Increasing molecular diversity is creating a need for the reinvention of process development and control strategies.

Process Development and Control for New Modalities

A thorough knowledge of both the upstream and downstream processes is required to ensure effective removal of residual impurities in biopharmaceuticals.

Removing Residual Impurities

Pharma companies set goals and adopt more sustainable alternatives.

Consumers Seek Sustainable Products

Learning from early market failures, the biopharma industry has worked to improve the fate of antibody drug conjugates.

Improving the Fate of ADCs

Experts reveal how to identify the “right” biochemical, the process of sourcing biochemicals, sourcing challenges, and what industry professionals should know about the space. 

Upstream Processing: Biochemicals and Raw Materials

Industry experts discuss best practices for certificates of analysis.

The Role of CoAs in Supplier Oversight

Various advances in contamination control are being utilized to reduce the chance pollutants contaminate a drug product.

The State of Contamination Control

Robert Thomas is a member of the Inorganic Subcommittee of the ACS Reagents Chemicals Committee.

High quality regent chemicals are crucial to the integrity of analytical testing for research and development purposes, as well as in the manufacturing of drug formulations. To meet these demands, the American Chemical Society (ACS) Committee on Reagent Chemicals has compiled the "de facto" source of monographs for ACS-grade reagent chemicals including guidelines, specifications, and analytical procedures, which is recognized by the US Pharmacopeia in its 

For the first time since its publication, ACS Reagent Chemicals is now available online in a searchable database, that can be accessed by anyone, anytime, anywhere in the world. Pharmaceutical’s producers can now learn how this resource can benefit their organization via:

Strategies to maintain compliance with regulatory agencies

Tips to expedite pharmaceutical development

Purity specifications for over 500 ACS reagent chemicals

A case study on replacing the sulfide precipitation test for heavy metals with plasma spectrochemistry

Guidelines for implementing meaningful validation protocols.

For more information, the full white paper can be downloaded 

Articles

The complete online database of ACS Reagent Chemicals is now available.

ACS-Grade Reagents’ Database Launched

Tareq Jaber, tareq.jaber@crl.com, is associate director at Charles River Laboratories.

Anja Tessarz, Anja.Tessarz@crl.com, is associate director RGDB, SME Viral Clearance at Charles River Laboratories.

Viral clearance (VC) studies are mandatory for biologic drugs, which are pharmaceutically derived from human and/or animal sources such as cell line-derived recombinant proteins, blood products, vaccines, and critical medical devices. In these studies, the potential of removal and/or inactivation of adventitious and endogenous viruses of certain steps of the manufacturing purification process is addressed in a small-scale approach. Though regulatory guidelines are in place, the design of such a VC study is often not as straightforward as expected. The current guidelines do not keep up with the fast pace of the industry in terms of acquired knowledge, evolvement of new product categories, new methodology, and new production modes, which often leaves room for interpretation. In addition, there are other challenges and pitfalls that need to be taken into consideration when performing VC studies. This article will cover VC studies, their challenges, and the quickly evolving biologic drugs industry.

The first recommendation addressing the VC for biologics produced in cell lines was published by FDA in 1993 (1). Followed by the first VC guideline from the European Medicines Agency (EMA) in 1995, which covers all the categories of medical biological products for human use, with the exception of live viral vaccines, including genetically engineered live vectors (2). After almost 30 years, the reference guidelines do not cover the non cell line-derived biologics, which are also not addressed in raw-material-specific guidelines, including the urine-derived medical products (3) or the human blood plasma products (4). The reference guideline cell line for cell line-derived biologics from the International Council for Harmonisation (ICH), the ICH Q5A (5), was initially released in 1997, revised two years later, and is currently undergoing a long overdue revision. Meanwhile, several other guidelines and recommendations have been released. Despite these documents being in place, for manufacturers to decide on a VC study scope, they still must consider many aspects as guidelines are often only valid in certain countries.

