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

Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Mary (Nora) Disis, MD, University of Washington

Pablo Guasp, PhD, Memorial Sloan Kettering Cancer Center (MSK)

American Society of Gene and Cell Therapy’s (ASGCT’s) 27th Annual Meeting

 in Baltimore, Md., which occurred May 7–11, 2024, Pablo Guasp, PhD, MSK asked himself the question, “What can we use to teach the immune system how to recognize cancer cells?” Replying, “… the neoantigen that arise from the accumulation of mutations in cancer cells can be good candidates … while a limitation is that neoantigens usually impose a restriction towards personalized treatments; therefore, we need a delivery platform that allows for modularity where we can include and exclude neoantigens based on the mutations of each individual patient. Also, we need a platform that allows us to do this in a timely manner, so we can treat patients soon after they are diagnosed. We believe that nucleic acid [developments] have been a breakthrough in this field, and in particular mRNA [messenger RNA] is showing very promising results”. Guasp then considered which patients benefit the most from this approach, stating, “If we look at vaccines against infectious agents we see that vaccines are always given in a prophylactic setting before the patient develop[s] the disease. But, paradoxically, cancer vaccines historically have been tested in patients with advanced and metastatic disease, and we think that this may not be the best scenario. We think that cancer vaccines may work best in patient with minimal disease, such as patients that had their tumors surgically resected” he averred. 

MSK partnered with BioNTech and Genentech to launch the first clinical trial of personalized mRNA cancer vaccines in pancreatic cancer. The results of this trial were published in 2023 (1). In only nine weeks, patients were receiving their own individualized cancer vaccine. This happened in such a timely manner, “because of a huge collaborative effort between all the members involved in the teams, but also because mRNA allows for this quick modularity, and this speed that I was mentioning before,” Guasp said.

During those nine weeks, the patient received a single dose of anti programmed cell death ligand 1 immunotherapy with atezolizumab and then received eight priming doses of the vaccine, followed by a standard-of-care chemotherapy and a single vaccine boost dose. “We identified specific responses elicited by the vaccine in half of the patients that receive[d] the vaccine. Not only that, but response to the vaccine correlate[s] with a delay recurrence time. … We know that this is a small clinical trial with a small number of patients, but the results are promising” Guasp added.

1. Rojas, L. A.; Sethna, Z.; Soares, K. C.; et al. Personalized RNA Neoantigen Vaccines Stimulate T Cells in Pancreatic Cancer. 

, 144–150. DOI: 10.1038/s41586-023-06063-y

Articles

In an ASGCT Panel on nucleic acid- and cell-based vaccines in oncology, work on a personalized mRNA vaccine was highlighted.

Highlighting Personalized mRNA-Based Vaccines for Pancreatic Cancer (ASGCT 2024)

Feliza Mirasol is the science editor for 

AGC Biologics announced on May 22, 2024 that is has formed a new strategic partnership with BioConnection, a contract manufacturing organization specializing in aseptic filling of vials and syringes for clinical and commercial production. The companies plan to provide end-to-end biopharmaceutical development and manufacturing capabilities for drug substance and drug product.

The goal of this partnership is to offer full-service clinical-stage development and manufacturing to shorten timelines and bring biopharmaceuticals to market more efficiently, a “gene to vial” value chain service that comprises a single contract and project management team for the project lifecycle, according to a company press release. The partnership addresses the industry’s ongoing needs in light of the proposed 

 proposed by US legislators in January 2024, which states, “Specifically, the bill prohibits executive agencies from 1) procuring or obtaining any biotechnology equipment or service produced or provided by a biotechnology company of concern, or 2) entering into a contract or extending or renewing a contract that uses such equipment or service or that will require the direct use of such equipment or services. Those agencies may not obligate or expend loan or grant funds for such purposes” (1).

“By having a combined end-to-end solution that uses facilities in Japan, the United States, and Europe, developers now have a reliable and secure supply of services for development, manufacturing (including freeze-drying) and aseptic filling for their drug product’s needs,” stated Biogen in its press release.

According to the release, AGC Biologics is well-positioned to support drug developers’ needs, especially those who may be impacted by the proposed legislation. “Developers seeking alternatives from their current outsourcing partner benefit from access to AGC Biologics’ single-use network utilizing ubiquitous bioreactor technology, enabling an easier transfer of platform processes and reduction in process changes associated with changing outsourcing partners,” the company stated in the press release.

