Full-day virtual event exploring the latest developments in formulation, manufacturing, innovative drug dosage forms and other crucial topics impacting the industry

2020 Bio/Pharma Virtual Congress: November 11, 2020

Remdesivir approved; Vaccine development agreements

COVID-19 Therapy Developments

More complex and challenging compounds require a tailored formulation approach.

Unique Molecules Push Formulation Boundaries

on Oct. 30, 2020 that it has identified a list of essential medicines, medical countermeasures, and critical inputs that should always be available in adequate amounts to protect against outbreaks of infectious diseases. The list was developed in response to an executive order issued in August 2020 to “ensure sufficient and reliable, long-term domestic production of these products, and to minimize potential shortages by reducing our dependence on foreign manufacturers of these products,” according to FDA.

The list, which was created in consultation with other federal FDA partners, includes 223 essential medicines and medical countermeasures and 96 device medical countermeasures. FDA identified essential medicines most needed for patients in acute care medical facilities. “The medical countermeasures we identified are FDA-regulated products (biologics, drugs, and devices) that meet the definition of a ‘medical countermeasure’ provided in the executive order and that we anticipate will be needed to respond to future pandemics, epidemics, and chemical, biological, and radiological/nuclear threats. When identifying essential medicines and medical countermeasures, we focused on including those that are medically necessary to have available in adequate supply which can be used for the widest populations to have the greatest potential impact on public health,” the agency stated in a press release. The agency identified APIs of essential medicines and medical countermeasures as critical inputs, “as well as ingredients or components that possess unique attributes essential in assessing the safety and effectiveness of such products.”

The agency will also coordinate with federal partners to develop strategies for acquiring products on the list, accelerate domestic manufacturing of these products, and investigate supply chain vulnerabilities. “The FDA believes that the adoption of innovative technologies, such as advanced manufacturing techniques could enable US-based pharmaceutical manufacturing to bolster its competitiveness with foreign countries and help ensure a stable supply of drugs critical to the health of US patients. As companies look to increase domestic manufacturing of the products on this list, we encourage them to consider adopting advanced manufacturing technologies,” FDA stated in the 

Articles

The agency, in response to an executive order, published a list of essential medicines, medical countermeasures, and critical inputs that should be available at all times in an adequate amount to serve patient needs.

FDA Identifies Essential Medicines

on Oct. 28, 2020 that researchers at the Center of Drug Evaluation and Research (CDER) have studied factors that might predict the possible submission of an abbreviated new drug application (ANDA). CDER researchers used proprietary data related to ANDAs, internal or public information, and information on drug sales to see if a drug’s characteristics, regulatory history, or market sales could predict the submission of an ANDA. The study separately analyzed drugs that were originally approved as new chemical entities (NCEs) and those that did not have NCE exclusivity.

The study found that ANDAs were more likely to occur in NCEs and non-NCEs that had higher revenues. “By contrast, designation of a brand-name product as a complex drug (for example, due to its structure, composition, or its mode of delivery) was negatively associated with ANDA submission for both NCEs and non-NCE drugs,” FDA stated in a press release. Challenges associated with complex drug substances or drug products may be a factor, according to the researchers.

Data showed that the availability of a published product-specific guidance (PSG) for non-NCE drugs was a positive factor in ANDA submissions. “Non-NCE drugs for which there was a PSG were approximately 3.8 times more likely to result in an ANDA submission than non-NCE drug products for which no PSG had been published (data not shown),” FDA stated. The study also found that patents did not have a significant impact on ANDA submissions. “…in the case of large-revenue drugs, that sponsors will challenge the patent even when they are unlikely to win, meaning that higher sales are associated with more pre-generic approval patent challenges (commonly referred to as ‘Paragraph IV’ challenges).”

The Center for Drug Evaluation and Research is studying factors that influence the development of generic versions of brand-name drugs.

Predicting Generic Drug Marketing Applications

on Oct. 30, 2020 has published clinical data supporting the marketing authorization application for Veklury (remdesivir) and a list of COVID-19 medicines and vaccines that have received scientific advice or informal guidance from the agency’s pandemic Task Force. The agency is releasing this information as part of its dedication to transparency of its activities in relation to COVID-19 vaccines and treatments.

