Evaluation of Risk-Based Approaches to the Registration of Medicines: Current Status Among African Regulatory Authorities.

BACKGROUND: Despite the worldwide need for increased access to safe and effective medicines, there is a lack of innovative medicines in many low- to middle-income countries. On the African continent, this is partly due to capacity limitations of National Regulatory Authorities (NRAs). One important approach to address this issue is work sharing and regulatory reliance. Therefore, the aim of this study of regulatory authorities on the African continent was to identify which risk-based approaches are being used as well as their foreseen role in the future. METHODS: The study employed a questionnaire to identify which risk-based models are used for the regulatory approval of medicines and to determine which frameworks are in place to enable a risk-based approach, as well as to provide insight into the future direction for risk-based models. The questionnaire was sent electronically to 26 NRAs in the African Continent. RESULTS: Twenty-one authorities (80%) completed the questionnaire. Work sharing was the most commonly used model, followed closely by unilaterial reliance, information sharing, and collaborative review. These methods were perceived to be an effective and efficient use of resources, enabling faster medicine availability for patients. The unilateral reliance approach by the authorities included abridged (85%), verification (70%) and recognition (50%) models for a range of products. However, challenges included a lack of guidelines to undertake a reliance review together with resource constraints, while access to assessment reports was the most common barrier to using a unilateral reliance model. CONCLUSIONS: Many authorities in Africa have adopted a risk-based approach to medicines registration and created work sharing, unilateral reliance pathways and regionalisation models to facilitate the availability of medicines. The authorities believe that in future, assessment routes should move from stand-alone reviews to risk-based models. However, this study indicated that there would be challenges to implement this approach in practice, which would include improving resource capacity and the number of expert reviewers as well as implementing electronic tracking systems.

Does India need a new pharmaceutical policy? Examining the implications of the drug price control order.

OBJECTIVES: This article aims to analyse the impact of the pharmaceutical policy on the availability, accessibility and affordability of medicines to the Indian populace. The article delves into the shortcomings of the Drug Price Control Order 2013 and highlights its real-world implications. METHODS: Published literature in the form of scientific articles on the proposed reforms that took place in the pharmaceutical policy was reviewed. The study used the memorandums, laws and government decisions published by the Department of Pharmaceuticals, Ministry of Health and Family Welfare and National Pharmaceutical Pricing Authority|National Pharmaceutical Pricing Authorities. RESULTS: The pharmaceutical policy in India underwent several changes during 2013-2020 to enhance the affordability and accessibility of drugs. The stringent policy hampered innovation due to the lack of profitability to the Multinational Companies. Moreover, it was found that the impact of the price control order on the low-cost local generic manufacturers affected much of the country's price-sensitive population. CONCLUSION: The pharmaceutical policy of India needs to be amended to extend its benefit to its stakeholders. The government should shift its attention to improving the quality of drugs, increasing competition amongst manufacturers and enhancing the accessibility of medicines through state/centre sponsored initiatives.

COVID-19 Treatments Sold Online Without Prescription Requirements in the United States: Cross-sectional Study Evaluating Availability, Safety and Marketing of Medications.