AGC Biologics protein-biologics services comprise cell line development through to commercial-scale manufacturing, and the company’s capabilities support drug substance manufacturing from microbial- and mammalian-based systems as well as plasmid DNA and messenger RNA. BioConnection’s aseptic filling capabilities for vials and syringes offer tailored solutions for clinical and commercial production of either liquid or freeze-dried products.

“Now more than ever global pharmaceutical companies and developers need reliable facilities to produce and fill their drug products, and by combining our resources with BioConnection we are offering a new end-to-end solution for them under one contract with AGC Biologics,” said Patricio Massera, CEO of AGC Biologics, in the press release. “We believe BioConnection has a strong acumen, and this established partnership will enhance our biopharmaceutical manufacturing offering by providing drug product services for protein biologics, allowing us to create deeper relationships with developers to help get their products to patients in need.”

Alexander Willemse, CEO of BioConnection, added in the release, "We are excited to join forces with AGC Biologics to offer integrated manufacturing solutions that address the complexities of biopharmaceutical development. Together, we are well-positioned to support our clients at every stage."

The partnership aims to provide end-to-end development and manufacturing for biopharmaceutical drug substance and drug product. 

AGC Biologics Partners with BioConnection to Offer Biopharma Drug Substance and Drug Product Development and Manufacturing

On May 22, 2024, Biogen announced that it is acquiring Human Immunology Biosciences (HI-Bio), a privately-held US-based clinical-stage biotechnology company specializing in targeted therapies for severe immune-mediated diseases (IMDs). The transaction is worth potentially up to $1.8 billion, which includes a $1.15 billion upfront payment and up to $650 million in potential milestone payments. The deal is expected to close in the third quarter of 2024, subject to necessary regulatory approvals and customary closing conditions.

With the acquisition, Biogen gains felzartamab, HI-Bio’s lead asset. Felzartamab is a fully human anti-CD38 monoclonal antibody (mAb) that has been shown to selectively deplete CD38+ cells in clinical studies. This selective depletion includes plasma cells and natural killer (NK) cells. This action may allow for additional applications that improve clinical outcomes in a broad range of immune-mediated diseases, Biogen stated in a company press release.

“We believe this late-stage asset, which has demonstrated impact on key biomarkers and clinical endpoints in three renal diseases with serious unmet needs, is a strategic addition to the Biogen portfolio as we continue to augment our pipeline and build on our expertise in immunology,” said Priya Singhal, MD, head of Development at Biogen, in the press release. “We look forward to welcoming HI-Bio employees into Biogen and, together, working to advance potential therapies for patients with rare immune diseases with high unmet need.”

FDA has granted felzartamab breakthrough therapy designation and orphan drug designation for development in treating primary membranous nephropathy (PMN). The mAb has also received orphan drug designation for treating antibody-mediated rejection (AMR) in kidney transplant recipients. Felzartamab has completed Phase II studies in PMN and AMR and remains in ongoing Phase II studies in immunoglobulin A nephropathy (IgAN). HI-Bio plans to advance the mAb to Phase III studies in each indication; the company is presenting two abstracts at the 

 in Stockholm, which is occurring May 23–26, 2024. HI-Bio’s presentation includes complete Phase II data from the AMR study in kidney transplant patients and interim data from the Phase II IgAN study, according to the press release. Studies have also generated clinical data for felzartamab in the AMR, PMN, and IgAN indications.

“With its deep development and commercialization capabilities, Biogen is in a position to accelerate the development of new medicines, including felzartamab, for patients with severe immune-mediated diseases,” said Travis Murdoch, MD, chief executive officer of HI-Bio, in the release. “We are excited to combine the HI-Bio team’s expertise with Biogen’s global footprint.”

In addition to the felzartamab lead program, HI-Bio’s pipeline consists of izastobart/HIB210, an anti-C5aR1 antibody currently in a Phase I trial. This candidate has the potential for continued development in a range of complement-mediated diseases. HI-Bio also has discovery-stage mast cell programs with potential application in a range of immune-mediated diseases.