There are 64 documents available on EMA’s clinical data website that give a clinical overview, summaries, and the final reports from pharmacokinetic and Phase I clinical studies. Interim study reports from Phase III clinical studies, clinical data from the compassionate use program, and the data anonymization report are also available.

“The publication of clinical data for Veklury is in line with EMA’s landmark policy to proactively publish clinical data supporting marketing authorization applications. The agency had to suspend the publication of clinical data at the end of 2018 as a result of its move from London to Amsterdam. It currently remains suspended due to ongoing business continuity linked to the COVID-19 pandemic and human resource constraints. EMA has decided to exceptionally publish clinical data for COVID-19 medicines given the unprecedented public interest for this information in the context of the ongoing pandemic,” EMA stated in a press release.

Information on the medicines that received scientific advice or guidance includes the stage of development in which the advice was given to help the developer prepare for a marketing authorization application. This advice may include “best methods and study designs for generating robust data on a medicine’s safety and effectiveness. It can also focus on quality aspects, such as manufacturing and testing, or on laboratory studies,” according to EMA.

The agency published clinical data on remdesivir and information about COVID-19 treatments that have received scientific advice or informal guidance from EMA’s pandemic Task Force.

EMA Implements Transparency Measures for COVID-19 Medicines

in October 2020 describing the requirements for electronically submitting standardized clinical and nonclinical study data under section 745A(a) of the Federal Food, Drug, and Cosmetic Act for new drug applications, abbreviated new drug applications, biologics license applications, and investigational new drug applications to the Center for Drug Evaluation and Research or the Center for Biologics Evaluation and Research. “Submissions that are not submitted electronically and electronic submissions that are not in a format that FDA can process, review, and archive will not be filed or received, unless exempt from the electronic submission requirements or if FDA has granted a waiver,” the guidance states.

The guidance discusses the requirements for electronic submission of study data including exchange format standards, study data standards, and controlled terminology standards. It also discusses the agency’s policy on waivers of electronic submission requirements.

FDA published guidance for submitting standardized study data in electronic format.

Guidance on Submitting Standardized Study Data 

The Research Center Pharmaceutical Engineering (RCPE) in Graz, Austria has been awarded FDA funding for two projects, set to begin in the fourth quarter of 2020, that will focus on using advanced technologies to improve pharmaceutical production processes, RCPE announced in an Oct. 29, 2020 press release. RCPE noted that FDA typically only awards five to 10 projects a year to European organizations, which demonstrates that these projects have the potential for high impact within the global pharma industry.

In the first project, RCPE will partner with global pharma companies, including MSD (known as Merck in the US and Canada) and Pfizer, to investigate the use of optical coherence tomography (OCT) for real-time monitoring and control of the drug tablet coating process. Researchers will seek to integrate OCT with artificial intelligence (AI), such as machine learning approaches, to prevent errors in tablet coating before they occur.

In the second project, RCPE will partner with MSD, Pfizer, and other collaborators to continue previous work with digital simulation tools for drug product manufacturing and process development. A digital twin-based platform will model products, processes, and conditions, using these simulations for evaluation, optimization, and scale-up. Replacing extensive lab-based experiments is expected to reduce drug development and manufacturing time and reduce energy consumption and carbon footprint for next-generation pharmaceutical production.

Professor Johannes Khinast, RCPE CEO and scientific director, said in the press release that the awards are an endorsement “of our pioneering approach to solving drug manufacturing challenges. Having achieved this important milestone, we look forward to working with our partners to improve their manufacturing technology, ultimately benefitting patients around the globe.”

Two FDA-funded projects at RCPE will look at real-time monitoring and control of drug tablet coating and developing a digital twin for drug production control.

RCPE Awarded FDA Funding to Develop Next-Generation Technology

On Oct. 27, 2020, the United States filed a civil complaint against Med-Pharmex (MPX), a Pomona, CA-based animal health company, regarding its manufacturing and distribution of adulterated animal drugs.

According to a press release from the Department of Justice, the complaint aims to stop the company from manufacturing and distributing animal drugs in conditions unsatisfactory to the minimum regulatory requirements to ensure safety and quality. In the complaint, it is noted that FDA inspected the company site several times, which resulted in a warning letter in 2017 that noted deficiencies at the company including the failure to properly clean and disinfect areas used to manufacture sterile drugs and the failure to conform to current good manufacturing practices. Additionally, the complaint also mentions MPX’s failure to sufficiently examine reports of the death or illness of animals receiving MPX drugs, the press release said.

