EMA stated in a press release (1).

Product information, which has advisory information about secondary malignancies, will be updated to include new information about T-cells. PRAC is discussing direct healthcare professional communication about CAR T-cell medicines and will inform professionals about its new conclusion.

There are six approved CAR T-cell treatments in the EU: Abecma, Breyanzi, Carvykti, Kymriah, Tecartus, and Yescarta. They treat a range of blood cancers.

In November 2023, FDA in the United States announced it was investigating the risk of T-cell malignancy following CAR T-cell immunotherapies (2). “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” FDA states on its website. “The initial approvals of these products included postmarketing requirements (PMRs) under Section 505(o) of the Federal Food, Drug, and Cosmetic Act (FDCA) to conduct 15-year long term follow-up observational safety studies to assess the long-term safety and the risk of secondary malignancies occurring after treatment.” The agency also said that patients of these treatments should be monitored for life for new malignancies.

EMA. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 10-13 June 2024. Press Release. June 14, 2024.

FDA. FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T Cell Immunotherapies. Nov. 28, 2024. 

https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous

PRAC is reviewing the risk of secondary malignancies in patients treated with CAR T-cell medicines. 

EMA Reviews Risks of CAR T-Cell Medicines and Painkillers

Global healthcare company, Grifols, announced on June 17, 2024 that its subsidiary Biotest has garnered its first FDA approval with the intravenous immunoglobulin (Ig) therapeutic, Yimmugo, which Grifols hopes to launch commercially in the United States in the second half of 2024 (1). FDA notified Biotest of the approval in a letter dated June 13, 2024 (2).

According to a press release from Grifols, Yimmugo was introduced in Europe at the end of 2022 and is being produced at a new, FDA-certified facility in Dreieich, Germany. This location was also previously approved for production and marketing throughout Europe.

Grifols cites a “growing demand for plasma-derived medicines” such as Yimmugo to treat primary immunodeficiencies (PIDs), meaning when a portion of the body’s immune system is missing or not functioning properly.

The Immune Deficiency Foundation further defines PIDs as a group of conditions, in excess of 450, which are considered rare, chronic, and disruptive to the immune system. They are also known as inborn errors of immunity (3).

Roland Wandeler, president of the Grifols Biopharma Business Unit, emphasized in the company’s press release the need for continued development of therapeutics for PIDs.

“The addition of Biotest’s Yimmugo to our strong portfolio of intravenous and subcutaneous immunoglobulins provides another innovative treatment option for patients with primary immunodeficiencies who rely on these essential medicines in their daily lives,” Wandeler said.

Two other plasma proteins being developed under the Biotest nameplate are currently in late-stage development for future clearance in the US and other worldwide markets. One is a fibrinogen concentrate (FC) for treatment of acquired fibrinogen deficiency; this would be the first FC approved for this indication in the US, according to Grifols (1). The other, trimodulin, is a polyvalent Ig to combat community-acquired and severe community-acquired pneumonia.

Grifols acquired Biotest in 2022 and called it “a strategic transaction that will contribute to expanding and diversifying Grifols’ plasma supply; strengthening its operations and revenues in Europe, Middle East and Africa; and supporting the company’s economic performance” (4). The acquisition increased the company’s available plasma-derived therapies and its fractionation capacity to more than 20 million liters of plasma annually.

“The Biotest acquisition is a fundamental milestone in our transformation plan, and is fully aligned with our growth strategy—strengthening our global plasma capacity, expanding our product portfolio in order to benefit more patients, complementing our innovation efforts with high value-added projects, and accelerating our presence in new markets,” said Víctor Grífols Deu, co-CEO of Grifols, at the time of the acquisition (4).

Grifols. Grifols’ Biotest Receives FDA Approval for Innovative Yimmugo® Immunoglobulin to Treat Primary Immunodeficiencies. Press Release. June 17, 2024. 

grifols.com/en/view-news/-/news/grifols-biotest-receives-fda-approval-for-innovative-yimmugo-immunoglubulin-to-treat-primary-immunodeficiencies

fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/yimmugo

primaryimmune.org/understanding-primary-immunodeficiency/what-is-pi

Grifols. Grifols Completes the Acquisition of Biotest: A Strategic and Transformational Transaction to Accelerate Growth and Innovation. Press Release. April 25, 2022. 

grifols.com/en/view-news/-/news/grifols-completes-the-acquisition-of-biotest-a-strategic-and-transformational-transaction-to-accelerate-growth-and-innovation

Yimmugo, which was introduced in Europe at the end of 2022, could be on the market in the US within months.

Featured Content

Digital Transformation in Pharma Manufacturing

Behind the Headlines, Episode 23

ICH Q12 and Post-Approval Changes

Drug Digest July 2025

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