Regulatory performance of the East African Community joint assessment procedure: The way forward for regulatory systems strengthening.

BACKGROUND: Seven national medicines regulatory authorities in the East African Community (EAC) have embraced regulatory reliance, harmonization and work sharing through the EAC Medicines Regulatory Harmonization programme. Measuring the performance of regulatory systems provides key baseline information to build on regulatory system-strengthening strategies. Therefore, the aim of the study was to evaluate the regulatory performance of the EAC joint scientific assessment of applications approved between 2018 and 2021. METHODS: Utilising a data metrics tool, information was collected reflecting timelines for various milestones including submission to screening, scientific assessment and communication of regional recommendations for biologicals and pharmaceuticals that received a positive regional recommendation for product registration from 2018 to 2021. RESULTS: Several challenges as well as possible solutions were identified, including median overall approval times exceeding the EAC 465-day target and median times to issue marketing authorisation following EAC joint assessment recommendation that far exceeded the 116-day target. Recommendations included establishment of an integrated information management system and automation of the capture of regulatory timelines through the EAC metric tool. CONCLUSIONS: Despite initiative progress, work is required to improve the EAC joint regulatory procedure to achieve regulatory systems-strengthening and ensure patients' timely access to safe, efficacious and quality medicines.

PMDA's Vision for Horizon Scanning of Emerging Technologies Potentially Relevant to the Development of New Medical Products: The Regulatory Challenge.

A key goal of regulatory agencies for medical products is to make innovative products available to patients and the medical community in a timely manner in order to improve the quality of public health and health care. Thus, regulators must respond quickly to emerging technologies. It is a horizon scanning method, based on which the Japanese regulatory agency will have the expertise prior to review of forthcoming products of evolving technologies.

Project Orbis: Global Collaborative Review Program.

In 2019, the FDA Oncology Center of Excellence launched Project Orbis, a global collaborative review program to facilitate faster patient access to innovative cancer therapies across multiple countries. Project Orbis aims for concurrent submission, review, and regulatory action for high-impact clinically significant marketing applications among the participating partner countries. Current Project Orbis partners (POP) include the regulatory health authorities (RHA) of Australia, Brazil, Canada, Singapore, and Switzerland. Project Orbis leverages the existing scientific and regulatory partnerships between the various RHA under mutual confidentiality agreements. While FDA serves as the primary coordinator for application selection and review, each country remains fully independent on their final regulatory decision. In the first year of Project Orbis (June 2019 to June 2020), a total of 60 oncology marketing applications were received, representing 16 unique projects, and resulting in 38 approvals. New molecular entities, also known as new active substances, comprised 28% of the received marketing applications. The median time gap between FDA and Orbis submission dates was 0.6 months with a range of -0.8 to 9.0 months. Across the program, the median time-to-approval was similar between FDA (4.2 months, range 0.9-6.9, N = 18) and the POP (4.4 months, range 1.7-6.8, N = 20). Participating countries have signified a strong commitment for continuation and growth of the program. Project Orbis expansion considerations include the addition of more countries and management of more complex applications.

The Current State of Opioid Prescribing and Drug Enforcement Agency (DEA) Action Against Physicians: An Analysis of DEA Database 2004-2017.

