Process and plasmid design optimization, disposable equipment, and flexible platform processes all play important roles.

Achieving High Yields in Upstream Processing of Plasmids

Decreasing vein to vein time saves lives.

High-titer Vector Producing Cells

There is growing pressure for robust and economically scalable viral-vector manufacturing technologies.

Tactics and Strategies for Designing an Ideal Lentiviral Vector Platform

Shifts in pharmaceutical packaging have spurred tremendous growth in the pre-filled syringe fill/finish industry.

Automated Inspection of Pre-filled Syringes and Biologics During Fill/Finish

Considerable efforts have been made over the years to resolve the key issues of stability and delivery of RNA-based therapeutics.

The Marriage of RNA and Mass Spectrometry

The bio/pharma outsourcing industry continues to be integral in the development and manufacture of medicines.

Outsourcing Still Vital

The trends shaping the growth of the biologics outsourcing industry demand attention.

The Logistics of Outsourcing Biologics

Feliza Mirasol is the science editor for 

Sanofi announced on March 16, 2023 that it will cut the US list price of Lantus (insulin glargine injection) 100 units/mL, a widely prescribed insulin, by 78%. The company will also establish a $35 per month cap on out-of-pocket costs for Lantus, which will apply to all patients with commercial insurance.

The price changes will go into effect on Jan. 1, 2024, and follows decisions made in June 2022 to lower diabetes medicines costs, such as the launch of an unbranded Lantus biologic at 60% less than the Lantus list price and a cap on out-of-pocket costs on insulin to $35 for all people without insurance. In addition, Sanofi will also cut the list price of its short-acting Apidra (insulin glulisine injection) 100 Units/mL by 70%.

In a similar move, Eli Lilly and Company announced in early March 2023 that 

it is capping its out-of-pocket cost for insulin

 to $35 per month for patients with commercial insurance and set lower list prices for its other insulin products (1).

“Sanofi believes that no one should struggle to pay for their insulin and we are proud of our continued actions to improve access and affordability for millions of patients for many years. We launched our unbranded biologic for Lantus at 60 percent less than the Lantus list price in June 2022 but, despite this pioneering low-price approach, the health system was unable to take advantage of it due to its inherent structural challenges,” said Olivier Bogillot, head of US General Medicines, Sanofi, in a company press release. “We are pleased to see others join our efforts to help patients as we now accelerate the transformation of the US insulin market. Our decision to cut the list price of our lead insulin needs to be coupled with broader change to the overall system to actually drive savings for patients at the pharmacy counter.”

1. Eli Lilly and Company. Lilly Cuts Insulin Prices by 70% and Caps Patient Insulin Out-of-Pocket Costs at $35 Per Month. Press Release, March 1, 2023.

Articles

Sanofi intends to cut its US list price for Lantus (insulin glargine injection) by 78% and cap out-of-pocket costs at $35 for all patients with commercial insurance.

Sanofi Drops Lantus US List Price by 78%, Capping Out-of-Pocket Costs at $35

On March 20, 2023, BioNTech and OncoC4, a US-based clinical-stage biopharmaceutical company, announced that they have entered into an exclusive worldwide license and collaboration agreement for the development and commercialization of OncoC4’s next-generation anti-cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) monoclonal antibody (mAb) candidate, ONC-392. The companies aim to co-develop and commercialize ONC-392 as a monotherapy or in combination therapy for various solid tumor cancer indications.

Under the agreement, OncoC4 will receive $200 million in an upfront payment. The company is also eligible to receive development, regulatory, and commercial milestone payments in addition to double-digit tiered royalties. The two companies will jointly develop ONC-392 as monotherapy and in combination with anti-programmed cell death (PD)-(L)-1 antibodies. The companies will be aiming for a range of solid tumor indications, including non-small cell lung cancer (NSCLC). The joint effort will continue until approval of the candidate is achieved. Both parties will share equally in the development costs for studies. The transaction is expected to close in the first half of 2023, dependent on customary closing conditions and regulatory clearances.

BioNTech will solely develop all combinations outside of the PD-1 inhibition indication—in particular all combinations with a compound in BioNTech’s pipeline. BioNTech will hold exclusive worldwide commercialization rights for any products it develops from these candidates, with OncoC4 participating in certain markets, which are to be negotiated in the future.

ONC-392 has received fast track designation from FDA as a monotherapy for immunotherapy-resistant NSCLC. It is also currently being evaluated in an additional Phase II trial as a combination therapy with pembrolizumab in platinum-resistant ovarian cancer.

