The emergence of new biotherapeutics is both the driver and result of innovative drug development technologies.

Next-Gen Therapies Drive Development Technologies

Moderna initiates BLA submission; GSK Earns EUA for mAb Treatment

Vaccine Makers Plan for Global Distribution

Mass spectrometry and automation are growing in importance for protein characterization.

Unraveling Protein Characteristics

The COVID-19 pandemic has triggered additional considerations to supplier oversight.

Are Your Contract Manufacturing Facilities Up to Speed?

 on June 11, 2021 that its committee for human medicines (CHMP) has approved Recipharm’s Monts, France facility for the production of Moderna COVID-19 vaccine finished product. Several other sites were given a positive opinion by CHMP for batch control/testing.

The new site follows two other sites approved by CHMP in June for the manufacture of API and finished product intermediates in the United States. “Together, these changes are expected to allow the production of an additional one to two million vials of ready-to-use vaccine for the European Union market every month. This will increase the supply of the vaccine in the European Union,” the agency stated in a press release.

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The new site in Monts, France, which is operated by Recipharm, will produce finished COVID-19 vaccine product.

EMA Approves New Manufacturing Site for Moderna COVID-19 Vaccine

on June 11, 2021 that supervisory authorities in the European Union have recommended not releasing batches of Janssen’s COVID-19 that contain API manufactured at Emergent BioSolution’s Maryland facility around the same time as a known contaminated batch. According to EMA, batches of the vaccine that have been released in the EU are not contaminated, and the recommendation is a precaution to safeguard supplies.

Vaccine production was suspended at Emergent’s Bayview, Md. facility in April 2021 after a manufacturing error caused loss of product and an 

 found good manufacturing practice violations.

EMA stated in a press release that it is working with FDA and international partners to ensure the quality of COVID-19 vaccines.

As a safety measure, supervisory authorities in the European Union have recommended not releasing batches of Janssen’s COVID-19 vaccine with API manufactured at Emergent BioSolutions’ Maryland facility.

EU Regulators Recommend Not Releasing Batches of Janssen COVID-19 Vaccine

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

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

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.”

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

Immuno-oncology company, Immodulon, has announced, in a June 8, 2021 press release, the receipt of an indication of allowability from the European Patent Office for the claims in its patent application relating to its lead drug candidate, IMM-101.

The patent application specifically relates to combining IMM-101 with various classes of immune checkpoint inhibitors (CPIs) for the treatment of any tumor type. If granted, the patent will further support the company’s intellectual property (IP) position around the lead drug candidate ahead of the commencement of a potentially pivotal study in 2022, and the expiration of the patent would be in 2034.

“We are pleased to have received this indication of allowability of the claims for this key European Patent Application that will bolster our IP position around IMM-101, our lead drug candidate, in combination with immune checkpoint inhibitors as a treatment for cancer,” said Jaap Kampinga, CEO of Immodulon, in the press release. “IMM-101 has a unique mechanism of action—principally activating dendritic cells of the human immune system via the Toll-Like receptor 2. Studies to date suggest that IMM-101 is synergistic to the effects of the main classes of checkpoint inhibitors and presents no added safety burden.”

Furthermore, Kampinga stated in the press release that the company has an open investigational new drug application in the United States for the lead drug candidate in sarcoma and has also been given orphan drug designation in the European Union and the US for treatment of pancreatic cancer.

Immodulon has received an indication of allowability from the European Patent Office for the claims in its patent application relating to its lead drug candidate.

Immodulon Gains Allowability of Claims for Key European Patent Application

 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

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

 on June 3, 2021, that provide recommendations for complying with the Drug Supply Chain Security Act (DSCSA) in order to identify and trace drug products as they move through the supply chain. Two final guidance documents and two draft guidance documents were issued.

Product Identifiers Under the Drug Supply Chain Security Act, Questions and Answers

clarifies the DSCSA requirement that manufacturers and repackagers put a product identifier on drug packages that includes a national drug code, serial number, lot number, and expiration date.

Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification

 offers certain trading partners aid in identifying a suspect product. It also describes how to notify FDA of illegitimate products.

Definitions of Suspect Product and Illegitimate Product for Verification Obligation under DSCSA

 describes terms used to define “suspect” and “illegitimate” products and revises the March 2018 draft guidance, and 

Enhanced Drug Distribution Security at the Package Level under DSCSA

 details requirements for enhanced drug distribution security at the package level and provides recommendations on the system attributes necessary for secure tracing of product at the package level.

The agency issued two final and two draft guidance documents to help identify and trace drug products in the supply chain.

FDA Publishes Guidance Documents to Enhance Supply Chain Security

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.

VIVEbiotech Launches Lentiviral Vector Manufacturing Plant for Cell and Gene Therapies

On June 7, 2021, AGC Biologics, a contract development and manufacturing organization (CDMO), announced that it has partnered with BioNTech to further supply plasmid DNA (pDNA) starting material for the Pfizer-BioNTech COVID-19 vaccine at AGC’s Heidelberg, Germany, facility. pDNA starting material is an essential component of BioNTech’s mRNA-based vaccine manufacturing process.

“We are honored that BioNTech has entrusted us to become part of their global supply network in an effort to make the vaccine available to as many people as possible around the world,” said Mark Womack, AGC Biologics’ chief business officer, in a company press release. “We are very proud of our efforts to provide our global customers with the essential materials needed to rapidly deliver vaccines in the fight against the COVID-19 pandemic.”

“The team at Heidelberg is enthusiastically embracing this important project with BioNTech,” said Dieter Kramer, AGC Biologics’ general manager, Heidelberg, in the press release. “[We] look forward to supporting BioNTech in the production of their mRNA-based COVID-19 vaccine with [p]lasmid DNA.”

AGC Biologics has partnered with BioNTech to further supply plasmid DNA starting material from its Heidelberg, Germany, facility for the Pfizer-BioNTech COVID-19 vaccine.

AGC Biologics to Supply More Plasmid DNA for Pfizer-BioNTech COVID-19 Vaccine

Boehringer Ingelheim and Zealand Pharma announced on June 2, 2021 that FDA has granted fast track designation to BI 456906, an investigational glucagon-like peptide 1 (GLP-1)/glucagon dual agonist, for the treatment of non-alcoholic steatohepatitis (NASH). BI 456906 is currently in a Phase II study in adults with NASH and liver fibrosis with and without diabetes.

GLP-1/glucagon is a compound derived from oxyntomodulin, a natural gut hormone, that activates both the GLP-1 and glucagon receptors critical for controlling metabolic functions. The dual agonist BI 456906 has the potential to be a new, once-weekly treatment and is also being investigated as a potential treatment for adults with diabetes and for adults with obesity.

“The FDA [f]ast [t]rack [d]esignation for our dual agonist is an important step forward in addressing the high unmet medical need among the up to 444 million adults estimated to be living with NASH,” said Waheed Jamal, MD, corporate vice-president and head of CardioMetabolic Medicine, Boehringer Ingelheim, in a company press release. “Together with our partner Zealand Pharma, we look forward to working closely with [FDA] as we explore the potential of the GLP-1/glucagon agonist to improve outcomes for adults with NASH.”

“Boehringer Ingelheim and Zealand Pharma are committed to delivering innovative solutions that address public health challenges of cardiometabolic diseases, including NASH,” said Adam Steensberg, executive vice-president and chief medical officer at Zealand Pharma, in the press release. “By combining Boehringer Ingelheim’s expertise in drug development in the cardio-metabolic area with our strength in the discovery of innovative peptide-based medicines, we have the potential to bring forward a novel therapy option in an area with limited available treatments.”

FDA has granted fast track designation to a GLP-1/glucagon dual agonist in development by Boehringer Ingelheim and Zealand Pharma for the treatment of NASH.

Featured Content

Next-Gen Therapies Drive Development Technologies

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Are Your Contract Manufacturing Facilities Up to Speed?