FDA CAUGHT IN POLITICAL CROSSFIRE

FDA's oversight of medical devices and diagnostics has put it in the hot seat for shortages of critical products for protecting medical personnel and for providing fast and accurate public testing for COVID infection. The result is that the White House has delayed in selecting an FDA commissioner, even though federal rules require Woodcock to vacate her acting position by mid-November unless the administration nominates a new commissioner, permitting her to continue on during the Senate confirmation process. The approval decision by CDER officials was blasted by members of Congress, the medical community and even some patient groups, but justified by the reviewers as likely to provide some benefit to some patients who lacked any alternative treatment for this devastating disease.

Can Pharma Quality Go High Tech?

"There were questions of how to handle tech transfer, factory and site acceptance tests, and regulatory inspections when the world was no longer travelling," he says. Since July, Stracquantanio says, usage of the platform has expanded by a factor of 17, and new site deployments by a factor of ten. The company is now using the remote approach with all major global regulatory agencies. Since Catalent hosts or performs more than 500 audits each year, new technology has allowed Catalent to keep pace, while observing social distancing requirements, Montano adds. Live facility tours are filmed with a 360-degree camera, and 3-D tours with a 3-D mapping camera, says Sandy Immerman, vice president of Information Technology (IT), Pharma Services. [...]this year, Immerman says, Thermo Fisher has hosted multiple regulatory inspections and more than 125 client audits, focusing efforts on current good manufacturing practice (CGMP) activities in work that has involved FDA, the European Medicines Agency, which issued formal guidance on the use of this technology last May (3), the Russian Ministry of Health (MoH), and the Swedish Medical Products Agency.

GERMANY'S HTA AGENCY SEEKS SUPPORT ON TRANSPARENCY ABOUT COVID-19 AGENTS

"EMA should support the international research community by publishing clinical study reports on medicine and vaccine trials at the time of marketing authorization and to inform treatment decisions." [...]Weiseler and Kaiser are acutely aware of the pressures that regulators are under in the face of a rising death toll, soaring infection and morbidity, and the wideranging economic and social consequences of extensive lock-downs. "Because of the severity of the current situation, regulators are aiming to accelerate the marketing authorization process," IQWiG comments, noting that first treatments have already been evaluated by regulators, as recently seen with the fast emergency use authorization of the antiviral remdesivir by the FDA, and that EMA has also started a "rolling review" of remdesivir. Data-sharing push The international research community is already undertaking coordinated efforts- IQWiG cites the living mapping and living systematic review of COVID-19 studies-to compile all emerging information on medicines and vaccines for the virus, it says, with a view to ensuring the optimal planning and conduct of research.

Adapting Regulations Post-Brexit

The UK government is taking advantage of the new regulatory flexibility, afforded by Brexit, to boost the country's competitiveness in pharma On 1 Jan. 2021, the United Kingdom formally left the European Union to become a third country and no longer a member of the Union's single market and customs union. The UK has, for example, decided to draw up its own version of the EU chemicals legislation-called REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals)-which sets technical standards for chemical ingredients for medicines (1). Because the UK is a separate legal entity-a third country-the UK's excipient producers and their raw material suppliers have started to be concerned about procedures like customs declarations and rules of origin. [...]by 18 Feb. 2021 the UK had vaccinated 26% of its population versus 8% in Denmark-the leading EU country for vaccines availability-6% in Germany, and 5% in France (6). NICE needs to change Industry believes that the National Institute for Health and Care Excellence (NICE), the government's health technology assessment (HTA) body, is being too restrictive with its evaluation of digitalization products, which ultimately sets the price paid by the government for them (9).

Inspecting GMP at a Distance

"The term 'virtual inspection' applies to inspections that are performed off-site through the use of enhanced communication and information technology to fulfil legal requirements of on-site inspections," IFMPA said in an updated document on virtual inspections in July (2). The European Medicines Agency (EMA), Heads of Medicines Agencies (HMA), representing national authorities, together with the European Commission have introduced a system during the pandemic under which the validity of GMP certificates for European manufacturing and importing sites for finished products and active substances will be extended to the end of 2021 (3). "The advantage of an assessment/inspection/ certification by a local inspectorate includes knowledge of the site-specific history, insight into culture, optimization of (regulatory agency) resources, and benefits from improved inspection logistics (e.g., no language barriers, less travel)," the EFPIA paper explained.

