Regulatory Affairs Research Articles

Design and conduct of a randomized controlled feeding trial in a residential setting with mitigation for COVID-19

BackgroundEvaluating effects of different macronutrient diets in randomized trials requires well defined infrastructure and rigorous methods to ensure intervention fidelity and adherence. MethodsThis controlled feeding study comprised two phases. During a Run-in phase (14–15 weeks), study participants (18–50 years, BMI, ≥27 kg/m2) consumed a very-low-carbohydrate (VLC) diet, with home delivery of prepared meals, at an energy level to promote 15 ± 3% weight loss. During a Residential phase (13 weeks), participants resided at a conference center. They received a eucaloric VLC diet for three weeks and then were randomized to isocaloric test diets for 10 weeks: VLC (5% energy from carbohydrate, 77% from fat), high-carbohydrate (HC)-Starch (57%, 25%; including 20% energy from refined grains), or HC-Sugar (57%, 25%; including 20% sugar). Outcomes included measures of body composition and energy expenditure, chronic disease risk factors, and variables pertaining to physiological mechanisms. Six cores provided infrastructure for implementing standardized protocols: Recruitment, Diet and Meal Production, Participant Support, Assessments, Regulatory Affairs and Data Management, and Statistics. The first participants were enrolled in May 2018. Participants residing at the conference center at the start of the COVID-19 pandemic completed the study, with each core implementing mitigation plans. ResultsBefore early shutdown, 77 participants were randomized, and 70 completed the trial (65% of planned completion). Process measures indicated integrity to protocols for weighing menu items, within narrow tolerance limits, and participant adherence, assessed by direct observation and continuous glucose monitoring. ConclusionAvailable data will inform future research, albeit with less statistical power than originally planned.

A proof of concept phase II study with the PDE-4 inhibitor roflumilast in patients with mild cognitive impairment or mild Alzheimer’s disease dementia (ROMEMA): study protocol of a double-blind, randomized, placebo-controlled, between-subjects trial

BackgroundResearch into the neurobiological underpinnings of learning and memory has demonstrated the cognitive-enhancing effects associated with diverse classes of phosphodiesterase (PDE) inhibitors. Specific PDE inhibitors have been identified to improve neuronal communication through selective inhibition of PDE activity. Roflumilast, a PDE4 inhibitor, has demonstrated efficacy in enhancing episodic memory in healthy adults and elderly participants with pronounced memory impairment, indicative of amnestic mild cognitive impairment (aMCI). In alignment with these findings, the present protocol aims to provide a proof of concept phase II of the potential of roflumilast to aid patients diagnosed with (a)MCI or mild Alzheimer’s disease (AD) dementia.MethodsThe study will be conducted according to a double-blind, randomized placebo-controlled, between-subjects design. Participants with (a)MCI and mild AD dementia will be recruited through the Memory Clinic at the Maastricht University Medical Centre + (MUMC +) in Maastricht, the Netherlands, alongside outreach through regional hospitals, and social media. The study will have three arms: placebo, 50 μg roflumilast, and 100 μg roflumilast, with a treatment duration of 24 weeks. The primary outcome measure will focus on the assessment of episodic memory, as evaluated through participants’ performance on the 15-word Verbal Learning Task (VLT). Our secondary objectives are multifaceted, including an exploration of various cognitive domains. In addition, insights into the well-being and daily functioning of participants will be investigated through interviews with both the participants and their (informal) caregivers, we are interested in the well-being and daily functioning of the participants.DiscussionThe outcomes of the present study aim to elucidate the significance of the PDE4 inhibition mechanism as a prospective therapeutic target for enhancing cognitive function in individuals with (a)MCI and mild AD dementia. Identifying positive effects within these patient cohorts could extend the relevance of this treatment to encompass a broader spectrum of neurological disorders.Trial registrationThe Medical Ethics Committee of MUMC + granted ethics approval for the 4th version of the protocol on September 10th, 2020. The trial was registered at the European Drug Regulatory Affairs Clinical Trials (EudraCT) registered on the 19th of December 2019 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004959-36/NL) and ClinicalTrial.gov (NCT04658654, https://clinicaltrials.gov/study/NCT04658654?intr=roflumilast&cond=mci&rank=1) on the 8th of December 2020. The Central Committee on Research Involving Human Subjects (CCMO) granted approval on the 30th of September 2020.

