Pharmaceutical Technology Editors

FDA announced on May 11, 2021 that it has made the final version of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 

Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

 available. The guidance provides a framework for managing postapproval chemistry, manufacturing, and controls (CMC) changes and discusses necessary elements for assuring product quality in a regulatory submission changed postapproval. The guidance also promotes manufacturing innovations through a risk-based approach to regulatory oversight and continued product improvement, which may mitigate manufacturing and quality issues. The guidance document’s Annexes provide examples of how tools described in ICH Q12 could be applied.

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The guidance provides a framework for the management of postapproval chemistry, manufacturing, and controls changes.

FDA Finalizes Guidance on Pharmaceutical Lifecycle Management

M9 Biopharmaceutics Classification System-Based Biowaivers

on May 11, 2021 to support biopharmaceutics classification of drug substances and the Biopharmaceutics Classification System (BCS)-based waiver of the 

 bioequivalence study requirement for drugs. The guidance was developed by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and supersedes FDA’s December 2017 guidance document, 

Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System

According to FDA, if two drugs contain the same drug substance, they are bioequivalent if the rate and extent of drug absorption after administration in the same molar dose are within the acceptable predefined limits. Using a BCS-based biowaiver approach reduces the need for in-vivo studies to determine bioequivalence and may reduce costs and increase efficiency in generic drug development. This approach applies to immediate release, solid orally administered dosage forms or suspensions that deliver the drug to the systemic circulation. Fixed-dose combination products may be eligible if all active drug substances fulfill the criteria. Drugs with a narrow therapeutic index are not eligible for the BCS-based biowaiver.

The guidance document gives recommendations to support biopharmaceutics classification of drug substances and the Biopharmaceutics Classification System-based waiver of the in-vivo bioequivalence study requirement for drugs. 

FDA Publishes Guidance on Biopharmaceutics Classification System-Based Biowaivers

Pfizer and BioNTech announced on May 20, 2021 that have entered into a new agreement with the European Commission (EC) to supply 900 million doses of Comirnaty, the companies’ COVID-19 vaccine, to the European Union (EU), with an option for the EC to request up to 900 million additional doses.

The added doses are expected to be delivered on a monthly basis starting in December 2021 and continuing into 2023, a Pfizer company press release said. This agreement is in addition to the 600 million doses that are currently committed to the EU through 2021. If the EC exercises their option for additional doses, the number of potential doses being delivered to the EU will climb up to 2.4 billion.

“Ongoing vaccination beyond 2021 is critical as COVID-19 continues to spread rapidly throughout Europe and the globe,” said Albert Bourla, chairman and CEO, Pfizer, in the press release. “More than a year later, we continue to learn about COVID-19 and are working to determine if, similar to seasonal influenza, annual vaccination may provide the most enduring protection. We are proud to be in a position to be a long-term partner in the EU’s fight against this devastating pandemic and remain steadfast in our commitment to potentially produce and deliver billions more doses of our vaccine each year.”

“There is growing evidence that COVID-19 will continue to pose a public health challenge for years. This contract with the European Commission will ensure sufficient doses of [Comirnaty] are available for all EU citizens in 2022 and 2023,” added Ugur Sahin, MD, CEO and co-founder of BioNTech, in the press release. “With these additional doses and our continued investments in research and development aimed at adapting our vaccine to address new and emerging variants, we will continue to make a significant impact in the EU’s efforts to protect public health.”

Pfizer and BioNTech have entered into a new agreement with the European Commission to supply 900 million doses of Comirnaty to the European Union with an option to request up to 900 million additional doses.

Pfizer and BioNTech to Supply EU with Up to 1.8 Billion Additional COVID-19 Vaccine Doses 

Thermo Fisher Scientific announced on May 19, 2021 that it has entered into a strategic alliance with the University of California, San Francisco (UCSF) to accelerate the development and manufacturing of cell therapies.

Under the terms of the agreement, Thermo Fisher will construct and operate a 44,000-ft

cell therapy development, manufacturing, and collaboration center on UCSF's Mission Bay campus, Thermo Fisher said in a company press release. The site, which is expected to open in 2022, will feature clinical and commercial current good manufacturing practice [CGMP] cell therapy manufacturing services, along with associated technology development support, to UCSF and other partners. The facility will also provide UCSF researchers with access to Thermo Fisher's portfolio of cell therapy systems reagents, consumables, and fit-for-purpose instrumentation and compliant software.

"We are bringing together UCSF's leadership in the newest forms of cellular immunotherapy and Thermo Fisher's extensive capabilities in cell therapy instrumentation, manufacturing, and distribution," said Mark Stevenson, executive vice-president and chief operating officer of Thermo Fisher Scientific, in the press release. "This powerful combination will provide customers—from emerging biotechs to large pharma companies—with integrated, end-to-end solutions to reduce costs and accelerate adoption of cell therapies, ultimately improving patient access to these transformative treatments."

