Pharmaceutical Technology Editors

According to an April 22, 2021 press release, executives that participated in the CPhI post-pandemic survey are predicting a push for repatriation of manufacturing globally as a result of the supply chain issues encountered during the COVID-19 pandemic.

The issue of offshore versus onshore manufacturing will be broached by an expert panel in the forthcoming CPhI Discover, which will take place on May 17–28, 2021, as a virtual gathering. Along with a more in depth look at onshoring, the panel will discuss whether or not reshoring presents a rethinking of innovation approaches, such as novel manufacturing technologies to improve efficiency.

More than 500 executives participated in CPhI’s survey, with a good majority (60%) anticipating that the COVID-19 pandemic will “greatly improve the business outlook in 2021 and beyond.” In line with the expanded demand for COVID treatments and upscaling, contract services are predicted to grow at an accelerated pace to meet demand.

On the opening day of CPhI Discover (May 18, 2021)—in a session moderated by Rita Peters, editorial director of the PharmTech Group—Eric Langer (president, BioPlan Associates), Peter Shapiro (editor, PharmSource, a GlobalData Company), and Kevin Sharp (head of Alliance Management, Samsung Biologics) will evaluate the key factors shaping the future of the contract services industry. The session is titled ‘Navigating the CDMO Market: Hurdles, Transformation & Opportunities’.

Another issue brought to light by the COVID-19 pandemic is the global reliance on supply of starting materials from Asian suppliers. Although the survey respondents were broadly ambivalent to the issue, approximately half suggested that it is realistic to “localize the manufacture of starting materials.” However, over a third of survey respondents suggested that a mass move to localized manufacture would be “too disruptive to a complex industry.”

Finished dose manufacturing is experiencing expansion and modernization, with a quarter of respondents believing that “filling and packaging systems” will be the machinery type that gains the most investment in 2021. Drivers for this investment are specified as being the fact that drug product contract manufacturing organizations/contract development manufacturing organizations are seeking to become one-stop-shops, to simplify and streamline services. Packaging and drug delivery are topics that will be covered in detail during the second day (May 19, 2021) of CPhI Discover.

“Our industry survey shows that pharma, ingredients providers, manufacturers, and the contract services pipeline have fared well through the last year, but structural changes in the industry and an expansion in the pipeline means demand is growing quickly,” said Nicola Souden, brand manager at Informa, in the press release. “In response, we have designed a detailed agenda to explore the biggest opportunities at CPhI Discover. Then armed with these new insights, attendees can utilize the second week of the event to meet new partners and consider the best approach to expedite growth and development.”

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Executives that participated in the CPhI post-pandemic survey are predicting a push for repatriation of manufacturing globally.

CPhI Post-Pandemic Survey Suggests Drive for Repatriation of Manufacturing

Evonik announced on April 22, 2021 that it has delivered the first batches of lipids for the Pfizer-BioNTech COVID-19 vaccine months ahead of schedule.

Under its strategic partnership with BioNTech, Evonik was tasked with producing two different lipids for the vaccine with lipid delivery scheduled for mid-2021, Evonik said in a company press release. Lipid production at Evonik’s Hanau, Germany site was set up in just eight weeks and met the high-quality requirements, allowing for the company to accelerate delivery time.

"Setting up production at this speed is a great achievement," said Christian Kullmann, chairman of Evonik's executive board, in the press release. "Increasing lipid production in Germany will also allow us to further accelerate the manufacturing of larger quantities of the vaccine. In this way, we are contributing to the fight against the pandemic."

Lipid production at Evonik’s Hanau, Germany, site was set up in eight weeks and met high-quality requirements, accelerating delivery time, which was originally set for mid-2021. 

Evonik Delivers First Batch of Lipids to BioNTech for its COVID-19 Vaccine

DFE Pharma, a pharmaceutical excipient solutions company located in Germany, announced on April 21, 2021 that it has launched BioHale, a new product line aimed at addressing worldwide supply challenges for biopharmaceutical companies.