“Despite being a prime target for more than a decade, we believe that targeting CTLA-4 has not reached its full potential in cancer immunotherapy," said Prof. Ugur Sahin, CEO and co-founder of BioNTech, in a company press release. "The data presented by OncoC4 on their ONC-392 antibody indicate a differentiated safety profile and encouraging clinical activity in various types of tumors. We believe that this antibody is a valuable addition to our immuno-oncology portfolio, whether used alone or in combination with our personalized immunotherapies.”

“Because of its specific mechanism of action, we believe ONC-392 has the potential to broaden the reach of CTLA-4-targeting immunotherapy,” said Yang Liu, co-founder, CEO and chief scientific officer of OncoC4, in the release. “We very much look forward to working hand-in-hand with BioNTech in developing ONC-392 for cancer indications with unmet medical needs.”

BioNTech will receive an exclusive worldwide license from OncoC4 to develop and commercialize its anti-CTLA-4 mAb candidate for solid tumor indications.

BioNTech and OncoC4 to Co-Develop mAb for Solid Tumor Indications

The March 2023 meeting of the Management Board of the European Medicines Agency (EMA) provided an update to the ongoing efforts of the agency’s Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG) to further monitor several critical shortages of medicines in the European Union/European Economic Area (EEA), specifically medicines containing the antibiotic amoxicillin.

The previous board meeting focused on the MSSG encouraging EU Member States to consider national regulatory flexibilities to allow the distribution of medicines that may not be authorized in their Member States. Additionally, the MSG discussed plans to mitigate shortages of antibiotics for the next autumn and winter season.

A new executive body, the Medical Devices Shortages Steering Group (MDSSG), met for the first time on March 15, with the intention to coordinate urgent actions in the EU related to the management of supply-and-demand issues of critical medical devices during public health emergencies. The board was further updated on the Head of Medicines Agencies (HMA)/EMA multi-stakeholder workshop on shortages which took place on March 1 and 2. Approximately 300 participants spoke about the work of the HMA/EMA Task Force on medicines shortages and availability, provided updates on ongoing initiatives in the area, and expressed strong commitment to work together to prevent shortages in the future.

Further, the Board looked at EMA’s annual report for 2022, which showed that EMA recommended 89 medicines for marketing authorization for human use, 41 of which contained new active substances, including the first gene therapy for the treatment of severe and moderately severe hemophilia B and the first medicine for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants.

Additionally, the MSG discussed plans to mitigate shortages of antibiotics for the next autumn and winter season.

EMA Management Board Continues to Monitor Critical Shortages of Medicines 

Alpha Teknova, a US-based producer of critical reagents, and Sartorius BIA Separations, a part of Sartorius, announced a collaboration on March 15, 2023 under which the two companies will aid gene therapy companies to streamline the downstream purification process, specifically for the recovery of adeno-associated virus (AAV) capsids.

Under the collaboration, Sartorius BIA Separations will combine its proprietary AAV platform, which is designed to optimize the separation of viral particles, with Teknova’s custom, high-quality buffer solutions, which have been developed to maximize capsid enrichment. The companies have conducted a robust design of experiment and have successfully created a screening kit with optimized buffer formulations, according to a company press release. The optimized buffer formulations drive consistency and increased purity when they are paired with Sartorius BIA Separations’ AAV platform (BIA CIMmultus QA monolith).

Through the collaboration, gene therapy companies focusing on AAV will get access to all required consumables as well as a protocol that will streamline and accelerate the downstream processing workflow. According to the company press release, this advantage will enable these gene therapy companies to discover novel breakthroughs faster. Teknova and Sartorius BIA Separations intend to continue developing data that demonstrate the improvements in AAV purification that result from their combined methods.

“Through our collaboration, we’re finding new tools to help our customers streamline the development of AAV therapies by optimizing their purification process and increasing the yield and purity of their AAV product,” said Stephen Gunstream, Teknova’s president and CEO, in the release.

“Teknova is the perfect partner for us as we explore robust, end-to-end solutions for our gene therapy customers seeking to achieve better results in the separation and analysis of viral particles,” said Aleš Štrancar, managing director at Sartorius BIA Separations, in the release. “Based on their ability to quickly manufacture high-quality, custom buffers that are consistent from batch to batch, we’ve been able to reliably reproduce results and confidently target the discreet differences in empty and full AAV particles.”

Sartorius BIA Separations and Teknova will collaborate to combine their technologies in an effort to streamline the downstream purification process.

