Live biotherapeutic products are an emerging class of biological medicines that rely on viable microorganisms to treat or prevent disease. Unlike probiotics marketed as foods or dietary supplements, live biotherapeutic products are regulated as drugs and are therefore subject to rigorous requirements for quality, safety, and clinical efficacy. Recent approvals of microbiota-based treatments for recurrent Clostridioides difficile (C difficile) infection, a bacterial illness that causes severe diarrhea, highlight their therapeutic potential and the regulatory challenges posed by using living organisms. This article examines regulatory expectations for live biotherapeutic products in the US and EU, with an emphasis on safety evaluation, clinical development strategies, and manufacturing controls.

As medical device innovation accelerates and regulatory requirements grow more complex, medtech companies face operational challenges in scaling their regulatory affairs (RA) functions. RA teams, which have historically been underfunded, must handle more activity with the same number of employees. This article examines the ensuing challenges RA teams face in bringing new products to markets and how using technology to manage regulatory information can help centralize information, structure documentation and data, and standardize and streamline workflows. The article emphasizes the importance of training and upskilling programs and shifting from reactive, manual processes to integrated, proactive systems.

Pediatric plans are regulatory frameworks ensuring that the well-being of the pediatric population is adequately considered during the development of new medicinal products. With global harmonization, regulatory writing becomes critical in drafting compliant, ethical, and scientifically robust pediatric study strategies. This article provides an overview of the differences in pediatric plan requirements across the European Medicines Agency (EMA), Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), and the US Food and Drug Administration (FDA), highlighting the regulatory submission process, writing considerations, and common challenges encountered during plan development.

This article examines the Eurasian Economic Union (EAEU) regulatory pathway following the completion of the transition period in December 2025, after which all medicinal products on the union's market must comply with unified registration rules. It provides a practical guide to the key regulatory institutions, the hierarchy of normative documents, registration procedures, and electronic common technical document (eCTD) dossier requirements. Particular attention is paid to document preparation, common applicant mistakes, and strategies to optimize the regulatory process. The recommendations are based on an analysis of the EAEU regulatory framework and the author’s extensive hands-on experience.

This article discusses how comparability protocols provide structured, pre-approved plans for managing postapproval chemistry, manufacturing, and controls (CMC) changes while ensuring product quality. These protocols explain the scientific rationale for the proposed change, outline the analytical strategy to demonstrate comparability, define the acceptance criteria, and specify the recommended reporting category. The use of comparability protocols aligns with the principles outlined in International Council for Harmonisation (ICH) guidelines, which stress risk-based decision making and strong lifecycle quality management. This article also discusses the advantages and limitations, differences between the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approaches, and practical implementation considerations for comparability protocols.

This article presents a case study outlining the development and submission of a commercial investigational new drug (IND) application for a new chemical entity (NCE) developed at The Ohio State University (OSU). Drawing on their experience as academic drug developers directly involved in the project, the authors describe the regulatory pathway from academic discovery to IND submission. They explore the unique challenges and opportunities for academic drug development and provide valuable insights for other academic institutions embarking on similar paths to an IND submission. Key lessons include the importance of thorough preparation, regulatory strategy, interdisciplinary collaboration, regulatory expertise, and the ability to swiftly respond to feedback.

This article is the first of two on strategic regulatory intelligence for cell and gene therapies (CGTs). It will examine how gaps between product approvals and patient access remain despite significant evolutions in the CGT landscape. Longer approval timelines and increasing product withdrawals underscore the need for robust regulatory intelligence frameworks that integrate geopolitical considerations, real-world evidence (RWE), artificial intelligence/machine learning (AI/ML) tools, and multistakeholder collaboration to build an effective regulatory strategy. The article examines the role of regulatory intelligence in advancing effective regulatory strategy across the full CGT and advanced therapy medicinal product (ATMP) lifecycles, including innovative clinical trial designs, chemistry, manufacturing, and controls (CMC) optimizations, and postauthorization surveillance across major global jurisdictions. The second article explores global CGT pricing and reimbursement models.

This is the second of two articles on cell and gene therapies (CGTs). CGTs are among the most transformative and commercially complex therapeutics with their curative potential and one-time administration model. However, their extremely high research, development, and manufacturing costs create a unique set of regulatory and market access challenges not adequately addressed by the existing frameworks. The article synthesizes comparative regulatory intelligence across five major jurisdictions and discusses the corresponding health technology assessments (HTA), payer expectations, and reimbursement landscapes governing commercial access for approved CGT products. The first article focuses on the role of strategic regulatory intelligence in shaping CGT strategy across the development lifecycle.

