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

Susan Haigney is managing editor of BioPharm International, susan.haigney@ubm.com.

Scorpius BioManufacturing, a contract research and contract development and manufacturing organization based in Texas, announced on March 21, 2023 that the company has appointed Gary Welch as interim president. Welch will lead the company in serving clients with mammalian and microbial biologics and new modalities. Welch, who has previously worked with AbbVie, Agensys, and CytomX, comes to the company with more than 30 years of experience.

The company also announced that it will open new microbial capacity to supplement the mammalian suites at its San Antonio facility. In addition, the company plans to construct a commercial-scale facility in Manhattan, Kan. to help their clients that are creating new microbial and mammalian modalities to start projects quickly and utilize Scorpius throughout the lifecycle of those modalities.

Articles

In addition to a new interim president, the company is opening new microbial capacity at its San Antonio facility and has plans to construct a commercial-scale facility in Manhattan, Kan.

Scorpius BioManufacturing Announces New Microbial Capacity and New Interim President

TrakCel announced on March 17, 2023 that their collaboration with Lonza has reached a new milestone, resulting in a secure, reliable combination of TrakCel’s cell orchestration platform OCELLOS and Lonza’s manufacturing MODA-ES(R) platform. This integration will translate into critical manufacturing steps, checks, and data flow directly into the Chain of Custody and Chain of Identity within the cell and gene therapy supply chain without the opportunity of being missed or not connecting with the patient journey.

For developers, this will assist in them gaining additional visibility and control while reducing product loss, delayed treatment, recalls, and poor-quality product. The combined solutions are currently available on the market.

The collaboration between TrakCel and Lonza includes a multi-phase rollout of connectivity with OCELLOS to other Lonza systems like SAP and LIMs. Other integrations are planned to follow the MES proof of concept and are likely to be completed in the second half of 2023.

The combined solutions are currently available on the market.

TrakCel and Lonza Reach Integration Milestone to Combine Cell and Gene Therapy Manufacturing, Orchestration Solutions 

Gyros Protein Technologies, a provider of peptide synthesizers and reagents, announced on March 21, 2023 the launch of three service offerings. These are intended to support the development and manufacturing of peptide-based drugs, and they are based on the company’s PurePrep EasyClean (PEC) orthogonal peptide purification technology.

“PEC-grade peptide service,” which is intended for custom synthesis of PEC-grade peptides

“Custom PEC process and kit development,” which is for scale-up and scale-out of the technology

“Enabling new modalities manufacturing with PEC,” which will help to accelerate the developments of novel and complex peptide-based drug modalities.

The new technology is now fully integrated into Gyros Protein Technologies’ offering via two kit types and the newly launched services, and the integration will help the company support customers throughout the whole workflow from synthesis to final purified product, which will accelerate drug development and manufacturing processes.

The services are based on the company’s PurePrep EasyClean (PEC) orthogonal peptide purification technology.

PurePep EasyClean Services Set to Accelerate Development and Manufacturing of Peptide-based Drugs 

AstraZeneca and MSD, known as Merck & Co., Inc., Rahway, NJ, USA in the United States and Canada, announced on March 20, 2023 that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for Lynparza (olaparib) in the United Kingdom for use as combination therapy with abiraterone and prednisone or prednisolone for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) when chemotherapy is not clinically indicated.

The decision was based on results from the PROpel Phase III trial, which showed that AstraZeneca and MSD’s Lynparza, in combination with abiraterone, significantly improved radiographic progression-free survival (rPFS) versus abiraterone alone as a first-line treatment for patients with mCRPC regardless of their biomarker status.

The results additionally show that combination therapy reduced the risk of disease progression or death by 34% versus abiraterone alone. As for adverse reactions, Lynparza has been associated with adverse reactions generally of mild or moderate severity and generally not requiring treatment discontinuation.

As for the most frequently observed adverse reactions across clinical trial in patients receiving Lynparza monotherapy were nausea, fatigue/asthenia, anemia, vomiting, diarrhea, decreased appetite, headache, neutropenia, dysgeusia, cough, leukopenia, dizziness, dyspnea, and dyspepsia.

We are delighted that olaparib has been authorised by the MHRA today, opening a new chapter in prostate cancer treatment. This additional therapy option supports our overall ambition to reduce the national burden of prostate cancer and we are continuing to work with NICE and NHS England to secure access as quickly as possible for patients. Medical advances like these offer hope of further progressing the UK as a leader in life science,” said Ed Piper, Medical and Scientific Affairs director, AstraZeneca UK, in a press release.

“Prostate cancer is the most common cancer in men in the UK and advanced prostate cancer is associated with a significant mortality rate. This approval from the MHRA marks important progress in advancing a new treatment option to address the significant unmet need of patients with metastatic castration-resistant prostate cancer,” said David Long, Head of Oncology at MSD UK, in the release.

The decision was based on results from the PROpel Phase III trial.

Lynparza Approved in UK as Combination Therapy for Treatment of Metastatic Castration-Resistant Prostate Cancer 

The European Commission (EC) has approved Dupixent (dupilumab) in the European Union to treat severe atopic dermatitis in children six months of age to five years of age who are candidates for systemic therapy. This approval makes the drug the first and only targeted medicine indicated to treat this population of children in Europe and the United States.

Dupixent is a subcutaneous injection at different injection sites and is intended for use under the guidance of a healthcare professional. It can be given in a clinic or at home by self-administration after training by a healthcare professional.

The approval is based on data from a Phase III trial that evaluates Dupixent every four weeks plus low-potency primarily topical corticosteroids (TCS) or TCS alone in 162 children between six months of age to five years of age with moderate-to-severe atopic dermatitis. The medicine improved skin clearance and reduced overall disease severity and itch at 16 weeks compared to placebo in the overall enrolled population.

In addition, Dupixent improved sleep quality, skin pain, and health-related quality of life compared to placebo in both the overall and severe populations, and the long-term efficacy data showed the clinical benefit at 16 weeks was sustained through 52 weeks, according to the Sanofi.

Common side effects across all indications include injection site reactions, conjunctivitis allergic, arthralgia, oral herpes, and eosinophilia.

This approval makes the drug the first and only targeted medicine indicated to treat this population of children in Europe and the United States.

European Commission Approves Dupixent as First, Only Targeted Medicine for Children with Severe Atopic Dermatitis

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.

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.