BACKGROUND: The COVID-19 pandemic has increased online purchases and heightened interest in existing treatments. Dexamethasone, hydroxychloroquine, and lopinavir-ritonavir have been touted as potential COVID-19 treatments. OBJECTIVE: This study assessed the availability of 3 potential COVID-19 treatments online and evaluated the safety and marketing characteristics of websites selling these products during the pandemic. METHODS: A cross-sectional study was conducted in the months of June 2020 to August 2020, by searching the first 100 results on Google, Bing, and Yahoo! mimicking a US consumer. Unique websites were included if they sold targeted medicines, were in English, offered US shipping, and were free to access. Identified online pharmacies were categorized as rogue, unclassified, or legitimate based on LegitScript classifications. Patient safety characteristics, marketing techniques, price, legitimacy, IP addresses, and COVID-19 mentions were recorded. RESULTS: We found 117 websites: 30 selling dexamethasone (19/30, 63% rogue), 39 selling hydroxychloroquine (22/39, 56% rogue), and 48 selling lopinavir-ritonavir (33/48, 69% rogue). This included 89 unique online pharmacies: 70% were rogue (n=62), 22% were unapproved (n=20), and 8% were considered legitimate (n=7). Prescriptions were not required among 100% (19/19), 61% (20/33), and 50% (11/22) of rogue websites selling dexamethasone, lopinavir-ritonavir, and hydroxychloroquine, respectively. Overall, only 32% (24/74) of rogue websites required prescriptions to buy these medications compared with 94% (31/33) of unapproved and 100% (10/10) of legitimate websites (P<.001). Rogue sites rarely offered pharmacist counseling (1/33, 3% for lopinavir-ritonavir to 2/22, 9% for hydroxychloroquine). Drug warnings were unavailable in 86% (6/7) of unapproved dexamethasone sites. It was difficult to distinguish between rogue, unapproved, and legitimate online pharmacies solely based on website marketing characteristics. Illegitimate pharmacies were more likely to offer bulk discounts and claim price discounts, yet dexamethasone and hydroxychloroquine were more expensive online. An inexpensive generic version of lopinavir-ritonavir that is not authorized for use in the United States was available online offering US shipping. Some websites claimed hydroxychloroquine and lopinavir-ritonavir were effective COVID-19 treatments despite lack of scientific evidence. In comparing IP addresses to locations claimed on the websites, only 8.5% (7/82) matched their claimed locations. CONCLUSIONS: The lack of safety measures by illegitimate online pharmacies endanger patients, facilitating access to medications without appropriate oversight by health care providers to monitor clinical response, drug interactions, and adverse effects. We demonstrated how easy it is to go online to buy medications that are touted to treat COVID-19 even when current clinical evidence does not support their use for self-treatment. We documented that illegitimate online pharmacies sidestep prescription requirements, skirt pharmacist counseling, and make false claims regarding efficacy for COVID-19 treatment. Health care professionals must urgently educate the public of the dangers of purchasing drugs from illegitimate websites and highlight the importance of seeking treatment through authentic avenues of care.

Japan's Special Approval for Emergency System During the COVID-19 Pandemic.

The development of drugs for coronavirus disease 2019 (COVID-19) is a global challenge. In Japan, remdesivir was approved in May 2020 for COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2021, a vaccine against COVID-19 was approved. These two approvals were made using the Special Approval for Emergency system in Japan. This Japanese system was started in 2010 and has been used to approve four drugs to date, including remdesivir and the Pfizer COVID-19 vaccine. This paper discusses future challenges for Japan's Special Approval for Emergency system and organizes what can be learned from experiences to date. As a result, I would like to point Out the following issues. (i) Special Approval for Emergency is a system for approving drugs approved overseas, not a system for approving drugs originally developed in Japan. A system to approve drugs that have not been approved in foreign countries needs to be considered. (ii) In the Special Approval for Emergency system, it is necessary to ensure that postmarketing activities are conducted in accordance with the Risk Management Plan and the conditions of approval, to disclose the results in a timely and speedy manner, and to judge the appropriateness of continued approval based on the results of postmarketing activities.

From sandbox to pandemic: Agile reform of Canadian drug regulation.

Public health urgency for emerging COVID-19 treatments and vaccines challenges regulators worldwide to ensure safety and efficacy while expediting approval. In Canada, legislative amendments by 2019 Omnibus Bill C-97 created a new "agile" licensing framework known as the "Advanced Therapeutic Pathway" (ATPathway) and modernized the regulation of clinical trials of drugs, vaccines, and medical devices. Bill C-97's amendments are worthy of attention in Canada and globally, as health product regulation bends to COVID-19. The amendments follow reforms elsewhere to accommodate health product innovation, however, the Canadian ATPathway is broader and more flexible than its counterparts in other jurisdictions. In addition, Bill C-97 informed Canada's COVID-19 response in important ways, particularly in relation to clinical trials. The measures adopted by the drug regulatory authority, Health Canada (HC) during COVID-19 may become the new norm in Canadian regulatory practice insofar as they help achieve the amendments introduced by Bill C-97. Finally, despite government rhetoric of transparency, the agenda-setting, formulation, and implementation of the amendments have occurred with little opportunity for scrutiny or public engagement.

"It was close enough, but it wasn't close enough": A qualitative exploration of the impact of direct-to-patient telemedicine abortion on access to abortion care.

