Food and Drug Administration Oversight: Origins and Contribution to the National Covid Response: Running Title: FDA Oversight: Origins and Contributions to the Covid Response

The Food and Drug Administration (FDA) has been a key actor in the USA’s response to the Covid-19 pandemic. The extensive use of Emergency Use Authorizations (EUAs) during the pandemic as part of its broader strategy to protect the health of the country has raised this federal agency to the public psyche. The FDA’s response has been guided by its position within the national governing framework as well as its own unique history. A review of this framework and the FDA’s history can be illuminating in understanding this agency’s response during a national crisis

Regulatory Impact Analysis for the Risk Based Lot Release Policy for Biological Products in Egypt

For public health and lifesaving, timely access to high-quality biological products is essential. However, barriers including resource scarcity, limited human capacity, and complex supply chains impede this goal. National regulatory authorities should enhance their frameworks and move forward for regulatory convergence and harmonization & enhancing reliance practice in order to address these concerns. A risk-based lot release policy is one of the enablers that ensure implementation of smart regulations and best practices was employed by Egyptian drug authority (EDA) to boost the effectiveness of the lot release framework while upholding safety, efficacy and quality criteria. The legal framework for lot release in Egypt was examined using a regulatory impact analysis method. With a considerable impact on time and cost savings, as well as a better net benefit value, the new risk-based lot release policy has the potential to greatly increase the efficiency of Egypt's LR regulatory system for biological products. Nevertheless, significant challenges and unexpected consequences were also noted, including the need for ongoing capacity building and growing regulatory requirements based on best practices. The findings have major reflections for drug policy makers and regulators looking to enhance their biological product regulatory systems; since the policy's benefits outweigh these possible challenges. This paper offers a full examination of the risk-based lot release policy used by the EDA, Egypt for biological products, assisting in understanding both the benefits and challenges of this approach

Repercussions of politicized regulation exemplified by compulsory new TC1507-maize 90-day rat feeding study

Politicized and prescriptive regulation of genetically modified (GM) crops has unintended adverse effects, including misdirected resources and reduced benefits.  In the case of animal testing, this suboptimal use of resources includes the needless sacrifice of animals.  Whole-food animal feeding studies are generally of negligible value in the risk assessment of GM crops, a position that was affirmed by the European Food Safety Authority (EFSA).  Contrary to EFSA’s 2011 position, in 2013, the European Commission directed that 90-day rat studies be conducted for new GM events.  As no EFSA guidance was available for hypothesis-free 90-day rat feeding studies, EFSA interpreted this as a mandate to develop a prescriptive study design.  Recently, EFSA has retroactively required 90-day rat studies be completed under new study guidelines for previously approved component single events as part of the approval of breeding stacks.  Having been unable to secure a derogation (exemption) from EFSA, a new compulsory 90-day rat study was conducted with TC1507 maize to support a breeding-stack submission.  As previously shown, TC1507 maize does not adversely affect rats.  This politically driven additional animal testing is risk disproportionate, at odds with European and international standards for animal welfare, and provides no scientific value to the safety assessment for GM breeding stacks

Use of a Portable X-Ray Fluorescence Analyzer for Rapid and Accurate Determination of Iron in Vitamins and Supplements

This study describes the development of an X-Ray Fluorescence (XRF) method to quantify iron in vitamins and supplements. Four different products and a NIST Standard Reference Material (SRM) were prepared by homogenizing 20 tablets in a mixer mill and diluting known masses of each sample into known masses of cellulose. Calibration standards were similarly prepared by diluting known masses of iron oxide into known masses of cellulose. Analyses were performed using a handheld XRF analyzer using one-minute analysis times. The method gave linear calibration curves with R2 values greater than 0.9995, and good accuracy as demonstrated by relative errors of 9% in the analysis of the NIST SRM. Experimentally determined concentrations of the samples were compared to the nominal concentration of the samples based on the mass of iron per tablet and the average tablet mass. XRF results gave relative differences of +4% and -4% for two iron supplements. XRF results gave a larger relative difference of -19% for the women’s vitamin product. Although the label on the men’s vitamin product stated it was iron-free, XRF and Microwave Plasma Atomic Emission Spectrometry (MP-AES) analyses showed it contained iron levels of 157 and 133 µg/g (ppm), respectively. This XRF method offers a simpler, faster, and less expensive alternative to conventional atomic spectrometry-based methods for this type of application