BACKGROUND: Prescribing opioids has become a challenge. The US Drug Enforcement Agency (DEA) and Centers for Disease Control and Prevention (CDC) have become more involved, culminating in the March 2016 release of the CDC's "Guidelines for Prescribing Opioids for Chronic Pain." OBJECTIVES: Given the new guidelines, we wanted to see if there have been any changes in the numbers, demographics, physician risk factors, charges, and sanctions involving the DEA against physicians who prescribe opioids, when compared to a previous DEA database review from 1998 to 2006. STUDY DESIGN: This study involved an analysis of the DEA database from 2004 to 2017. SETTING: The review was conducted at the Henry Ford Health System Division of Pain Medicine. METHOD: After institutional review board approval at Henry Ford Health System, an analysis of the DEA database of criminal prosecutions of physician registrants from 2004-2017 was performed. The database was reviewed for demographic information such as age, gender, type of degree (doctor of medicine [MD] or doctor of osteopathic medicine [DO]), years of practice, state, charges, and outcome of prosecution (probation, sentencing, and length of sentencing). An internet-based search was performed on each registrant to obtain demographic data on specialty, years of practice, type of medical school (US vs foreign), board certification, and type of employment (private vs employed). RESULTS: Between 2004 and 2017, Pain Medicine (PM) had the highest percentage of in-specialty action at 0.11% (n = 5). There was an average of 18 prosecutions per year vs 14 in the previous review. Demographic risk factors for prosecution demonstrated the significance of the type of degree (MD vs. DO), gender, type of employment (private vs. employed), and board certification status for rates of prosecution. Having a DO degree and being male were associated with significantly higher risk as well as being in private practice and not having board certification (P < .001). In terms of type of criminal charges as a percent of cases, possession with intent to distribute (n = 90) was most prevalent, representing 52.3% of charges, with new charges being prescribing without medical purpose outside the usual course of practice (n = 71) representing 41.3% of charges. Comparison of US graduates (MD/DO) vs. foreign graduates showed higher rates of DEA action for foreign graduates but this was of borderline significance (P = .072). LIMITATIONS: State-by-state comparisons could not be made. Specialty type was sometimes self-reported, and information on all opioid prosecutions could not be obtained. The previous study by Goldenbaum et al included data beyond DEA prosecution, so direct comparisons may be limited. CONCLUSION: The overall risk of DEA action as a percentage of total physicians is small but not insignificant. The overall rates of DEA prosecution have increased. New risk factors include type of degree (DO vs. MD) and being in private practice with a subtle trend toward foreign graduates at higher risk. With the trend toward less prescribing by previously high-risk specialties such as Family Medicine, there has been an increase in the relative risk of DEA action for specialties treating patients with pain such as PM, Physical Medicine and Rehabilitation, neurology, and neurosurgery bearing the brunt of prosecutions. New, more subtle charges have been added involving interpretation of the medical purpose of opioids and standard of care for their use. KEY WORDS: Certification, CDC, criminal, DEA, opioid, prescribing, prosecution, sanctions.

New Japanese Regulatory Frameworks for Post-Marketing Management of Pharmaceutical Products.

Dossiers on approved pharmaceutical products must be kept updated and current during the products' life cycles. The coalition, merger and acquisition along with corporate strategy that pursues efficiency and profitability of pharmaceutical companies have led to the globalization of supply chains for pharmaceutical ingredients and instruments in the post-marketing phase, and progress in manufacturing technologies can improve manufacturing processes during this phase. Regulatory requirements for post-marketing management of pharmaceutical products sometimes differ among countries around the world depending on national/regional policies or situations, even though the basic concepts of each regulation are the same. Therefore, an understanding of up-to-date region specific regulatory management frameworks is important for the optimal provision of pharmaceutical products by pharmaceutical industries. The amendment of the Japanese Pharmaceutical and Medical Device Act (Act No. 63 of 2019) was promulgated in December 2019, and will be enforced from September 2020 onwards. The amended Act sets out regulatory frameworks for post-marketing management systems, including inspection for good manufacturing practice of drugs, quasi-drugs, and gene-, cell-, and tissue-based products; and post-approval change-management protocols. Here, we review these new Japanese post-marketing management frameworks.

Adaptation of Animal and Human Health Surveillance Systems for Vector-Borne Diseases Accompanying Climate Change.

Anthropogenic climate change is causing temperature rise in temperate zones resulting in climate conditions more similar to subtropical zones. As a result, rising temperatures increase the range of disease-carrying insects to new areas outside of subtropical zones, and increased precipitation causes flooding that is more hospitable for vector breeding. State governments, the federal government, and governmental agencies, like the Animal and Plant Health Inspection Service (APHIS) of USDA and the National Notifiable Disease Surveillance System (NNDSS) of the U.S. Centers for Disease Control and Prevention, lack a coordinated plan for vector-borne disease accompanying climate change. APHIS focuses its surveillance primarily on the effect of illness on agricultural production, while NNDSS focuses on the emergence of pathogens affecting human health. This article provides an analysis of the current framework of surveillance of, and response to, vector-borne infectious diseases, the impacts of climate change on the spread of vector-borne infectious diseases, and recommends changes to federal law to address these threats.

Nationwide Survey on Implementation of 2011 Nuclear Regulatory Commission Policy on Release of Patients After 131I Therapy for Thyroid Cancer.