OBJECTIVE: To understand how obtaining a medication abortion by mail with telemedicine counseling versus traditional in-clinic care impacted participants' access to care. STUDY DESIGN: We conducted a qualitative study with semi-structured telephone interviews with individuals who completed a medication abortion by mail through the TelAbortion study. We asked participants how they learned about telemedicine abortion, reasons for choosing it, what their alternative would have been, and about their experience. We transcribed, coded, and performed qualitative content analysis of the interviews and are presenting a subset of themes related to access to care when the restrictions on clinic dispensing of mifepristone are removed. RESULTS: We interviewed 45 people from January to July 2020. Direct-to-patient telemedicine abortion was more convenient and accessible than in-clinic abortion care when considering the burdens of travel, clinic availability, logistics, and cost that were associated with in-clinic abortion. Stigma led to a prioritization of privacy, and by going to a clinic, participants feared a loss of privacy whereas obtaining a medication abortion by mail made it easier to maintain confidentiality. Faced with these barriers, 13% of participants stated they would have continued their pregnancy if TelAbortion had not been an option. Participants found direct-to-patient telemedicine abortion to be acceptable and recommended it to others. Benefits of telemedicine were amplified during the COVID-19 pandemic due to concerns around infection exposure with in-clinic care. CONCLUSION: Going to a clinic was a burden for participants, to the point where some would not have otherwise been able to get an abortion. Medication abortion by mail with telemedicine counseling was a highly acceptable alternative. IMPLICATIONS: Medication abortion by mail can increase access to abortion with the added benefits of increased perceived privacy and decreased logistical burdens. Removing the in-person dispensing requirement for mifepristone would allow direct-to-patient telemedicine abortion to be implemented outside of a research setting without compromising the patient experience.

Federal, state, and institutional barriers to the expansion of medication and telemedicine abortion services in Ohio, Kentucky, and West Virginia during the COVID-19 pandemic.

OBJECTIVES: We aimed to characterize the combined impact of federal, state, and institutional policies on barriers to expanding medication and telemedicine abortion care delivery during the COVID-19 pandemic in the abortion-restrictive states of Ohio, Kentucky, and West Virginia. STUDY DESIGN: We analyzed 4 state policies, 2 COVID-related state executive orders, and clinic-level survey data on medication abortion provision from fourteen abortion facilities in Ohio, Kentucky, and West Virginia from December 2019 to December 2020. We calculated the percent of medication abortions provided at these facilities during the study period by state, to assess changes in medication abortion use during the pandemic. RESULTS: We ascertained that COVID-19-executive orders in Ohio and West Virginia that limited procedural abortion in Spring 2020 coincided with an increase in the overall number and proportion of medication abortions in this region, peaking at 1613 medication abortions (70%) in April 2020. Ohio and West Virginia, which had executive orders limiting procedural abortion, saw relatively greater increases in April compared to Kentucky. Despite temporary lifting of the mifepristone REMS, prepandemic regulations banning telemedicine abortion in Kentucky and West Virginia and requiring in-person clinic visits for medication abortion distribution in Ohio limited clinics' ability to adapt to offer medication abortion by mail. CONCLUSIONS: Our findings illustrate how restrictive medication and telemedicine abortion policies in Ohio, Kentucky, and West Virginia created additional obstacles for patients seeking medication abortion during the pandemic. Permanently lifting federal regulations on in-clinic distribution of mifepristone would only advantage abortion seekers in states without restrictive telehealth and medication abortion policies. State policies that limit access to comprehensive abortion services should be central in larger efforts toward dismantling barriers that impinge upon reproductive autonomy. IMPLICATION STATEMENT: We find that abolishing the REMS on mifepristone would not be enough to expand access to patients in abortion-restrictive states with telemedicine and medication abortion laws. While the REMS is a barrier, it represents one of several hindrances to the expansion of telemedicine abortion distribution across the United States.

Common themes in early state policy responses to substance use disorder treatment during COVID-19.

