Biopharma responds to demand dynamics for upstream bioprocessing capacity.

Upstream Processing Drives Maximum Output

Strategies to Prevent Drug Shortages and Resolve Capacity Challenges

BioPharm International's Technology Forum Series

Pfizer vaccine has good results in adolescents; More vaccine capacity announced

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Spiking studies evaluated a range of critical processing conditions.

Using AEX Membrane Adsorbers for Virus Clearance 

Emergent BioSolutions agreed with an FDA request that the company not initiate manufacturing of new drug substance for COVID-19 vaccines and to quarantine existing material manufactured at the company’s Bayview, Md., facility. Production is halted pending the completion of an FDA inspection and any required remediation, according to Emergent’s 

 with the US Securities and Exchange Commission (SEC).

Emergent reported that it agreed to the halt in manufacturing on April 16, 2020; FDA initiated an inspection of the facility on April 12, 2021. The inspection follows the announcement of a manufacturing error at the Bayview facility that led to the loss of 15 million potential doses of Johnson & Johnson’s COVID-19 vaccine.

that it assumed responsibility for manufacturing the drug substance for its live viral vector vaccine at the Bayview facility.

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Pending a completed FDA inspection, Emergent BioSolutions halts manufacture of vaccine drug substance at Maryland facility. 

Emergent BioSolutions Pauses Vaccine Manufacturing 

Pfizer and BioNTech announced on April 19, 2021 that they will supply an additional 100 million doses of their COVID-19 vaccine, COMIRNATY, to the European Union (EU) member states in 2021.

The additional doses are a result of the European Commission’s (EC) expanded advance purchase agreement, which brings the total number of doses delivered to the EU to 600 million, Pfizer said in a company press release.

“We remain committed to moving as quickly and safely as possible to bring this vaccine to more people in Europe, as the deadly virus continues to wreak havoc across the continent.” said Albert Bourla, chairman and CEO, Pfizer, in the press release. “To date, we have met all of our supply commitments to the EC and we plan to deliver 250 million doses to the European Union in Q2 [second quarter], a four-fold increase on Q1’s [first quarter’s] agreed quantity.”

“The additional 100 million doses from this option exercise will further help to support the acceleration of the vaccination campaigns throughout the EU. We now intend to deliver a total of 600 million doses to the EU this year, which covers two thirds of the EU population and represents the largest cumulative supply agreement for COMIRNATY that we have agreed to date globally,” added Sean Marett, chief business and chief commercial officer, BioNTech, in the press release.

The additional doses are a result of the European Commission’s expanded advance purchase agreement, which brings the total number of doses delivered to the EU to 600 million.

Pfizer and BioNTech to Supply EU with 100 Million Additional COVID-19 Vaccine Doses

 on April 16, 2021 that it has revoked the Emergency Use Authorization (EUA) for the monoclonal antibody bamlanivimab to be administered alone to treat mild-to-moderate COVID-19 in adults and certain pediatric patients. The decision was based on analysis of scientific data that included a look at SARS-CoV-2 variants that appear to be resistant to bamlanivimab alone. This resistance, according to FDA, resulted in an increased risk of treatment failure, and the agency determined the benefits “no longer outweigh the known and potential risks for its authorized use.” FDA had issued EUA for bamlanivimab to be administered alone to treat mild-to-moderate COVID-19 in November 2020 based on the scientific evidence that was available at the time.

“While the risk-benefit assessment for using bamlanivimab alone is no longer favorable due to the increased frequency of resistant variants, other monoclonal antibody therapies authorized for emergency use remain appropriate treatment choices when used in accordance with the authorized labeling and can help keep high risk patients with COVID-19 out of the hospital,” said Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research, in a press release. “We urge the American public to seek out these therapies when needed while we continue to use the best data available to provide patients with safe and effective treatments during this pandemic.”

The agency revoked EUA status for the monoclonal antibody bamlanivimab to be administered alone to treat mild-to-moderate COVID-19.

FDA Revokes Emergency Use Authorization for COVID-19 Treatment

CordenPharma announced on April 19, 2021 that it is expanding its lipid purification capacity at its Colorado site.

According to a CordenPharma press release, the expansion will include the addition of new production lines, which will be merged into the lipid manufacturing process in April 2021. By July 2021, the company expects a decrease in lipid shipment delivery time due to the expansion.

“CordenPharma is proud to contribute this major capital expansion to increase important lipid production for the global market,” said Michael Quirmbach, CEO and president, CordenPharma. “We have drawn upon longstanding expertise in specialized lipids to create an even stronger integrated network of facilities to support current and future projects.”

The company, who has also expanded its lipid supply chain at its facilities in Switzerland and France, manufactures four lipids used to formulate messenger RNA (mRNA)-based vaccines. They include:

Cationic lipids that condense negatively charged mRNA

PEGylated lipids that form a protective hydrophilic layer, which sterically stabilizes the lipid nanoparticle (LNP)

DiStearoylphosPhatidylCholine (DSPC), a phospholipid that offers a stable bilayer-forming structure

Plant-based cholesterol (CP BotaniChol), which stabilizes the LNP structures and enables endosome escape.

CordenPharma’s expansion will include the addition of new production lines which will be merged into the lipid manufacturing process in April 2021.

CordenPharma to Expand Lipid Purification Capacity at its Colorado Site

On April 16, 2021, Sartorius, opened a new state-of-the-art manufacturing facility for downstream bioprocessing equipment in Havant, Hampshire, United Kingdom. The company announced that the opening marks the official relocation of more than 90 employees to the new facility from Sartorius’ former Portsmouth site, located a few miles away.

The new 58,000-ft2 site will bring together skilled engineers with biochemical, electrical, and mechanical backgrounds who will design and manufacture a range of systems for the biopharmaceutical market, including chromatography columns and filtration systems that will save time and costs. These systems are crucial elements for the manufacture of injectable drugs needed to treat cancer and diabetes and for the production of vaccines to prevent the spread of viruses, Sartorius reported in a company press release. In addition to a 28,000- ft2 production area, the center accommodates a 4000- ft2 customer test lab to demonstrate the functionality of Sartorius equipment.