The treatment of IMDs has largely benefitted from the evolution of targeted biologic therapies. Targeted biologics have demonstrated efficacy, speed of onset, and tolerability. What’s more, research efforts have shown that clinically unrelated immune-mediated inflammatory conditions can share similar immune dysregulation. This discovery has since led to a shift in way IMDs and other inflammatory disorders are managed (1).

1. Kuek, A.; Hazleman, B. L.; Ostör A. J. Immune-Mediated Inflammatory Diseases (IMIDs) and Biologic Therapy: A Medical Revolution. 

 (978), 251–260. DOI: 10.1136/pgmj.2006.052688

With the acquisition, Biogen gains felzartamab, HI-Bio's lead investigational mAb candidate being developed for the treatment of a range of immune-mediated diseases. 

Biogen to Acquire HI-Bio in Deal Worth Potentially Up to $1.8 Billion

Merck KGaA, Darmstadt, Germany, will acquire Mirus Bio, a US-based life science company, in a $600 million deal, or approximately €550 million, according to a May 22, 2024 announcement. Pending regulatory clearance and other customary closing conditions, the transaction is expected to close in the third quarter of 2024.

The acquisition will strengthen Merck KGaA’s offerings in the viral vector manufacturing sector because Mirus Bio specializes in the development and commercialization of transfection reagents. Transfection reagents are used to introduce genetic material into cells and play a key role in producing viral vectors for use in cell and gene therapies (CGTs), according to a company press release.

“This strategic acquisition is a further building block for accelerating growth in the break-through technologies of the future. As a leader in the production of viral vectors, our goal is to make the significant potential of cell and gene therapy available for patients worldwide,” said Belén Garijo, chair of the executive board and CEO of Merck KGaA, Darmstadt, Germany, in the company press release.

The Mirus Bio acquisition represents an important step towards Merck KGaA’s goal to offer solutions for every step of viral vector manufacturing for the advancement of CGTs, from preclinical through commercial production, the company stated in the press release. Merck KGaA’s services cover a variety of viral vector types, including adeno-associated virus, lentivirus, and adenovirus. Additionally, the company offers both contract testing services and a range of comprehensive contract development and manufacturing services for viral vector manufacturing.

According to the company, the global market for process products for novel modalities such as CGTs, antibody-drug conjugates, and messenger RNA (mRNA) is expected to grow by approximately 20% per year over the mid-term (i.e., within 10 years). The overall number of CGTs in development has doubled since 2019, and more candidates are advancing to the commercial stage, for example.

“Novel modalities, such as viral vector-based cell and gene therapies, hold immense promise to improve the lives of patients. Combining Mirus Bio's leading technology with our bioprocessing expertise and portfolio allows us to provide solutions for almost every step of viral vector development and manufacturing,” said Matthias Heinzel, member of the executive board of Merck KGaA, Darmstadt, Germany, and CEO Life Science, in the press release. “With our integrated offering along the viral vector value chain, we are now well-positioned to support our customers in this fast-growing market to positively impact the lives and health of patients worldwide.”

Viral vectors are a key component in the production of these therapies. Thus, to support that growth, Merck KGaA opened its second Carlsbad, Calif.-based viral vector contract development manufacturing facility in 2021 (1). The company invested €100 million (US$108 million) in the site, which more than doubled the company’s capacity for supporting large-scale commercial and industrial manufacturing for viral vector-based gene therapies.

In addition to its second viral vector manufacturing facility, Merck KGaA also continues to invest in R&D that will enable new therapeutics to be brought to market. In April 2024, the company announced it was investing more than €300 million (US$325 million) to establish a new life science research center at its global headquarters in Darmstadt (2). The investment will harness research on key technologies for the manufacture of antibodies, novel modalities such as CGTs and mRNA applications, and additional products required for biotechnological production.

“We have been driving innovation in nucleic acid delivery for two decades,” said Dale Gordon, CEO of Mirus Bio, in the press release. “The broad portfolio, scale, and global reach of Merck KGaA, Darmstadt, Germany, combined with our leading transfection reagents, will help take our business to even greater heights and allow us to serve more customers, and ultimately patients, worldwide.”

