New biotherapeutics both drive and benefit from innovative development technologies.

Innovation Demands and Spurs Invention

FDA releases some J&J vaccines from Emergent facility; EU puts release on hold

Novavax Reports 90% Efficacy for Vaccine

Complex formulations, personalized medicines, and more are driving innovations in drug packaging.

Injecting Innovation into Drug Packaging

A task force establishes scientific data for integrity test activities. 

Reducing Sterile Filtration Risk

Automation offers benefits for sterile manufacturing in 503B facilities. 

Robotics for Drug Compounding

The Cell and Gene Therapy Catapult (CGT Catapult) has formed a consortium of more than 20 organizations aimed at advancing the technology development and lowering costs of cell and gene therapy manufacturing.

In a June 8, 2021 press release, CGT Catapult announced the formation of the consortium, which will assess multiple process analytical technologies (PAT) that are either new or routinely used in other industries. Through collaboration and sharing of information, the consortium will act as a catalyst to accelerate the development of the necessary knowledge and understanding at reduced cost and investment risk to each organization.

“The industry needs to make a giant leap in terms of analytical capability and the dynamic use of information to control and improve processes, product, and costs,” said Matthew Durdy, CEO at CGT Catapult, in the press release. “The coming together of these leaders in the field is a very important first step towards achieving this.”

“By sharing knowledge and data, the consortium members will be able to reap potentially huge benefits that could lead to more efficient processes in this vital field,” added Nicholas Medcalf, deputy challenge director—Medicines Manufacturing for Innovate UK, in the press release. “The Cell and Gene Therapy Catapult—supported by Innovate UK—is demonstrating its fantastic convening power in harnessing these leading industry players for the greater good of UK enterprise and innovation.”

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The CGT Catapult has formed a consortium aimed at advancing the technology development and lowering costs of cell and gene therapy manufacturing.

CGT Catapult Forms Consortium to Accelerate Manufacturing Technology Development

Researchers from the Chalmers University of Technology (Sweden) and AstraZeneca have developed a new method of detecting and testing lipid nanoparticles, which is hoped to be able to accelerate the development of messenger RNA (mRNA) medicines.

According to a June 9, 2021 press release, the novel automated process has been designed to allow for the simultaneous monitoring and testing of large numbers of different lipid nanoparticles. Using fluorescent markers, the researchers have been monitoring and analyzing the movement of lipid nanoparticles through cells. Additionally, the new method has allowed the researchers to see if the mRNA, which is packed into the lipid nanoparticle, is able to produce the encoded protein once delivered.

“Instead of just seeing which lipid nanoparticles work best, we can now also understand what makes them work optimally, and use that knowledge to develop and test new improved nanoparticle formulations,” said Michael Munson, postdoctoral fellow at AstraZeneca R&D, who is affiliated to the research centre FoRmulaEx and is the first author of the study that was recently published in the journal 

“To reduce the risk of side effects, such as the immune system being triggered by the lipid particles, we want to use the lowest possible dose. This is particularly true for diseases which require long-term treatment,” added Elin Esbjörner, associate professor of Chemical Biology at Chalmers University of Technology and co-author of the study, in the press release. “In those cases, it is vital that the moment of endosomal escape is optimally timed, to allow the mRNA to get out into the cytoplasm with maximum effect.”

Furthermore, the researchers can assess how efficiently the lipid particles are delivered and how well they work in different types of cells using the method. Therefore, through the information gained from the method, it could be possible for drugs to be developed that are tailored to target specific tissues.

“The lipid nanoparticles work differently in different cell types. A formulation that works well for delivery to liver cells, for example, could be significantly different in lung cells,” stated Esbjörner, in the press release. “Our new method could help us understand why such differences exist, and to harness this knowledge to design new lipid nanoparticles tailored for different targets in the body.”

Researchers from the Chalmers University of Technology and AstraZeneca have developed a new method of detecting and testing lipid nanoparticles.