The company will invest more than €400 million in 2021 to expand manufacturing capacities around the world to meet the growing demand in the biopharmaceuticals market. In line with these investments, Sartorius aims to expand its Havant site and is now offering positions for process engineers, project managers, and design engineers as well as several support functions, among other job vacancies. With the new facility in Havant, the company now has five locations in the UK, employing more than 900 staff members.

“The new facility in Havant will be an important part of our global operations network as it will enable our business to grow to meet the requirements of the expanding industry,” said Thorsten Peuker, head of operations, BPS Systems, at Sartorius in the press release. “The new facility increases Sartorius’ capacity to deliver support in all areas of our business and provide the highest quality equipment and services to our customers.”

Sartorius has expanded in the United Kingdom with the relocation to a new facility in Havant, Hampshire, for downstream processing equipment.

Sartorius Opens New Downstream Center of Excellence Facility in UK

 on conducting remote inspections, or, as the agency is calling them, “voluntary remote interactive evaluations (VRIEs)” at pharmaceutical and biologics facilities, using videoconferencing software, 360-degree video inspection, and other tools. The agency had been criticized for failing to take a stand on the use of remote inspection technologies in light of a growing backlog of plant inspections and delays in new drug approvals due to concerns about putting inspection staffers at risk of contracting COVID-19.

The guidance’s wording makes it clear that the agency views use of these technologies as a temporary measure, only for as long as US health authorities continue to define the COVID-19 pandemic as a public health emergency. However, it also suggests that FDA may use remote technologies in the post-COVID-19 world, as a way to supplement inspections, gain additional insights into issues found during a traditional inspection, or clarify questions or support a new drug application. The guidance also hints that technology may be used as a preliminary step, to better define the scope, depth, and timing required for future in-person inspections.

The guidance was issued without the customary public comment period, although FDA’s conservative approach and silence on the subject of remote technology had been discussed widely in the press and at industry events. Remote interactive evaluations would be used for pre- and post-approval inspections, surveillance inspections, follow-up and compliance visits, and bioresearch monitoring inspections.

FDA will use risk-management tools to determine when to ask a facility to participate, and may requests records or ask the company to take part in a VRIE before an on-site inspection.The agency also emphasized that it will not accept requests from facilities to perform inspections remotely, but will notify the facility if it wishes to set up a VRIE. FDA will contact the company and ask for information required to plan the evaluation ahead of time.

In order to prepare for the evaluation, FDA will schedule a brief meeting with the company to discuss staffing, key contacts and roles, logistics, expectations, and to outline key responsibilities. It will also ascertain any time zone differences and needs for interpreters.

Among the issues to be examined would be the facility’s capacity to host such evaluations, specifically the host facility’s internet access and its ability to live stream video and audio during an actual inspection. Discussions will come to an end if it is found that there is insufficient bandwidth or that remote video will not give adequate visibility into the operations or segments of the facility being evaluated.

FDA also says that it will not issue a Form 482 for these evaluations and that it will use its own government-issued Microsoft Teams, Zoom, and Adobe Connect platforms. It also asks that facilities be sure to make electronic documents accessible for sharing.

FDA also asks that facilities that are still using paper documentation ensure that it is scanned into PDFs when possible.

The agency will use technology for “voluntary remote interactive evaluations” for pre- and post-approval and other types of inspections.

FDA Weighs in on Remote Inspections

Thermo Fisher Scientific announced on April 15, 2021 that it has acquired PPD, a clinical research services provider, for $17.4 billion.

The acquisition, which is expected to be completed by the end of 2021, will give Thermo Fisher access to PPD’s drug development platform, patient recruitment capabilities, and laboratory services, Thermo Fisher said in a company press release. The collaboration is expected to offer new solutions for customers, while reducing the time and cost of the drug development process.

"Pharma and biotech is our largest and fastest growing end market, and our customers value us as a strategic partner and an industry leader. The acquisition of PPD is a natural extension for Thermo Fisher and will enable us to provide these customers with important clinical research services and partner with them in new and exciting ways as they move a scientific idea to an approved medicine quickly, reliably, and cost effectively," said Marc N. Casper, chairman, president, and CEO, Thermo Fisher Scientific, in the press release. "Longer term, we plan to continue to invest in and connect the capabilities across the combined company to further help our customers accelerate innovation and drive productivity, while driving further value for our shareholders."

"This is a very exciting announcement for our shareholders and will provide customers with an even better opportunity to bring meaningful innovation to the market faster and more efficiently,” added David Simmons, chairman and CEO, PPD, in the press release. “Thermo Fisher is a world-class company with a very similar culture and values and will provide a great foundation for our colleagues to continue to deliver for our customers and to develop their own skills and careers."

The acquisition, which is expected to be completed by the end of 2021, will give Thermo Fisher access to PPD’s drug development platform, patient recruitment capabilities, and laboratory services.

Thermo Fisher to Acquire PPD for $17.4 Billion

Abzena, a US-based global partner research organization, announced on April 15, 2021 that it has chosen Sanford, NC, as the location for its new good manufacturing practices (GMP) facility.

The new facility, which will be designed specifically for phase III and commercial manufacturing of biologics, will initially include four modular suites with up to two 2000-L bioreactors, followed by the addition of two more 2000 L suites, Abzena said in a company press release. The facility will also handle continuous manufacturing and perfusion, with manufacturing beginning in 2022.

“We are delighted to announce the investment of our newest site in Sanford, NC,” said Jonathan Goldman, MD, CEO of Abzena, in the press release. “Our goal is to support our partners and the patients they serve with this expansion in [C]GMP [current good manufacturing practice] biologics manufacturing services. We are pleased to provide integrated asset development with a full suite of in-house services from discovery through clinical and commercial phases without the need for technology transfer. We are very pleased to be welcomed by North Carolina.”

The new Abzena facility will initially include four modular suites with up to two 2000-L bioreactors, followed by the addition of two more 2000 L suites.