COVID-19 Stresses EMA Resources

EMA has pleaded with the European Commission (EC) for more funds to finance the costs of its increased duties (2). "The GMP standards will be applied to the manufacture of sterile vials for the vaccines as per standard requirements, regardless of location," said a spokesman for the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK, where a COVID-19 vaccine being jointly developed by AstraZeneca and Oxford University is considered likely to be among the first to gain authorization for mass distribution. Manufacturers of vaccines and their containers could be subject to two waves of standards-checking inspections- one for GMP and the other for pharmacovigilance. Because the latter will be the most extensive covering, for example, requiring surveillance quality systems in all the operations of a business, a manufacturer that is considered to be compliant with pharmacovigilance standards is unlikely to be breaching GMP rules. Other priorities include the work of key working parties and groups, drawing up of certain guidelines, the fight against anti-microbial resistance (AMR), co-operation with health technology assessment (HTA) bodies, innovation (especially in emerging therapies), clinical data publication, and international co-operation.

Quality Still a Priority

The quality of pharmaceutical products continued to be a focus, but many facility inspections were postponed in 2020, and US Food and Drug Administration (FDA) officials evaluated their inspection programmes during the pandemic and issued guidance for remote monitoring and other virtual activities (1-3). [...]responding to a 483 and/or warning letter requires familiarity with processes, systems, and data because a proper response should address how you are going to fix the situation observed, how you are going to prevent the situation observed from recurring, and why the situation observed did not impact the patient safety/product quality of the product that was released before the situation was corrected," says Schniepp. [...]a company must be able to demonstrate regular [documented] meetings between senior management and the quality department.

Fragmented Transparency: The Visibility of Agency Science in European Union Risk Regulation

Responding to mistrust in the European agencies' risk assessments in politically salient cases, the European Union (EU) legislator, the European Food Safety Authority and the European Medicines Agency alike have accelerated their efforts to foster EU regulatory science transparency. These simultaneous endeavours have, however, taken place in a fragmented legislative and administrative context, with each agency operating under a different legal framework. By focusing on authorisation procedures, from registration of studies to authorisation of novel foods, pesticides and human medicines, this article examines the resulting regimes governing the disclosure of scientific data by EU agencies to identify common trends and sectoral specificities. Against the background of an overall shift towards enhanced transparency, we shed light on, first, the circulation of institutional arrangements and practices among agencies and, second, the new dimensions of transparency emerging from these developments. We also highlight the remaining sectoral differences and argue that they could have potentially large impacts on the amount and type of information disclosed and on the level of transparency perceived by stakeholders and citizens. We argue that more coherence across the sectoral transparency regimes is needed, in particular in light of the agencies' contested legitimacy and of their increasing cooperation on cross-cutting issues like antimicrobial resistance and medicine and pesticide residues in food.

Seven days in medicine: 6-12 May 2020

In a report summarising the feedback it had received,2 the charity noted a litany of "horrendous” safety concerns, as workers were concerned about a lack of personal protective equipment and about their mental health. NICE: assess covid patients for kidney injury Patients with suspected or confirmed covid-19 should be assessed for acute kidney injury (AKI) on hospital admission or transfer, said the National Institute for Health and Care Excellence (NICE). In a new guideline aimed at healthcare professionals who are not kidney specialists, the institute said that patients with suspected or confirmed covid-19 should be monitored for AKI throughout their stay in hospital and managed appropriately if it develops.