"We expect breakthrough treatments for many different diseases and conditions to come from cell therapies,” added Sam Hawgood, chancellor of UCSF, in the press release. “Establishing cell therapy manufacturing in such close proximity to our scientists, clinicians, and patients will enable UCSF to catalyze innovation in living therapeutics and use the resulting discoveries to benefit our patients."

Under the terms of the agreement, Thermo Fisher will construct and operate a 44,000-ft2 cell therapy development, manufacturing, and collaboration center on UCSF's Mission Bay campus.

Thermo Fisher and UCSF Enter into Alliance to Accelerate Cell Therapy Development

 on May 13, 2021 that it has collaborated with Angels for Change, a non-profit patient advocacy group, and Vizient, a group purchasing organization, to develop a predictive model for improving the supply chain of 17 pediatric oncology drugs, 13 of which have experienced shortages in the past three years. Expertise and data were brought together to produce insights to prevent and/or mitigate supply chain interruptions on providers and patients and create the Drug Supply Resiliency Model.

The three organizations worked together to collect data on pediatric oncology drug shortages. Angels for Change, in consultation with clinical experts, identified 17 drugs for the pilot project. USP, which developed the model, contributed upstream supply chain data by leveraging insights from more than 22,000 locations that use USP standards. USP also used its Medicine Supply Map to analyze the 17 identified drugs. Vizient, which identifies medications that may be impacted by supply chain disruptions, provided downstream demand data.

“Pediatric oncology drugs have long been at high risk of shortage, and this has impacted hospital costs and led to adverse patient outcomes. The Drug Supply Resiliency Model, which builds on the Pediatric Drug Shortage Project implemented by CHA and Vizient, helps us quantify the root causes and further identify solutions as we work to eliminate pediatric drug shortages,” said Terri Wilson, Director, Supply Chain Services–Pharmacy at Children’s Hospital Association and an advisor on the project, in a press release.

“Understanding upstream supply chain risk is important for governments, GPOs and manufacturers to prioritize investments in improving the resiliency of the supply chain. Data on the medicine supply chain is fragmented, but private sector collaborations such as this can bring together a more complete picture and help governments, GPOs, manufacturers and other stakeholders work together to improve the resiliency of the supply chain and prevent patients from experiencing drug shortages,” said Stephen Schondelmeyer, co-Principal Investigator of the Resilient Drug Supply Project at the University of Minnesota’s Center for Infectious Diseases Research and Policy (CIDRAP) and advisor on the project, in the press release.

USP worked with a patient advocacy group and a purchasing organization to create a predictive model for improving supply chain resilience for critical pediatric oncology drugs.

USP, Angels for Change, and Vizient Collaborate to Improve Supply Chain for Pediatric Drugs

Bristol Myers Squibb announced on May 18, 2021 that it has entered into a definitive agreement with Agenus, a US-based clinical-stage immuno-oncology (I-O) company, for up to $1.56 billion for a global exclusive license to Agenus’ proprietary bispecific antibody program, AGEN1777, that blocks T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motifs domain (TIGIT) and a second undisclosed target.

Under the terms of the agreement, Agenus will obtain an upfront payment of $200 million and up to $1.36 billion in development, regulatory, and commercial milestones along with tiered double-digit royalties on net product sales, Agenus said in a company press release. Additionally, Bristol Myers Squibb will be responsible for the development and commercialization of the program and any related products worldwide.

Agenus plans to file an investigational new drug application with FDA for the development of AGEN1777 in the second quarter of 2021, while Bristol Myers Squibb intends to advance the research and development of the program in I-O for high priority tumor indications, including non-small cell lung cancer.

“AGEN1777’s differentiated mechanism of action provides the potential for potent anti-tumor activity; catalyzing our clinical TIGIT strategy aimed at serving more patients with unmet needs in cancer,” said Debbie Law, senior vice-president, head of Tumor Microenvironment Thematic Research Center, Bristol Myers Squibb, in the press release. “We look forward to working with Agenus to develop this important therapy as we continue to combat I-O resistance.”

“We are pleased to partner with Bristol Myers Squibb to develop and commercialize AGEN1777. Their stellar record of success in this area has been an important determinant for our decision to enter into this transaction,” said Garo Armen, PhD, chairman and CEO of Agenus, in the press release. “Through such transactions we are able to balance between advancing our portfolio with highly qualified collaborators, while retaining our other innovations for speedy development and commercialization by Agenus.”

Bristol Myers Squibb has entered into a definitive agreement with Agenus for a global exclusive license to Agenus’ proprietary bispecific antibody program, AGEN1777, that blocks TIGIT and a second undisclosed target.