Novel Automated Process May Speed Up Development of New Medicines

Roambee, a California-based supply chain visibility provider, has acquired Modum, a Swiss pharma last mile-focused cold chain monitoring player, it was announced in a June 8, 2021 press release.

Through this acquisition, Roambee will be able to expand its cold chain visibility, covering primary, secondary, and the last mile delivery use cases. The acquisition will see key executives from Modum take up leadership roles at Roambee, which will provide the company with pharma domain knowledge and last mile expertise for its product strategy.

“Joining forces with Roambee was natural for Modum due to our shared mission to ensure the timely availability of effective, original products in the medical supply chain,” said Modum's CEO Simon Dössegger, in the press release. “Modum will enhance Roambee's cold chain footprint with a proven last mile visibility technology to extend the Roambee product proposition to a unique global end-to-end visibility solution. When combined with Roambee's strong multimodal shipment monitoring capabilities, we can offer granular visibility all the way from manufacturing to a patient's home at scale.”

“While most visibility service providers claim to deliver real-time visibility, they rely on carrier data. Insights will never be as granular, real-time, and accurate as sensor driven insights, which is key to logistics automation,” added Sanjay Sharma, CEO of Roambee, in the press release. “With Modum, Roambee will enable customers to automate their logistics through radically simple access to sensor-driven signals, delivered by our immersive, location-aware platform—not only for pharma, but also for fresh produce and food/beverages.”

Roambee has acquired Modum, a Swiss pharma last mile-focused cold chain monitoring player, expanding its cold chain visibility capabilities.

Roambee Expands Cold Chain Visibility Offering Through Modum Acquisition

Bioprinting start-up company, Brinter, has successfully closed a €1.2 million (US $1.5 million) seed funding round, which was led by the early-stage venture capitalist Innovestor. The financing announcement was made in a June 10, 2021 press release.

The monies raised will be used by Brinter to expand operations internationally in Europe and the United States. The company’s modular multi-material 3D bioprinting solution offers a scalable approach to shorten and enhance the productivity of the scientific process and bio-manufacturing.

“We are excited to have the backing of Innovestor who can help us accelerate the development of our operational capabilities and scale in new geographies,” said Brinter CEO Tomi Kalpio, in the press release. “Bioprinting has the capability to rapidly unlock the opportunities behind long-running but unrealized science and research, and plays a key role in pushing the frontier of medical science. This will result in an improved quality of life for patients through the expansion of more personalized treatment and the ongoing development of bioprinted ‘spare parts’ that can save lives.”

“Brinter is an exciting addition to our portfolio as it not only fits in our focus areas of industrial and health technologies, but the company’s competitive advantages of multi-material printing capabilities, modularity, and scalability combined with their own easy-to-use software application were very convincing,” added Wilhelm Lindholm, CEO of Innovestor, in the press release.

Brinter has successfully closed a €1.2 million (US $1.5 million) seed funding round, which was led by the early-stage venture capitalist Innovestor.

Brinter Successfully Closes Seed Funding Round Led by Innovestor

Research-driven biopharmaceutical company, Boehringer Ingelheim, has joined the Quantum Technology and Application Consortium (QUTAC) as a founding member, it was revealed in a June 10, 2021 press release.

Ten German companies, based in the fields of pharmaceuticals, chemistry, insurance, and the automotive industry, make up the consortium, which is aimed at exploring industrial applications for quantum computing. Through advancing the potential industrial applications of quantum computing, QUTAC founding members hope to make a contribution to progressing the technology across both the German and European markets.

“As part of QUTAC, we will contribute to further advance the research for industrial solutions in the field of quantum computing,” said Michael Schmelmer, member of the board of managing directors of Boehringer Ingelheim with responsibility for Finance and Group Functions, in the press release. “Together with our partners at QUTAC, we want to create the basis for an efficient use of the quantum computing potential in the future. Even though it may still take some years until this technology is ready for industrial use, we need to define and explore a variety of specific use-cases across several industries now.”

