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During the COVID-19 pandemic, eight COVID-19 vaccines were authorised in the European Union (EU); as a result of emerging SARS-CoV-2 variants and waning immunity, some of these have been adapted to broaden the immunity against circulating variants. The pace at which variants emerge challenges the technical feasibility to make adapted vaccines available in a suitable timeframe and in sufficient quantities. Despite the current absence of a clear-cut seasonal spread for COVID-19, the EU regulatory approach thus far is a pragmatic approach following a pathway similar to that of seasonal influenza. This approach currently requires chemistry, manufacturing, and controls (CMC—the design, development and consistent manufacture of a specified medicinal product of good quality) and non-clinical data (from product laboratory and animal studies), as well as demonstrating that updated vaccines induce an immune response that can predict clinical efficacy and safety in humans. For CMC data, COVID-19 mRNA vaccine adaptations generally made use of the same formulation, control strategy, manufacturing process, and inclusion of registered manufacturing sites for the drug product; therefore assessment was generally streamlined. The experience gained from the vaccine adaptations, combined with a continuous early regulator-developer scientific discussion, permits increasingly greater predictability for timing and positive regulatory outcomes. Here, we review key aspects of the quality control and manufacture of updating COVID-19 vaccines to protect against new variants. Although most experience has been gained with mRNA vaccines, we note that investment in the streamlining of manufacturing processes for recombinant protein vaccines would facilitate future strain updates/adaptations thereby safeguarding availability of different COVID-19 vaccine types, which is considered of value for public health. We also reflect on the challenges and opportunities in establishing more predictable regulatory mechanisms for future COVID-19 vaccine adaptions and more widely for future vaccines containing rapidly evolving pathogens with the potential to cause health threats. [ABSTRACT FROM AUTHOR]

Abstract The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Control (CMC) Community hosted a virtual panel discussion on July 15, 2022, to provide a forum to discuss industry and regulator CMC challenges associated with emergency use authorizations.

The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Control (CMC) Community hosted a virtual panel discussion on July 15, 2022, to provide a forum to discuss industry and regulator CMC challenges associated with emergency use authorizations. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, eight COVID-19 vaccines were authorised in the European Union (EU); as a result of emerging SARS-CoV-2 variants and waning immunity, some of these have been adapted to broaden the immunity against circulating variants. The pace at which variants emerge challenges the technical feasibility to make adapted vaccines available in a suitable timeframe and in sufficient quantities. Despite the current absence of a clear-cut seasonal spread for COVID-19, the EU regulatory approach thus far is a pragmatic approach following a pathway similar to that of seasonal influenza. This approach currently requires chemistry, manufacturing, and controls (CMC—the design, development and consistent manufacture of a specified medicinal product of good quality) and non-clinical data (from product laboratory and animal studies), as well as demonstrating that updated vaccines induce an immune response that can predict clinical efficacy and safety in humans. For CMC data, COVID-19 mRNA vaccine adaptations generally made use of the same formulation, control strategy, manufacturing process, and inclusion of registered manufacturing sites for the drug product; therefore assessment was generally streamlined. The experience gained from the vaccine adaptations, combined with a continuous early regulator-developer scientific discussion, permits increasingly greater predictability for timing and positive regulatory outcomes. Here, we review key aspects of the quality control and manufacture of updating COVID-19 vaccines to protect against new variants. Although most experience has been gained with mRNA vaccines, we note that investment in the streamlining of manufacturing processes for recombinant protein vaccines would facilitate future strain updates/adaptations thereby safeguarding availability of different COVID-19 vaccine types, which is considered of value for public health. We also reflect on the challenges and opportunities in establishing more predictable regulatory mechanisms for future COVID-19 vaccine adaptions and more widely for future vaccines containing rapidly evolving pathogens with the potential to cause health threats.

Abstract The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Controls (CMC) Community hosted two virtual panel discussions focusing on several novel regulatory review pathways for innovative oncology products: Real-Time Oncology Review (RTOR), Project Orbis, and the Product Quality Assessment Aid (PQAAid). The panel sessions were held on August 27, 2021, for the discussion of RTOR, and January 21, 2022, for the discussion of Project Orbis and the PQAAid. Both panel sessions included representatives from the US Food and Drug Administration (FDA) and subject matter experts from the pharmaceutical and biotechnology industries, with the aim of facilitating knowledge sharing on CMC-specific advantages, challenges, eligibility criteria for participation, and operational modifications instituted through the utilization of these acceleration initiatives. Key topics included managing cross-regional regulatory CMC requirements, adapting to expedited development timelines, coordinating interactions between health authorities and industry, and potential opportunities for future improvement and expansion of these programs. As RTOR, Project Orbis, and PQAAid are relatively new initiatives, the experiences shared by the panel experts are valuable for providing deeper insight into these new regulatory pathways and processes.

The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Controls (CMC) Community hosted two virtual panel discussions focusing on several novel regulatory review pathways for innovative oncology products: Real-Time Oncology Review (RTOR), Project Orbis, and the Product Quality Assessment Aid (PQAAid). The panel sessions were held on August 27, 2021, for the discussion of RTOR, and January 21, 2022, for the discussion of Project Orbis and the PQAAid. Both panel sessions included representatives from the US Food and Drug Administration (FDA) and subject matter experts from the pharmaceutical and biotechnology industries, with the aim of facilitating knowledge sharing on CMC-specific advantages, challenges, eligibility criteria for participation, and operational modifications instituted through the utilization of these acceleration initiatives. Key topics included managing cross-regional regulatory CMC requirements, adapting to expedited development timelines, coordinating interactions between health authorities and industry, and potential opportunities for future improvement and expansion of these programs. As RTOR, Project Orbis, and PQAAid are relatively new initiatives, the experiences shared by the panel experts are valuable for providing deeper insight into these new regulatory pathways and processes. [ABSTRACT FROM AUTHOR]

Herein, we review a translational development plan to advance allopregnanolone to the clinic as a regenerative therapeutic for neurodegenerative diseases, in particular Alzheimer's. Allopregnanolone, an endogenous neurosteroid that declines with age and neurodegenerative disease, was exogenously administered and assessed for safety and efficacy to promote neuro-regeneration, cognitive function and reduction of Alzheimer's pathology. Allopregnanolone-induced neurogenesis correlated with restoration of learning and memory function in a mouse model of Alzheimer's disease and was comparably efficacious in aged normal mice. Critical to success was a dosing and treatment regimen that was consistent with the temporal requirements of systems biology of regeneration in brain. A treatment regimen that adhered to regenerative requirements of brain was also efficacious in reducing Alzheimer's pathology. With an optimized dosing and treatment regimen, chronic allopregnanolone administration promoted neurogenesis, oligodendrogenesis, reduced neuroinflammation and beta-amyloid burden while increasing markers of white matter generation and cholesterol homeostasis. Allopregnanolone meets three of the four drug-like physicochemical properties described by Lipinski's rule that predict the success rate of drugs in development for clinical trials. Pharmacokinetic and pharmacodynamic outcomes, securing GMP material, development of clinically translatable formulations and acquiring regulatory approval are discussed. Investigation of allopregnanolone as a regenerative therapeutic has provided key insights into mechanistic targets for neurogenesis and disease modification, dosing requirements, optimal treatment regimen, route of administration and the appropriate formulation necessary to advance to proof of concept clinical studies to determine efficacy of allopregnanolone as a regenerative and disease modifying therapeutic for Alzheimer's disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)