In general, the regulatory guidelines ask biomanufacturers to prove the potential of at least two separate process steps independently. As a consequence, a combination of solvent/detergent and/or low pH treatment followed by a chromatography and virus-retentive filtration is being addressed. When it comes to the virus panel to be tested, the guidelines highly recommend addressing the known or suspected contaminates while covering all biophysical properties in terms of RNA or DNA, enveloped and/or non-enveloped viruses. Therefore, each VC study must be reviewed on a case-by-case basis to evaluate the risk factors associated with each tested product, including raw materials.

In the past 20 years, VC knowledge and data has accumulated especially for Chinese hamster ovary (CHO)-derived recombinant products. Additionally, considerations to reduce the VC study scope (e.g., standardized protocol ASTM E2888-12R19) for low pH treatment has been taken into account in which, under certain requirements, a 5 log10 clearance for murine leukemia virus (MuLV) can be claimed. However, the increase in knowledge and recommendations are only in place for certain territories, which raises the uncertainty and challenges in the industry regarding VC study scopes.

One challenge in VC studies is the demand of a scaled-down version of the process step. When scaling down is accomplished successfully, and its validity is demonstrated, a second challenge follows in that this established scaled-down version has to be communicated to a VC testing team. This team works in a laboratory setting, which is separated from the production site to prevent contamination of manufacturing processes. Often times, the VC studies are carried out by an external contract research organization. Therefore, a good understanding of the process and efficient communication between the manufacturer and the VC testing team are crucial for a seamless VC study.

Recently, as the industry optimizes their manufacturing processes to increase profit, new challenges have arisen. For instance, product concentrations are massively increasing in manufacturing. This increases the general risk of aggregation, especially upon addition of a high-titer virus spike that is being added for VC testing. In many cases, this also requires additional adjustments of common de-coupled VC study set-ups to inline process. This is a specific process where pre-filtering is employed directly before the chromatography or virus-retentive filter, which, due to the more sensitive material, cannot be de-coupled. Even though data obtained in recent years indicate that some pre-filters do indeed have the potential to remove viruses, the potential cannot be claimed. Authorities argue that integrity tests for these filters are not in place. Hence, the impact of the pre-filter on its own has to be addressed in addition to the inline set-up.

Another aspect is that biomanufacturing is transitioning from batch-mode processing to continuous processing (CP). This transition, of course, bears an exceptional challenge when it comes to establishing a scaled-down model and calls for innovative alternatives, which results in specifically tailored scaled-down models for VC testing purposes that should take into consideration the integration of linked-unit operations. Additional key issues for both increased protein concentrations and CP in manufacturing include the increases in volumetric throughput and product load across a retentive filter, which will cause virus breakthrough once critical thresholds are met. Thus, suitable sizing and scaling of the retentive filter is of paramount importance to accommodate the increased load.

Maintenance of a high standard of purity is a requirement of any biotherapeutic products. Many of the biotherapeutic products utilize cell culture for production, which increases the risk of contamination. Therefore, it is crucial for VC to be part of the known three principles—selection, testing, and reduction—to prevent the transmission of pathogens, in addition to sourcing and testing. Recently, it was shown that no manufacturer is immune to contamination events (6). In this study, though only 18 cases of contamination were reported in 35 years (6), contamination is still a real threat to all industries, including gene therapy. Contamination can occur in all stages of a product lifecycle. According to Barone 

, most of the contamination in CHO-cell-derived products originated from raw materials or intermediate components, while most of the contamination in human/primate cell lines originated from manufacturing operators or the cell line itself (6).

What about gene therapy products? What is the source of contamination? Considering the adeno-associated virus (AAV) system as an example, cell lines and helper viruses can be the potential source of contamination. Therefore, biological starting materials for gene therapy products are considered key in the assessment of viral safety testing and VC. The adventitious agents can be introduced into the manufacturing process using those biological starting materials, reagents, and raw materials such as animal-derived serum. Moreover, over the past decade, there is a steady increase in investigational new drug (IND) filings of gene therapy products. Because of the backlog for manufacturing, which is a result of limited manufacturing facilities, gene therapy products are increasingly manufactured at multi-product facilities. This situation increases the possibility of unintentional introduction of adventitious agents into the manufacturing process due to cross-contamination at multi-product facilities and raises several questions: what is the best course of action for manufactures to employ? Are there any specific guidelines that can be followed to evaluate if VC studies are needed, and how they can be applied? Unfortunately, there are no current and specific guidelines to direct the gene therapy industry to the required steps to follow regarding VC validation. Based on regulatory agencies, especially FDA, the current available documents might be used as reference guidelines. Some of these documents include the ICH Q5A 

Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin

Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications

The principles of ICH Q5A cover topics that can be applied to gene therapy products. For instance, according to the ICH Q5A document, contamination could arise from the cell line starting material by use of contaminated cell substrate or by endogenous contaminants, which can be applied to some gene therapy products. Systems that use baby hamster kidney (BHK) cells with potential retrovirus-like particles (RVLPs); systems that use human embryonic kidney 293 (HEK293 cells) with potential adenovirus contamination; and systems that use Spodoptera frugiperda 9 (SF9) cells with potential rhabdovirus contamination are examples of cell-line-derived contamination risks. Other sources of contamination include raw materials serum/medium, process-related components, such as helper viruses (e.g., baculovirus and adenovirus), and manufacturing operators or the facilities themselves.

It must be kept in mind that VC is not required for all early stages of gene therapy products as it is in recombinant protein products. If there is no risk of copurification of a helper virus or of an adventitious virus (e.g., from the cell line, such as an endogenous retrovirus or rhabdovirus, or from raw material), then a VC study might not be required in the early stages in such cases. The risk assessment for adventitious agents should be performed by each sponsor on a case-by-case basis to assess if VC is needed.

On the other hand, VC is required in certain conditions. The baculovirus/SF9 system can be used as an example of how to address some of the challenges that a system faces under a VC evaluation. Although the helper virus is not a human virus, and the system is mainly serum-free, there is a potential of detecting contaminants in the final product. There are two common sources of contaminations: Sf-rhabdovirus (Sf-RhV) and the baculovirus helper virus itself. Sf-RhV was one source of contamination that was reported in Sf9 cells (7). Small amounts of Sf-RhV particles in the final product may be immunogenic and can cause inflammation. Meanwhile, regarding the baculovirus helper virus, residues of this helper virus were detected in the final product, and those residues also have the potential to activate the innate immune system. Therefore, a VC study should be applied in this case.

One of the challenges in VC studies arises when it is applied to Sf9/baculovirus products because high residues of baculovirus are detected in, not only the harvest material and affinity chromatography load, but also the affinity product and anion exchange chromatography load material. These high residues of virus can impact the sensitivity of VC assays (either in a cell-based assay or in a quantitative polymerase chain reaction [PCR]). It is difficult to overcome the high-endogenous-virus-level background without applying significantly high non-toxic/non-interfering dilutions, which, consequently, will impact the titration limit of detection. This background might be higher than the total load titer of the baculovirus model that is spiked in the load material during the performance of the VC study.

One of the options to overcoming this issue is to use the residues of baculovirus in the tested material as the target virus to be removed or inactivated by the evaluated steps in the VC study, instead of spiking an additional baculovirus in the material.However, the obstacle here is that all the titration assay systems that are used by VC vendors are validated based on their own cell banks and virus banks. Each SF9/baculovirus system’s manufacturer must first establish a validation study at the VC facility to validate the titration assay for their specific baculovirus on the vendor’s cell system. This validated assay can be used mainly in the detergent treatment and affinity chromatography steps in VC studies.

What about other gene therapy viral vector systems, such as lentivirus and herpes simplex virus (HSV)? While it is still applicable to evaluate inactivation steps (e.g., detergent and heat treatments, and a nano-filtration step with certain sizes, such as 30–35-nm filters) in VC studies for AAV systems, these steps cannot be considered with gene therapy products using enveloped virus systems that are larger sizes than AAV. Chromatography steps might be the only options that can be employed to evaluate the downstream processes.

Because the possibilities of applying virus clearance steps during production are limited for many types of gene therapy products, the viral safety of these products should be ensured with the application of a combination of measures, including selection and control of starting materials, raw materials, and equipment. One possible solution involves the prevention of contamination at the upstream level, such as, for instance, implementing methods to remove or inactivate viruses in media or components (e.g., ultraviolet-C, irradiation, high temperature, nanofiltration), development of media that do not require animal/human-derived raw materials, and use of closed systems to avoid contamination by environmental sources, where applicable.