Portable Spectroscopy for Food Safety and Adulteration Screening

In this review we discuss various applications of portable vibrational spectroscopy in food adulteration analyses and authentication confirmation. These applications generally involve the adulteration of a food product with materials which may be of lesser monetary value and may also be detrimental to human health. Portable spectroscopic testing for food authentication opens potential for rapid and on-site analyses of food products at various stages in the food production chain. These portable techniques also require the development of data analysis methods for each individual application, which will also be discussed in this review. Specific food safety applications for portable spectroscopy to be discussed include adulteration detection and evaluation of authenticity. Adulteration detection examples focus on the commonly adulterated milk powder and spice commodities, as well as the potential for component substitution (e.g., artificial sweeteners). For authentication, examples from marine oil dietary supplements, olive oils, honeys, coffees, and grains are presented along with examples of speciation (e.g. fish) and growth conditions (bell peppers)

Rapid, field-deployable method for determination of seafood decomposition by compact mass spectrometry

Seeking alternatives to sensory which can be performed in non-laboratory field environments has been a recent emphasis in regulatory assessment of seafood decomposition.  To this end, an international sampling effort produced samples of 23 different seafood products, which were subjected to controlled decomposition of varying levels on ice. This produced samples of each product for a wide range of decomposition states, and these were scored by a sensory expert on a standard 1-100 scale. Samples were then analyzed by a novel technique involving headspace analysis and compact mass spectrometry. The mass spectrometry data was used to create computer models, guided by the sensory data, to generate a calculated score analogous to a sensory score. Models based on a training set of samples were then used to calculate scores for a test set, and accuracy was assessed by comparing these calculated scores to original sensory data. Calculated scores agreed with sensory findings with respect to overall decomposition state for 96.3% of samples (n=547), with seven false positive (1.3%) and 13 false negative (2.4%) findings. Reproducibility was also assessed via triplicate analysis on separate days for low, middle, and high decomposition states. All sample ranges for these replicates were within 20 points, with 89% (n=66) within 15 points, 73% within 10, and 35% within five. Given the performance of the method, along with the small form factor and manageable operation requirements of the instrument as well as simplicity of sample preparation, this appears to offer a potentially useful technique for field testing of seafood decomposition

Regulatory Science: The Maturation of an Evolving Scientific Discipline

Regulatory science encompasses the participation of a large array of scientific disciplines involved in the regulatory process. Although each discipline addresses different phenomenology and exploits different methodologies, the common scientific core is the same:  objective pursuit of verifiable and useful knowledge.  This paper updates the definition and scope of the practice of regulatory science, starting with a concise historical overview. It then examines the different phases of regulatory science applications: initial, exploratory, and standard operating. The paper also reviews the definitions of regulatory science used by various agencies and provides abbreviated scientific definitions. The paper summarizes Best Available Regulatory Science (BARS) and Metrics for Evaluation of Scientific Claims (MERSC), along with key elements and tools of regulatory science: peer review; regulatory science ethics, including the so-called Jeffersonian principle; mathematical models; cost benefit analysis; and stakeholder participation. The paper concludes with a brief description of these key tools and elements, highlighting their importance in the field of regulatory science

Enabling Pharmaceutical Traceability in The Nigerian Supply Chain using GS1 Global Standards: Lean Traceability Including In-Country Serialization of COVID-19 Vaccines