Sartorius and Teknova Team Up for Gene Therapy Process Development

Samsung Biologics announced on March 17, 2023 that it will begin construction of a fifth plant (Plant 5) near its current Songdo International Business District site in Incheon, South Korea, that will hold a capacity of 180,000 L. The company will invest more than ₩1.9 trillion (US$1.5 billion) in the new facility as part of its strategic capacity expansion, which is in response to increased market demand.

The company expects to break ground in the first half of 2023 and aims to start up operations in 2025. Plant 5 will be the first facility of the company’s second campus (Bio Campus II), which encompasses 96,000 m2, and, upon full completion, Samsung Biologics will hold a total of 784,000 L of manufacturing capacity.

The new plant is expected to further maximize operational efficiency and introduce advanced digitalization and sustainability features, according to a company press release. Samsung Biologics, which purchased 360,000 m2 of land in July 2022 for Bio Campus II, expects to house additional large-scale plants and an open innovation center on the campus. Overall, the company plans to invest ₩7.5 trillion (US$5.7 billion) in Bio Campus II.

The existing Plants 1 through 3 are at near-full utilization, while Plant 4, which started partial operations in October 2022, is expected to ramp up to full operations by mid-year 2023, according to the press release.

“Given the continuing increase in the demand for outsourced manufacturing of biopharmaceuticals, we are proactively making this investment in alignment with our growth strategy to further strengthen our standing as a leading CDMO [contract development and manufacturing organization],” said John Rim, president and CEO of Samsung Biologics, in the release. “The new facility will enable us to provide our customers with even greater innovation and services that will increase speed to market and flexibility.”

Samsung Biologics plans to invest more than ₩1.9 trillion (US$1.5 billion) in the new Incheon, South Korea, facility, which will hold a manufacturing capacity of 180,000 L.

Samsung Biologics to Build Plant 5 as Part of Capacity Expansion to Bio Campus II

Grant Playter is the Assistant Editor for 

Polyplus, a French provider of solutions for advanced biologic and cell and gene therapy production, announced a novel cationic lipid nanoparticle (LNP) formulation for messenger RNA (mRNA) therapeutic and vaccine development on March 14, 2023. Set for release in April 2023, the LipidBrick IM21.7c is a formulation designed to expand the scope of LNP usage in various therapeutic and oncology applications, as well as prophylactic vaccines.

The formulation is designed to overcome current-generation ionizable lipid challenges used in current LNPs by enabling a wider 

biodistribution and decreasing accumulation in the liver. According to a company press release, proof of concept work demonstrated that it successfully modulates the overall charge of LNPs, improving drug efficiency and formulation stability with no additional safety concerns.

“Polyplus draws on over 20 years legacy in cationic polymer and lipid-based delivery systems for both 

 models to power mRNA therapeutics,” said Mario Philips, CEO, Polyplus, in the release. “As we carry forward this legacy, we are working to ensure that our offer opens new possibilities to improve LNP formulation to meet the growing demand of the mRNA therapeutic market. LipidBrick IM21.7c is already used in jetMESSENGER and liposomal formulations for mRNA delivery, as a ready-to-use solution that requires no onsite formulation.”

Polyplus’ LipidBrick is designed to expand the scope of lipid nanoparticle formulation usage in mRNA therapeutics and vaccine development.

Polyplus Introduces Novel LNP Formulation for Use in mRNA Therapeutics

Stevanato Group, an Italian provider of drug containment, drug delivery, and diagnostic solutions, announced a collaboration with Recipharm, a Swedish contract development and manufacturing organization, on March 16, 2023. Under the agreement, Stevanato will support development and production of pre-fillable syringes for use in Recipharm’s soft mist inhalers.

Stevanato will provide and manufacture its proprietary glass pre-fillable syringe, Alba, assembled with the integrated spray module of Recipharm’s soft mist inhaler technology, the Pre-Filled Syringe Inhaler (PSFI). According to a company press release, the goal of this partnership is to deliver drug products more efficiently to the respiratory airways, as well as provide biopharma companies with a containment solution that features enhanced stability and safety.

“By leveraging Stevanato Group's integrated capabilities, from plastic injection molding and assembly capabilities to comprehensive scientific and analytical support services, we will be able to offer a turnkey solution, and accelerate and de-risk our pharmaceutical customers’ development programs,” said Bernhard Muellinger, general manager and chief operational officer, Resyca (a joint venture between Recipharm and Medspray), in the release. “This is particularly true for novel inhaled biological products.”

“Biopharma companies are advancing patient care with new, innovative treatments, particularly in biologics and mRNA [messenger RNA] therapies,” said Mauro Stocchi, chief business officer, Stevanto Group, in the release. “These products require specialized, high-performance drug containment systems, like our Alba syringe platform, together with patient-centric drug delivery devices [such as] the PFSI.”