Background: Limited research has examined how states have changed policies for treatment of substance use disorder (SUD) during the COVID-19 pandemic.Objectives: We aimed to identify themes in state policy responses to the pandemic in the context of SUD treatment. Identifying themes in policy responses provides a framework for subsequent evaluations of the relationship between state policies and health service utilization.Methods: Between May and June 2020, we searched all Single State Agencies for Substance Abuse Services (SSA) websites for statements of SUD treatment policy responses to the pandemic. We conducted Iterative Categorization of policies for outpatient programs, opioid treatment programs, and other treatment settings to identify themes in policy responses.Results: We collected 220 documents from SSA websites from 45 states and Washington D.C. Eight specific themes emerged from our content analysis: delivery of pharmacological and non-pharmacological services, obtaining informed consent and documentation for remote services, conducting health assessments, facility operating procedures and staffing requirements, and permissible telehealth technology and billing protocols. Policy changes often mirrored federal guidance, for instance, by expanding methadone take-home options for opioid treatment programs. The extent and nature of policy changes varied across jurisdictions, including telehealth technology requirements and staffing flexibility.Conclusion: States have made significant policy changes to SUD treatment policies during COVID-19, particularly regarding telehealth and facilitation of remote care. Understanding these changes could help policymakers prioritize guidance during the pandemic and for future health crises. Impacts of policies on disparate treatment populations, including those with limited technological access, should be considered.

Abortion exceptionalism and the mifepristone REMS.

Since its initial approval, mifepristone has been regulated with a strictness out of proportion to its risks. This paper explores how the regulation of mifepristone, specifically the Risk Evaluation and Mitigation Strategies (REMS) requirements, are a manifestation of abortion exceptionalism-the phenomenon of abortion being treated differently under the law than other comparable health care. The weight of medical and public health evidence demonstrates that mifepristone is extremely safe and the REMS are unnecessary. In fact, the mifepristone REMS is neither justified by the absolute risk of the medication itself, nor comprehensible as a logical response to the risks actually posed by mifepristone. Nevertheless, the REMS remain in place. From July 2020 through January 2021, enforcement of the REMS elements requiring in-person distribution of mifepristone were enjoined by court order due the COVID-19 pandemic. In other words, COVID-19 created a context so exceptional as to temporarily outweigh abortion exceptionalism. However, the reprieve did not last-in January 2021, the Supreme Court ruled to dissolve the injunction, allowing FDA to resume enforcement of the in-person requirements. In response, advocates called on the incoming Biden administration to direct FDA to suspend enforcement once more. This regulatory whiplash is itself further evidence that the REMS flow from political, rather than scientific, concerns. Abortion exceptionalism is apparent in the specific requirements of the REMS, and it is also apparent in the precarity of the regulatory scheme itself.

Regulatory status quo and prospects for biosurfactants in pharmaceutical applications.

The concept of going 'green' and 'cold' has led to utilizing renewable resources for the synthesis of microbial biosurfactants that are both patient and eco-friendly. In this review, we shed light on the potential and regulatory aspects of biosurfactants in pharmaceutical applications and how they can significantly contribute to novel concepts for the Coronavirus 2019 (COVID-19) vaccine and future treatment. We emphasize that more specific guidelines should be formulated to regulate the approval of biosurfactants for human use. It is also crucial to implement a risk-based approach from the early research and development (R&D) phase in addition to establishing more robust standardized techniques and assays to evaluate the characteristics of biosurfactants.

The drug war must end: The right to life, liberty and security of the person during the COVID-19 pandemic for people who use drugs.

Since the start of the opioid epidemic in 2016, the Downtown Eastside community of Vancouver, Canada, has lost many pioneering leaders, activists and visionaries to the war on drugs. The Vancouver Area Network of Drug Users (VANDU), the Western Aboriginal Harm Reduction Society (WAHRS), and the British Columbia Association People on Opiate Maintenance (BCAPOM) are truly concerned about the increasing overdose deaths that have continued since 2016 and have been exacerbated by the novel coronavirus (SARS-COVID-19) despite many unique and timely harm reduction announcements by the British Columbia (B.C.) government. Some of these unique interventions in B.C., although in many cases only mere announcements with limited scope, are based on the philosophy of safe supply to illegal street drugs. Despite all the efforts during the pandemic, overdose deaths have spiked by over 100% compared to the previous year. Therefore, we urge the Canadian federal government, specifically the Honorable Patty Hajdu, the federal Minister of Health, to decriminalize simple possession immediately by granting exemption under the Controlled Drugs and Substances Act. The Canadian federal government has a moral obligation under Sect. 7 of the Canadian Charter of Rights and Freedoms to protect the basic human rights of marginalized Canadians.