1. Merck KGaA. Merck KGaA, Darmstadt, Germany, Completes New Viral Vector Contract Development Manufacturing Facility for Gene Therapy. Press Release, Oct. 12, 2021.
2. Merck KGaA. Merck KGaA, Darmstadt, Germany, Invests More Than € 300 Million in New Life Science Research Center. Press Release, April 25, 2024.

With this acquisition, Merck KGaA will have the capability to offer integrated services for viral vector manufacturing.

Merck KGaA Announces $600 Million Deal to Acquire Mirus Bio

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

Hospira, a Pfizer company, announced on May 21, 2024 that it was voluntarily recalling the lots listed in the table below of Buprenorphine Hydrochloride Injection Carpuject Units and Labetalol Hydrochloride Injection, USP Carpuject Units because of incomplete crimp seals. The company also received a customer complaint of a leaking unit.

The recalled lots were distributed nationwide to wholesalers/hospitals in the United States from September 2023 through April 2024. The National Drug Code (NDC), lot number, expiration date, and configuration details for the recalled lots are as follows:

Buprenorphine Hydrochloride Injection–CIII, Carpuject Single-dose Cartridge/Tube Unit with Luer Lock. NDC: Carton 0409-2012-32, Cartridge 0409-2012-03; lot number HJ3965, expiration date 2024/09; lot number HJ8546, expiration date 2024/10. Both have a concentration of 0.3 mg base/mL and are 10 cartridge units/carton.

Labetalol Hydrochloride Injection, USP Carpuject Single-dose Cartridge Unit with Luer Lock. NDC: Bundle 0409-2339-34, Carton/Cartridge 0409-2339-24; lot number HJ7566, expiration date 2025/05; lot number HN8747, expiration 2025/09; HN8749 expiration date 2025/09. Both have a concentration of 20 mg/4 mL (5 mg/mL) and are 10 carton/ cartridge units/bundle. 

While Pfizer has not received any related reports of adverse events, if an impacted product is administered, there is an increased risk for lack of efficacy and systemic infection that might require additional treatment, according to the company. Adverse events may be reported to FDA through the agency’s MedWatch program.

“Pfizer places the utmost emphasis on patient safety and product quality at every step in the manufacturing and supply chain process. Pfizer has notified direct consignees by letter to arrange for the return of any recalled product,” the company stated in a press release (1).

Buprenorphine HCl Injection, a clear, sterile, injectable agonist-antagonist analgesic intended for intravenous or intramuscular administration, is used to manage pain for which alternate treatments are inadequate. Labetalol HCl Injection is a treatment for controlling blood pressure in severe hypertension.

In December 2023, the company had another voluntary recall. That recall was of lots of 4.2% Sodium Bicarbonate Injection, USP ABBOJECT Glass Syringe, 5 mEq/10 mL; 8.4% Sodium Bicarbonate Injection, USP Lifeshield ABBOJECT Glass Syringe, 50 mEq/50 mL; and Atropine Sulfate Injection, USP Lifeshield ABBOJECT Glass Syringe, 1 mg/10 mL because of the presence of glass particulate matter found during product inspection (2).

“Potential complications related to injection of visible and subvisible inert particles include inflammation of a vein, granuloma, and blockage of blood vessels or life-threatening blood clot events. The frequency and severity of these adverse events could vary depending upon a variety of factors including the size and number of particles in the drug product, patient comorbidities (such as age, compromised organ function), and presence or absence of vascular anomalies,” the company stated in the release (2).

Hospira. Hospira Inc. Issues a Voluntary Nationwide Recall for Buprenorphine Hydrochloride Injection CarpujectTM Units and Labetalol Hydrochloride Injection, USP CarpujectTM Units Due to the Potential for Incomplete Crimp Seals.

Hospira. Hospira, Inc. Issues A Voluntary Nationwide Recall For 4.2% Sodium Bicarbonate Injection, 8.4% Sodium Bicarbonate Injection, and Atropine Sulfate Injection Due to the Potential Presence of Glass Particulate Matter. Press Release. 

The units are being recalled because of incomplete crimp seals and one complaint of a leaking unit.