Study Outlines Challenges of Repurposing Oil and Gas Wells for Geothermal Applications

_ This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper SPE 215751, “Challenges for Repurposing Oil and Gas Wells for Geothermal Applications,” by Livio Santos, SPE, and Arash Dahi Taleghani, SPE, The Pennsylvania State University. The paper has not been peer reviewed. _ This work provides insights into the technical and economic viability of repurposing oil and gas wells for geothermal energy production for direct heating. The potential benefits—especially for areas that are highly dependent on fossil fuels for heating—and challenges of this approach are assessed, while technical, market, and policy barriers for future development are identified. Repurposing oil and gas wells for geothermal energy requires a multidisciplinary approach that involves expertise in geology, engineering, and regulatory affairs. Introduction Repurposing abandoned wells for power generation in geothermal energy projects can present challenges because of the low temperatures associated with these wells. The low temperature gradients and thermal energy available in such wells have been found to limit overall power-generation potential. The same low-temperature geothermal resources can still be used effectively, however, for community heating applications. Community heating systems have lower temperature requirements compared with those necessary for power generation and are compatible with available heat from low-temperature geothermal sources. In particular, closed-loop geothermal systems, specifically designed for community heating, offer several advantageous features. The closed-loop design ensures that the fluid remains contained within the system. These systems are environmentally compatible because they do not extract or discharge water from natural sources. Additionally, with better control over the working fluid and heat-exchange process, closed-loop systems deliver optimized system performance, energy efficiency, and cost savings. They also require less maintenance and feature lower operational risks because of the closed circuit. Closed-loop systems offer fluid-selection flexibility and streamlined regulatory compliance. Not all abandoned wells are suitable for repurposing, however. Thorough feasibility assessments and well-integrity evaluations are necessary to ensure that the abandoned well is structurally sound, has the appropriate depth and geological characteristics, and can extract geothermal heat effectively. The condition of the well casing, cementing, and any potential wellbore damage also must be evaluated. An economic analysis is performed to assess the financial viability and cost-effectiveness of the geothermal community heating system. Finally, an environmental impact assessment evaluates the environmental consequences of the geothermal community heating system.

Product Development within the National Institutes of Health Radiation and Nuclear Countermeasures Program.

The Radiation and Nuclear Countermeasures Program (RNCP) at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) was established to facilitate the development of medical countermeasures (MCMs) and diagnostic approaches for use in a radiation public health emergency. Approvals for MCMs can be very challenging but are made possible under the United States Food and Drug Administration (FDA) Animal Rule, which is designed to enable licensure of drugs or biologics when clinical efficacy studies are unethical or unfeasible. The NIAID portfolio includes grants, contracts, and inter-agency agreements designed to span all aspects of drug development and encompasses basic research through FDA approval. In addition, NIAID manages an active portfolio of biodosimetry approaches to assess injuries and absorbed radiation levels to guide triage and treatment decisions. NIAID, together with grantees, contractors, and other stakeholders with promising products, works to advance candidate MCMs and biodosimetry tools through an established product development pipeline. In addition to managing grants and contracts, NIAID tests promising candidates in our established preclinical animal models, and the NIAID Program Officers work closely with sponsors as product managers to guide them through the process. In addition, a valuable benefit for stakeholders is working with the NIAID Office of Regulatory Affairs, where NIAID coordinates with the FDA to facilitate interactions between sponsors and the agency. Activities funded by NIAID include basic research (e.g., library screens to discover new products, determine early efficacy, and delineate mechanism of action) and the development of small and large animal models of radiation-induced hematopoietic, gastrointestinal, lung, kidney, and skin injury, radiation combined injury, and radionuclide decorporation. NIAID also sponsors Good Laboratory Practice product safety, pharmacokinetic, pharmacodynamic, and toxicology studies, as well as efficacy and dose-ranging studies to optimize product regimens. For later-stage candidates, NIAID funds large-scale manufacturing and formulation development of products. The program also supports Phase 1 human clinical studies to ensure human safety and to bridge pharmacokinetic, pharmacodynamic, and efficacy data from animals to humans. To date, NIAID has supported >900 animal studies and one clinical study, evaluating >500 new/repurposed radiation MCMs and biodosimetric approaches. NIAID sponsorship led to the approval of three of the six drugs for acute radiation syndrome under the FDA Animal Rule, five Investigational New Drug applications, and 18 additional submissions for Investigational Device Exemptions, while advancing 38 projects to the Biomedical Advanced Research and Development Authority for follow-on research and development.

