Regulatory agilities impacting review timelines for Pfizer/BioNTech's BNT162b2 mRNA COVID-19 vaccine: a retrospective study.

The appropriate use of regulatory agilities has the potential to accelerate regulatory review, utilize resources more efficiently and deliver medicines and vaccines more rapidly, all without compromising quality, safety and efficacy. This was clearly demonstrated during the COVID-19 pandemic where regulators and industry rapidly adapted to ensure continued supply of existing critical medicines and review and approve new innovative medicines. In this retrospective study, we analyze the impact of regulatory agilities on the review and approval of Pfizer/BioNTech's BNT162b2 mRNA COVID-19 Vaccine globally using regulatory approval data from 73 country/regional approvals. We report on the critical role of reliance and provide evidence that demonstrates reliance approaches and certain regulatory agilities reduced review times for the COVID-19 vaccine. These findings support the case for more widespread implementation of regulatory agilities and demonstrate the important role of such approaches to improve public health outcomes.

Dynamic Regulatory Assessment: Unpacking the Process Reveals Readiness to Pilot for Europe-An EFPIA View.

The medicines regulatory network of the European Economic Area comprises 30 countries, their National Competent Authorities (NCA), and the European Medicines Agency (EMA). The NCAs and EMA are involved at different stages of the medicine life cycle; not all are engaged in a particular medicine's development discussions. As a result, knowledge management (ie, acquisition and transfer between medicine developer and the NCAs) is fragmented and inefficient. Dynamic regulatory assessment (DRA), a regulatory science concept developed by the European Federation of Pharmaceutical Industries and Associations (EFPIA), could drive increased connectedness supporting more continuous knowledge building. DRA works via iterative release and assessment of discrete data packets (DDPs) at mutually agreed milestones during development, culminating in more efficient development and faster authorization. This commentary seeks to build on an earlier article by unpacking the DRA concept, with a particular focus on DDPs. Its aim is to show how DDPs can support efficient and predictable release of data to encourage development and assessment of promising medicines, and it makes the case for piloting the DRA concept with European regulators now.

Walking the talk in digital transformation of regulatory review.

Cloud-based regulatory platforms have the potential to substantially transform how regulatory submissions are developed, transmitted, and reviewed across the full life cycle of drug development. The benefits of cloud-based submission and review include accelerating critical therapies to patients in need globally and efficiency gains for both drug developers and regulators. The key challenge is turning the theoretical promise of cloud-based regulatory platforms into reality to further the application of technology in the regulatory processes. In this publication we outline regulatory policy journeys needed to effect the changes in the external environment that would allow for use of a cloud-based technology, discuss the prerequisites to successfully navigate the policy journeys, and elaborate on future possibilities when adoption of cloud-based regulatory technologies is achieved.

Impact of genetically modified organism requirements on gene therapy development in the EU, Japan, and the US.

Advanced therapies are emerging as an important class of medicinal products; among these, gene therapies are advancing at an exceptional rate. However, one of the major challenges for gene therapies relates to the additional regulatory requirements for genetically modified organisms. In this paper, we provide an overview of the regulatory requirements for genetically modified organisms in the European Union, Japan, and the United States. We share our experience in managing these requirements and their impact on the adeno-associated virus gene therapies that are under development at Pfizer. Specifically, we discuss the relative complexity of the approval process and the impact of risk assessment expectations on the clinical development of genetically modified organisms. We also compare the regulatory processes and timelines of various regions based on our experience with adeno-associated viral vectors. Finally, we propose that genetically modified organisms, for which pathogenicity and replication competency are well controlled, should be regulated solely under medicinal product regulations and be exempt from additional requirements for genetically modified organisms. Even if an exemption is not implemented, it should still be possible to significantly reduce the sponsor and agency burden by simplifying and harmonizing documentation and data requirements as well as timelines for applications for genetically modified organisms.

Dynamic Regulatory Assessment: evolving the European Regulatory Framework for the Benefit of Patients and Public Health-an EFPIA View.