This article is the second of two on the EU Artificial Intelligence Act (EU AI Act) and its interaction with the EU Medical Devices Regulation (EU MDR) for AI‑enabled medical devices. The first article focuses on risk classification and the points of convergence and divergence between the two frameworks. Building on that foundation, this article identifies key implementation gaps and proposes ways manufacturers can operationalize EU AI Act obligations using existing EU MDR processes and international standards, including risk management, data governance, transparency, and postmarket monitoring, until CEN-CENELEC harmonized standards and common specifications become available. The article also provides a decision tree to help readers prepare for the phased rollout of EU AI Act implementation.

This article discusses the role and importance of excipients in medicines, focusing on regulatory aspects crucial for pharmaceutical companies. The aim of the article is to provide an overview of regulatory considerations in excipient selection and management, elucidating the complex landscape companies must navigate.

The European Medicines Agency (EMA) oversees the centralized marketing authorization procedure for medicinal products across the EU. While this procedure provides a single authorization valid throughout the EU, country-specific requirements must still be met. This article examines key regulatory requirements for registering and maintaining EU-authorized medicines in Spain. It explores the registration steps and marketing authorization holder (MAH) responsibilities, including labeling, pharmacovigilance, anticounterfeiting measures, pricing and reimbursement, and requirements for promotional materials. The article provides practical insights into navigating the Spanish regulatory landscape within the broader EU framework, offering regulatory professionals a comprehensive guide to facilitate successful market access and ongoing compliance.

Representative enrollment is crucial for credible benefit-risk assessments and the external validation of clinical evidence. Despite evolving terminology and policies, the need for clinical trial populations to reflect the intended US patient population remains. This article discusses a practical framework for regulatory planning, highlighting scientific rationale, operational levers, enabling technologies, real-world evidence, and approaches for sustaining momentum amid changing policies. The article offers actionable insights for embedding representation throughout the product lifecycle while maintaining validity and feasibility.

This article presents a comparative analysis of the regulatory requirements for convenience kits and procedure packs in the US and EU, with an emphasis on classification criteria, labeling and unique device identifier (UDI) requirements, and registration obligations. The article examines the regulatory framework for convenience kits in the US and compares it with the applicable requirements under the EU Medical Devices Regulation (EU MDR) and related guidance documents from the Medical Device Coordination Group (MDCG). The article also highlights regulatory considerations and offers practical insights into navigating both markets. A comprehensive understanding of these regulatory considerations is crucial for facilitating compliant market entry and optimizing global distribution strategies.

The 2025 edition of the Chinese Pharmacopoeia (CPh) of the People's Republic of China includes systematic revisions and improvements across a range of entries. A key aim of the Chinese Pharmacopoeia Commission is to continually harmonize the ChP with other international pharmacopoeias. This article examines that approach, using the example of human plasma to produce blood products and including comparisons with the US Pharmacopeia (USP) and European Pharmacopoeia (Ph. Eur.).

This article examines how technology can be leveraged to expand direct-to-consumer access to medications under the US Food and Drug Administration's (FDA) new regulatory pathway, which took effect in May 2025. Driven by unmet patient medical needs, shortages of healthcare professionals (HCPs), and technological advancements that can help reduce barriers to treatment, the FDA has introduced a new incremental NDA pathway that allows sponsors to propose alternative mechanisms to support appropriate medication access without the supervision of an HCP legally authorized to prescribe or administer the drug. This pathway has important potential benefits for branded prescription medicines, generic manufacturers, consumer healthcare companies, and most importantly, consumers or patients.

This article provides a detailed examination of the evolution of the framework for predetermined change control plans (PCCPs) in the US from concept to implementation and its emergence as a potential global standard. Building on perspectives shared by regulatory, legal, and technical experts, it analyzes key elements of two recent US Food and Drug Administration (FDA) guidance documents for PCCPs for artificial intelligence-enabled device software functions and for all medical devices. The article further explores best practices for drafting and maintaining PCCPs across the total product lifecycle and considers their strategic implications for manufacturers and regulators.

The regulatory affairs (RA) function within the medtech industry is managing an unprecedented surge in compliance complexity and volume, driven by major regulatory shifts like the EU's Medical Device Regulation and In Vitro Diagnostic Regulation and increased guidance from the US Food and Drug Administration (FDA). At the same time, generative artificial intelligence (genAI) has emerged, promising significant efficiency gains: up to a 75% reduction in content creation and billions of dollars in annual productivity savings, according to some sources. This article provides an overview of the role of genAI in regulatory operations, benchmarking model performance in RA-specific contexts, and highlighting key application areas. It also provides practical, actionable guidance for RA professionals and executives on defining robust use cases, securing executive buy-in, essential upskilling, and adopting best practices to ensure the safe, effective, and compliant implementation of genAI.