Civil society involvement in harm reduction drug policy: reflections on the past, expectations for the future.

BACKGROUND: A range of civil society organisations (CSOs) such as drug user groups, non-governmental/third sector organisations and networks of existing organisations, seek to shape the development of drugs policy at national and international levels. However, their capacity to do so is shaped by the contexts in which they operate nationally and internationally. The aim of this paper is to explore the lived experience of civil society participation in these contexts, both from the perspective of CSOs engaged in harm reduction advocacy, and the institutions they engage with, in order to inform future policy development. METHODS: This paper is based on the presentations and discussions from a workshop on 'Civil Society Involvement in Drug Policy hosted by the Correlation - European Harm Reduction Network at the International Society for the Study of Drugs Policy (ISSDP) annual conference in Paris, 2019. In the aftermath of the workshop, the authors analysed the papers and discussions and identified the key themes arising to inform CSI in developing future harm reduction policy and practice. RESULTS: Civil society involvement (CSI) in policy decision-making and implementation is acknowledged as an important benefit to representative democracy. Yet, the accounts of CSOs demonstrate the challenges they experience in seeking to shape the contested field of drug policy. Negotiating the complex workings of political institutions, often in adversarial and heavily bureaucratic environments, proved difficult. Nonetheless, an increase in structures which formalised and resourced CSI enabled more meaningful participation at different levels and at different stages of policy making. CONCLUSIONS: Civil society spaces are colonised by a broad range of civil society actors lobbying from different ideological standpoints including those advocating for a 'drug free world' and those advocating for harm reduction. In these competitive arena, it may be difficult for harm reduction orientated CSOs to influence the policy process. However, the current COVID-19 public health crisis clearly demonstrates the benefits of partnership between CSOs and political institutions to address the harm reduction needs of people who use drugs. The lessons drawn from our workshop serve to inform all partners on this pathway.

Regulators, Pivotal Clinical Trials, and Drug Regulation in the Age of COVID-19.

Medicine regulators rely on pivotal clinical trials to make decisions about approving a new drug, but little is known about how they judge whether pivotal trials justify the approval of new drugs. We explore this issue by looking at the positions of 3 major regulators: the European Medicines Agency, Food and Drug Administration, and Health Canada. Here we report their views and the implications of those views for the approval process. On various points, the 3 regulators are ambiguous, consistent, and demonstrate flexibility. The range of views may well reflect different regulatory cultures. Although clinical trial information from pivotal trials is becoming more available, regulators are still reluctant to provide detailed information about how that information is interpreted. As medicines and vaccines come up for approval for treatment of COVID-19, transparency in how pivotal trials are interpreted will be critical in determining how these treatments should be used.

Regulatory Agilities in the Time of COVID-19: Overview, Trends, and Opportunities.

PURPOSE: Crucial steps have been adopted by health and regulatory authorities around the world to respond to the COVID-19 pandemic. This review aims to highlight these steps by providing an overview of the regulatory approaches adopted during the onset of the pandemic, provide an assessment of observed trends, and offer some reflections and proposals to leverage learnings and opportunities from this current pandemic. METHODS: Documents and informational materials on regulating the development and management of medical products during the COVID-19 pandemic were collected and classified. These materials were sourced from official websites and press releases from health authorities and international bodies from selected markets across the globe, and covered the period between January and July 2020. Additional information to support this study was gathered through a literature review and analysis of related data available from the public domain, and was complemented with the authors' personal experience. FINDINGS: Communication has been vital in addressing the impact of COVID-19. A total of 1705 documents and informational materials related to health or regulatory response to the COVID-19 pandemic were gathered. Of these, 343 (around 20%) were identified as regulatory agilities. These agile approaches were classified into 3 categories, namely, where health and regulatory authorities had: (1) facilitated product management across the entire lifecycle, notably in expediting medical product use for COVID-19, ensuring the continuity of clinical trials, and addressing supply chain issues; (2) strengthened international cooperation; and (3) addressed regulatory burden with the adoption of electronic and digital tools. IMPLICATIONS: While many regulatory measures have been introduced temporarily as a response to the COVID-19 crisis, there are opportunities for leveraging an understanding from these approaches in order to collectively achieve more efficient regulatory systems and to mitigate and address the impact of COVID-19 and further future-proof the regulatory environment.