Drug Discovery and Big Data: From Research to the Community

Technology and artificial intelligence, alongside the COVID-19 pandemic vastly increasing technology use in health care, have precipitated an escalation of big data. Although real-world data (RWD) and real-world evidence (RWE) have contributed to determining outcomes outside the scope of randomized clinical trials (RCTs), RWD and RWE are underutilized in demonstrating drug effectiveness. Utilizing RWD may enhance the ability of regulatory agencies to approve drugs, provide drug effectiveness insight to payers, and improve personalized medicine. Additionally, RWD and RWE may assist in overcoming the limitations of RCT data such as treatment adherence and underrepresented patient subgroups and may support and expedite drug repositioning. Even though the limitations of using RWE and RWD include fragmented data context, poor data quality, and information governance, healthcare analytics hubs such as the European Health Data Space are designed to foster synergy among private and public healthcare players and may assist in overcoming these potential limitations. Such healthcare analytics hubs may enhance the utilization of RWE and/or RWD, which could ultimately result in better patient outcomes. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Identifying Critical Factors Affecting the Resilience of Additive Manufacturing Architecture Supply Chain

Building a resilient and stable supply chain has become an important strategy for many countries. Studies have shown that the application of additive manufacturing (AM) technology in construction can help offset the negative impact of "black swan events” on supply chains. This study examines the construction industry based on AM technology and analyzes the impact of changes in the industry chain on the supply chains. The specific factors that affect the resilience of AM construction supply chains were identified through literature research and expert interviews, including 7 dimensions and 21 secondary indicators. An intuitionistic fuzzy analytic hierarchy process (IFAHP) evaluation model was established. Finally, an example of an AM construction manufacturer, YC Enterprise, was introduced to quantify the various factors and determine the weights. The results show that the essence of building a supply chain with AM is creating a closed-loop supply chain. The impact of AM construction manufacturers on supply chain resilience (SCR) is the most critical, followed by that of regulatory authorities and general contractors. The AM construction SCR assessment index system and evaluation method constructed in this paper have important significance in filling the gap in the quantitative evaluation of the impact of AM on supply chains.

Customer Attitude toward Digital Wallet Services

The goal of this study is to examine and identify the factors influencing customer attitude toward and intention to use digital wallets (electronic wallets, e-wallets) during and after the COVID-19 pandemic. A total of 257 correctly fulfilled questionnaires from an online survey were summarized. The main features of e-wallet payment systems were classified with a focus on consumer satisfaction via the integration of classic and modern data analysis methods. Structural Equation Modeling (SEM) was preferred to reveal the dependencies between the variables from e-wallets users' perspective. The designed model can discover and explain the underlying relationships that determine the e-wallets' adoption mechanism. The obtained results lead to specific recommendations to stakeholders in the value chain of payment processing. Financial regulatory authorities could employ the presented results in planning the development of payment systems. E-commerce marketers could utilize the proposed methodology to assess, compare and select an alternative way for order payment. E-wallet service providers could establish a reliable multi-criteria system for the evaluation of digital wallet adoption. Being aware of the most important components of e-wallets value, managers can more effectively run and control payment platforms, enhance customer experience, and thus improve the company's competitiveness. As the perceived value of customer satisfaction is subjective and dynamic, measurements and data analysis should be conducted periodically.

Religion vs ethics: hedge and safe haven properties of Sukuk and green bonds for stock markets pre- and during COVID-19

PurposeThis study aims to examine the hedge and safe-haven properties of the Sukuk and green bond for the stock markets pre- and during the COVID-19 pandemic period.Design/methodology/approachTo test the hedge and safe-haven characteristics of Sukuk and green bonds for stock markets, the study first uses the methodology proposed by Ratner and Chiu (2013). Next, the authors estimate the hedge ratios and hedge effectiveness of using Sukuk and green bonds in a portfolio with stock markets.FindingsStrong safe-haven features of ethical (green) bonds reveal that adding green bonds into the investment portfolios brings considerable diversification avenues for the investors who tend to take fewer risks in periods of economic stress and turbulence. The hedge ratio and hedge effectiveness estimates reveal that green bonds provide sufficient evidence of the hedge effectiveness for various international stocks.Practical implicationsThe study has significant implications for faith-based investors, ethical investors, policymakers and regulatory bodies. Religious investors can invest in Sukuk to relish low-risk and interest-free investments, whereas green investors can satisfy their socially responsible motives by investing in these investment streams. Policymakers can direct the businesses to include these diversifiers for portfolio and risk management.Originality/valueThe study provides novel insights in the testing hedge and safe-haven attributes of green bonds and Sukuk while using unique methodologies to identify multiple low-risk investors for investors following the uncertain COVID-19 pandemic.