This article discusses the shift from paper labels to electronic labels and explains how manufacturers and regulators may modify the way important product information is communicated. It examines the status of regional initiatives in the US, Singapore, and the EU; describes the operational and regulatory obstacles to global adoption; and suggests feasible, evidence-based implementation strategies. To achieve a globally harmonized e-labeling ecosystem, the discussion emphasizes the importance of stakeholder collaboration, data integrity, accessibility, and sustainability.

This article reports the findings from a 2025 benchmarking survey on the adoption of regulatory artificial intelligence (regulatory AI) across pharmaceutical and life sciences industries to learn how regulatory affairs organizations are turning their AI ambitions into action. Industry leaders are investing in AI solutions for regulatory intelligence, drafting assistance, and research assistance, unlocking measurable gains in efficiency, compliance, and insight. Although adoption remains uneven, with many organizations seeking clearer evidence of return on investment (RoI), some are realizing measurable impact. The findings highlight the emerging practices and strategies defining the next era of regulatory excellence and how organizations can improve implementation and scale readiness during the AI revolution.

Welcome to the December issue of RF Quarterly, featuring a selection of articles adapted from presentations at the 2025 RAPS Convergence in Pittsburgh, PA, on 7-9 October. The articles cover global regulatory pathways for orphan medical devices, best practices for effective collaboration around companion diagnostics, e-labeling in drugs and medical devices, and artificial intelligence (AI) in the regulatory setting – specifically, the use of generative AI (gen AI) for scaling up regulatory operations , and survey findings on how regulatory functions are adopting AI

Regulatory project managers (RPMs) in the pharmaceutical, biotechnology, and medical device sectors play a pivotal role that extends beyond traditional project management. RPMs have specialized expertise in drug development, clinical trial phases, and multidisciplinary team dynamics and are uniquely positioned to anticipate and mitigate risks that could jeopardize regulatory programs. This article explores the value of RPMs with advanced skills and deep industry knowledge by examining three cross-sectional projects, demonstrating how their strategic approach and broad understanding enhance regulatory submissions and overall project success.

This article discusses the impact of US state laws banning food ingredients. It examines two recently enacted state laws that require a warning or disclosure statement on the label, but do not outright ban ingredients. The article also examines federal developments that may, in part, be the result of, or a response to, the state initiatives.

This article explores how the analytic hierarchy process (AHP) can be used as a tool for selecting an optimal global regulatory strategy, using the New Zealand dietary supplement industry as an example. The AHP framework provides a structured and systematic approach that allows businesses to evaluate and prioritize various factors effectively. By quantifying and weighing these factors, AHP can facilitate informed and rational decision making, leading to improved performance, resource optimization, and strategic alignment with organizational goals. In the case study, AHP ranked the US and Canada as the top export markets, though sensitivity testing demonstrated that these rankings could shift under alternative assumptions.

The International Council for Harmonisation (ICH) has endorsed the eCTD – the electronic common technical document – as the message standard for electronic submissions. This article presents an in-depth analysis of the implementation journey of the eCTD version 4.0 (eCTD v4.0) based on industry involvement in the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) and the US Food and Drug Administration (FDA) technical pilots. It highlights the importance of harmonizing metadata, managing two different eCTD formats during the transition period, and ensuring interoperability between vendor tools and regulatory systems. Analyses of the eCTD v4.0 specifications are based on the authors' practical experience in submitting sequences in eCTD v4.0 format in Japan, industry involvement in the planning and preparation of eCTD v4.0 implementation, and limited participation during PMDA and FDA technical pilots.

Medical device manufacturers are required to undertake a range of postmarket surveillance (PMS) activities to comply with regulatory requirements to ensure the safety and performance of their devices in the marketplace. This review outlines the requirements for key international jurisdictions and harmonization efforts underway to reduce impediments to market access.

Global regulatory harmonization in the medical device sector is essential for ensuring timely patient access to safe and effective technologies while reducing redundant regulatory burdens. This article explores the evolving landscape of harmonization efforts, focusing on the convergence of regulatory frameworks across key markets such as the EU, US, and Asia-Pacific region. It highlights the role of international initiatives such as the International Medical Device Regulators Forum (IMDRF), reliance models, and mutual recognition agreements in shaping a more unified global approach. Furthermore, the article examines how regulatory reliance, streamlined documentation, and shared clinical evidence are being leveraged to accelerate approvals and maintain compliance. It also addresses the challenges of aligning diverse regulatory expectations, particularly in postmarket surveillance (PMS), labeling, and quality system requirements. The discussion underscores the importance of cross-functional collaboration, digital transformation, and proactive engagement with notified bodies and competent authorities, emphasizing the importance of a strategic, risk-based approach to global regulatory operations that balances innovation, patient safety, and market agility.