The European Union regulatory framework supports development, review, authorization, and maintenance of medicines to benefit public health; however, many elements are 2 decades old and undergoing review. Scrutiny was triggered by the coronavirus disease 2019 pandemic, the need to support future innovative medicines, the digital transformation of data exchange, and the need to address efficiency and capacity limitations. There are also ongoing evolutions in regulatory science for medicines (eg, cell and gene therapies), medical device combinations, and software, as well as the need to fully leverage contemporary information technology (IT). Important initiatives to address these challenges include the European Medicines Agency (EMA) Regulatory Science Strategy,1 the EU Regulatory Network Strategy,2 and the Big Data Steering Group,3 alongside European Commission-led initiatives such as the Pharmaceutical Strategy.4 Dynamic regulatory assessment (DRA) is a concept that seeks to integrate these various elements to re-imagine regulatory review interactions across the product life cycle. DRA calls for iterative regulatory dialogue, data submission, and evidence assessment, enabled by contemporary IT. DRA will facilitate iterative interaction and data assessment as it accumulates over a product's life cycle, bringing significant efficiencies for all product types. The DRA concept primarily evolved through dialogue within working groups of the European Federation of Pharmaceutical Industries and Associations. This article describes the long-term vision of the European Federation of Pharmaceutical Industries and Associations and outlines important strategic elements of progress, including: aligning on a multi-stakeholder vision for DRA in the European Union and across regions; leveraging learnings from ongoing initiatives; and advancing IT, governance, and standards considerations. Ultimately, DRA should consider outcomes that deliver optimal benefits for patients in the European Union and worldwide.

Digital Innovation in Medicinal Product Regulatory Submission, Review, and Approvals to Create a Dynamic Regulatory Ecosystem-Are We Ready for a Revolution?

The pace of scientific progress over the past several decades within the biological, drug development, and the digital realm has been remarkable. The'omics revolution has enabled a better understanding of the biological basis of disease, unlocking the possibility of new products such as gene and cell therapies which offer novel patient centric solutions. Innovative approaches to clinical trial designs promise greater efficiency, and in recent years, scientific collaborations, and consortia have been developing novel approaches to leverage new sources of evidence such as real-world data, patient experience data, and biomarker data. Alongside this there have been great strides in digital innovation. Cloud computing has become mainstream and the internet of things and blockchain technology have become a reality. These examples of transformation stand in sharp contrast to the current inefficient approach for regulatory submission, review, and approval of medicinal products. This process has not fundamentally changed since the beginning of medicine regulation in the late 1960s. Fortunately, progressive initiatives are emerging that will enrich and streamline regulatory decision making and deliver patient centric therapies, if they are successful in transforming the current transactional construct and harnessing scientific and technological advances. Such a radical transformation will not be simple for both regulatory authorities and company sponsors, nor will progress be linear. We examine the shortcomings of the current system with its entrenched and variable business processes, offer examples of progress as catalysts for change, and make the case for a new cloud based model. To optimize navigation toward this reality we identify implications and regulatory design questions which must be addressed. We conclude that a new model is possible and is slowly emerging through cumulative change initiatives that question, challenge, and redesign best practices, roles, and responsibilities, and that this must be combined with adaptation of behaviors and acquisition of new skills.

Domestic Risk Factors for Atopic and non-Atopic Asthma in First Nations Children Living in Saskatchewan, Canada.

Both allergic and non-allergic asthma phenotypes are thought to vary by specific housing and other indoor environmental conditions. This study evaluated risk factors for allergic asthma phenotypes in First Nation children, an understudied Canadian population with recognized increased respiratory morbidity. We conducted a cross-sectional survey with a clinical component to assess the respiratory health of 351 school-age children living on two rural reserve communities. Asthma was defined as parental report of physician diagnosed asthma or a report of wheeze in the past 12 months. Atopy was determined by a ≥ 3-mm wheal response to any of six respiratory allergens upon skin prick testing (SPT). Important domestic and personal characteristics evaluated included damp housing conditions, household heating, respiratory infections and passive smoking exposure. Asthma and atopy prevalence were 17.4% and 17.1%, respectively. Of those with asthma, 21.1% were atopic. We performed multivariate multinomial logistic regression modelling with three outcomes: non-atopic asthma, atopic asthma and no asthma for 280 children who underwent SPT. After adjusting for potential confounders, children with atopic asthma were more likely to be obese and to live in homes with either damage due to dampness (p < 0.05) or signs of mildew/mold (p = 0.06). Both natural gas home heating and a history of respiratory related infections were associated with non-atopic asthma (p < 0.01). Domestic risk factors for asthma appear to vary by atopic status in First Nations children. Determining asthma phenotypes could be useful in environmental management of asthma in this population.