Abzena Names North Carolina Location for New GMP Manufacturing Facility

Catalent announced on April 15, 2021 that it has expanded its services at its clinical supply services facility in Philadelphia to include cryogenic capabilities for the support of cell and gene therapy development.

With the added cryogenic storage, cell therapies and other biological materials will be preserved in liquid nitrogen vapor at temperatures of around minus -180°C, Catalent said in a company press release. Additionally, the facility will have the ability to package, label, and distribute cryogenic materials.

“Establishing robust clinical supply chain services for cell and gene therapies is complex and challenging, and Catalent has undertaken an in-depth strategic review to evaluate how it can establish a safe, efficient, and flexible approach to support this fast-growing area of the industry,” said Ricci Whitlow, president, Catalent Clinical Supply Services, in the press release. “The solution we have implemented at Philadelphia not only meets current needs, but also provides a template for us to easily replicate at other facilities in our global network, allowing incremental capacity expansion within the new infrastructure as demand grows.”

Catalent plans to add cryogenic capabilities to its facility in Philadelphia, which will strengthen its ability to cryogenically preserve cell therapies and other biological materials.

Catalent to Add Cryogenic Capabilities to Support Cell and Gene Therapy Development

Hyalo Technologies, a US-based biopharmaceutical company has unveiled a new patented technology, called Sterilization with the Hyalo Matrix. This new method adds a matrix to enhance stability, allow for sterilization without degradation, and allow maintenance of drug efficacy at room temperature. The ability to remain stable at room temperature will ease up global distribution and reduce dependency on cold chain distribution of pharmaceuticals and biopharmaceuticals, including genetic materials, attenuated viruses, viral vectors, biologics, antibodies, biosimilars, protein subunits, nanosuspensions, and small and large molecules, the company reported in a March 29, 2021 press release.

Furthermore, when added to the drug molecule, the matrix can also effectively be sterilized, preventing degradation and preserving the integrity of temperature-sensitive materials.

The company's latest studies yielded positive results, which showed that the Hyalo Matrix is able to protect and enhance the stability of various biologics, antibodies, and biosimilars. After the matrix was added to each of these types of drug molecules and sterilized, the drugs were analyzed, with ≥ 95% of the drug molecules recovered. These results show the Hyalo Matrix helps preserve efficacy and enhance stability of each drug molecule.

Currently under the COVID-19 pandemic, vaccine manufacturers have been having issues with scaling up manufacturing as well as delayed distribution, bringing cold chain logistics into the spotlight. Hyalo Technologies reported in its press release that the current stats for cold chain logistics are as follows:

Roughly 80% of drugs require temperature-controlled transportation, and that trend is on the rise.

Cold chain requires close consideration of factors, including shipping modes, climate zones, storage capabilities, and healthcare settings.

Pharmaceutical manufacturers, distributors, logistics providers, and others risk the loss of temperature-sensitive products and, therefore, the loss of billions of dollars as evidenced by following:

30% of discarded pharmaceuticals can be attributed solely to cold chain logistics issues

25% of vaccines reach their destination degraded because of incorrect storage and transport during shipping

20% of temperature-sensitive products are damaged during transport because the cold chain has been broken at some point in the process.

"This new technology could eradicate the need for cold chain storage and transport as a drug can now be stable at room temperature, which will make global distribution quicker and more eficient," said Shalabh Jain, chairman and CEO of Hyalo Technologies, in the press release.

"This game-changing technology has the potential to enhance drug delivery and distribution," said Bob Oliver, executive advisor and board member of Hyalo Technologies, in the press release.

This new technology could eliminate the need for cold chain storage, transport, and distribution of temperature-sensitive molecules.

Hyalo Technologies Unveils Room Temperature Drug-Stabilizing Technology

On April 14, 2021, ATMPS, a UK-based provider of blockchain-based “vein-to-vein” cell orchestration platforms for advanced therapies, and Ori Biotech, an innovator in cell and gene therapy (CGT) manufacturing platforms, announced that they have formed a global non-exclusive collaboration to create an integrated digital data platform to support the development of advanced therapies.

Under the agreement, the partnership will integrate Ori’s proprietary CGT manufacturing platform’s data architecture with ATMPS’ Hataali, a secure data sharing platform that is specially designed to be a scalable system for advanced therapies. The combination of the two proprietary platforms is expected to provide improved product tracking, scheduling, and live monitoring of the manufacturing status across the entire CGT supply chain from vein-to-vein.

Hataali works by encrypting and storing data using distributed ledger technology through a process known as hashing. This process ensures data security is protected through a system of private keys and cryptography. The data platform was the first cell orchestration platform installed in a hospital globally, and ATMPS was the first blockchain company to integrate with the UK National Health Service for the delivery of advanced therapies, the company stated in a press release.

“Ori selected ATMPS’ Hataali technology for integration with our platform to allow the secure sharing of relevant process data with therapy developers, contract development and manufacturing organizations, and even clinicians or patients in real-time. This collaboration will provide increased visibility into the treatment process for those involved at each stage of the treatment process,” said Jason C. Foster, CEO, Ori Biotech, in the press release. “The addition of established technologies from companies like ATMPS allows Ori to further its mission of enabling partners across the CGT industry to bring therapies as safely, cost effectively, and quickly as possible to large numbers of patients with few alternative therapeutic options.”

“Ori is an ideal partner for ATMPS, as both companies share a common mission to lower the costs and improve processes for cell and gene therapies. Ori’s work in helping innovators scale from preclinical to commercial is a massive step towards reducing complexity and bringing these vital therapies to patients more quickly,” said Raja Sharif, CEO, ATMPS, in the press release. “We all know how challenging and expensive the development and manufacturing of CGTs can be. With the help of Hataali, Ori can securely leverage vein-to-vein data to advance their manufacturing solutions much more efficiently. This will enable real-time therapy tracking, improved patient trust, and expediated clinical development.”

The ATMPS and Ori Biotech collaboration aims to improve visibility and reporting of cell and gene therapy manufacturing through a pre-integrated data solution.