Over the past decade, the global landscape of medical device quality management has undergone a significant transformation. While ISO 13485:2016 provides a common foundation, regional adaptations create overlapping audits and complex compliance pathways. The Medical Device Single Audit Program (MDSAP) and unique device identification (UDI) initiatives have advanced harmonization but remain limited by narrow scopes and database interoperability challenges. Quality management system (QMS) reforms in key markets highlight a growing emphasis on accelerating patient access. This article provides an overview of current quality trends, identifies persistent gaps, and offers a prognosis for future convergence.

Regulatory reliance allows national regulatory authorities (NRAs) to draw on the scientific assessments and decisions of trusted, more experienced regulators while preserving their sovereign decision-making authority. This approach streamlines approvals, optimizes resources, and expands timely patient access to medicines and medical devices. Reliance also complements harmonization efforts, strengthens regulatory systems, and builds trust among stakeholders. This article provides an overview of reliance principles, highlights global and regional initiatives, and explores their implications for regulatory efficiency and capacity building. By fostering collaboration and mutual trust, regulatory reliance contributes to equitable and improved patient access to medicines and medical devices.

Welcome to the September issue of RF Quarterly, focusing on global regulatory harmonization and including articles on early experiences in implementing version 4 of the electronic common technical document (eCTD v4.0); regulatory reliance in optimizing resources and accelerating patient access to therapies; and harmonization efforts in the medical device setting, specifically, quality standards, postmarket surveillance (PMS), and the role of global organizations in facilitating harmonization.

Regulatory science applies scientific knowledge and methodologies to guide regulatory policies and practices. As opportunities to better understand contamination risks and implement risk mitigations arise, regulatory science can help guide contamination controls and sterility assurance for sterile products, supporting patient safety and product innovation. This article discusses how collaboration between manufacturers, regulatory agencies, researchers, and healthcare providers is critical to developing future requirements that will support innovation and international harmonization.

The Office of Therapeutic Products (OTP) within the Center for Biologics Evaluation and Research (CBER) at the US Food and Drug Administration (FDA) initiated a six-month pilot in July 2023 to reduce the number of original investigational new drug (IND) applications that are placed on clinical hold during the initial 30-day review. This article examines changes in OTP's processing of INDs, pilot results, and future steps for the FDA and sponsors of advanced therapies.

In October 2023, the US Food and Drug Administration (FDA) announced a new pilot program called Support for Clinical Trials Advancing Rare Disease Therapeutics (START). The program's purpose is to accelerate the pace of development for novel drug and biological products intended to treat rare diseases for which there is an unmet medical need through enhanced communication with the FDA. This article provides an overview of the program and the current status of development for each drug product selected for participation in the pilot program. Information about sponsor challenges and patient impact is unavailable, given that the program is still in its early stages. Future assessments will be valuable as more data emerge.

This article discusses the current and future market for on-body delivery systems (OBDS), the current regulatory pathways for drug delivery systems, future connectivity trends, and the regulatory implications of 'connected OBDS” in the US.

This article explores the transition to the EU Clinical Trials Regulation (EU CTR), focusing on the operational challenges sponsors and applicants faced. Key topics include harmonizing country-specific documents prior to transition submissions, operational and functionality issues within the Clinical Trials Information System (CTIS), transparency requirements, and the need for regular updates on guidance and Q&A documents during the transition period. The article highlights the need for ongoing communication between stakeholders to address these challenges.

Postmarket clinical follow-up (PMCF) surveys are a proven method for collecting the data used for EU Medical Device Regulation (EU MDR) submissions, but there is limited guidance on survey procedure and use. This article explores the challenges in planning and executing high-quality Level 4 and general/usability Level 8 PMCF surveys, as outlined in Appendix III of the Medical Device Coordination Group (MDCG) 2020-6 guidance document. It addresses poor survey design, insufficient statistical justification, unmet endpoints, and recruitment issues. It will also suggest strategies for addressing these challenges and best practices for effectively implementing the survey.

This article highlights the similarities and differences in the acceptance of real-world evidence (RWE) as clinical data for medical devices in the US and the EU. It will explore the industry perspective on the use of RWE in the US and the notified body perspective on accepting RWE as clinical evidence. The article includes four anonymized case studies in which RWE collected by postmarket clinical follow-up (PMCF) activities was accepted by a notified body in support of CE marking.

Clinical immunogenicity studies have been required for biopharmaceuticals for more than 30 years to address unwanted immunogenicity by identifying and characterizing antidrug antibodies (ADA) and neutralizing antibodies (NAb). Bespoke ADA/NAb assays, which must be valid and meet regulatory requirements, are used to test serum samples from clinical trials and must demonstrate fit for purpose. Testing must be performed in a good clinical laboratory practice (GCLP) environment. This article describes the regulatory dynamics of unwanted immunogenicity testing over the last 15 years.