“Americans depend on animal drugs being safe and effective,” said Acting Assistant Attorney General Jeffrey Bossert Clark of the Justice Department’s Civil Division, in the press release. “We will continue working with FDA to ensure all drug manufacturers abide by public safety requirements.”

“Ensuring FDA-approved animal medications are safe, effective, and manufactured using current good manufacturing practices is an important part of the FDA’s mission to protect human and animal health,” added FDA Chief Counsel Stacy Amin, in the press release. “The FDA will continue to pursue actions against those who put animal patients in harm’s way by manufacturing and distributing adulterated animal drug products.”

The complaint aims to stop the company from manufacturing and distributing animal drugs in conditions unsatisfactory to the minimum regulatory requirements to ensure safety and quality.

The Department of Justice Files a Complaint Against Animal Health Company for the Distribution of Adulterated Animal Drugs

Takeda and Moderna announced on Oct. 29, 2020 that they are entering into a three-way agreement with the Government of Japan’s Ministry of Health, Labor, and Welfare to import and distribute 50 million doses of Moderna’s COVID-19 vaccine candidate, mRNA-1273, beginning in the first half of 2021.

Through the agreement, Takeda will handle securing the regulatory approvals before distributing the doses, while Moderna will supply the finished product, a Takeda press release said. Currently, a Phase III clinical trial for the vaccine candidate in the United States is fully enrolled.

This collaboration follows Takeda’s recent announcement that it is planning to manufacture Novavax’s COVID-19 vaccine candidate at its facilities in Japan to support the long-term supply of the treatment to the Japanese population.

“Takeda is collaborating with the Japanese Government and vaccine developers to provide rapid and sustained access to COVID-19 vaccines in Japan,” said Rajeev Venkayya, MD, president of the Global Vaccine Business Unit, Takeda, in the press release. “We have chosen to work with Novavax and Moderna, both of which have promising vaccine candidates, and will continue to support the global response to COVID-19 through R&D efforts across Takeda.”

Through the agreement, Takeda will handle securing the regulatory approvals before distributing the doses, while Moderna will supply the finished product.

Takeda, Moderna, and the Government of Japan to Collaborate to Distribute 50 Million COVID-19 Vaccine Doses

AstraZeneca and Daiichi Sankyo announced on Oct. 28, 2020 that their supplemental biologics license application (sBLA) for Enhertu (trastuzumab deruxtecan), an antibody drug conjugate (ADC) for treating HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma, was accepted by FDA and granted priority review.

FDA’s acceptance of the sBLA was based on positive results from a Phase II trial (Destiny-Gastric01), which showed improvement in objective response rate, the primary endpoint, and overall survival in patients treated with the therapeutic, according to an AstraZeneca press release.

“Once patients with HER2-positive metastatic gastric cancer progress following initial treatment with an anti-HER2 regimen, there are no approved HER2-directed medicines,” said José Baselga, executive vice-president, Oncology R&D, AstraZeneca, in the press release. “The prognosis for these patients is poor, as available treatment options offer only limited clinical benefit. This milestone brings us one step closer to delivering a potentially practice-changing medicine to patients with gastric cancer in the [United States].”

“The results of the Destiny-Gastric01 trial are unprecedented as they represent the first time a HER2-directed medicine has demonstrated an improvement in survival following chemotherapy and HER2 treatment in the metastatic setting,” added Antoine Yver, executive vice-president and global head, Oncology R&D, Daiichi Sankyo, in the press release. “Building on the recent [b]reakthrough [t]herapy [d]esignation, the filing of the application, and [p]riority [r]eview by [FDA] for this potential new indication for Enhertu reflects the importance of the data and the significant unmet need for patients with previously treated HER2-positive metastatic gastric cancer.”

FDA has granted priority review for the companies’ sBLA for Enhertu, an ADC for treating gastric cancers.