Traceability of the pharmaceutical products across a supply chain creates an environment that provides visibility of the product status from plant to patient.  The supply chain is the trade journey products make to consumers or retail stores (e.g. pharmacy store, patented drug store, medical store etc.,) via a network of producers, manufacturers, distributors, transporters and vendors taking that product from creation to delivery. Some of the key benefits of introducing traceability in the Nigerian pharmaceutical sector besides securing the supply chain includes an increment in the quality of data to support pharmacovigilance, decrease in the presence of substandard and falsified (SF) medications and ultimately ensuring patient safety. The drug distribution system in Nigeria is largely undefined and there have been in-country efforts to sanitize it. One such effort has produced a national policy document referred to as the Nigeria Pharmaceutical Traceability Strategy which stipulates the plan to achieve supply chain visibility, prevent infiltration of the SFs and strengthen existing regulatory and legal frameworks in Nigeria using GS1 global standards. The National Agency for Food and Drug Administration and Control (NAFDAC) and other drug regulatory agencies in Africa jointly signed a Call to Action during the 2nd GS1 African Healthcare Conference held in Lagos, Nigeria on September 16-20, 2019 to demonstrate commitment to pursue pharmaceutical traceability by adopting global supply chain standards. This article focuses on how NAFDAC in collaboration with GS1 Nigeria, National Primary Health Care Development Agency (NPHCDA) and other partners have implemented traceability as a public sector pilot for the COVID-19 vaccines received in Nigeria from March 2021 to December 2021.  This included the serialization of COVID-19 vaccines that were received without serial numbers that uniquely identify the secondary packing of the COVID-19 vaccines. The lessons learned from the pilot would be used to support development and dissemination of tracebility regulation, publish guidelines for traceability implementation, and engage stakeholders meaningfully as Nigeria implements full track and trace of pharmaceutical products

A national probabilistic characterization of local crop proximity and density for refining US screening level exposure estimates of pesticides in surface water arising from agricultural use

Rising world population and changing diets are increasing the need for efficient and effective food and fiber production. Pesticides are used across the US to control pests and improve food yield and quality, but these benefits are offset by their potential to reach and possibly impact aquatic or terrestrial ecosystems. Regulatory agencies rely on prospective exposure models that often start with conservative simplifying assumptions that are refined with additional information if needed. The USEPA ecological risk assessment framework for pesticides assumes, at screening level, that 100% of the area draining to a water body is cropped. However, at the grower’s real-world scale, this simplifying assumption is generally not realistic and should be refined for higher tier assessment. The present study developed a US-wide spatially explicit analysis of crop density and proximity to surface waters to characterize the potential for pyrethroid insecticides to enter flowing surface waters. Reliable, transparent, and publicly available government spatial cropping and hydrology datasets were employed at the catchment-scale across the full extent of agricultural production in the US were used to generate fifteen novel crop-specific probabilistic distributions describing the extent and proximity of each crop to the flowing water body defining small catchments. These were used to refine estimated environmental concentrations using USEPA standard regulatory scenarios to evaluate the importance of considering agricultural landscapes when refining aquatic pesticide concentrations. Incorporating these real-world probabilities of crop occurrence and proximity showed that, while potential maximal aquatic exposure concentrations are unchanged, the probability of exceeding regulatory decision-making concentration endpoints is much lower than predicted by standard assumptions (e.g., 1.9 to ~50-fold reductions by crop for 90% of catchments). Additionally, we show that the relative ranking of crops by their aquatic pesticide exposure potential may change from that indicated when cropping density and proximity are considered

Putting It in Writing: Purpose and Best Practices of Letter-to-File for Medical Devices

In the medical device industry, the practice of creating a "Letter to File," "Note to File," or "Memo to File" is employed to document modifications to a device in the USA for regulatory and compliance purposes. Although the U.S. Food and Drug Administration (FDA) have provided guidance on this topic over the years, there has not been a thorough exploration of this concept. Medical device manufacturers frequently make changes to their FDA-cleared products, but determining whether to handle the change internally using a Letter to File or notify the FDA can be unclear. This article provides a comprehensive overview of what a Letter to File is, the purpose of writing one, and the appropriate situations in which a company might use it. Additionally, it also discusses the contents of a typical Letter to File, including the necessary elements and the best practices for writing it effectively and consequences of making the wrong decision. By providing guidance on the Letter to File process, this article aims to assist professionals in the medical device industry in maintaining precise records that can support their organizations in any regulatory situation