ATMPS and Ori Biotech Collaborate on Integrated Digital Platform for Cell and Gene Therapy

 Washington Editor, jillwechsler7@gmail.com.

FDA Acting Commissioner Janet Woodcock announced this week that Patrizia Cavazzoni will become the director of the Center for Drug Evaluation and Research (CDER), shifting from her role as acting director since spring 2020. While not a surprise, the move makes clear that Woodcock will not return to that position at CDER, which she had held for much of the past 30 years (1).

Instead, Woodcock remains in limbo as the temporary head of FDA, a situation that has been lamented on all sides. Several months ago, she was expected to get the top job until that move drew opposition from certain consumer activists who regard her as too cozy with industry and responsible for permitting deadly long-acting opioids on the market. The situation has led to inaction at the White House, leaving the leadership of FDA as one of the few unfilled top administration positions, a notable concern in this time of public health emergency. Woodcock’s long experience and strong leadership at FDA makes her a prime choice to lead the agency after a year of indecision and errors under Stephen Hahn, who came to the job with little knowledge of FDA or federal government operations. With the COVID-19 pandemic still raging across the United States and the world despite effective vaccines and therapeutics, FDA continues to face difficult decisions as it strives to shepherd new therapies to patients.

In only three years at FDA, Cavazzoni has impressed colleagues and FDA stakeholders for being a capable administrator and creative problem-solver. Woodcock brought her to CDER in 2018 as deputy center director for operations, and she briefly served in 2019 as acting principal deputy commissioner. Before coming to FDA, she held executive positions involving pharmacovigilance and drug safety at Pfizer, Sanofi, and Eli Lilly. In the past year, Cavazzoni kept the drug regulatory process running smoothly, as the pandemic placed added pressures on drug development and approvals, particularly with the halt to field inspections needed to vet product quality.

A main challenge for Cavazzoni will be to explain and reassure Congressional leaders of the strength of various CDER programs and decisions, as the agency continues to face sharp scrutiny for its handling of drug testing and product approvals during the pandemic. CDER will be in the spotlight as it seeks approval of new drug user fee agreements and sufficient resources in the coming months. And with a number of long-term FDA officials poised to retire, Cavazzoni will face the challenging task of recruiting and retaining capable staff under difficult circumstances.

Woodcock was named FDA acting commissioner in January 2021 when the Biden administration took office. In closing her announcement about Cavazzoni, Woodcock acknowledged that, in addition to serving temporarily as the agency head, her official FDA position now is principal medical advisor to the commissioner, the role she assumed when detailed last May 2020 to head therapeutics development at Operation Warp Speed. Under current law, she can serve as acting commissioner only until mid-August, unless she or another person is named to the commissioner’s job. Woodcock could remain at FDA in her medical advisory role under a new commissioner, but it won’t surprise anyone if the chooses to retire from the agency at that time.

1. J. Woodcock, A Message From the Acting Commissioner, Personnel Update–CDER Director, April 12, 2021.

Patrizia Cavazzoni will become the director of the Center for Drug Evaluation and Research, and Janet Woodcock remains in limbo as the temporary head of FDA.

Leadership Change at CDER Spotlights Imperative to Name New FDA Commissioner

Lonza and aTyr Pharma, a US-based biotherapeutics company, announced on April 14, 2021 that they have entered into an agreement for the manufacture of ATYR2810, aTyr’s monoclonal antibody (mAb) that targets the neuropilin-2 (NRP2) protein. The mAb is currently in preclinical development for the treatment of cancer.

Through the agreement, Lonza will use its fully integrated end-to-end program, Ibex Design, to manufacture current good manufacturing practice (CGMP) material for the mAb while supporting the process from gene to investigational new drug (IND) filing, Lonza said in a company press release. Additionally, Lonza will offer drug substance and drug product for toxicological studies in animals and early clinical development in humans; full process support, including cell line development, process development, and supply chain simplification; and drug substance and drug product manufacturing at its sites in Visp and Stein, Switzerland.

“We look forward to supporting aTyr as they advance their novel therapeutic antibody from preclinical stages into the clinic. This collaboration signifies our commitment and flexibility in accommodating the specific and unique needs of small biotech companies,” said Jennifer Cannon, senior vice-president, global head of Mammalian Biologics, Lonza, in the press release.

“As we prepare to advance ATYR2810 to clinical stage development, we are pleased to work with Lonza, a partner with extensive and proven capability in antibody manufacturing, for the production of our first anti-NRP2 antibody,” added Sanjay S. Shukla, president and CEO, aTyr, in the press release. “Having recently initiated IND-enabling activities for ATYR2810 following some compelling preclinical data in triple-negative breast cancer, strengthened by additional data in lung cancer, this agreement with Lonza reflects our commitment to this program and will support our efforts to advance ATYR2810 to in-patient trials in cancer, including certain aggressive tumors where NRP2 is implicated.”

Through the agreement, Lonza will use its fully integrated end-to-end program, Ibex Design, to manufacture cGMP material for the mAb while supporting the process from gene to IND.

Lonza Partners with aTyr Pharma for mAb Manufacturing

Patrizia Cavazzoni was named director of FDA’s Center for Drug Evaluation and Research (CDER) on April 12, 2021, having served in an acting director role for more than one year.

Cavazzoni was appointed acting director in 2020 when then CDER Director Janet Woodcock left FDA to oversee therapeutics development for Operation Warp Speed, the federal government efforts to combat COVID-19. Woodcock, current acting commissioner for FDA, made the announcement via 

Cavazzoni joined FDA in January 2018 as CDER’s Deputy Director for Operations; she was acting principal deputy commissioner of food and drugs from January–February 2019.

Cavazzoni earned a medical degree at McGill University in Canada. She was an investigator in clinical trials of novel antipsychotic and antidepressant medications, was appointed to the faculty of medicine at the University of Ottawa, and joined the Mood Disorders Program at the Royal Ottawa Hospital. Later, Cavazzoni worked in the pharmaceutical industry and held senior positions in clinical development, regulatory affairs, and safety risk management across multiple therapeutic areas, until she joined FDA in 2018.