AstraZeneca and Daiichi Sankyo Granted Priority Review for Gastric Cancer sBLA

Catalent has signed an agreement with Bone Therapeutics for the acquisition of Skeletal Cell Therapy Support SA (SCTS), which is a subsidiary of Bone Therapeutics. The acquisition, which is expected to close in November 2020, was announced in an Oct. 29, 2020 press release.

Under the terms of the agreement, Catalent will acquire the subsidiary company, and all of its assets located in Gosselies, Belgium, through the purchase of all SCTS shares that are currently owned by Bone Therapeutics. The deal will include a purpose-built current good practice (CGxP) facility of approximately 41,000 ft2, which incorporates quality control and product development laboratories, warehouse, grade C and B cleanrooms and equipment, and land for further development. Additionally, Catalent will take on the manufacturing of clinical material for Bone Therapeutics’ ALLOB—an allogenic osteoblastic cell therapy product derived from 

The acquired facility is located next to Catalent’s existing cell therapy site, which will enable Catalent to expand its cell therapy capabilities and advanced clinical and commercial supply, as well as create an integrated European center of excellence in cell therapy. All the SCTS manufacturing employees will remain with the company and become part of the Catalent workforce.

“Catalent is committed to supporting the development and manufacture of next-generation therapies and bringing life-changing treatments to patients in need,” said Manja Boerman, president, Catalent Cell & Gene Therapy, in the press release. “Following the acquisition of MaSTherCell, the additional manufacturing capacity and technical expertise that this deal with Bone Therapeutics gives us will immediately expand our functional clinical and commercial capacity for current late-stage customers. This addition also creates a strong center of cell therapy excellence for Catalent in Europe and will serve as a hub for the growing cell therapy pipeline.”

“This agreement with Catalent is an important strategic step for Bone Therapeutics and is the result of our continuous effort to optimize our operations,” added Miguel Forte, CEO, Bone Therapeutics, in the press release. “The integration of our manufacturing subsidiary into Catalent, one of the premier contract manufacturers in the cell therapy space, significantly increases our operational flexibility. It enables Bone Therapeutics to maximize the efficient use of our manufacturing assets by combining the manufacturing facility and specialist operators with Catalent’s global network of clinical and commercial manufacturing facilities. This will ensure the most efficient ongoing global production of ALLOB.”

Catalent has signed an agreement with Bone Therapeutics for the acquisition of Skeletal Cell Therapy Support SA (SCTS).

Catalent Acquires Bone Therapeutics’ Cell Manufacturing Facility 

Contract development and manufacturing organization (CDMO), 3P Biopharmaceuticals, and Oxford University spin-out, SpyBiotech, have signed a vaccine contract manufacturing agreement, it was announced in an Oct. 26, 2020 press release.

SpyBiotech’s SpyCatcher/SpyTag platform technology enables antigens to be displayed onto virus-like particles with a covalent, irreversible bond in a stable and effective way with specific orientation/epitope presentation and high density. The company states that the technology has broad applicability in vaccine development and has established proof of concept data in viral, bacterial, parasitic diseases, chronic diseases, and cancer.

In June 2019, SpyBiotech selected 3P Biopharmaceuticals for the manufacture of a current good manufacturing practice (CGMP) batch of its virus-like particle carrier, with the aim for production to be completed in 2021. Through this latest agreement, 3P Biopharmaceuticals will demonstrate its capacity to perform processes and manufacturing of molecules developed for diverse therapeutic applications.

“It is amazing being part of a project which presents an opportunity to develop treatments for a broad range of diseases,” said Dámaso Molero, CEO of 3P Biopharmaceuticals, in the press release. “We are helping to support manufacturing which we believe will open the door for pioneering vaccines which could offer a hope for improving the lives of many people. That is extremely exciting.”

Genevieve Labbe, senior scientist and GMP project manager for SpyBiotech added in the press release, “It’s critical to have a trusted partner in place for cell line and CGMP production. SpyBiotech is looking forward to advancing this product and we are delighted to be working with 3P Biopharmaceuticals.”

3P Biopharmaceuticals, and Oxford University spin-out, SpyBiotech, have signed a vaccine contract manufacturing agreement.

Featured Content

2020 Bio/Pharma Virtual Congress: November 11, 2020

COVID-19 Therapy Developments

Unique Molecules Push Formulation Boundaries