Stevanato Group will support development and production of pre-fillable syringes for use in Recipharm’s soft mist inhalers.

Stevanato Group and Recipharm to Collaborate on Pre-fillable Syringes for Soft Mist Inhaler

Evotec announced on March 16, 2023 that there has been progress within its strategic partnership with Bristol Myers Squibb (BMS) relating to building a molecular glue-based pipeline. Performance-based and program-based achievements will total $75 million to Evotec.

The companies entered their strategic protein degradation partnership in 2018 and expanded it in May 2022. Evotec has scaled up its activities to develop compounds from Bristol Myers Squibb’s library of cereblon E3 ligase modulators since the expansion. The partnership’s goal is to develop high-value targets in the field of oncology and more by building a pipeline of novel molecular glue degraders. According to a company press release, molecular glue degraders are compounds that induce interactions between an E3 ubiquitin ligase and a molecular target, which results in ubiquitination and subsequent degradation of the protein. The molecular glue itself is not degraded in the process, meaning it can trigger the degradation process several times over, which can lead to longer-lasting therapeutic effects.

“The recent extension and expansion of our partnership with BMS continues to deliver high value programs,” said Cord Dohrmann, chief scientific officer of Evotec, in a company press release. “Our Omics-based, highly systematic, and industrialized approach to identify very promising molecular glues continually exceeds all expectations and will translate into an extraordinary pipeline of first-in-class product opportunities.”

Evotec and Bristol Myers Squibb have announced progress in their strategic protein degradation partnership. 

Evotec and Bristol Myers Squibb Progress Strategic Partnership

Cancer Research Horizons announced on March 17, 2023 that it has partnered with Predictive Oncology to drive the development of oncology drugs. The collaboration will use Predictive Oncology’s PEDAL artificial intelligence and machine learning platform technology to determine which cancer types and patient populations are most likely to respond to treatment with Cancer Research Horizon’s pre-clinical drug inhibitors of glutaminase. By addressing tumor heterogeneity during pre-clinical stages, the probability of clinical success increases, according to Predictive Oncology.

The agreement joins together non-profit and industry and offers the potential for Cancer Research Horizons to incorporate PEDAL technology into future drug discovery processes.

“Our collaboration with Cancer Research Horizons represents a fundamental shift in drug discovery that could lead to the accelerated development of cancer therapies using compounds originating from the CRUK network and developed by Cancer Research Horizons in partnership with their global network,” said Raymond F. Vennare, CEO of Predictive Oncology, in a company press release. “We now have the ability to impact the most critical stage of early drug discovery in a way that has never been done before.”

“We are committed to working closely with scientists to discover and advance therapies that can help in the fight against cancer. Ensuring that patients receive the right treatment for them is of paramount importance and is why we are excited to work with Predictive Oncology to identify the most suitable population for the further development of our compounds. We look forward to applying Predictive Oncology’s expertise, enabling technology and dedication to progress exciting cancer therapeutics,” explained Tony Hickson, chief business officer for Cancer Research UK and Cancer Research Horizons, in the release. “We consider the potential of this collaboration a win for patients not just in the UK or US, but worldwide.”

Predictive Oncology and Cancer Research Horizons have partnered to pursue development of cancer drugs utilizing the PEDAL platform.

Predictive Oncology and Cancer Research Horizons Partner for Cancer Drug Development

Sandoz, the generics and biosimilars division of Novartis, announced on March 9, 2023 that it has signed a memorandum of understanding to build a new biologics production plant in Lendava, Slovenia. The company expects to invest at least $400 million in this project, which represents one of the largest international private-sector investments in Slovenia, according to a company press release.

Work on the new plant is set to begin in 2023, and full operations are provisionally planned for late 2026. The facility will support the increasing global demand for biosimilars.

“Biosimilar medicines increase access to cutting-edge biologic therapies for the patients who need them most. This investment underscores our ambition to be the sustainable global leader in biosimilars, a segment projected to grow double-digit annually over the next decade,” said Richard Saynor, CEO, Sandoz, in the press release.

“This state-of-the-art site will … enable[e] us to meet growing demand for our current and future biosimilars in the mid- to long-term. The location offers us a strong combination of political stability, proximity to our existing European-based production and commercial operations, and competitive costs,” said Glenn Gerecke, global head of Technical Operations, Sandoz, in the release.