The objective of this nationwide survey was to evaluate whether there has been a change in the practice regarding hospital release of differentiated thyroid cancer patients treated with 131I since the publication of Nuclear Regulatory Commission Regulatory Issue Summary 2011-01 addressing patient release. Methods: A survey was emailed to approximately 25,000 members of ThyCa: Thyroid Cancer Survivors' Association, Inc., and was available online from March to August 2018. Responses were included from adult patients regarding their most recent 131I therapy received between 2011 and 2018 ("after 2011"). Responses to this survey were compared with those of a similar previous survey for 131I therapies received between 1997 and 2009 ("before 2009"). Results: Of the 2,136 responses, 1,111 met the inclusion criteria. A similar percentage (∼98%) of patients were given oral or written radiation safety instructions (RSIs) after 2011 and before 2009, with a shift away from nuclear medicine physicians providing instructions after 2011 (43%) in comparison with before 2009 (54%; P < 0.001). More patients were able to discuss and individualize the RSIs after 2011 (67%) than before 2009 (29%; P < 0.001). However, 2% of patients do not recall ever receiving RSIs after 2011. After 2011, more patients were treated as outpatients (87%) than before 2009 (66%; P < 0.001). For outpatients, more patients were discharged within 30 min after receiving 131I therapy after 2011 (78%) than before 2009 (72%; P = 0.002). The same percentage (0.6%) of patients traveled more than 2 h with at least 2 occupants in the vehicle within approximately 1 m of the patient after 2011 and before 2009. Immediately after therapy, a similar percentage of patients stayed in a nonprivate residence after 2011 (4%) and before 2009 (5%; P = 0.28). Of the 27 outpatients released within 30 min to nonprivate residences, 2 patients received 5.55-11.1 GBq (150-299 mCi) of 131I. Conclusion: This survey suggests that since publication of the Nuclear Regulatory Commission Regulatory Issue Summary 2011-01 on patient release after radioiodine therapy, there have been improvements in some radiation safety practices on release of outpatients, as well as improvements in patient compliance on travel and lodging.

Training and Education Requirements for Authorized Users of Therapeutic Radiopharmaceuticals: Changes Under Consideration for 10CFR35.390 and Their Potential Impact.

The US Nuclear Regulatory Commission (NRC) and 38 Agreement States have the regulatory authority to promulgate and enforce regulations related to the use of radioisotopes for medical purposes. Elements of these regulations include training and experience (T&E) requirements for individuals authorized to use the agents. These regulations are specified in 10CFR35.390. At this time, the NRC is considering significant revisions to the T&E requirements. This article describes current regulations and concerns related to the proposed changes and details the ACR organizational response.

The requirements for manufacturing highly active or sensitising drugs comparing Good Manufacturing Practices.

BACKGROUND: To date there exist no internationally recognised Good Manufacturing Practices (GMP) that clearly outline universally accepted standards for manufacturing highly active or sensitising ingredients. The pharmaceutical industry is faced with a twofold problem: determining which drugs need dedicated production areas and identifying the different regulations required in different countries. The aim of this paper is to find, by comparing the current regulations of the various Regulatory Agencies, the differences between containment requirements for the production of highly active or sensitising ingredients. METHODS: An analysis of the following Regulatory Agencies' GMPs was performed: Europe (EMA), China (CFDA), Mexico (COFEPRIS), United States (FDA), Canada (Health Canada) Brazil (ANVISA), India (CDSCO), PIC/S and WHO in order to examine the differences in terms of  containment requirements set by the different Regulatory Authorities for the manufacture of highly active or sensitising ingredients. RESULTS: Our analysis found that the majority of Regulatory Agencies require that beta-lactams (sensitising materials) be produced in dedicated and segregated facilities. For "certain" highly active pharmaceutical ingredients (APIs), COFEPRIS, FDA, HC, EMA, PIC/S and WHO require that they be produced in facilities similar to those required for beta-lactams, while CDSCO, CFDA and ANVISA require that production takes place in segregated areas. Further differences between the Agencies  have emerged regarding classes of highly APIs that require dedicated production. CONCLUSION: A study of GMP adopted by Regulatory Agencies has uncovered significant differences, in particular concerning containment requirements for the production of APIs. For this reason, the harmonisation of GMP following  up-to-date quality standards based on cutting-edge science which are globally applicable is fundamental and will benefit companies and patients alike. Pharmaceutical companies would not be obliged to follow requirements enforced by the State in which they intend to manufacture a product, and patients would benefit from high-quality drugs regardless of their place of production.