Rolling Reviews During COVID-19: The European Union Experience in a Global Context.

PURPOSE: Many regulators offered new ways of working to help combat the COVID-19 pandemic, and the rolling review procedure is an important and successful example. In rolling reviews, data are submitted and reviewed as they become available before the full data package is available. This approach is resource intensive but faster than standard review processes and therefore of benefit to society and patients during a health emergency. In this study, we analyze the European Medicines Agency (EMA) rolling review process and extract learning, based on the vaccines and treatments that have been approved to date (November 2021), and formulate 3 suggestions for the future. METHODS: Data and information on rolling reviews and similar related processes were collected from health authority websites across the globe with a focus on the EMA. Literature searches in PubMed and checking company websites for additional information were conducted to complement and corroborate findings as required. FINDINGS: The duration of a rolling review cycle and the number of cycles before a conditional marketing authorization differ among different applications. Through the rolling review process, COVID-19 vaccines could be approved in record times, ranging from 17 to 36 days. The rolling review process is not limited to vaccines but is applied to promising treatments as well. IMPLICATIONS: This study indicates that rolling reviews can be successfully conducted during a health emergency, such as the COVID-19 pandemic, to meet an unmet medical need. Other critical conditions or life-threatening diseases with unmet needs exist and may be suitable to be addressed by a rolling review process to accelerate patient access to life-changing treatments. Indeed, we call for an evaluation of the rolling review process, its use, and its efficiency to capture learning with the aim of building a new, lean, and effective expedited review procedure that could be institutionalized and added to the regulatory toolbox.

Real-World Data in the Postapproval Setting as Applied by the EMA and the US FDA.

PURPOSE: This article provides an analysis of the various regulatory decisions available in the public domain that suggest the use of real-world data (RWD) for postmarketing surveillance activities of products that have a marketing authorization approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The study focuses on the cases in which RWD was used for postapproval commitments or requirements (and to a lesser extent label extensions, as this has been previously published) of medicinal products comprising small molecules and biologics to support efficacy claims or confirm an acceptable safety profile. METHODS: Clarivate Analytics was commissioned to collect data from cases in which RWD was used in the postapproval settings submitted to the EMA (data were found covering the last 14 years) and the FDA (data were found spanning 23 previous years). The query resulted in 165 cases in which regulatory approval was associated with RWD. The data were then categorized and expanded with supporting information gathered from public databases and company websites. FINDINGS: The use of RWD to support regulatory decision-making in the postmarketing surveillance setting has increased in recent years. Most postmarketing surveillance activities are legally enforced requests on the marketing authorization holder to further document the product's safety profile. Data drawn from registries tend to be the most common source in this regard. IMPLICATIONS: RWD have increasingly been used in recent years, both for new product approvals and line extensions and, as shown in this study, in the postapproval setting. There is now a growing appreciation of the potential of RWD as a source in its own right to support regulatory decision-making on the benefits and risks associated with clinical interventions.

The Utility of Remote Inspections During the COVID-19 Health Emergency and in the Postpandemic Setting.

PURPOSE: The COVID-19 pandemic has affected the management and operation of regulatory agencies and the pharmaceutical industry around the world. It has prompted regulatory authorities to consider new ways of working and introduced, among others, remote inspections to validate the integrity of the regulatory data submitted by companies, to evaluate the quality of production and manufacturing sites, and to ensure the conformity with Good Regulatory Practices with the overall goal of guaranteeing patient safety during the crisis. METHOD: This article summarizes and discusses remote inspection guidelines and other related information made available by the Therapeutic Goods Administration (Australia), the European Medicines Agency (EMA), the Pharmaceutical and Medical Devices Agency (Japan), the Medicines and Healthcare Products Regulatory Agency (United Kingdom), and the US Food and Drug Administration (FDA). We also analyze the effect of the pandemic on inspections conducted by the inspectorates of the EMA and the FDA. FINDINGS: The regulatory authorities that we studied all recognized the importance of implementing regulatory policies on remote inspections in response to the COVID-19 pandemic. The remote inspection guidelines from the 5 selected regulatory authorities aimed at mitigating the impact of the pandemic but, while providing valuable advice to the pharmaceutical companies and being similar in intent, were not always aligned in terms of approach and solutions. IMPLICATIONS: On-site inspections are likely to continue to be the norm and the preferred standard for the foreseeable future. However, health authorities will need to further adopt a risk-based inspection approach and stimulate the increased uptake of inspection reliance as proposed by the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme not to overwhelm the pharmaceutical companies with repeat and redundant inspections. Remote inspections have proven to be a new inspection tool, but health authorities should align on their approach to remote inspections in terms of methods applied and documentation requested.