In addition to this biologics production facility, Sandoz also 

recently announced in 2022 an additional €50 million (US$53 million) investment

 (1) to expand its European-based antibiotics production network. Altogether, the company’s total new investment commitment in the past few years to expand its European-based antibiotics production network comes to €250 million (US$266 million).

1. Sandoz, “Sandoz Announces Further Investment in Key Manufacturing Facility in Austria, to Support Increased Global Demand for Essential Antibiotics,” Press Release, Nov. 7, 2022.

Sandoz, a Novartis division, is expected to invest at least $400 million to build a new biologics manufacturing facility in Lendava, Slovenia, to support growing demand for biosimilars.

Sandoz to Build New Biologics Production Facility in Slovenia

On March 16, 2023, Catalent announced that it has signed a licensing agreement with India-based Bhami Research Laboratory (BRL) that will provide Catalent with access to BRL’s formulation technology. Using the technology, Catalent intends to develop formulations that will help enable the subcutaneous delivery of high-concentration biologics. Financial terms of the agreement were not disclosed.

The agreement authorizes Catalent to collaborate with its customers to evaluate BRL’s formulation technology so that Catalent and its customers can explore ways to reduce viscosity and deliver high-concentration biologic products. BRL’s technology is applicable to a wide range of monoclonal antibodies and fusion proteins. Successful programs could be integrated into Catalent’s formulation and manufacturing services at scale.

According to a Catalent press release, the subcutaneous delivery of small volume, low viscosity biotherapeutics can provide superior patient benefits over traditional intravenous injections. Such benefits include improved access to healthcare, reduced need for hospitalization and overall treatment cost, and the opportunity to employ new delivery technologies, such as auto-injectors.

“The patented, high-concentration, low-viscosity protein drug delivery platform has been designed to make patient care convenient, affordable, and safe,” said Bhami Shenoy, co-founder and chief scientific officer of BRL, in the press release.

“This agreement allows Catalent Biologics to offer its customers a novel patented formulation that may be evaluated for enabling the delivery of high-concentration therapies by reducing viscosity,” said Julien Meissonnier, Catalent’s chief scientific officer, in the release. “The potential for maintaining the stability of a drug with the convenience of a pre-filled syringe or auto-injector could have a significant impact on reducing the barriers to subcutaneous delivery of therapies and improving the patient experience.”

Under a technology licensing agreement with Bhami Research Laboratory, Catalent intends to develop formulations that will allow for the delivery of high-concentration biologics subcutaneously.

Catalent Licenses Bhami Research Laboratory Technology for Biologics Formulation Development

Genuv, a South Korean-based clinical-stage biotechnology company, announced on March 15, 2023 that it has entered into a partnership with South Korea-based biopharmaceutical company Celltrion to jointly discover and develop novel therapeutic antibodies. Under the agreement, the companies will use Genuv's proprietary SHINE MOUSE platform.

According to the agreement, Genuv will conduct antibody discovery services using its mouse platform technology. Drug discovery will be followed by a research collaboration. Celltrion has the option for joint research and development projects that, if exercised, will trigger agreed-upon milestones, which include development milestones of up to $25 million followed by total commercial milestones of up to $680 million. The latter amount will be triggered dependent upon the accumulation of $7.5 billion in sales per candidate antibody.

The advantage that the SHINE MOUSE platform offers rests in the platform’s ability to generate a greater diversity of antibodies than conventional mice can generate. This ability led to the discovery of the experimental, novel anti-programmed cell death protein 1 monoclonal antibody, GNUV201. GNUV201 holds unique features, such as exceptional interspecies cross-reactivity and binding affinity, which allows for preclinical disease animal model studies that have increased clinical relevance, according to a company press release.

Genuv is also developing GNUV205, an improved interleukin-2-based immunocytokine anticancer drug that is made tumor-specific by leveraging the properties of GNUV201.

“We are excited to embark on our mouse platform business with Celltrion as our first partner,” said Sungho Han, founder and CEO of Genuv, in the press release. “We believe Celltrion's in-depth knowledge and experiences in antibody development and production and Genuv's expertise in novel antibody discovery with our SHINE MOUSE platform could generate great synergies in providing innovative antibody therapeutics.”

“Celltrion is continuously interested in antibody-based new drugs and anticipates to discover differentiated antibodies through innovative antibody discovery platform technology. We look forward to partnering with Genuv for the development of innovative antibody therapeutics that will bring new hope to patients with high unmet needs,” said Kisung Kwon, head of the R&D unit of Celltrion, in the release.

The collaboration between Genuv and Celltrion will utilize Genuv's proprietary mouse platform for antibody discovery.