According to a company press release, the new line will offer market purity and low endotoxin excipients for use in formulation, while providing drug developers and manufacturers with high quality excipient technology and services to advance therapeutic formulation.

“As a trusted solution provider and development partner to leading pharma brands, we are committed now to supporting customers in the formulation process for efficacious delivery of biologics,” said Bas van Driel, CEO of DFE Pharma, in the press release. “With the high purity and low endotoxin quality of BioHale excipients, combined with increased security of supply and stringent control over relevant supply chain processes, we can meet, if not exceed, the growing demands of new biopharma customers, as well as existing customers.”

DFE’s new line will offer market purity and low endotoxin excipients for use in formulation, while providing drug developers and manufacturers high-quality excipient technology and services. 

DFE Pharma to Launch New Biopharma Excipient Solution 

Vertex Pharmaceuticals and CRISPR Therapeutics announced on April 20, 2021 that they have amended their collaboration agreement to include the development, manufacture, and commercialization of CTX001, an investigational CRISPR/Cas9-based gene editing therapy for sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT).

Under the terms of the agreement, CRISPR will receive an upfront payment of $900 million, with the potential for an additional $200-million payment upon the first regulatory approval of CTX001, Vertex said in a company press release. Vertex will handle the global development, manufacturing, and commercialization of the gene editing therapy and will be responsible for 60% of program costs, while receiving 60% of profits from future sales. CRISPR will be accountable for 40% of costs and will obtain 40% of profits.

“Cell and genetic therapies are key to our strategy of developing transformative therapies for serious diseases, and this agreement is an important next step in cementing our leadership in these modalities as we bring forward our broad gene and cell-based therapeutics portfolio. As we take the lead on CTX001, we want to acknowledge the foundational contributions by the team at CRISPR Therapeutics,” said Jeffrey Leiden, MD, PhD, executive chairman of Vertex, in the press release. “Our increased investment in our partnership with CRISPR is based on the compelling clinical profile of CTX001, which shows its potential to be a durable cure for patients with SCD and TDT, and the rapid progress that we and our partners at CRISPR have made toward registration and commercialization. We see a significant commercial opportunity for CTX001, and we believe we will be able to further enhance that opportunity by fully leveraging the breadth of Vertex’s capabilities—including our established and proven R&D and commercialization expertise in serious diseases—to bring CTX001 to more patients around the world, more quickly.”

“Given the transformative results and momentum that we have generated with this program, we are adopting a new operating model to enable a globally coordinated launch of CTX001, leveraging Vertex’s best-in-class global capabilities and leadership in development, manufacturing, and commercialization to enable this medicine to reach all patients that can benefit from it as quickly as possible,” added Samarth Kulkarni, PhD, CEO of CRISPR Therapeutics, in the press release. “We remain deeply committed to the sickle cell and thalassemia patient communities and look forward to continued success in our partnership with Vertex.”

Vertex and CRISPR have amended their collaboration agreement to include the development, manufacture, and commercialization of CTX001, an investigational CRISPR/Cas9-based gene editing therapy for sickle cell disease and transfusion-dependent beta-thalassemia.

Vertex Pharmaceuticals and CRISPR Therapeutics Amend Agreement for $1.1 Billion

Waters Corporation and Genovis, a US-based enzymes and technologies provider, announced on April 13, 2021 that they have entered into a collaboration to develop and market complete routine biopharmaceutical characterization workflows based on the Waters BioAccord LC–MS System, Andrew+ pipetting robot, and Genovis SmartEnzymes.

Under the terms of the agreement, the companies will work to develop automated workflows for the fast and constant characterization of critical quality attributes of monoclonal antibodies and other protein-based drugs in bioprocess development, formulation, stability testing, and quality control, Waters said in a company press release. The workflows in development will focus on product variant analysis, bioprocess stability monitoring, and biosimilar glycosylation analysis.