Cavazzoni is certified by the American Board of Neurology and Psychiatry and is a fellow of the Canadian Royal College of Physician and Surgeons and the Canadian College of Neuropsychopharmacology.

“Having spent most of my career with CDER, I have a deep appreciation of the role. Dr. Cavazzoni’s credentials are of the highest caliber, and I know she will continue to excel in advancing the FDA’s public health mission for the benefit of all,” Woodcock noted on Twitter.

, Cavazzoni thanked Health and Human Services Secretary Xavier Becerra and Woodcock “for entrusting me with leading CDER, and I look forward with gratitude and anticipation to serving the center and the public for many years to come.”

Acting FDA commissioner announces permanent appointment of Patrizia Cavazzoni as CDER director, following year-long acting-director role.

Cavazzoni Named CDER Director

FDA and the Centers for Disease Control (CDC) 

 on April 13, 2021 that they are evaluating six cases in the United States of a rare and severe type of blood clot, cerebral venous sinus thrombosis (CVST), that occurred in women after they received the Johnson & Johnson (J&J) vaccine. The CVST clot was seen in combination with low levels of blood platelets and occurred in women ages 18–48. The symptoms appeared 6–13 days after vaccination.

CDC’s Advisory Committee on Immunization Practices (ACIP) will hold a meeting on Wednesday, April 14, 2021 to review the cases. FDA will then review the CDC analysis as a part of its investigation into the matter. “Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution. This is important, in part, to ensure that the health care provider community is aware of the potential for these adverse events and can plan for proper recognition and management due to the unique treatment required with this type of blood clot,” FDA stated in a press release.

FDA’s decision to pause the use of the J&J vaccine is cautionary, stating the rarity of the adverse events. The agency recommends, however, that anyone who develop severe headache, abdominal pain, leg pain, or shortness of breath within three weeks of the J&J COVID-19 vaccination contact their health care provider.

CDC and FDA are reviewing data from reported cases of a rare type of blood clot in people that received the Johnson & Johnson COVID-19 vaccine. 

FDA Recommends Pausing Use of J&J COVID-19 Vaccine After Reports of Blood Clots 

Woodstock Sterile Solutions, a blow-fill-seal (BFS) contract development and manufacturing organization, announced on April 12, 2021 that it has named Bill Hartzel as its first Chief Commercial Officer.

Hartzel, who will now be responsible for the commercial activities and strategy for the company, previously served as product manager in Medication Delivery Solutions; director of Strategic Execution; regional director of Commercial Operations; and global vice-president of Business Development for Analytical, Respiratory, and Ophthalmics for Catalent, Woodstock’s predecessor, the company said in a press release.

“We are pleased to welcome a dynamic, customer-focused leader like Bill Hartzel to the Woodstock executive team,” said Paul Josephs, CEO, Woodstock, in the press release. “Bill has had an impressive career in the BFS industry and we look forward to him bringing the exceptional business and technical acumen he has demonstrated throughout his career to our leadership team to help us drive sustainable growth for the organization.”

“I am very excited about the opportunities and the potential for growth for Woodstock Sterile Solutions in the pharmaceutical and healthcare industry,” added Hartzel in the press releease. “BFS is an untapped technology and it is primed for growth and expansion—not just in the respiratory and ophthalmic space—but as a sterile delivery platform, where it can help to mitigate the risks involved with sterile manufacturing. The Woodstock business is uniquely positioned to support complex formulations seamlessly from development through commercial production. I look forward to helping Woodstock Sterile Solutions reach its full potential in this market.”

Bill Hartzel has been named as Woodstock’s first Chief Commercial Officer. 

Woodstock Sterile Solutions Appoints First Chief Commercial Officer

Catalent announced on April 13, 2021 that it has completed its expansion of two new mammalian cell culture suites at its biologics drug substance development and manufacturing facility in Madison, Wis.

Each suite feature a 2x2000-L single-use bioreactor system aimed at processing batches of 2000 liters or 4000 L for current good manufacturing practice (CGMP) clinical and commercial manufacturing, Catalent said in a company press release. The first engineering batch in one new suite started in March 2021, with the first CGMP batch expected to be manufactured during May 2021. The second suite is set to begin its first engineering batch in May 2021 and its first CGMP batch in July 2021. The new manufacturing suites add to an existing 2×2,000-L suite, a 1000-L suite, and a 500-L suite.

“This new capacity will allow us to meet growing clinical and commercial demand from both existing and new customers,” said Mike Riley, region president, Biologics, North America, Catalent, in the press release. “Catalent’s continued investment in technology and capacity will enable us to bring our customers’ important and innovative treatments to patients faster.”

Catalent’s new mammalian cell culture suites in Madison, Wis. use single-use bioreactor systems for CGMP clinical and commercial manufacturing.

Catalent Completes Expansion of its Biologics Drug Substance Facility in Wisconsin  

Airway Therapeutics, a US-based biopharmaceutical company, announced on April 12, 2021 that FDA has accepted its investigational new drug (IND) application for the development of its novel human recombinant protein, AT-100 (rhSP-D), as a treatment for COVID-19.

Following the IND acceptance, the company will begin a Phase Ib clinical trial to determine the feasibility of intratracheal administrations of AT-100 and its safety and tolerability profile, Airway said in a company press release. In previous preclinical studies, the protein reduced inflammation and infection while regulating immune response for multiple respiratory diseases inside and outside the lung. Studies have also shown AT-100 has the potential to prevent SARS-CoV-2 duplication and promote viral elimination while reducing secondary infections in COVID-19 patients who are ventilated in intensive care.

“The pre-clinical data are encouraging and lead us to believe that AT-100 has therapeutic potential against COVID-19 by reducing infection and inflammation in mechanically ventilated seriously-ill patients who require a range of treatment options,” said Marc Salzberg, MD, CEO of Airway, in the press release. “We are excited to advance the clinical development of AT-100 with the goal of delivering a novel therapy for severely ill COVID-19 patients who are in need of new treatment options.”

FDA has accepted Airway’s investigational new drug application for the development of its novel human recombinant protein, AT-100 (rhSP-D), as a treatment for COVID-19.