To Study the Regulatory Guidelines for API of Ibuprofen: A Review

The registration structure of pharmaceutical outcomes is governed by pharmaceutical medication regulatory affairs. It has a broad scope that encompasses all aspects of documentation and marketing in a legitimate format. In our country, the pharmaceutical business is one of the most coordinated industries. Regulatory affairs experts require a current market overview in order to connect pharmaceutical companies with international regulatory bodies. Regulatory issues RA is a career that overlaps a number of industries, including pharmaceuticals, medical devices, and biotechnology. Within the pharmaceutical sector, RA has a specific connotation. DRA is a dynamic field that encompasses both scientific and legal aspects of drug development. DRA professionals are dedicated individuals who take pride in their contribution to improving humanity’s health and quality of life. The scope of RA as a profession is much more than the registration of outcomes. They provide strategic and practical advice to businesses at a high level. Their small continues through preparation, marketing, and post-marketing. Professionals from RA help the organisation avoid problems caused by sloppy records, incorrect scientific reasoning, or poor data presentation. The claims that can be made for the product on labelling or in advertising are usually restricted in most outcomes areas where regulatory limitations are imposed.

The Ever-Expanding Role of Regulatory Affairs

The Ever-Expanding Role of Regulatory Affairs

Gut Microbiome Integration in Drug Discovery and Development of Small Molecules.

Human microbiomes, particularly in the gut, could have a major impact on the efficacy and toxicity of drugs. However, gut microbial metabolism is often neglected in the drug discovery and development process. Medicen, a Paris-based human health innovation cluster, has gathered more than 30 international leading experts from pharma, academia, biotech, clinical research organizations, and regulatory science to develop proposals to facilitate the integration of microbiome science into drug discovery and development. Seven subteams were formed to cover the complementary expertise areas of 1) pharma experience and case studies, 2) in silico microbiome-drug interaction, 3) in vitro microbial stability screening, 4) gut fermentation models, 5) animal models, 6) microbiome integration in clinical and regulatory aspects, and 7) microbiome ecosystems and models. Each expert team produced a state-of-the-art report of their respective field highlighting existing microbiome-related tools at every stage of drug discovery and development. The most critical limitations are the growing, but still limited, drug-microbiome interaction data to produce predictive models and the lack of agreed-upon standards despite recent progress. In this paper we will report on and share proposals covering 1) how microbiome tools can support moving a compound from drug discovery to clinical proof-of-concept studies and alert early on potential undesired properties stemming from microbiome-induced drug metabolism and 2) how microbiome data can be generated and integrated in pharmacokinetic models that are predictive of the human situation. Examples of drugs metabolized by the microbiome will be discussed in detail to support recommendations from the working group. SIGNIFICANCE STATEMENT: Gut microbial metabolism is often neglected in the drug discovery and development process despite growing evidence of drugs' efficacy and safety impacted by their interaction with the microbiome. This paper will detail existing microbiome-related tools covering every stage of drug discovery and development, current progress, and limitations, as well as recommendations to integrate them into the drug discovery and development process.