News in brief

[...]there's no guidance." On 1 May, the US Food and Drug Administration (FDA) granted an 'emergency-use authorization' for clinicians to use the drug, which is administered intravenously, in hospitals for people with severe COVID-19. On 29 April, Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID), said that the latest clinical trial, involving more than 1,000 people, showed that those taking remdesivir recovered in 11 days on average, compared with 15 days for those on a placebo.

Post-pandemic comeback and breakthroughs for electric flight

Miller discusses post-pandemic comeback and breakthroughs for electric flight. In May, Federal Aviation Administration (FAA) released its Air Traffic by the Numbers with updated data for 2021. The covid-19 pandemic continued to suppress the general aviation community, but there were signs of improvement. In 2020, there were 204,100 active general aviation aircraft across the US. In 2021, active pilot certificates increased by 4.2% in 2021 to 720,603;drone pilot certificates increased by 23.4% to 254,587. There are 5,184 public-use airports and 14,539 private-use airports across the country. General aviation is the manufacturing and operation of aircraft that have been issued an airworthiness certificate by the FAA--other than aircraft used for scheduled commercial air service or operated by the military--and includes on-demand Federal Aviation Regulations Part 135 operations.

Editorial - RAEP 2nd edition 2022

[...]in recognition of the importance of the work of academics who have supported the journal, especially in its early stages, an Honorary Board was created, keeping them in evidence and with fair recognition for their support. Undoubtedly, the pandemic as a context challenged professionals in different spectrums. [...]the importance of the investigation was to highlight the need for awareness and prevention of depression in graduate students, as well as the adoption of effective strategies for its confrontation in general, that is, even after the pandemic period. Besides this regional diversity, we must recognize the distinct public and private educational institutions that collaborated to make this publication possible.

Vaccine development

The Center for Biologics Evaluation and Research, established by the FDA in 1987, has rigorously evaluated the use of vaccines in the United States for the past 35 years.1,2 The details of vaccine evaluation are well documented in the Code of Federal Regulations (Title 21), and FDA guidance documents that form the "Bible" for vaccine manufacturers (known as sponsors) to follow.3 The guiding principles for vaccine evaluation can be summed up in 3 words-safety, efficacy, and quality. Vaccine development first begins in the laboratory, where the goal of basic research is to understand the complex interactions between pathogens and their human hosts and to generate the knowledge and technology essential for developing a vaccine candidate.5 In advancing the development of a vaccine candidate, scientists build on the extensive research accumulated from the development of more than 80 vaccines currently licensed in the United States and elsewhere while also accessing new technological advances, including improvements in adjuvants and the development of mRNA technology, used in several COVID-19 vaccines.6-8 Preclinical testing in nonhumans Before any vaccine is tested in humans, preclinical research, involving animal studies (eg, with rodents or nonhuman primates) and/or in vitro testing is required. All human studies are required to be conducted under Good Clinical Practice (GCP) regulations established by the FDA as well as the Declaration of Helsinki, a statement of ethical principles for medical research first written in 1964.11,12 The safety and human rights of study participants are rigorously enforced in every clinical trial through well-defined processes for informed consent, study oversight, and protection of privacy. Most vaccines have been required to have a prelicensure safety database of at least 3000 participants vaccinated with the dosing regimen intended for licensure.13 Assessment of safety in 3000 individuals allows for a 95% chance of detecting the occurrence of more common adverse events in 1 in 1000 participants (the "rule of 3").14 The COVID-19 trials for mRNA vacci nes for adults were considerably larger (> 15,000 and > 13,000 vaccine recipients followed for safety);subsequent studies to authorize use in children aged 6 months to 4 to 5 years involved several thousand children followed for a median of 2 months.7,8,15,16 Clinical trials for other vaccines have included safet y data on more than 5900 infants for the pen-tavalent DTaP, IPV, Hib-combina-tion vaccine, more than 7000 infants and toddlers for 3 pneumococcal conjugate vaccines, and more than 15,000 children and young adults (8-26 years) for 3 HPV vaccines.17-19 The FDA may request a larger safety database if a possible safety signal is identified or in response to new information from other vaccines.