Regulatory writing is an important function in the development of new medicines. Documents must be carefully crafted to convey the sponsor's key messages for regulatory agencies to review. This article provides an introduction to regulatory writing, a case study of drafting a clinical overview, best practices, and an assessor's viewpoint in preparing documentation for regulatory submissions. Suggestions to streamline the authoring of clinical documents and the possibilities for applying AI in regulatory writing are also provided. Keywords – artificial intelligence, assessor's viewpoint, clinical overview, clinical regulatory writing, first-time quality

Welcome to the June issue of RF Quarterly, which focuses on regulatory writing and includes articles on a clinical overview case study and key takeaways, generative AI in regulatory writing, considerations in writing for a regulatory audience, and using process infographics for streamlining regulatory document development.

The digital IND/NDA/BLA is an innovative conceptual framework for regulatory applications that leverage in silico modeling using artificial intelligence, machine learning, and neural network technologies. These frameworks establish fully digital submission pathways where nonclinical simulation (no animal testing), in silico clinical pharmacology, clinical study modeling, and the creation of regulatory data and documents through submission are conducted in AI applications with expert human supervision. This article will examine generative artificial intelligence (gen AI) in producing regulatory documents, looking at time savings, current vendors, writing and editing style, the impact of company size, and augmentation. It also addresses vendor evaluation and cost/return on investment considerations. Keywords – biologics license application, digital submission, generative AI, investigational new drug, in silico, human supervision, new drug application

This article discusses the development and use of process infographics to streamline regulatory document development by increasing process efficiency and writer productivity. Process infographics in regulatory writing may enhance consistency and alignment across writers, help increase adaptability and reduce onboarding time, enhance clarity and comprehension of processes, and reduce errors and ambiguity. A thoughtful and carefully designed client-specific process infographic could easily become one of the most value-added visual tools in regulatory document development. Keywords – document development, process infographics, regulatory writing, visual workflow

Artificial intelligence (AI) tools are becoming increasingly common across various regulatory functions. This article reviews the privacy policies and terms of service of a selection of AI tools to help regulatory professionals make informed decisions about data management and vendor qualification when using AI. The tool selection is based on a 2024 RAPS article by Meredith Brown-Tuttle and Jay Mashburn. This review will explore the qualitative ratings for each tool established by the community project Terms of Service;Didn't Read.

The US Food and Drug Administration's (FDA's) Office of Prescription Drug Promotion (OPDP) conducts several research studies each year focused on the advertising and promotion of prescription drugs. This article explores the intersection between OPDP research and recent enforcement actions, highlighting trends and providing insights for regulatory affairs advertising and promotion (ad promo) professionals. The article describes how OPDP research informs enforcement actions and offers guidance on staying current with the office's evolving requirements. Keywords – enforcement, OPDP, research, trends

Software can have different applications in healthcare, with many benefits for healthcare systems, physicians, and patients. Qualifying and classifying medical software and applying the appropriate regulatory requirements is important to ensure quality and safety. This article describes and compares the requirements for market entry of medical device software in the EU and US, based on the different applications and intended use that software can have in healthcare. The article examines the EU Medical Devices Regulation (EU MDR; 2017/745), the European regulation applicable to medical devices, and the Medical Device Coordination Group (MDCG) guidelines for medical device software in the EU. The Federal Food, Drug, and Cosmetic Act (FD&C Act), the US Code, Title 21, and the US Food and Drug Administration (FDA) guidelines applicable to medical device software are examined for the regulatory framework applicable in US.

In the EU, safety and effectiveness must be demonstrated for in vitro diagnostic medical devices before they can be made available on the regional market. As demonstrated by comparing the clinical evidence with the current state of the art, devices must maintain a favorable benefit-risk ratio throughout the entire product lifecycle. Risk management, documentation of the state of the art, performance evaluation, and postmarket performance follow-up are continuous processes that manufacturers must carry out until product obsolescence. This article describes the steps needed to conclude that the device has a favorable benefit-risk ratio, and how this conclusion should be continuously re-evaluated.

Welcome to the March issue of RF Quarterly, which focuses on regulatory project management and includes articles on the biotech asset journey (from early development to market-ready success), the transition from bench science to project management, the RPM's role in the alliance setting, and tools and techniques for regulatory project management.

The regulatory project manager role in the pharmaceutical, biopharmaceutical, biotechnology, and medical device industries has become a defined career path. This article explores the tools and technologies that assist RPMs in schedule, risk, resource, and communication management. It highlights the importance of project plans, risk mitigation strategies, resource allocation, and effective communication for successful regulatory project management.

Complex generics (CGx) encompass categories of products that require specific studies beyond those needed for simple generic products to demonstrate therapeutic equivalence with innovator drugs. This article, adapted from presentations by the authors at the complex generics session at RAPS Convergence 2024, describes the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) regulatory approaches for complex generics/hybrid medicines and the results of studies by the United States Pharmacopeia (USP) in Brazil, China, India, Japan, and Mexico where approvals and regulatory and pharmacopeial requirements were assessed for selected complex products, both complex innovators and the corresponding complex generics, also marketed in the US. The benefit of convergence is discussed in the context of these findings and agency regulations.