A Review on regulatory affairs and regulatory requirements for drug approval

Regulatory affairs are a new profession that can be developed for the controlling the safety, quality and efficacy of the drug products by submitting the investigational new drug application (IND) and new drug application (NDA) to regulatory authority. The whole process may be done in conscious manner in order to release a safe drug product to protect the public from toxic effects of drugs during and after the usage of drugs. The main intention of this article was to aware the peoples towards the role of regulatory affairs department, requirements for new drug approval and the involvement of the regulatory professionals in this process as well as how crucial it is to perform and monitor the clinical and nonclinical trials of the drug before marketing the drug.

Quality assurance and maintaining trust in the Official Veterinarian system.

By assuring the quality of work carried out by official veterinarians and others, the APHA helps maintain confidence in the UK's standards of animal health, certification and disease surveillance - something that is vital for securing international trade. Sue Quinney, veterinary head of OV regulatory affairs for the APHA, explains more….

Reforming the Federal Regulatory Review Process

For decades, the Office of Information and Regulatory Affairs (OIRA) has overseen the development of federal regulatory policies with a strong emphasis on benefit-cost analysis. Despite its conceptual appeal, this analytic tool consistently shortchanges environmental and public health protection, with especially negative consequences for environmental justice communities. In this article, we address some of those shortcomings, focusing in particular on the standard agency practice of arithmetically discounting regulatory costs and benefits that accrue in the future. We propose that the OIRA abandon this practice as it relates to non-market goods, such as human lives saved, and instead work toward a more flexible and holistic approach to regulatory review. In addition, we urge the OIRA to better address environmental justice concerns by placing greater emphasis on distributional and cumulative impacts, highlighting numerous analytic tools that the OIRA could use or adapt in service of that goal. Finally, we discuss ways in which the OIRA could foster a more inclusive and accommodating administrative culture—one more attuned to the needs of environmental justice communities—by reforming both its external and internal processes.

Letter of PTAAARMIGAN (Patent and Trademark Attorneys, Agents, and Applicants for Restoration and Maintenance of Integrity in Government) to Office of Information and Regulatory Affairs re Information Collection 0651-0031 and DOCX rule (June 20, 2024)

Letter of PTAAARMIGAN (Patent and Trademark Attorneys, Agents, and Applicants for Restoration and Maintenance of Integrity in Government) to Office of Information and Regulatory Affairs re Information Collection 0651-0031 and DOCX rule (June 20, 2024)

GRA appoints Prof. Nesrin Erçelen as Director of Regulatory Affairs

GRA appoints Prof. Nesrin Erçelen as Director of Regulatory Affairs

The Effect of Legal Uncertainties on the Pharmaceutical Industry

The pharmaceutical industry operates under stringent legal frameworks that are subject to frequent changes and interpretations, creating a landscape riddled with uncertainties. These uncertainties can impede strategic decision-making, regulatory compliance, and stakeholder engagement. This study aims to elucidate the effects of legal uncertainties on the operational, strategic, and interpersonal facets of the pharmaceutical industry, offering insights into how companies navigate these challenges. A qualitative research design was utilized, involving semi-structured interviews with 28 professionals from various sectors of the pharmaceutical industry, including regulatory affairs, R&D, legal, and corporate governance. Theoretical saturation was achieved to ensure comprehensive coverage of the topic. Data were analyzed using NVivo software to perform thematic analysis, allowing for the identification and exploration of recurring themes and concepts within the collected data. The analysis revealed three main themes: Regulatory Compliance Challenges, Strategic Decision-Making, and Stakeholder Perceptions and Reactions. Regulatory Compliance Challenges included subthemes such as Licensing Processes, Legal Risk Management, and Impact on R&D. Strategic Decision-Making covered Market Entry Strategies, Product Life Cycle Management, Investment Uncertainty, and Corporate Governance. Stakeholder Perceptions and Reactions encompassed Industry Reputation, Regulatory Relationships, and Employee Impact. Each category was populated with specific concepts illustrating the pervasive and varied impact of legal uncertainties. Legal uncertainties significantly influence various dimensions of the pharmaceutical industry. Effective navigation of these uncertainties requires robust compliance structures, proactive strategic planning, and vigilant management of stakeholder relationships. By understanding and addressing these challenges, pharmaceutical companies can enhance their resilience against legal risks and better support their operational and strategic objectives.