“Biologics analysis is an area that is ripe for improvement. What takes analytical scientists several days to do, should take hours or minutes instead,” said Jeff Mazzeo, vice-president, Global Marketing and Scientific Operations, Waters Corporation, in the press release. “Today, up-front sample preparation is a major bottleneck to productivity, largely due to the number of manual steps involved and the outmoded technology by which samples are readied for analysis. By combining Genovis’ SmartEnzymes with automation, liquid chromatography/time-of-flight mass spectrometry, and application-specific software workflows from Waters, we intend to move biotherapeutic analysis forward in ways never thought possible.”

“The BioAccord LC–MS system and the Andrew+ pipetting robot align perfectly with our strategies and vision at Genovis to bring simplified, robust, and automated enzyme-driven workflows to the biopharma industry,” added Fredrik Olsson, CEO, Genovis, in the press release. “The enzymatic workflows that we will develop in collaboration with Waters will help our customers in their efforts to bring safe and novel therapeutics to patients, faster.”

Waters and Genovis will work to develop automated workflows for the fast and constant characterization of critical quality attributes of monoclonal antibodies and other protein-based drugs in bioprocess development, formulation, stability testing, and quality control.

Waters and Genovis to Collaborate on Biopharmaceutical Characterization Workflows

FDA inspectors identified nine conditions at Emergent BioSolutions’ Maryland vaccine manufacturing facility that could lead to product quality issues including unsanitary conditions, inadequate facility size for proper operations, inadequate written procedures, and substandard employee training.

The observations were listed in a redacted FDA inspection closeout report, or 

 (PDF), released on April 21, 2021 following a multi-day inspection of the facility. The facility, slated to manufacture Johnson & Johnson’s (J&J’s) COVID-19 vaccine, has not been authorized by FDA to manufacture or distribute the vaccine.

 and distribution of the vaccine drug substance at the Bayview plant on April 16, 2021, two weeks after

 of its vaccine drug substance at the facility. Previously, J&J reported that vaccine drug substance materials for 15 million doses of the company’s COVID-19 vaccine were rejected due to a manufacturing problem.

Observations identify human, process, and facility errors

FDA inspectors noted that Emergent did not thoroughly investigate several unexplained discrepancies including cross-contamination of a viral vaccine drug substance batch.

 about manufacturing problems at vaccine production facility.

The building used for manufacturing the vaccine drug substance was not maintained in a clean and sanitary condition; peeling paint and brown or black residue was observed on floors and walls. In addition, FDA inspectors noted in the Form 483 that the building used to manufacture the viral vaccine drug substance was “not of suitable size, design, and location to facilitate cleaning, maintenance, and proper operations.” Waste handling procedures were inadequate, and areas of the facility were overcrowded, FDA said.

The facility also was cited for not following written production and process control procedures and a lack of documentation. Infractions included employees compacting, by hand, unsealed bags of medical waste from manufacturing in an area where raw materials were staged, removing protective garments onto the warehouse floor where raw materials were staged, and failing to follow proper gowning procedures when switching from different manufacturing areas.

Product components, containers, and closures were not handled properly, FDA reported. Unsealed bags of manufacturing waste were handled near raw materials.

Written procedures to assure the identity, strength, quality, and purity of the drug substance were inadequate, FDA noted, and employees were not trained in operations they performed. Inadequate equipment, utensils, and laboratory space were also observed.

In a press release announcing the Form 483, FDA noted that the agency is working with the company to identify ways to remedy the issues. “Indeed, it is often in the public’s best interest that the FDA work with firms to quickly resolve compliance matters to ensure that the public has access to medical products that meet the agency’s high standards for quality, safety, and effectiveness,” FDA noted in the statement.

Additional testing will be performed on vaccines already manufactured at the facility before any potential distribution, FDA reported.

Post-inspection report reveals nine sanitary and process problems at Bayview, Md., facility.