FDA Accepts IND for Airway Therapeutics’ Treatment for Severe COVID-19 Patients

Eli Lilly and Company announced on April 12, 2021 that it has modified its purchase agreements with the US government for its emergency use authorized COVID-19 neutralizing antibody therapies, bamlanivimab and etesevimab, to be supplied and used together rather than individually.

Through the modified agreement, the supply of etesevimab will now complement the doses of bamlanivimab that the US government already purchased, concluding the purchase agreement for bamlanivimab alone and cancelling the remaining 350,856 doses that were scheduled to be delivered by the end of March 2021, Eli Lilly said in a company press release.

Currently, bamlanivimab and etesevimab together and bamlanivimab alone have not been approved by FDA, and it is not known if the neutralizing antibody therapies are a safe treatment for COVID-19.

Eli Lilly has modified its purchase agreements with the US government for its emergency use authorized COVID-19 neutralizing antibody therapies, bamlanivimab and etesevimab, to be supplied and used together rather than individually.

Eli Lilly Modifies COVID-19 Purchase Agreement with the US Government

Sanofi announced on April 12, 2021 that it will invest €400 million (US$476 million) over the course of five years to develop a vaccine production center in Singapore.

In collaboration with the Singapore Economic Development Board (EDB), the new site will supply the Asian region and will include multiple fully digitalized modules for the production of three to four vaccines simultaneously, Sanofi said in a company press release. Additionally, the facility will have the capacity to utilize several vaccine manufacturing technology platforms based on different cell types for the production of a specific vaccine in a faster timeframe to meet public health needs.

The facility is currently in its design phase with construction expected to begin in the third quarter of 2021. It is set to be fully operational in the first quarter of 2026 if all qualifications and validations of the first manufactured vaccine have been completed.

“As a major healthcare player, it’s our responsibility to act and to meet the unprecedented growing demands for vaccines. By investing in a new production site in Singapore, Sanofi is aiming to strengthen production capacity to meet ever-growing global demands on vaccines, and answer more rapidly to future pandemics,” said Thomas Triomphe, executive vice-president and global head of Sanofi Pasteur, in the press release. “We are very pleased by the strong collaboration with the Singapore Economic Development Board to achieve this exciting milestone.”

“Sanofi’s decision to locate its first-in-Asia digitally-enabled vaccine production center in Singapore, to supply markets in the region and beyond, is an endorsement of Singapore’s position as a leading center for advanced manufacturing,” added Beh Swan Gin, chairman, EDB, in the press release. “EDB will continue to promote digitalization, automation, and innovation to transform the manufacturing sector and create good jobs for Singaporeans.”

In collaboration with the Singapore Economic Development Board, the new site will supply the Asian region and will include multiple fully digitalized modules for the production of three to four vaccines simultaneously

Sanofi to Invest $476 Million into New Singapore Vaccine Production Center 

For anyone who was wondering in recent weeks what was holding up FDA Emergency Use Authorization for Johnson & Johnson (J&J) to distribute vaccine produced by the Emergent BioSolutions Bayview facility in Baltimore, the reason is clear from the multiple red flags and violations at the facility cited in an April 2020 field inspection report. Even before Emergent disclosed that it had to discard 15 million doses of the J&J vaccine drug substance, FDA inspectors had uncovered multiple deficiencies and quality control issues. Journalists and investigators have disclosed additional government reports and complaints about Emergent’s operations and practices, raising multiple questions about how and why federal health officials continued to ramp up contracts with the company.

A picture of wide manufacturing violations appears in a recently disclosed 

on a site visit to Emergent’s Baltimore vaccine plant conducted from April 9, 2020 to April 20, 2020. The report describes inadequate controls for computer and records systems, disregard of established test procedures and laboratory control mechanisms, failure to investigate deviations from test methods, unclear quality control unit responsibilities and procedures, and lack of employee training on current good manufacturing practices (cGMP) practices.

Most prescient is the last observation citing deficient operations to prevent contamination or mix-ups of products by having separate or defined areas for holding rejected components before disposition. The FDA investigator noted the absence of a report on a non-conforming material held in the “reject cage,” which was needed to explain the rejection and how the material was disposed. The year-old inspection report indicates that Trump administration officials and subsequently Biden staffers were aware of the serious quality control issues at the Emergent facility, even before the discovery that millions of doses of J&J vaccine doses were, in fact, discarded due to a mix-up with vaccine ingredient being produced for AstraZeneca. Despite the serious concerns raised by FDA and other analysts, pandemic preparedness officials continued to award ever-larger contracts to Emergent for vaccine ingredient production.

that it would assume full responsibility for manufacturing its vaccine drug substance at the Emergent facility. The company is shifting operations and quality experts to the site and “significantly increasing the number of manufacturing, quality, and technical operations personnel” to work with Emergent staffers. At the same time, Emergent was instructed by the Biden administration to halt production of the AstraZeneca vaccine, offering to assist the company in identifying other facilities to handle its production.

Even so, Emergent executives downplayed the situation, emphasizing in a press release that it was receiving an additional $23 million from the Biomedical Advanced Research and Development Authority (BARDA) to improve its manufacturing operations to expand J&J vaccine production. CEO Robert Kramer 

highlighted the company’s long-standing collaboration with the federal government

 in expanding vaccine production, and that the Bayview facility remains an Emergent property. This followed an 

that its quality control checks had identified only one single noncompliant batch, and that there was nothing unusual in having to discard some material in the complex vaccine production process.

The continued award of ever-larger manufacturing contracts to Emergent reflects its political connections in Washington as well as still limited US capacity for producing large quantities of critical vaccines. J&J has imported its vaccine substance from its plant in the Netherlands and also signed an agreement for Merck to produce its vaccine and has expanded its collaboration with Catalent to ramp up production of its vaccine at its Bloomington, Ind. facility.

One result of “uneven” production from the Emergent Baltimore plant is that federal health authorities now indicate that J&J will provide less than a million vaccine doses in the coming weeks, 85% less than the expected 5 million doses a week.