Hospira Recalls Buprenorphine Hydrochloride Injection Carpuject Units and Labetalol Hydrochloride Injection, USP Carpuject Units 

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

Bristol Myers Squibb (BMS) announced on May 22, 2024 that it is creating a 10-year plan—ASPIRE (Accessibility, Sustainability, Patient-centric, Impact, Responsibility and Equity)—to expand access to its therapies to more than 200,000 patients in low- and middle-income countries (LIMCs) by 2033. The ASPIRE plan will include strategies and the development of access plans to increase affordability and availability of BMS’ medicines in LMICs to ensure 100% of the company’s marketed products are supported by access plans. 

BMS has introduced local brands of their drugs, with the company filing 11 local brands in 2023; five have received regulatory approvals. “BMS local brands are making an impact in countries [such as] Thailand, which has the highest prevalence of beta thalassemia, by providing treatment options [such as] Rojusna to help combat this widespread disease,” the company stated in a press release (1).

Part of the ASPIRE plan is for BMS to collaborate with the Access to Oncology Medicines (ATOM) Coalition to bring its cancer treatment, Opdivo (nivolumab), to Pakistan, Rwanda, Zambia, and other countries. ATOM is led by the Union for International Cancer Control and includes 40 global partners to address the challenges of availability, affordability, and appropriate use of oncology medicines.

“Access to potentially life-saving innovative medicines is very limited in some parts of the world, leaving patients with few treatment options for serious diseases [such as] cancer,” said Christopher Boerner, PhD, board chair and chief executive officer, Bristol Myers Squibb, in the press release. “Bristol Myers Squibb believes patients who can benefit from our medicines should have access to them. Our ASPIRE strategy is an important step toward accelerating and expanding patient access to these much-needed treatments.”

In countries where BMS does not have a commercial presence, the company is making its medicines available through the Direct Import and the Direct-to-Institution (DTI) pathways. BMS is providing 12 medicines using a tiered pricing commensurate to more than 80 LIMCs through the Direct Import pathway. The DTI pathway, which provides safe, broad, and timelier access to BMS medicines through collaboration with local institutions, includes efforts in five LMICs in East Africa and Pakistan and West Africa in 2025. The goal is to include more than 15 LMICs by 2026.

“By investing in solutions that reduce quality-of-care gaps and strengthen health systems, BMS will help drive equitable access to innovative medicines to patients around the world, regardless of where patients live. Enabling timely access to innovative medicines in LMICs is part of BMS’ commitment to health equity globally and our Environmental, Social and Governance (ESG) strategy,” the company stated in the release.

 that it is has established an agreement with Cellares, a US-based integrated development and manufacturing organization specializing in cell therapy manufacturing, to reserve global capacity and supply for manufacturing chimeric antigen receptor T-cell therapies. The deal is valued at up to $380 million in upfront and milestone payments (2). 

Bristol Myers Squibb Announces 10-Year Strategy to Reach More Patients in Low- and Middle-Income Countries.

Bristol Myers Squibb. Bristol Myers Squibb and Cellares Announce a $380M Worldwide Capacity Reservation and Supply Agreement for the Manufacture of CAR T Cell Therapies to Bring the Promise of Cell Therapy to More Patients, Faster. Press Release. April 22, 2024.

The company is collaborating with the Access to Oncology Medicines Coalition to expand patient access to immuno-oncology therapy Opdivo.

Bristol Myers Squibb Plans 10-Year Strategy to Expand Access to Medications

AstraZeneca announced on May 20, 2024 that it is planning a new $1.5 billion antibody drug conjugate (ADC) facility in Singapore. The new facility is supported by the Singapore Economic Development Board (EDB) and will be the company’s first end-to-end ADC production site. ADCs deliver highly potent cancer-killing agents directly to cancer cells and require multiple process steps, including antibody production, drug and linker synthesis, conjugation of the drug-linker to the antibody, and filling of the completed ADC. Among its drug candidates, AstraZeneca has six wholly owned ADCs in the clinic and others in preclinical development.

“AstraZeneca has built an industry-leading portfolio of cancer medicines including antibody drug conjugates which have shown enormous potential to replace traditional chemotherapy for patients across many settings,” said Pascal Soriot, chief executive officer of AstraZeneca, in a press release (1). “Singapore is one of the world’s most attractive countries for investment given its reputation for excellence in complex manufacturing, and I am excited for AstraZeneca to locate our $1.5 billion ADC manufacturing facility in the country.”