Quantum computing has potential in research and development of pharmaceuticals, particularly for the accurate simulation and comparison of much larger molecular structures. Early research processes, which is an area of expertise for Boehringer Ingelheim, could benefit from this technology.

“Last year, we set up a dedicated Quantum Lab to explore specific applications for pharmaceutical research and development. Apart from these internal developments, partnerships with academia and the industry play an important role,” added Schmelmer in the press release.

Boehringer Ingelheim has joined the Quantum Technology and Application Consortium (QUTAC) as a founding member.

Boehringer Ingelheim Joins QUTAC as Founding Member

Syntegon Technology’s new GKF 60 for lab-scale capsule filling provides multiple dosing systems, including a new piezo dosing system as well as conventional dosing modules for dry powder inhalation (DPI), pellets, tablets, or liquids. The system has a mini-bowl station to ease scale-up to the next larger production machine.

The compact machine has six stations, and three filling stations can be integrated in parallel. The piezo station is designed to fill small quantities flexibly and, if possible, without product loss, which is especially important for high-priced active ingredients. This station can dose quantities as small as 0.1 mg filling weight, for example for toxicity or first-in-man studies. Each dosing station can be optionally equipped with a gravimetric, 100% weighing system for each component dosed.

A new Automated Process Development (APD) tool developed by Syntegon can be used on the GKF 60 to determine the optimum parameters for filling and automatically adjust them during the filling process.

The filler is available in a standard version, a version with containment, or a combi solution, and the machine has a new design for quick changeover that uses exchangeable cabin elements and a sophisticated cleaning concept. The standard version can also be easily retrofitted.

In addition, scale up to production is easy because the GKF 60 is compatible with the Syntegon's smallest production-scale capsule filling machine (the GKF 720).

New features of Syntegon’s GKF 60 capsule filler include a piezo dosing system, an Automated Process Development tool, and quick changeover to containment. 

Lab-Scale Capsule Filler Provides Flexibility for Dosing Small Quantities

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

FDA’s surprise decision this week to approve Biogen’s treatment for Alzheimer’s disease has raised serious questions about the validity and value of the agency’s accelerated approval process. The 

Aduhelm (aducanumab) based on data from one clinical trial that shows some effect on reducing amyloid beta plaques in patients with mild cognitive impairment. Unlike most surrogate markers supporting early approval, that effect has not been linked to clinical benefit, challenging its validity for anticipating patient gains.

The broad labeling approved for the new drug, moreover, has generated heated debate among scientists, researchers, patients, and payers as to the long-term impact of the approval decision on the credibility and independence of FDA decisions. Coming in the wake of an assessment of several cancer therapies that gained accelerated approval but failed to document long-term benefit, the decision has raised questions about approving new drugs and biologics based on preliminary evidence of possible benefit that awaits later confirmation. FDA emergency use authorizations (EUAs) for some questionable and harmful anti-COVID-19 treatments already have eroded public confidence in the scientific and medical validity of some agency actions, and many research leaders fear this recent decision will heighten those concerns.

The very high price tag set by Biogen for the treatment also is heightening the debate over pharmaceutical costs, reimbursement, and prescribing. In setting a price of $56,000 a year, way above the cost-effective threshold of $2500 to $8000 calculated by the Institute for Clinical and Economic Review (ICER), Biogen stands to earn some $17 billion a year from the drug, according to Wall Street analysts, particularly with a label that opens prescribing to both early and severely debilitated Alzheimer’s patients. All eyes are on how Medicare and health and drug plans will set coverage parameters and how doctors and medical authorities will identify those individuals most suitable for treatment. 

the drug’s appropriate use and insurance coverage at a meeting on July 15, 2021. Biogen says it has begun to negotiate value-based contracts with major payers such as Cigna and CVS Health to support access to the drug. But just how the parties will link payment to treatment outcomes remains to be seen.