Assessment of soil microclimate in an urban park of Budapest, Hungary

Investigation of urban parks is a particular research section in the frame of urban geology, with increasing social importance. Both natural and anthropogenic factors affect these green sites, giving special scientific importance to their investigation. Thus, the behavior of such a ’composite’ system is expected to be quite complex. Based on the general circumstances, a research project was introduced in 2016 in the former Mining and Geological Survey of Hungary (now: Supervisory Authority for Regulatory Affairs). The ongoing project was focused on the behavior of urban parks. Within the frame of this research, between 2016 and 2019, field studies were started in 4 parks of Budapest. This paper is targeting one of these parks, namely Honvéd square. Our objective is to understand the behavior of urban parks under special conditions (e.g., during heat island effects) by getting information from well-defined positions. This can be essential to perform more sustainable water management in an urban park. Within the frame of the field works soil temperature and soil moisture measurements were being recorded manually every week in every park, at four different locations within a park. Observation points were selected to describe the different microclimates of the parks. A statistical analysis of the data reveals that the urban heat island (UHI) effect is reflected in soil temperatures at a citywide scale and that by moderating urban soil surface temperature extremes, trees and shrubs may help to reduce the adverse impacts of urbanization on microclimate, soil processes, and human health. It can be stated, that beside the manual measurements, the automated soil temperature detection was significantly influenced by soil depth at the Honvéd square park. At 100 cm below the surface, the soil temperature is relatively constant. It was approved that not only do deeper soil layers undergo less drastic seasonal temperature fluctuations but also the changes taking place lag further behind those of shallower soil layers.

Plant-derived exosomes: a green approach for cancer drug delivery.

Plant-derived exosomes (PDEs) are natural extracellular vesicles (EVs). In the current decade, they have been highlighted for cancer therapeutic development. Cancer is a global health crisis and it requires an effective, affordable, and less side effect-based treatment. Emerging research based on PDEs suggests that they have immense potential to be considered as a therapeutic option. Research evidences indicate that PDEs' internal molecular cargos show impressive cancer prevention activity with less toxicity. PDEs-based drug delivery systems overcome several limitations of traditional drug delivery tools. Extraction of PDEs from plant sources employ diverse methodologies, encompassing ultracentrifugation, immunoaffinity, size-based isolation, and precipitation, each with distinct advantages and limitations. The core constituents of PDEs comprise of lipids, proteins, DNA, and RNA. Worldwide, a few clinical trials on plant-derived exosomes are underway, and regulatory affairs for their use as therapeutic agents are still not understood with clarity. This review aims to comprehensively analyze the current state of research on plant-derived exosomes as a promising avenue for drug delivery, highlighting anticancer activity, challenges, and future orientation in effective cancer therapeutic development.

Implementation Status and Challenges of Pharmacovigilance Program in Ethiopia: A Mixed-Methods Study

Functional pharmacovigilance systems are vital to ensure patient safety. There is a paucity of information on the organizational functionality of pharmacovigilance program in Ethiopia. This study assessed the pharmacovigilance programs and its implementation status in Ethiopia. A mixed study design was employed to assess pharmacovigilance functionality in hospitals, pharmaceutical companies, and the National Regulatory Authority. World Health Organization’s Pharmacovigilance Indicators and Key Informant Interview Guide were used for data collection. Quantitative data were analyzed using Microsoft Excel (2013), while thematic analysis was used for qualitative study. Of the 30 hospitals covered, only one had a Pharmacovigilance Unit with a dedicated budget, three (10%) had assigned staff, and seven (23.3%) had implemented Standard Operating Procedures. Similarly, 4 (12.5%) of the 32 pharmaceutical companies had separate pharmacovigilance divisions, 12 (37.5%) had a regulatory affairs unit, and 5 (15.6%) had a pharmacovigilance budget. The National Pharmacovigilance Center has the most structure, process, and pharmacovigilance practices. Resource constraints and a weak reporting system were identified as major challenges, while patient harm, loss of confidence, increased circulation of unsafe products, and economic costs were reported as consequences. Increasing training, engaging stakeholders, and improving the regulatory system were recommended as key interventional strategies. Most hospitals and pharmaceutical companies lack most of pharmacovigilance system indicators. However, the national regulatory authority fulfilled most of the elements of Pharmacovigilance systems.