The most common downstream steps in gene therapy products that can be evaluated for VC studies are summarized in 

 Potential virus clearance process steps. AAV is adeno-associated virus. HSV is herpes simplex virus. AEX is anion exchange.

Finally, the viral safety of each gene therapy must be ensured; this procedure is summarized in EMA’s 

Guideline on the Quality, Non-clinical and Clinical Aspects of Gene Therapy Medicinal Products

“Contamination with extraneous viruses and residues of viruses used during production, such as production and helper viruses needs to be excluded as far as possible … Rigorous testing of seed and cell banks, intermediates, and end products for the presence of adventitious virus needs to be conducted in accordance with principles outlined in ICH guideline Q5A (R1)” (8).

The guideline highlighted the importance of testing raw materials of biological origin thoroughly or manufacturing them by production processes that can remove/inactivate adventitious and endogenous viruses. Therefore, when applicable, VC studies should be considered to validate these production processes to determine the reduction factors for each of the tested steps (8).

Points to Consider in the Characterization of Cell Lines Used to Produce Biologics

 (CBER, 1993).
2. EMA, EMA/CPMP/BWP/268/95, 

Note for Guidance on Virus Validation Studies

 (Feb. 14, 1996).
3. EMA, EMA/CHMP/BWP/126802/2012, 

Guideline on the Adventitious Agent Safety of Urine-Derived Medicinal Products

 (May 26, 2015).
4. WHO, “WHO Guidelines on Viral Inactivation and Removal Procedures Intended to Assure the Viral Safety of Human Blood Plasma Products,” 

, 2004 Annex 4 (March 1, 2004).
5. ICH, Q5A(R1) 

Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin

, Step 4 version (1999).
6. P.W. Barone, et al., 

 38 (5) 563–572 (2020 ).
7. P.H. Ma, et al., 

 88 (12) 6576–6578 (2014).
8. EMA, EMA/CAT/80183/2014, 

Tareq Jaber, tareq.jaber@crl.com, is associate director, and Anja Tessarz, Anja.Tessarz@crl.com, is associate director RGDB, SME Viral Clearance; both at Charles River Laboratories.


Vol. 35, No. 12
December 2022
Pages: 18–21,33

When referring to this article, please cite it as T. Jaber and A. Tessarz, “Viral Clearance Studies: Challenges and Beyond,” 

The design of viral clearance studies must keep pace with the quickly evolving biologic drugs industry.

Viral Clearance Studies: Challenges and Beyond

Catalent announced on Dec. 1, 2022 that it has completed the expansion of its clinical supply facility in the Waigaoqiao Free Trade Zone (FTZ) in Shanghai, China.

The expansion increased the facility by approximately 30,000 ft2, which has allowed for the installation of additional refrigerated and deep-frozen storage, as well as expansion of secondary packaging capabilities. The completion of the facility will be marked by two events on Dec. 1 and Dec. 6, 2022, where the facilities at the site will be showcased and workshops on clinical supply management and new GMP policies will be held.

The Waigaoqiao facility is one of two clinical supply facilities that Catalent operates in Shanghai; the other is located in Tangzhen, outside of the FTZ. The two facilities provide sponsors with optimized supply solutions for studies being undertaken in China, the Asia-Pacific region, and globally. These include clinical supply management, comparator sourcing, FastChain demand-led supply, primary and secondary packaging, storage, and global distribution, as well as clinical returns and destruction.

“China is the fastest growing clinical trials market in the Asia-Pacific region, and Catalent continues to invest and expand its facilities and services to offer reliable, flexible, and integrated support to customers,” said Tracey Clare, general manager, APAC Operations, Catalent, in a company press release. “These additional capabilities increase the site’s ability to support clinical trials for advanced therapeutics, which often require specialized storage and handling capabilities.”
Source: 

Catalent has completed the expansion of its clinical supply facility located in Shanghai, China. 