was launched in the 1980s to provide early access to treatment for dying AIDS patients with no available treatment. Since then, it has been used to speed approvals of new therapies, primarily for AIDS and cancer where validated surrogate markers have provided evidence that a drug has potential for curbing disease. Many accelerated approval products have been able to document continued benefit from post-approval studies, building support among industry sponsors and patient advocates for the process. Some consumer groups and health care providers, though, complain of long delays in confirming benefit and have questioned the often high cost of paying for unproven treatments.

of its Oncologic Drugs Advisory Committee to evaluate supplemental indications for several leading cancer therapies where confirmatory trials provided only limited evidence of ongoing clinical benefit. Although FDA revoked the added indication for only one product, it continues to examine these therapies and to struggle with the difficulties in conducting postapproval trials. Biogen is not expected to provide confirmatory data from a postapproval study for years, if not decades, further undermining the accelerated approval paradigm.

It remains to be seen whether the flexibility applied by FDA reviewers to the new Alzheimer’s drug reflects a broader, less rigorous approach to approving treatments for devastating conditions with urgent need of treatment. The significance of FDA’s action is apparent in a personal message from Patrizia Cavazzoni, director of the Center for Drug Evaluation and Research (CDER). She notes that 

CDER reviewers carefully vetted highly complex data

 to reach its conclusion that the surrogate endpoint is “reasonably likely” to predict clinical benefit. Cavazzoni acknowledges “residual uncertainties” about the drug and its potential for reducing clinical decline from Alzheimer’s disease, but critics maintain that this and earlier studies show no link between reducing amyloids in the brain and improved health. In basing its approval on “potential benefit,” as opposed to clear clinical benefit, FDA has angered and confused both its critics and advocates.

Some industry analysts predict that this more flexible approval standard will drive a surge in R&D for additional Alzheimer’s drugs as well as other experimental treatments for rare and lethal diseases. Several leading pharma companies are testing new Alzheimer’s treatments that also aim to reduce amyloid in the brain or to clear other invasive substances. But many scientists fear that approvals based on limited evidence of clinical benefit may generate confusion and uncertainty that only deters investment in R&D.

One outcome, though, is that FDA analysts and pundits no longer will assume that agency reviewers will follow the recommendations of its advisory committees, as usually is the case. The advisory committee that assessed the Biogen drug last November voted almost unanimously against approval based on the limited evidence of effectiveness, but FDA reached its own conclusion.

FDA’s approval of Biogen’s treatment for Alzheimer’s disease has raised questions about the agency’s accelerated approval process. 

New Alzheimer’s Drug Heightens Debate Over FDA Accelerated Approval Process

FDA announced in a June 4, 2021 release that it had approved an abbreviated new drug application submitted by Sandoz for albuterol sulfate inhalation aerosol 90 mcg (base)/actuation in a metered dose inhaler on June 1. The drug is used for the treatment or prevention of bronchospasm (i.e., narrowing of the airways) in patients four years of age and older with reversible obstructive airway disease, such as asthma, and for the prevention of exercise-induced bronchospasm in patients four years of age and older.

In the release, the agency said, “The FDA recognizes the increased demand for certain products during the COVID-19 public health emergency and has prioritized the review of generic drug applications for potential treatments and supportive therapies for patients with COVID-19. We remain deeply committed to facilitating access to safe and effective medical products to help address critical needs of the American public.”

Sandoz had previously announced in a March 16, 2021 press release that it had in-licensed commercial distribution rights to the brand and authorized generic of respiratory inhalation medicine Proventil HFA (albuterol sulfate) Inhalation Aerosol from Kindeva Drug Delivery, which is a global contract development and manufacturing organization, for patients in the United States. Both the brand and generic drug of Proventil are manufactured in California.

Sandoz noted in the March press release that there has been a surge in demand for albuterol medicines over the past year from both hospitals and pharmacies in the US.

An ANDA from Sandoz for albuterol sulfate inhalation aerosol was approved by FDA.