The synergy of artificial intelligence and machine learning in revolutionizing pharmaceutical regulatory affairs

The synergy of artificial intelligence and machine learning in revolutionizing pharmaceutical regulatory affairs

An assessment of positions, perceptions and valued leadership competencies of pharmacists that work in manufacturing pharmaceutical companies (MPCs) in South Africa

Pharmacists are custodians of medicines and play a significant role in the healthcare system as the profession responsible for managing medicines. A self-administered online questionnaire was distributed to pharmacists who are members of the South African Association for Pharmacists in Industry (SAAPI). A majority (66%) of responses received was from females, 87.9% identified experience as the attribute necessary for pharmacists to enter positions of strategic leadership as opposed to availability of opportunities (69.7%) and having an additional business-related qualification (60.6%). Pharmacists that work in the manufacturing sector of the industry were mostly working at technical levels. They were in positions such as responsible pharmacist (RP) (24,1%, n=66), regulatory affairs (18,5%, n=66), quality assurance (16,7%, n=66) production (11,1%, n=66) pharmacists. The pharmacists felt that experience was the key attribute required for entry into strategic leadership positions of manufacturing pharmaceutical companies (MPCs), the attribute for possessing business-related qualifications followed this. The need for a quota system that makes provision for a pharmacist to be present in certain strategic leadership positions of an MPC, was supported by respondents (58%, n=66), 91% of the respondents deemed it necessary for all MPCs to have a pharmacist in the strategic leadership of MPCs. The presence of pharmacists in the strategic leadership of MPCs was limited. The pharmacists who participated in the study felt that their presence could add value as strategic leaders of MPCs.

Navigating the Regulatory Landscape: Key Trends Shaping Today's Regulatory Affairs Environment

Regulatory Science, positioned at the intersection of Science, policy, and law, is essential for safeguarding public health and ensuring the safety and effectiveness of products and practices. It spans various sectors, including pharmaceuticals, medical devices, food and agriculture, environmental protection, and emerging technologies. It faces challenges and opportunities such as rapid technological advancements, global market globalization, and complex scientific discoveries.
 This review paper examines current trends and future directions in Regulatory Aspects within the Pharmaceutical World. It explores how regulatory authorities address challenges and delves into the historical development of pharmaceutical regulation globally. The paper also explores innovative approaches and technologies influencing the regulatory processes, investigates future directions in regulation, and proposes recommendations for the future of pharmaceutical regulations.
 In conclusion, regulatory Science, with its rich history, holds promise for a bright future. Adapting to technological advancements, embracing collaborative approaches, and investing in research and education are crucial for navigating the complexities of the modern world. Regulatory Science will continue to play a vital role in safeguarding public health and fostering innovation.

A Review of Registration and Approval Process of Medical Device in India and Japan

Today, millions of people rely on medical device-based treatment to manage and diagnose a variety of disorders. The regulatory requirements determine the device's quality and safety. Because of the enormous population and the potential severity of the consequences of introducing inferior and dangerous materials to the market, medical device production in India should be regarded seriously. As a result, a legislation including suitable guidelines for rules and regulations is required to monitor the introduction of such devices into public health use. Currently, the regulatory body CDSCO governs device regulation in India, and amendments to the law will give public health safety ensure over time. In Japan, pharmaceutical regulatory affairs are overseen by the Ministry of Health, Labor, and Welfare (MHLW or Koseirodosho in Japanese). Formal authorization and licenses obtained from the MHLW are required for drug marketing in Japan. The regulatory plans are one of the most difficult components of launching a medical device because every medical device is unique. Every significant market, such as India and Japan, has its own specific set of legal requirements. Understanding the critical need for national standardization in order to reduce regulatory burdens, ease commerce, and provide access to innovative technology requires more research.