Catalent Completes Expansion of Clinical Supply Facility

Eisai and Biogen announced results from Eisia’s global Phase III confirmatory Clarity Alzheimer’s disease (AD) clinical study of lecanemab on Nov. 29, 2022. Lecanemab is an investigational anti-amyloid beta protofibril antibody intended for the treatment of mild cognitive impairment (MCI) stemming from AD and mild AD (also known as early AD) with confirmed presence of amyloid pathology in the brain.

The study was a placebo-controlled, double-blind, parallel-group, randomized study of 1795 people with early AD in North America, Europe, and Asia. According to a company press release, the primary endpoint was change from baseline at 18 months in the clinical dementia rating sum of boxes (CDR-SB), a global cognitive and functional scale.

The mean change of CDR-SB in patients who received lecanemab was 1.21, while patients who received placebo had a mean change of 1.66, which the researchers found to be highly statistically significant. Key secondary endpoints, such as reduction in amyloid plaque burden, slowed decline of cognitive function on the Alzheimer’s disease assessment scale–cognitive subscale, and a decline of daily living activities, also showed statistically significant responses relative to placebo.

“Today’s exciting results offer our best hope yet for not only delaying symptom progression for people with early stage Alzheimer’s, but, significantly, slowing the loss of quality of life for them and their carers,” said Dr Richard Oakley, associate director of research, Alzheimer’s Society, in an agency press release concerning the findings.

Results from Eisai and Biogen’s Alzheimer's treatment, lecanemab, indicated significantly slowed cognitive decline in patients relative to placebo.

Eisai and BioGen Alzheimer’s Drug Shows Promising Results in Phase III Study

Merck, known as MSD outside of the United States and Canada, and BigHat BioSciences, a biotechnology company specializing in machine learning (ML)-guided antibody discovery and development, announced a research collaboration on Nov. 29, 2022 in which Merck will use BigHat’s Milliner platform to design candidates for up to three drug discovery programs.

According to a company press release, the Milliner platform combines high-speed characterization with ML capabilities to engineer antibodies with more complex functions and better biophysical properties. The goal of this approach is to reduce the difficulty of optimizing antibodies and other therapeutics.

“We are excited to begin this collaboration to advance next-generation antibody therapeutics to patients,” said Elizabeth Schwarzbach, chief business officer, BigHat, in the press release. "This agreement with Merck brings us a major step closer to our goal of [three to five] deep collaborations with leading biopharma [companies] to complement our internal therapeutic pipeline."

“This agreement with BigHat expands Merck’s strategy of applying AI [artificial intelligence]/ML across our drug discovery capabilities,” said Juan Alvarez, vice-president of Biologics Discovery, Merck Research Laboratories, in the release. “We look forward to working with the team to leverage BigHat’s technology and expertise in enabling molecular design of novel biologic candidates.”

Merck will use BigHat’s AI/machine learning-enabled platform to design candidates for up to three drug discovery programs.

Merck and BigHat BioSciences Partner on Drug Discovery Programs 

Chris Spivey is the editorial director of 

The combined market capitalization of the five companies focusing on messenger RNA (mRNA) platform development was approximately US$15 billion at the end of 2019 and more than US$300 billion as of August 2021, according to Xie 

(1). While that’s staggering, in many ways its entirely understandable. In October 2022, I helped organize and run a high caliber event in San Diego, CA for “mRNA day” with TriLink BioTechnologies, to discuss common manufacturing, supply, and regulatory challenges relating to mRNA as a platform. Interspersed between the high cost of required enzymes, the need to be serious about how to manage DNA as a starting medium, and cut off points for potency assays, we devoted significant time and energy to discussing what benefits might accrue from establishing a supplier-developer consortium.

Standards and regulatory streamlining came quickly. But during a hour-and-a-half panel, we added the idea of a central railway station system for supply shortage oversight, easy access to best new publications, and centralized advocacy for staff recruitment though university and technical college classes, alongside staff training best practices generally. Because of the tricky intellectual property landscape and competitive commercial aspects involved, we all thought “consortia” might have unhelpful exclusionary connotations. “Alliance” or “organization” was accepted as reducing hesitancy instead. It was a genuine pleasure and delight to be part of this wonderful event. We said heartfelt goodbyes, I took a deep breath, then headed off to the high-octane capaciousness of CPHI Frankfurt, and thence a deserved week’s holiday in Germany.