"We welcome AstraZeneca's decision to establish a manufacturing presence in Singapore for the first time. It will also be a first for AstraZeneca—an end-to-end manufacturing facility for novel antibody drug conjugates that enables precision therapy for cancer,” said Png Cheong Boon, chairman, EDB, in the release. “This greenfield investment is a strong show of confidence in Singapore's biopharmaceutical manufacturing capabilities and talent, strengthens our ecosystem in supporting the development and manufacturing of precision medicines, and creates meaningful jobs and economic opportunities for Singapore. We look forward to a successful partnership with AstraZeneca."

AstraZeneca will work with the Singapore's government and other partners on sustainability solutions for the new ADC facility. The company plans for the facility to have zero carbon emissions. Construction on the new facility will begin at the end of 2024 with a target of 2029 for full operation.

In an email commenting on AstraZeneca’s Singapore investment (2), 

, managing director and head of European Healthcare at Houlihan Lokey, said:

“With a wide portfolio of in-house [a]ntibody-[d]rug [c]onjugates (ADCs) at various stages of clinical and pre-clinical development, AstraZeneca’s plan to build a new facility by 2029 exemplifies the long-term strategic thinking of large-cap pharmaceutical companies aiming to control their supply chains more effectively. This move reflects the industry's recognition of the complexities and costs associated with developing and manufacturing ADCs, which necessitates substantial investment in infrastructure to ensure quality and efficiency in production.

“The construction of this facility also highlights a broader trend within the pharmaceutical industry, where strategic initiatives are being directed towards high-growth market segments. ADCs, for instance, represent a significant opportunity with an estimated market size of $10 billion, growing at a rate exceeding 15% annually, driven largely by their promising applications in oncology. By investing in dedicated facilities, companies are positioning themselves to capitalize on this rapid growth and technological advancement.

“The strategic significance of ADCs in the pharmaceutical industry is underscored by other recent high-profile acquisitions. 

AbbVie’s $10 billion acquisition of ImmunoGen

 was partly motivated by the latter's expertise in ADCs, particularly in the area of solid tumor oncology. Similarly, 

 for $43 billion significantly bolstered its oncology capabilities, integrating Seagen's pioneering ADC technology.

“These acquisitions illustrate how major pharmaceutical companies are significantly expanding their oncology portfolios and technological capabilities to maintain a competitive edge in the market. AstraZeneca in particular, stands out as a market leader in the increasingly competitive market for ADCs, with the development of the site in Singapore further cementing its position.”

1. AstraZeneca. AstraZeneca Plans $1.5 Billion Manufacturing Facility for Antibody Drug Conjugates (ADCs) in Singapore. Press Release. May 20, 2024.
2. Tomasic, P. Commenting on AstraZeneca Building a $1.5bn Manufacturing Site in Singapore. Email Distributed by Dynevor, S. Houlihan Lokey, May 20, 2024.

The new facility will be the company’s first to offer full manufacturing processing for antibody drug conjugates.

AstraZeneca Plans $1.5 Billion ADCs Facility in Singapore

The European Medicines Agency (EMA) announced on May 17, 2024 that its Pharmacovigilance Risk Assessment Committee (PRAC) has recommended the suspension of medicines that contain 17-hydroxyprogesterone caproate (17-OHPC). Drugs that contain 17-OHPC are used to prevent premature birth or loss of pregnancy. Other authorized uses include treatment of gynecological and fertility disorders.

The recommendation comes after a PRAC review that found there is a possible “but unconfirmed” risk of cancer developing in people that were exposed to 17-OHPC in the womb. The review also found that 17-OHPC is not effective in preventing premature birth and may not be effective in other authorized uses.

“In view of the concern raised by the possible risk of cancer in people exposed to 17-OPHC in the womb, together with the data on the effectiveness of 17-OHPC in its authorized uses, the PRAC considered that the benefits of 17-OHPC do not outweigh its risks in any authorized use. The Committee is therefore recommending the suspension of the marketing authorizations for these medicines. Alternative treatment options are available,” EMA stated in a press release (1).

PRAC will develop direct healthcare professional communication (DHPC) for 17-OPHC medicines that recommends use of alternative treatment options. Once approved, the DHPC will be provided to healthcare professionals by the marketing authorization holder.