There is an effort to increase women's health-focused design innovations, including tailoring vaginal product designs to meet women's healthcare needs. Essential to this effort is the integration of social, geographic, and cultural sensitivities into specific product designs to meet the unique preferences and needs of women globally. Chemistry, manufacturing, and controls (CMC), in collaboration with other disciplines, aims to address these needs by ensuring the development of dosage forms that can be both safe and effective without compromising patient compliance. Therefore, appropriate dosage forms for topical administration through the vaginal route continue to be developed and optimized. Data collected from actual-use studies and focus groups help define the desired attributes of vaginal dosage forms. Among the topical dosage forms, intravaginal rings are gaining interest as they present promising in vivo performance and high potential for optimization. CMC enables the optimization of vaginal rings through physicochemical characterization, quality controls, and product performance tests.

This article will examine how project management skills can be applied in developing and managing an alliance, from setting goals and development stages, outlining the respective roles and responsibilities, addressing risk and risk mitigation, identifying a platform/software for data and document storage, and tracking performance. Keywords – alliance management, regulatory project management

Preventive vaccines used to fight infectious diseases in developing countries are general first approved in developed countries. New regulatory avenues to improve vaccine supply to developing countries are now in place. In particular, the EU-Medicines for all (EU-M4all) procedure, a cooperative effort between the European Medicines Agency (EMA) and the World Health Organization (WHO), and the emergency use listing (EUL) procedure for pandemic-related rapid use of vaccines are discussed in this article.

A successful 510(k) submission can make or break a product's entry into the medical device market. This article provides insights on the best practices for preparing and submitting a 510(k) submission using the US Food and Drug Administration's (FDA's) eSTAR program. The authors provide guidance on how to create a 510(k) submission that will have the greatest chance of achieving a substantial equivalence determination. It includes suggestions on how to keep the submission organized, use the help texts offered by eSTAR, and identify appropriate standards and guidances for a specific medical device.

This article offers strategies for success in concurrent submissions through suggested lessons learned and tips for avoiding common pitfalls. It addresses the complexities of concurrent submissions, including diverse regulatory requirements, resource allocation, and the importance of maintaining consistency. It also emphasizes enhancing efficiency through tools and collaboration, highlighting the use of digital tools and cross-functional teamwork. Additionally, it explores robust risk management strategies, including proactive risk assessment and mitigation planning.

While most clinical holds are eventually lifted, the associated time and cost can be substantial. Fortunately, experience has shown that the risk and impact of a hold can often be mitigated through sound regulatory strategy. This article presents various studies of holds associated with each of the core IND disciplines (nonclinical, clinical, and quality), emphasizing what is needed for a complete application and the value of strategic thinking in the evaluation and mitigation of identified risks.

Effective partnerships between regulatory and marketing teams drive product success through alignment on clear messaging, optimizing labels, and fostering innovative marketing strategies. This collaboration, known as the medical, legal, and regulatory (MLR) ecosystem, enables streamlined workflows, clear communication, and compliance in promoting pharmaceutical products. Through early engagement, cross-discipline learning, and shared accountability, teams can achieve efficient product launches and impactful engagement with healthcare professionals and patients. This article will examine these elements of the MLR ecosystem and includes case studies that illustrate the value of synchronized messaging and technological adoption in enhancing efficacy.

This article discusses the importance of human factors engineering (HFE) in the development of drug-led combination products. It highlights the unique challenges and areas of ambiguity faced by industry in the implementation of a robust HFE program and provides suggestions that may be adopted to develop robust regulatory strategies to navigate these ambiguities.

This paper summarizes the findings from an in-depth analysis of biologics and biosimilars license applications reviewed by Center for Drug Evaluation and Research (CDER). By understanding the common regulatory findings, review issues, and postmarketing commitments/requirements related to the chemistry, manufacture, and controls (CMC) information provided in Module 3 of a biologics license application (BLA), regulatory professionals can better prepare their submissions and potentially shorten approval timelines. The recommendations are intended to guide small biotech companies through the complexities of CMC submissions, ensuring that the quality aspects of their applications meet US Food and Drug Administration (FDA) standards and contribute to a successful outcome.

Welcome to the December issue of RF Quarterly, with selected presentations from RAPS Convergence 2024 adapted as articles focusing on eSTAR best practices, regulatory challenges for medtech start-ups, product quality review of biologics and biosimilars, navigating an IND clinical hold, human factors development, the regulatory-marketing partnership, and concurrent regulatory submissions.