Tuning out work for a week was delightful, refreshing, and against expectation. Arriving at each new city, getting our bearings required tuning into WiFi at the train station (Hauptbanhof). Each and every time, a new message also turned up from one of the San Diego attendees. They had “been thinking” and wanted to share a “new suggestion” for a secondary role the mRNA alliance might play. When an idea follows you around the globe, when you feel tracked down at a train station, you know something special is happening. This feels like the field of proteomics 20 years ago. There is a real need for both consolidation and standardization of resources. It’s not a train we necessarily all need to get onboard immediately, but we should know where the central train station is located, and what it connects us to.

1. W. Xie, B. Chen, and J. Wong, “Evolution of the Market for mRNA Technology,” Nature Reviews Drug Discovery, 


Volume 46, Volume 12
Dcember 2022
Page: 10

When referring to this article, please cite it as C. Spivey, "mRNA Hauptbahnhof," 

mRNA may not be a train we necessarily all need to get onboard immediately, but we should know where the central train station is located, and what it connects us to.

mRNA Hauptbahnhof

Mike Hennessy Jr. is the President and CEO of 

No matter how busy or complicated life becomes, science news can occasionally stop us in our tracks. Science news can be just so weird, or weirdly useful, that everything else recedes as we ponder whether it is true and what consequences it might bring.

For example, the armadillo is the only known host for the leprosy bacterium other than humans. Unimpressed? What if I told you this bacterium has the power to convert one type of bodily tissue into another? Results from a recent study show that the liver nearly doubles in size in armadillos infected with the leprosy bacterium (1). This kind of growth on the surface looks destined to be defective or even cancerous (inherent to some cell and gene therapy approaches) but the livers in the infected animals were found to be both healthy and functional, including the full complement of blood vessels, enzymes, and bile ducts that would be found in a normal liver. Professor Anura Rambukkana, who led the study, heads a group in regenerative medicine at the University of Edinburgh, that for the last decade has been pioneering an approach around cellular reprogramming. The leprosy causing bacterium hijacks the plasticity of adult tissue niche Schwann cells, reprograming them to modified stem cells, weirdly, to simply have more tissue to feed off.

There may be several practical outcomes from elucidating this mechanism. The leprosy bacterium practices this biomolecular “alchemy” at a relatively slow and natural pace, largely outflanking paths typically understood to also promote cancer growth. Because the bacterium is doing this for reasons of prosecuting its plans to “infect” its host, understanding details here may well lead to new avenues to treat or inhibit infectious disease and related pathologies such as inflammation. On his university webpage, Rambukkana states, “We are also studying how these reprogrammed progenitor/stem cells can be combined with endogenous innate immune cells with natural regenerative properties to promote repair processes in demyelinating neurodegenerative, neuromuscular, and liver diseases in varying model systems” (2).

It feels odd to say it, but I am now genuinely looking forward to hearing more about what leprosy can do for us in the future. Science, or knowledge of how the natural world works, is full of unexpected twists and turns, heroes and villains, saints and sinners. If we can turn the tables and make a villain a hero—how wonderful will that be!

When referring to this article, please cite it as M. Hennessy, “Of Mice and Men and Armadillos,” 

Science news can be just so weird, or weirdly useful, that everything else recedes as we ponder whether it is true and what consequences it might bring.

Of Mice and Men and Armadillos

Immutep, a clinical-stage biotechnology company, announced that it had signed a second clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany, and Pfizer, on Nov. 29, 2022. The new agreement concerns INSIGHT-005, a Phase I clinical study of Immutep’s lead candidate eftilagimod alpha, a soluble lymphocyte activation gene 3 fusion protein, in combination with avelumab in patients with urothelial cancer. It follows the INSIGHT-004 trial, which evaluated the treatment in patients with advanced solid cancers and posted results in June 2021.