Results from a large population-based study that looked at the risk of cancer in those exposed to 17-OHPC in the womb was used to make PRAC’s decision. While data suggested there was an increased risk of cancer compared to people not exposed to these medications, the study had limitations, according to PRAC. “The Committee therefore concluded that the risk of cancer in people exposed to 17-OHPC in the womb is possible but cannot be confirmed due to uncertainties” (2). PRAC also considered effectiveness data of other authorized uses of these medicines in a study of more than 1700 pregnant women with a history of preterm delivery. PRAC found 17-OHPC to be no more effective than placebo in preventing recurrent premature birth or medical complications.

In April 2023, FDA withdrew the approval of Makena (hydroxyprogesterone caproate injection) after post-marketing data found that the drug was not effective and there were risks associated with its use. Makena had been originally approved under FDA’s accelerated approval pathway in 2011 (3).

“It is tragic that the scientific research and medical communities have not yet found a treatment shown to be effective in preventing preterm birth and improving neonatal outcomes—particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women,” said FDA Commissioner Robert M. Califf in a press release at the time of the withdrawal (3). “Fundamentally, however, the touchstone of FDA drug approval is a favorable benefit-risk assessment; without that favorable assessment, the drug should not have the status of being FDA-approved.”

“We acknowledge at the outset the serious problems of preterm birth with respect to both maternal and neonatal health and the contribution of institutional forces that have led to health disparities, including preterm birth, among Black women,” said FDA Chief Scientist Namandjé Bumpus in the release. “Nothing in this opinion today is intended to minimize these concerns—to the contrary, our hope is that this decision will help galvanize further research.”

EMA. Meeting Highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 13-16 May 2024. Press Release. May 17, 2024.

EMA. Hydroxyprogesterone Caproate-containing Medicinal Products–Referral. 

FDA. FDA Commissioner and Chief Scientist Announce Decision to Withdraw Approval of Makena. Press Release. April 6, 2023.

After a review, the agency concluded there was a possible risk of cancer to those exposed to 17-hydroxyprogesterone caproate in the womb.

EMA Suspends Hydroxyprogesterone Caproate Medicines in Europe

Regeneron’s Bari Kowal gave insight into how the biopharma industry views the application of AI in R&D.

Exploring the use of AI in R&D at the US Pharma and Biotech Summit

® at the US Pharma and Biotech Summit, Regeneron's Bari Kowal, senior vice-president, head Development Operations & Portfolio Management, talked about the implementation of artificial intelligence (AI) in the R&D space. For example. Regeneron, Kowal explained, has been using AI for quite some time. Though not a new technology, she observed, AI has allowed the company to leverage many large language models and advanced searches for the past few years. Because of this, the company has built up collections of data in different areas, such as in genomics, protein databases, or for operational uses, including patient populations, study-level data, information about investigators, and quality of documents, among others.

“[Much] of our work is crossing over multiple facets of the drug development lifecycle early on in the discovery space, looking at how we manufacture and improving those processes, but also really looking at how we execute trials and reach out to the patients create diversity in the populations,” Kowal said. “We utilize some of the genomic data for finding the targets and more personalized medicine. [There are many] ways that we're leveraging AI.”

However, she emphasizes that the real value of AI is the ability to use it for existing data, especially in the search for optimizing operational efficiency. “Looking in the future, how do we use this to help our decision making and really better predict molecules that will have a tremendous effect? The biggest benefit that I can see, at least today, is that operational efficiency. If we can streamline drug development, from start to finish, our mission is to bring important medicines to patients at the end of the day, and so the time it takes today for drugs to be developed is too long. It's not measured in years, it's measured in decades,” she remarked. “If we can go from the research space to the development space in [a] few years, that is so much better and more beneficial to the patients that are waiting for those treatments.”

While speaking on a panel at the summit about diverging schools of thought on how AI should be used in R&D, Kowal observed that there were not necessarily divergent views by the panelists on how to use AI, but rather that the panelists had like-minded views on the topic. “I think we all believe that AI can be transformative. I think we believe that, ultimately, we're scratching the surface of what AI can do, but we also understand the human component and the context of human intelligence that you have to apply,” she stated.

 occurred on May 16, 2024 in New York, NY.

Videos

Bari Kowal, senior vice-president, head Development Operations & Portfolio Management, Regeneron, discussed the utility of AI and how it can benefit R&D work.