Building a Better Approach for the Benefit of Patients: 10 Pillars to Strengthen Regulatory Review Systems Globally.

In the current pharmaceutical regulatory environment, patients continue to benefit from great advances in medical care. Sophisticated regulatory review systems have also evolved to ensure that safe and effective medicines are approved. However, these systems are not optimized in all countries. Gaps in individual regulatory agency capabilities together with duplication in non-value added national regulatory requirements, particularly in low- and middle-income countries (LMICs), can slow down regulatory approvals and therefore impede patient access to new medicines. These gaps exist despite the achievements in both regulatory convergence and harmonization of technical requirements by bodies such as the International Conference on Harmonization (ICH). There is a pressing need to strengthen regulatory review systems in emerging market economies as highlighted by the World Health Organization (WHO). These diverse challenges may seem overwhelming to individual national regulators, in part because of the sheer number of initiatives by multiple stakeholders, combined with a lack of information on concise practical actionable measures that can have a positive impact on review efficiency. This commentary presents 10 pillars that we believe represent the key hallmarks of strong regulatory review systems. Leveraging our internal company expertise at the global, regional, and country level across our entire product portfolio (both innovative and generic), we selected features proven to work in leading regulatory agencies, such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), which are also relevant for other regulatory authorities, especially in LMICs.

Determinants of excessive daytime sleepiness in two First Nation communities.

BACKGROUND: Excessive daytime sleepiness may be determined by a number of factors including personal characteristics, co-morbidities and socio-economic conditions. In this study we identified factors associated with excessive daytime sleepiness in 2 First Nation communities in rural Saskatchewan. METHODS: Data for this study were from a 2012-13 baseline assessment of the First Nations Lung Health Project, in collaboration between two Cree First Nation reserve communities in Saskatchewan and researchers at the University of Saskatchewan. Community research assistants conducted the assessments in two stages. In the first stage, brochures describing the purpose and nature of the project were distributed on a house by house basis. In the second stage, all individuals age 17 years and older not attending school in the participating communities were invited to the local health care center to participate in interviewer-administered questionnaires and clinical assessments. Excessive daytime sleepiness was defined as Epworth Sleepiness Scale score > 10. RESULTS: Of 874 persons studied, 829 had valid Epworth Sleepiness Scale scores. Of these, 91(11.0%) had excessive daytime sleepiness; 12.4% in women and 9.6% in men. Multivariate logistic regression analysis indicated that respiratory comorbidities, environmental exposures and loud snoring were significantly associated with excessive daytime sleepiness. CONCLUSIONS: Excessive daytime sleepiness in First Nations peoples living on reserves in rural Saskatchewan is associated with factors related to respiratory co-morbidities, conditions of poverty, and loud snoring.

Regulatory considerations in oncologic biosimilar drug development.

Biosimilar monoclonal antibodies are being developed globally for patients with different types of solid tumors and hematologic malignancies. Applications for proposed biosimilar monoclonal antibodies are being submitted to the regulatory authorities around the world and may increase patient access to key treatment options upon approval. An understanding among stakeholders (e.g., physicians, patients and their caregivers, pharmacists, payers) of the approval criteria, as well as the similarities and differences in regulatory pathways involved in biosimilar approval in different countries, as presented in this review, will facilitate identification of high-quality, safe, monoclonal antibodies that have been developed according to strict, biosimilar regulatory standards. Further guidance and resolution of the ongoing discussions on biosimilar labeling, naming, automatic substitution, and indication extrapolation may ensure, in the future, an effective and appropriate use of biosimilar monoclonal antibodies by oncologists and other stakeholders in daily clinical practice.

Clinical considerations for the development of biosimilars in oncology.

Despite availability of biologic therapies, limited patient access to many of the most-effective cancer treatments affects overall health outcomes. To address this issue, many governments have enacted legislation for the approval of biosimilars. The term "biosimilar" refers to a biologic product that is developed to be highly similar, as opposed to identical, to a licensed biologic product (the reference or innovator product), such that, per US Food and Drug administration draft guidelines, "no clinically meaningful differences [exist] between the biological product and the reference product in terms of safety, purity, and potency." This article presents some considerations about the development of biosimilars in cancer treatment through an overview of biosimilars from a clinical perspective. Topics covered include the development requirements and unique regulatory requirements for biosimilars, labeling considerations, potential limitations to the uptake of biosimilars, and review of some biosimilars in development for oncology indications.