According to a company press release, INSIGHT-005 will be an investigator-initiated explorative, open-label study evaluating the safety and efficacy of the drug in up to 30 patients with metastatic urothelial cancer. Jointly funded by Immutep and Merck KGaA, the study will be conducted in Germany by the Institute of Clinical Cancer Research, Krankenhaus Nordwest. It is expected to begin enrollment in the first half of 2023.

“We are very pleased to be deepening our collaboration with Merck KGaA, Darmstadt, Germany and Pfizer through this new study in patients with urothelial cancer, the sixth most common cancer in the US, who are in need of treatment options,” said Marc Voigt, CEO, Immutep, in the release.“INSIGHT-005 builds on the encouraging clinical efficacy and safety previously reported from the combination of [eftilagimod alpha] and avelumab in various solid cancers, including deep and durable responses in patients with low or no [programmed death-ligand 1] expression and in indications that typically do not respond to immune checkpoint therapy.”

The agreement will see Immutep and Merck KGaA, Darmstadt, Germany jointly fund the INSIGHT-005 study.

Pfizer, Merck KGaA, and Immutep Enter into Second Clinical Trial Collaboration Agreement

AstraZeneca announced its acquisition of Neogene Therapeutics, a clinical-stage biotechnology company developing next-generation T-cell receptor therapies (TCR-Ts), on Nov. 29, 2022. AstraZeneca will pay $200 million in upfront fees, with an additional $120 million to be paid in both contingent milestones and non-contingent consideration. The transaction is expected to close in the first quarter of 2023.

Neogene Therapeutics has focused on developing TCR-Ts for the treatment of cancer. According to a company press release, while most T-cell therapies focus on modifying the immune system’s T cells to recognize proteins expressed on the surface of cancer cells. TCR-Ts, however, can recognize intracellular targets like cancer-specific mutations, which presents opportunities for previously inaccessible targets.

“This acquisition represents a unique opportunity to bring innovative science and leading experts in T-cell receptor biology and cell therapy manufacturing together with our internal oncology cell therapy team, unlocking new ways to target cancer,” said Susan Galbraith, executive vice-president, Oncology R&D, AstraZeneca, in the press release. “Neogene’s leading TCR discovery capabilities and extensive manufacturing experience complement the cell therapy capability we have built over the last three years and allow us to accelerate the development of potentially curative cell therapies for the benefit of patients.”

“We are excited to work together with AstraZeneca towards our shared mission of transforming the treatment options for patients with solid tumors using next-generation [TCR-Ts],” said Carsten Linnemann, CEO, Neogene, in the release. “Our expertise, clinical portfolio and platform technologies in this area combined with AstraZeneca’s leadership in oncology and global footprint mean we are well-positioned to translate pioneering science into novel treatments for hard-to-treat cancers.”

AstraZeneca inked a deal worth up to $320 million to purchase Neogene Therapeutics, a biotech start-up focused on T-cell receptor therapies.

AstraZeneca Acquires Neogene Therapeutics for $320 Million

Aptamer Group, a synthetic antibody provider, announced the opening of its new facility in York Science Park, United Kingdom, on Nov. 28, 2022. The 18,000 ft² facility is designed to increase capacity and facilitate delivery of the company's Optimer binders, next-generation aptamers that can be used as synthetic antibody alternatives. In addition to discovery and development, a portion of the new lab will be dedicated to validation and assay development.

“We are excited to move to the new purpose-developed site for Aptamer Group,” said Arron Tolley, CEO, Aptamer Group, in a company press release. “This will enable us to keep up with the increased demand for our Optimer technology and the growth of the team at our new larger lab and office facilities. This expansion will mean Aptamer is able to work on larger-scale projects that can be processed faster to support our partners with Optimers as a robust and much-needed alternative to antibodies.”

Aptamer’s new 18,000 ft² facility will expand the company's capacity to deliver novel binders for bioprocessing, diagnostic, and drug development.

Aptamer Group Opens New Facility in United Kingdom

Etihad Cargo has been awarded Center of Excellence for Independent Validators (CEIV) Pharma recertification by the International Air Transport Association (IATA), and it is one of the only 37 airlines to hold IATA CEIV Pharma certification globally, according to the company. 