The journey of a medical device start-up from concept to market is fraught with challenges, particularly when meeting stringent regulatory requirements for clinical data. This article provides a comparative analysis of these requirements between the EU and US, with a particular focus on the unique hurdles faced by start-ups and spin-offs and the resources available to them.

Asset lifecycle management is a key tenet of strategic planning for ensuring that pharmaceutical products reach the market and sustain their competitive edge throughout their lifecycle. This article will explore the management of the distinct early and late lifecycle phases through a corporate lens, highlighting the challenges, opportunities, and critical success factors that drive successful lifecycle strategies.

A single marketing application is usually sufficient to obtain authorization for a combination product in the US, including its underlying constituent parts. However, for a cross-labeled combination product, where the constituent parts are separately provided, applicants may sometimes find it beneficial to submit separate marketing applications for the individual constituent parts of the combination product. This article highlights the strategic and practical considerations in determining whether to submit single or separate marketing applications for a cross-labeled combination product in the US.

Applying artificial intelligence (AI) in medical device risk management could significantly improve regulatory compliance, safety, and operational efficiency. AI technologies, particularly machine learning (ML), can enhance traditional risk management by automating processes and providing real-time analyses of clinical and operational data to identify noncompliance and emerging risks. This integration facilitates predictive analytics, fraud detection, and anomaly detection, ensuring the integrity and cybersecurity of medical devices.

This article examines good machine learning practices (GMLPs) and highlights their application in the real-world setting as a way to improve transparency and explainability for medical device development.

Welcome to the September issue of RF Quarterly, which includes articles examining artificial intelligence (AI) in medical devices, focusing on the global regulatory landscape, contact-free AI devices in clinical trials, AI-driven strategies for regulatory compliance medical devices, the role of data in AI governance, and machine learning (ML) best practices. As always, we hope the articles will provide guidance and resources for regional and global regulatory professionals. We thank the authors for their time and generosity in sharing their expertise and real-world knowledge and experience with the RAPS community.

Artificial intelligence (AI) devices are emerging as potential solutions to streamline the product lifecycle and increase the speed at which therapies are being introduced in the market. AI plays an evolving role in optimizing the management of clinical trials. Within this space of optimizing clinical trials, contact-free AI devices are emerging as tools to enhance data collection, patient surveillance, and decision making. This article highlights the types of contact-free AI devices used in clinical trials, their applications, the challenges, and their future scope.

Digital health has revolutionized the healthcare sector. Artificial intelligence (AI) and machine learning (ML) have gained widespread recognition because of their promising benefits in enhancing diagnosis, decision making, and treatment capabilities. A robust regulatory framework is essential for Al/ML-enabled medical devices to balance innovation while safeguarding public health. This article provides an overview of the global regulatory landscape for AI/ML-enabled medical devices, focusing on the framework in the US, EU, Canada, UK, Singapore, China, Hong Kong, Brazil, South Korea, Australia, and the International Medical Device Regulators Forum (IMDRF).

This article examines the role of data protection and privacy laws in artificial intelligence (AI) development in healthcare across three regions: the US, EU, and Canada. It introduces key AI concepts and emphasizes the critical role of robust legal frameworks in safeguarding personal data. The analysis covers existing and proposed regulations, highlighting the interplay between data protection and general AI legal frameworks. It underscores the importance of understanding these evolving legal landscapes for AI developers navigating compliance challenges and market access strategies in an increasingly complex regulatory environment.

Ingestible medical devices offer novel diagnostic, monitoring, and treatment capabilities. This article explores the regulatory landscape of ingestible devices in the US, highlighting the US Food and Drug Administration (FDA) classifications, clearance, and approval processes. It discusses preclinical and clinical data considerations, postmarket requirements, and challenges in bringing these devices to the market. The article includes examples of ingestible devices cleared and approved in the last decade, their timelines, and the potential of these emerging technologies to revolutionize patient care.

Historically, the pediatric population was not considered in drug development, which resulted in a dearth of information on medicines for children and high off-label use for this vulnerable population. The 2007 EU Paediatric Regulation created a solid framework for setting up new measures to address those shortcomings. This article reviews current improvements in the regulation and the residual challenges associated with it. It also examines the planned changes for the EU legislation reform and its possible role in alleviating limitations in pediatric drug development.

This article examines how various stakeholders, including academic institutions, regulatory-focused professional organizations, and prospective employers in the US, can train and support newcomers to regulatory affairs. These entry-level individuals include those making a midcareer transition from another field to regulatory affairs and who have work experience but not in the regulatory setting and recent undergraduates or graduates with master's degrees in regulatory affairs but with no work experience. The article also addresses the shortage of qualified and experienced regulatory affairs professionals, the challenges for both job candidates and employers in filling positions, and how these contribute to the prevailing talent gap in the profession. The article is based on a presentation at the Regulatory Affairs Professionals Society (RAPS) Annual Convergence in Montreal, Canada, in October 2023.1

Artificial intelligence (AI) and machine learning (ML) tools have the potential to expedite and enhance many regulatory functions, from writing and research to strategy and submissions. However, AI technology is evolving, and current AI solutions have limitations in fully automating complex regulatory tasks. This article reviews a selection of free AI tools and how they can be applied to support the creation of quality regulatory deliverables.