Assessment of the Quality of MedDRA Coding in a Sample of COVID-19 Vaccine Medication Error Data: An International Journal of Medical Toxicology and Drug Experience

Introduction: High interest in the last two years was globally put by Health Authorities on the recording, coding, and reporting of medication errors to ensure the safety and effectiveness of the use of medicines and to provide reliable information to healthcare professionals and patients. Medical coding is a prerequisite for efficient, effective, and reproducible data outputs. Objective: Not applicable. Methods: A sample of medication error coding results was assessed for accuracy and consistency of MedDRA coding and identification of main types of coding errors. It included 1500 coded reported terms for COVID-19 vaccines medication errors, assigned to MedDRA codes by national regulatory authorities or pharmacovigilance centers and drawn from the Uppsala Monitoring Centre (UMC) VigiBase through August 25, 2021. Results: One-third of the records could not be assessed due to incomplete or unclear verbatims. In one-third, code assignments were correct, but another third of the sample was not adequately coded. Most frequent coding errors corresponded to vague PT assignments, while more detailed information was available for a more precise coding. This observation is similar to the EudraVigilance database, where some of the most assigned MedDRA terms for medication errors also represent vague concepts. Conclusion: These findings indicate that understanding of medication error documentation and assessment and of MedDRA content and coding guidelines need to be reinforced. The MedDRA Maintenance and Support Services Organization (MSSO) offers several MedDRA coding trainings, including coding of medication errors. The authors provide valuable references to the latter, to the applicable ICHEndorsed Guides for MedDRA Users, and to relevant EMA guidance.

COVID-19 Pandemic: A Surge in Counterfeit Medicines: An International Journal of Medical Toxicology and Drug Experience

Introduction: Falsified medical products may contain no active ingredient, the wrong active ingredient, or the wrong amount of the correct active ingredient [1]. The prevalence of falsified medicines spans from 1% in developed settings to 10% in the Global South [2]. Due to broken supply chains, strong demand for medicines and limited capacities of law enforcement, the COVID-19 pandemic created the optimal conditions for the falsified medicines' market to expand. Objective: Aim of this is to present evidence about the surge in counterfeit medicines amid the COVID-19 crisis. Methods: This review examines the existing published scientific literature and peer-to-peer networks, grey literature as well as briefs and policy reports on counterfeit medicines amid COVID-19 pandemic. Results: According to EOCD, People's Republic of China and India are the primary producers of counterfeit medicines, with the United Arab Emirates, Singapore and Hong Kong (China) serving as transit economies [3]. The review has identified three areas of impact for counterfeit medicines amid COVID-19. These are: (i) the increased demand for COVID-19-reated medicines, due to the medical supply restrictions related to the pandemic. These restrictions have been introduced by local authorities (e.g. supply restriction for Chloroquine and Azithromycin) or occurred because of air traffic reduction. Over 60 countries have implemented export restrictions and 25% of restricted products were medicines [4];(ii) E-commerce as a relevant platform for substandard medicines. For instance, advertisements of illicit COVD-19-related medical products have been reported on social media platforms, such as Instagram. According to the industry, online distribution becomes predominant and about 50% of purchases of illicit medicines are done on-line [5];(iii) weak regulatory frameworks, including insufficient technical capacity, constrained access and ineffective over-sight to address substandard and falsified medical products. WHO reports that 30 per cent of national regulatory authorities do not have full effective capacity to perform their functions [6]. Conclusion: COVID-19 pandemic has increased the vulnerability to counterfeit medicines, leading to serious damage to the health of individuals or failure to treat their medical needs adequately. The identifies three relevant governance gaps (increased demand, E-commerce and weak regulatory frameworks) to be further addressed in dedicated fora.