FDA Approves ANDA for Albuterol Sulfate

The United Kingdom’s Medicines and Healthcare products Regulatory Authority (MHRA) announced on June 4, 2021, that it was giving temporary authorization of Pfizer and BioNTech’s COVID-19 vaccine for individuals aged 12 and older. Similarly, in a May 28, 2021 press release, Pfizer and BioNTech announced that the Conditional Marketing Authorization (CMA) for the COVID-19 Vaccine Comirnaty in the European Union (EU) has been expanded to include individuals 12 to 15 years of age, following the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) positive opinion to authorize the vaccine in this age group. The United States expanded authorization of the Pfizer/BioNTech COVID-19 vaccine to ages 12 to 15 on May 10, 2021.

“[The] extension of our COVID-19 vaccine authorization in the European Union is another critical milestone in our collective effort to broaden vaccination programs to as many people as possible,” said Ugur Sahin, MD, CEO and Co-founder of BioNTech, in the press release. “Making vaccines available to adolescents will help reopen schools and support the return to a normal day-to-day life.”

A Phase III clinical trial, which enrolled 2260 participants aged 12 to 15 years, showed a vaccine efficacy of 100% in participants with or without prior SARS-CoV-2 infection and robust antibody responses. A pediatric study evaluating the safety and efficacy of the COVID-19 vaccine in children 6 months to 11 years of age is ongoing. Data for children 2–5 years of age and 5–11 years of age are anticipated in September 2021, and the data readout and submission for the cohort of children six months to two years of age is expected in the fourth quarter of 2021.

BioNTech is the Marketing Authorization Holder of the vaccine in the European Union, and the holder of emergency use authorizations or equivalents in the US (jointly with Pfizer), the UK, Canada, and other countries.

The vaccine is now authorized for ages 12 and older in European Union member states and the UK.

Pfizer and BioNTech COVID-19 Vaccine Authorized in UK and Europe for Adolescents

VIVEbiotech, a gene transfer technologies contract development and manufacturing organization (CDMO) specializing in lentiviral vectors, announced on June 4, 2021 that it has opened new facilities in Spain for the manufacture of lentiviral vectors for the cell and gene therapy sector.

This expansion will allow the company to significantly increase its production capacity by 400% and deliver commercial-size batches of lentiviral vectors. The expansion also translates to an increase in average batch size per year from 20 batches in 2020 to 80 batches in 2022 of vector material. Furthermore, the facilities are capable of supplying material for early stage research as well as for good manufacturing practice (GMP) clinical- and commercial-scale quantities.

VIVEbiotech also plans to install the largest bioreactor currently available on the global market within the new facilities and seven cleanrooms specifically set up for lentiviral-vector manufacturing, the company stated in a press release. VIVEbiotech said it is using a flexible design that will allow it to further add more cleanrooms in the future as well as accommodate a larger number of batches.

The construction of these new facilities follows an authorization granted by the Spanish Agency of Medicines and Medical Products that allows VIVEbiotech to manufacture drugs to be administered 

 in clinical trials. VIVEbiotech has also been authorized to manufacture intermediate products. The company currently works in accordance with European Medicines Agency and FDA regulatory requirements.

“The continued expansion of the gene and cell therapy sector has resulted in a significant increase in the demand for lentiviral vectors. In order to meet the exponential growth of lentiviral demand to support the growth of the wider cell therapy industry, VIVEbiotech has invested in new, state-of-the-art, manufacturing facilities [that] will enable the commercial-scale production of our products,” said Gurutz Linazasoro, CEO, VIVEbiotech, in the press release.

“VIVEbiotech [is] one of the few companies that have fully specialized [capabilities] in the manufacture of lentiviral vectors, with expertise in all phases of development, from drug discovery to commercial scale-manufacturing. The new facilities will enable VIVEbiotech to develop new projects and increase our offering to our growing customer base,” Linazasoro added in the press release.

VIVEbiotech has opened its new lentiviral vector manufacturing facilities in Spain, expanding capacity for lentiviral vectors for use in cell and gene therapies.

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