Even before Emergent disclosed that it had to discard 15 million doses of the J&J vaccine drug substance, FDA inspectors had uncovered multiple deficiencies and quality control issues.

FDA Inspectors Cited Critical Problems at Emergent Facility

Sanofi announced on April 9, 2021 that it has acquired Tidal Therapeutics, a US-based pre-clinical stage biotech company, for $470 million.

Under the terms of the agreement, Sanofi will provide an upfront payment of $160 million and up to $310 million upon achievement of certain milestones, Sanofi said in a company press release. The deal will also give Sanofi access to Tidal’s novel messenger RNA (mRNA)-based approach for 

 reprogramming of immune cells, which will expand Sanofi’s research capabilities in immuno-oncology and inflammatory diseases.

“We anticipate that this next-generation, off-the-shelf approach has the potential to bring CAR-T cell [chimeric antigen receptor T cell] therapy to a much broader patient population,” said Frank Nestle, global head of Research and chief scientific officer at Sanofi, in the press release. “We believe that the underlying mRNA targeting platform will create disruptive therapeutic approaches across a variety of oncology and autoimmune conditions.”

“Teaming up with Sanofi gives us the opportunity to further develop our unique platform and rapidly apply it to ultimately help patients across a range of diseases,” added Ulrik Nielsen, president and CEO, Tidal Therapeutics, in the press release.

The deal will give Sanofi access to Tidal’s novel mRNA-based approach for in-vivo reprogramming of immune cells, which will expand Sanofi’s research capabilities in immuno-oncology and inflammatory diseases.

Sanofi to Acquire Tidal Therapeutics for $470 Million

BeiGene, a commercial-stage biotechnology company, announced on April 7, 2021 that the China National Medical Products Administration has given the company the green light to begin manufacturing commercial supply of its approved anti-programmed cell death (PD)-1 antibody, tislelizumab, at its biologics facility in Guangzhou, China.

The 1 million-ft.2 facility currently has 8000 Lof biologics capacity approved for commercial supply, with 64,000 additional liters planning to be added to the site by the end of 2022, BeiGene said in a company press release.

“We started building this large-scale, commercial biologics manufacturing facility in 2017 to meet our expected future demand. Since that time, tislelizumab has been approved in several indications in China, included in the National Reimbursement Drug List, and licensed to Novartis in Europe, North America, and Japan,” said Xiaobin Wu, PhD, president, chief operating officer, and general manager of China at BeiGene, in the press release. “With significantly expanded capacity for tislelizumab and for other biologics in our pipeline, we are continuing our strong commitment to the quality, safety, and compliance of our products.”

The China National Medical Products Administration has given the company the green light to begin manufacturing commercial supply of its approved anti-PD-1 antibody, tislelizumab, at its biologics facility in Guangzhou, China.

China Approves BeiGene for Commercial Manufacturing at its Biologics Facility

Merck, known as MSD outside of the United States and Canada, and Alkermes, a biopharmaceutical company headquartered in Ireland, announced on April 7, 2021 that they have entered into a collaboration and supply agreement to conduct a Phase III study to evaluate nemvaleukin alfa, Alkermes' novel investigational engineered interleukin-2 (IL-2) variant immunotherapy, in combination with Merck’s Keytruda (pembrolizumab), in patients with platinum-resistant ovarian cancer.

The combination is currently being evaluated in two 1/2 phase studies, ARTISTRY-1 and ARTISTRY-2, to determine its safety, tolerability, efficacy, and pharmacokinetic and pharmacodynamic effects, Alkermes said in a company press release.

"We are pleased to collaborate with [Merck] to evaluate nemvaleukin in combination with Keytruda in patients with platinum-resistant ovarian cancer, a patient population for which there are limited treatment options available and overall survival remains low. Importantly, there are no anti-PD-1 treatments currently approved for this tumor type," said Jessicca Rege, PhD, vice-president, head of Oncology at Alkermes. "Nemvaleukin in combination with Keytruda has demonstrated antitumor activity in heavily pre-treated patients with platinum-resistant ovarian cancer in the ongoing ARTISTRY-1 study, with durable and deepening responses observed. We look forward to initiating this Phase III study to further evaluate the potential clinical utility of this combination in this tumor type and advancing our interactions with regulatory authorities related to potential registration strategies for the combination in platinum-resistant ovarian cancer."

The Phase III study will evaluate nemvaleukin alfa, Alkermes' novel investigational engineered interleukin-2 variant immunotherapy, in combination with Merck’s Keytruda (pembrolizumab), in patients with platinum-resistant ovarian cancer.

Merck and Alkermes Collaborate on Phase III Study for Ovarian Cancer Treatment

Takeda and CSL Behring, co-founders of the CoVIg-19 Plasma Alliance, announced on April 2, 2021 that a Phase III inpatient treatment with anti-coronavirus immunoglobulin clinical trial did not meet its endpoints. The year-long collaboration of the companies in the Alliance has ended with the end of the clinical trial, but it provides a framework for future collaboration, the companies said in the press release.

According to a Takeda press release, the trial, which was sponsored and funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, intended to determine whether CoVIg-19, an investigational anti-coronavirus hyperimmune intravenous immunoglobulin medicine, could lessen the risk of disease progression when added to standard care treatment including remdesivir in hospitalized adult patients at risk for serious complications.

“While the results of this particular clinical trial are disappointing, we are proud that as an industry we proactively and collaboratively pursued this work, and that the program may contribute to a growing understanding of this challenging virus and strategies for patient care,” said Bill Mezzanotte, MD, executive vice-president, head of Research and Development and chief medical officer, CSL Behring, and co-leader of the CoVIg-19 Alliance, in the press release. “Since we embarked on this development program, and throughout the pandemic, we have learned much from our scientific research. Importantly, we learned that as an industry we have the fortitude and capability to quickly work together for the greater good of human health.”