A Discussion on Using AI in R&D at the US Pharma and Biotech Summit

Jeff Odum, CPIP, is practice lead, ATMPs & Biologics, at Genesis AEC.

Multimodal manufacturing is a strategic approach that harnesses the power of diverse manufacturing methods to optimize and streamline the production process, specifically within the realm of human therapeutics in the advanced therapy medicinal products (ATMP) space. This concept involves integrating different manufacturing techniques/platforms to improve efficiency, reduce costs, and enhance the overall quality of the manufacturing process and the eventual therapeutic product slated for licensure. 

Exploring Multimodal Biomanufacturing and Its Drivers

Pharmaceutical Technology’s Trends in Manufacturing

In a White House report, Bold Goals for US Biotechnology and Biomanufacturing, a prominent objective is to test and de-risk new biomanufacturing practices for next-generation biotechnology products in commercial manufacturing facilities (1). The growing focus in cell-based therapies, a key component of the next generation of human therapeutics, has led many organizations to focus their development efforts into a multitude of platforms.

Multimodal is not new. For the ATMP space, it was identified back in 2017 as a viable manufacturing option for clinical needs. In the context of the biotechnology ATMP space, multimodal manufacturing techniques are being applied to optimize the production of complex biological compounds and therapies that are studied in multi-omic research, such as gene editing (1).

In reality, many contract development and manufacturing organizations have been operating in a quasi-multimodal manner for decades. Multimodal can include vaccines, monoclonal antibodies (mAbs), viral vectors, plasmids, allogeneic cell therapies, and autologous cell therapies. The challenge is crafting a manufacturing plan that supports one’s business without attempting to become a one-size-fits-all solution for every need.

The forecasted growth of the cell and gene therapy (CGT) market is significant. The ATMP space, where CGT continues to serve as the primary catalyst for growth, is predicted to grow at a compound annual growth rate of 39.4% for the period from 2024 until 2030 (2).

In this growth projection, cell therapies account for 15% of the growth and gene therapies account for another 30% of growth, with many of these products advancing out of early-stage clinical manufacturing toward commercialization (2).

Just as the 1990’s large-molecule market saw a “fork-in-the-road” decision regarding single vs. multi-product manufacturing and the technologies to implement (3), the ATMP space is grappling with critical questions around asset size, cost, technology implementation, flexibility, scale, and many others. Transitioning to a multimodal manufacturing strategy could very well emerge as the most prudent business and operational solution.

Another key driver fueling the multimodal manufacturing discourse is the rapid pace of advancement in research, developing different modes of therapy to address multiple human therapeutic targets. Combination therapies using multiple therapeutic modalities have elevated anti-cancer activity while lowering doses of agents, thus reducing side effects (4). As previously referenced, gene editing tools such as clustered regularly interspaced palindromic repeats (CRISPR)-Cas, transcription activator-like effector nucleases (TALENs), and base editing have brought about multiple therapeutic solutions that are being provided for chronic diseases and oncolytic cancer treatments, as well as advanced chimeric antigen receptor T cell (CAR-T) and T-cell receptor (TCR) therapies.

Pharmaceutical Technology’s Trends in Manufacturing May 2024 eBook

1. The White House. Bold Goals for US Biotechnology and Biomanufacturing: Harnessing Research and Development to Further Societal Goals. White House, Executive Order 14081, March 2023.
2. Vision Research Reports. Cell and Gene Therapy Market (By Therapy Type: Gene Therapy, Cell Therapy; By Application: Oncology, Genetic Disorders, Dermatology Disorders, Musculoskeletal Disorders, Others; End-Users: Hospitals, Cancer Care Centers, Wound Care Centers, Others)—Global Industry Analysis, Size, Share, Growth, Trends, Regional Outlook, and Forecast 2022-2030. Market Research Report, July 2022.
3. Witcher, M.F.; Carbonell, R.;Odum, J.; et al. Facility of the Future: Next Generation Biomanufacturing Forum Parts I, II, III. 

When referring to this article, please cite it as Odum, J. Exploring Multimodal Biomanufacturing and Its Drivers. 

A combination of rapid sterility methods with the industry standard compendial method should ensure maximum safety.

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