The achievement of IATA CEIV Pharma certification was first achieved in 2019 in conjunction with the hub at Abu Dhabi International Airport and Etihad Airport Services Cargo. Following this, Etihad went on to become the first airline in the Middle East and the third globally to hold the trilogy of CEIV Pharma, CEIV Fresh, and CEIV Live Animals certifications. 

The recertification was achieved following an audit by independent validators that assessed the carrier’s capacity to control and enhance its processes through a checklist that focused on Etihad’s Cargo’s Quality Management System that incorporates elements such as supplier management, training programs, processes and procedures, audit programs, and quality enhancement. 

Reaching recertification status represents the company’s dedication to pharmaceutical transportation product PharmaLife’s full compliance with specific pharmaceutical regulations, like IATA Temperature Control Regulations (TCR), Good Distribution Practices (GDP), a quality system for warehouses and distribution centers dedicated to medications and life sciences products.

"Etihad Cargo is proud to achieve IATA CEIV Pharma recertification following an extensive audit. This industry-wide standard ensures Etihad Cargo's operations and staff comply with all applicable standards, regulations and guidelines expected from pharmaceutical manufacturers. The benefits of CEIV Pharma certification extend to Etihad Cargo's customers, who can be assured the carrier's dedicated pharma cargo management constantly monitor and analyze the quality and safety of Etihad Cargo's PharmaLife product performance,” said Martin Drew, senior vice president, Global Sales & Cargo at Etihad Aviation Group, in a press release. "Etihad Cargo fully supports Abu Dhabi's vision of becoming a life sciences and pharmaceutical hub. Achieving recertification and providing world-class pharmaceutical logistics solutions demonstrates Etihad Cargo's capabilities in seamlessly transporting life-saving medicines and the latest treatments around the world from the carrier's Abu Dhabi hub."

Etihad Cargo is one of the only airlines to hold IATA CEIV Pharma certification globally. 

Etihad Cargo Achieves IATA CEIV Pharma Recertification for Pharmaceutical Logistics

Novartis and Medicines for Malaria Venture (MMV) have decided to progress ganaplacide/lumefantrine-solid dispersion formulation (SDF) into Phase III development for the treatment of patients with acute uncomplicated malaria due to 

. This decision comes from the threat of resistance to current malaria treatment growth.

Ganaplacide is a novel agent combined with a new formulation of lumefantrine optimized for once-daily dosing, and it has the potential to clear malaria infection, like artemisinin-resistant strains, and to block the transmission of the malaria parasite.

 malaria is primarily treated with artemisinin-based combination therapies (ACTs), like artemether-lumefantrine, and are still highly effective and well tolerated.

A Phase II, open-label, randomized controlled study was conducted in 524 adults and children with acute uncomplicated malaria due to plasmodium falciparum infection. Further, the ganaplacide/lumefantrine-SDF combination met the primary objective in both adults and children. The patients who received a once-daily dose of ganaplacide/lumefantrine-SDF throughout a three-day duration had a similar response to treatment to the rate observed in patients who received twice-daily artemether-lumefantrine control therapy during three days.

A large Phase III pivotal trial that is set to start in 2023 will compare the efficacy of ganaplacide/lumefantrine-SDF to the current “gold standard” artemether-lumefantrine.

“The emergence of artemisinin resistance demands urgent action to develop new antimalarials. We need non-artemisinin-based medicines with novel mechanisms of action against resistant parasites, and simple, easy-to-follow dosing schedules to help increase treatment adherence,” said Sujata Vaidyanathan, MD, Head Global Health Development Unit, Novartis, in a press release. “The earlier we have new compounds and the faster the world adopts them, the better chance we stand of beating resistance.”

FDA granted Fast Track Designation and Orphan Drug Designation in August 2022 for the combination of ganaplacide and lumefantrine-SDF for the treatment of acute, uncomplicated malaria.

“We are increasingly seeing parasites with decreased sensitivity to artemisinin, even in Africa,” said Timothy Wells, MD, Chief Scientific Officer, MMV, in a press release. “If the Phase III trial is successful, this new combination will increase the number of options available to countries and help save the lives of children at risk of this devastating disease.”

The decision to move forward in Phase III development stems from the threat of resistance to current malaria treatment growth.