The FDA's Quality Management Maturity (QMM) Program continues to evolve in response to the escalating challenge of therapeutic drug shortages. This article examines the rollout of the program and reports on results from the initial QMM pilot studies and industry stakeholders' feedback, recommendations, and consensus opinions that informed the agency's launch of the QMM Prototype Assessment Protocol Evaluation Program scheduled to begin later in 2024. The article also addresses the potential impact of the QMM program.

A regulating body's approval of a proposed drug substance retest period and proposed drug product shelf life depends on the data generated from stability testing. The stability data of pharmaceutical products are crucial because they correlate to the quality, safety, and efficacy of the product. This article, the first of three on pharmaceutical stability testing, provides readers with an overview of stability and its importance in drug safety and highlights the common pitfalls of stability testing programs. The second article addresses stress testing, and the third, bracketing and matrixing designs for stability testing. The series is based on current stability guidelines from the International Council for Harmonisation (ICH).

Stability stress testing consists of investigating the durability and performance of drug substances and/or drug products under varying stress conditions, such as light and/or temperature fluctuations. By analyzing the effects of photo-degradation and stress-induced alterations, researchers gain insights into the long-term stability and reliability of drug substances and/or products. This integrated approach contributes to the development of robust materials and ensures quality standards are maintained throughout light exposure and mechanical stress. This article, the second of three on stability, examines stability stress testing. The first article provides an overview of stability and its importance in drug safety, and the third addresses bracketing and matrixing designs for stability stress testing. The series is based on current stability guidelines from the International Council for Harmonisation (ICH).

Bracketing and matrixing are critical strategies in stability testing of drug substances and/or drug products. These designs aim to minimize resources while ensuring product integrity. Bracketing involves studying only the most extreme storage conditions, assuming intermediate conditions will remain stable. Matrixing explores a subset of conditions to cover all possible scenarios. Both approaches accelerate stability studies, streamline regulatory requirements, and offer cost-effective solutions for assessing stability profiles, which ensures safe and efficacious medications. This article, the third of three on stability, examines bracketing and matrixing designs for stability testing. The first article provides an overview of stability and its importance in drug safety, and the second addresses stability stress testing. The series is based on current stability guidelines from the International Council for Harmonisation (ICH).

An organization-wide efficient and effective quality management system (QMS) is crucial, but the implementation is challenging. This article outlines factors that affect the QMS and provides guidance on controlling them with a pragmatic, risk-based approach that fosters stakeholder engagement. It addresses identifying needs and mapping activities and processes and explains how to prioritize and refine procedures and templates, manage training, and adapt to changes.

Cellular and gene therapy (CGT) products are complex and diverse compared with traditional biologics. Demonstrating CGT products to be safe, pure, potent, effective, and stable poses challenges often related to the complex nature of the manufacturing process, high product variability, and limited material or time for testing. Regulatory agencies recommend a lifecycle approach in which product quality assurance increases with clinical development. This article discusses the product quality considerations and regulatory expectations during the development of CGT products.

This article explores the quality considerations for international generic pharmaceutical products launched in the Chinese market. It covers the fundamental principles of developing regulatory specifications, focusing on the stringent standards set by the Chinese Pharmacopoeia (ChP) for residual solvents, heavy metals, and ignition residue. It also discusses control strategies and limit-setting considerations for nitrosamine impurities. Understanding and addressing these challenges is pivotal for successful market entry.

Welcome to the June issue of RF Quarterly, which includes a selection of articles examining quality considerations for cellular and gene therapy (CGT) products and for generic drugs entering the Chinese market, implementation of an efficient and effective quality management system (QMS), and a three-part series on pharmaceutical stability testing.

A regulating body's approval of a proposed drug substance retest period and proposed drug product shelf life depends on the data generated from stability testing. The stability data of pharmaceutical products are crucial because they correlate to the quality, safety, and efficacy of the product. This article, the first of three on pharmaceutical stability testing, provides readers with an overview of stability and its importance in drug safety and highlights the common pitfalls of stability testing programs. The second article addresses stress testing, and the third, bracketing and matrixing designs for stability testing. The series is based on current stability guidelines from the International Council for Harmonisation (ICH).

There is no specific definition in the People's Republic of China regulatory framework clarifying the term 'digital health,” but there is general acceptance that the term refers to digital technologies applied across the healthcare sector.1,2 This article describes recent updates to the regulatory framework for digital health applications that qualify as medical devices under China's regulations.