“We are especially proud that we pooled resources, brought our plasma expertise and infrastructure together at our own cost to benefit public health and added to our understanding of a complex field. We are extremely thankful to all those who collaborated day and night for one year in testing circumstances to develop and manufacture a potential solution for COVID-19, including those organizations from outside the industry who chose to support us,” added Julie Kim, president of Plasma-Derived Therapies Business Unit, Takeda and co-leader of the CoVIg-19 Alliance, in the press release. “We express our sincere gratitude to the COVID-19 survivors who generously donated their plasma to make our work possible, the patients who graciously participated in the trial, and to the regulatory and government agencies for their partnership and flexibility to support our efforts."

A Phase III clinical trial of anti-coronavirus immunoglobulin did not meet its endpoints, concluding the year-long CoVIg-19 Plasma Alliance, Takeda and CSL Behring announced.

Plasma-Based COVID-19 Treatment Alliance Ends its Project as Trial Fails to Meet Endpoints

The National Horizons Centre (NHC) in the United Kingdom has been confirmed as a National Training Centre that will deliver on-site advanced therapies and vaccine manufacturing specific practical and digital training.

NHC was announced as a preferred bidder in December 2020 to become one of the initial three centers to provide hands-on training for advanced therapy medicinal products (ATMPs) and vaccine manufacture as part of the Advanced Therapies Skills Training Network (ATSTN)—a UK-wide initiative. ATSTN has been awarded funding by the Department for Business Energy and Industrial Strategy for the delivery of training centers across the UK that will help to develop practical skills and address the growing need in vaccine and ATMP manufacturing.

The on-site training being offered by NHC will be focused on good practice (GxP) manufacturing, process development, and bioprocessing techniques. In addition to hands-on training, NHC will also create a virtual reality (VR) training facility, which will include four VR stations alongside a tutor demonstration station. The VR facility will be used in conjunction with the NHC laboratory and teaching facilities to deliver the training courses.

“The UK cell and gene industry is a great place for people to build their future. We want to see that opportunity opened up to everyone,” said Matthew Durdy, CEO at Cell and Gene Therapy Catapult, in a March 31, 2021 press release. “With its cutting-edge training facilities, the [NHC] will be an integral part of the [ATSTN’s] unique offering to anyone in the UK who wants to advance their career in advanced therapies.”

“With the rush to develop and deliver a COVID-19 vaccine, the importance of the biomanufacturing and bioprocessing sectors has never been so apparent,” added Jen Vanderhoven, director of NHC, in the press release. “We’ve worked very closely with leading figures across the bioindustry sector to ensure that each of these courses will address the requisite technical and digital needs. We pride ourselves on our ability to be responsive to the sector’s needs, so we’re very pleased to have been able to react quickly and develop these courses, which will deliver vital skills needed for vaccine manufacturing and advanced therapies and to grow this important industry.”

The training courses will be available at NHC from May 2021. Courses will cover upstream and downstream bioprocessing, analytical techniques for bioprocessing, process control and automation, viral vector manufacturing, biologics manufacturing, data integrity, computer systems validation and IT compliance, good manufacturing practice for biologics, practical proteomics, and flow cytometry for bioprocessing.

The UK's National Horizons Centre has been confirmed as a National Training Centre that will deliver on-site advanced therapies and vaccine manufacturing specific training.

National Horizons Centre to Provide ATMP and Vaccine Manufacture Training

Sterling Pharma Solutions has announced its acquisition of ADC Biotechnology, a bioconjugation development services business specializing in antibody drug conjugates (ADCs), in an April 6, 2021 press release. The acquisition follows the strategic investment by contract development and manufacturing organization (CDMO), Sterling, in December 2020.

Through the acquisition, the ADC Bio facility, which is based in North Wales in the United Kingdom, will be rebranded and become part of the Sterling Pharma Solutions international network. Combining Sterling’s experience in current good manufacturing practice (CGMP) manufacturing, quality processes, and compliance, with the expertise of ADC Bio, the companies are aiming to establish a center of excellence for bioconjugation and ADC development and manufacturing services.

Financial investment is being made to support to growth of the ADC capabilities, including expansion and development of the existing bioconjugation technical services team and analytical services team (particularly in the CGMP area). Additionally, the companies plan to create CGMP bioconjugation/ADC manufacturing at the North Wales facility in 2022.

“We are delighted to confirm the acquisition of the ADC Bio business, this investment provides us with the opportunity to offer a wider portfolio of services to our customers in the fast-growing ADC and bioconjugation market, as well as providing additional services to existing ADC Bio customers,” said Kevin Cook, CEO at Sterling Pharma Solutions, in the press release. “Integrating our HPAPI [highly potent API] capabilities with the expertise already found at Deeside means that we will also be able to offer the development and manufacture of toxin linkers. This is an exciting time for both businesses as we embark on a period of growth and diversification to ensure we always stay ahead of the next innovation. I’d like to welcome all ADC Bio employees to the Sterling family.”

Alan Raymond, executive chairman of ADC Bio, added in the press release, “This is fantastic news for our employees and our customers; targeted investment in both people and processes will allow the team to continue supporting important advances in drug development with additional services, and importantly with the additional support and experience from the Sterling team.

Sterling Pharma Solutions has acquired ADC Biotechnology, a bioconjugation development services business specializing in antibody drug conjugates.

Sterling Pharma Solutions Confirms ADC Bio Acquisition

Catalent announced on April 6, 2021 that it has expanded its strategic collaboration with Moderna by dedicating a new high-speed vial-filling line at its biologics facility in Bloomington, IN, for the manufacture of Moderna’s COVID-19 messenger RNA (mRNA)vaccine and other investigational programs in Moderna’s pipeline.

Under the terms of the expanded agreement, Catalent will provide Moderna with the filling line until June 2023 along with inspection, labeling, cartoning, and final packaging for the potential pipeline programs, Catalent said in a company press release.

The companies’ initial agreement was announced in 

 and involved Catalent providing aseptic vial filling and packaging from its Bloomington site to support production of an initial 100 million doses of Moderna’s vaccine.

Under the terms of the expanded agreement, Catalent will provide Moderna with a new high-speed vial filling line until June 2023 along with inspection, labeling, cartoning, and final packaging for potential pipeline programs.

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