In tight times, companies fill the funding gap.

With federal budgets under pressure, scientists turn to corporations for research support.

Drug Promotions Between Ethics, Regulations, and Financial Interests.

BACKGROUND: The promotion of the latest medicines produced by the pharmaceutical industry is an important issue both from an ethical point of view (the level of accessibility, the way research is carried out) and from the point of view of marketing and especially from the lobbying issues raised. AREAS OF UNCERTAINTY: The ethical dilemmas raised by the promotion of new drugs revolve between the need to discover new molecules important for treating a wide range of diseases and the need to establish a battery of ethical rules, absolutely necessary for regulations in the field to be compliant with all ethical principles. DATA SOURCES: A literature search was conducted through PubMed, MEDLINE, Plus, Scopus, and Web of Science (2015-2023) using combinations of keywords, including drugs, medical publicity, and pharma marketing plus ethical dilemma. ETHICS AND THERAPEUTIC ADVANCES: The promotion of medicines is governed by advertising laws and regulations in many countries, including at EU level, based on the need for countries to ensure that the promotion and advertising of medicines is truthful, based on information understood by consumers. The ethical analysis of the issues raised is more necessary and complex as the channels used for promotion are more accessible to the population, and the information, easier to obtain, can be the cause of increased self-medication and overeating. Large amounts of money invested in the development of new molecules, but also the risk of scientific fraud through manipulation of data during clinical trials, selective or biased publication of information can have repercussions on the health of the population. CONCLUSIONS: The development of new pharmaceutical molecules is necessary to intervene and treat as many conditions as possible, but marketing must not neglect the observance of ethical principles. The promotion of medicines should be the attribute especially of the medical staff, which should also be a mandatory part of the mechanism for approving the marketing methods and means used by the pharmaceutical companies.

Intellectual property licensing of therapeutics during the COVID-19 crisis: lessons learnt for pandemic preparedness and response.

During the COVID-19 pandemic, intellectual property licensing through bilateral agreements and the Medicines Patent Pool were used to facilitate access to new COVID-19 therapeutics in low- and middle-income countries (LMICs). The lessons learnt from the application of the model to COVID-19 could be relevant for preparedness and response to future pandemics and other health emergencies.The speed at which affordable versions of a new product are available in LMICs is key to the realization of the potential global impact of the product. When initiated early in the research and development life cycle, licensing could facilitate rapid development of generic versions of innovative products in LMICs during a pandemic. The pre-selection of qualified manufacturers, for instance building on the existing network of generic manufacturers engaged during the COVID-19 pandemic, the sharing of know-how and the quick provision of critical inputs such as reference listed drugs (RLDs) could also result in significant time saved. It is important to find a good balance between speed and quality. Necessary quality assurance terms need to be included in licensing agreements, and the potentials of the new World Health Organization Listed Authority mechanism could be explored to promote expedited regulatory reviews and timely access to safe and quality-assured products.The number, capacity, and geographical distribution of licensed companies and the transparency of licensing agreements have implications for the sufficiency of supply, affordability, and supply security. To foster competition and support supply security, licenses should be non-exclusive. There is also a need to put modalities in place to de-risk the development of critical pandemic therapeutics, particularly where generic product development is initiated before the innovator product is proven to be effective and approved. IP licensing and technology transfer can be effective tools to improve the diversification of manufacturing and need to be explored for regional manufacturing for accelerated access at scale in in LMICs and supply security in future pandemics.

Endeavours made by trade associations, pharmaceutical companies and regulators in the replacement, reduction and refinement of animal experimentation in safety testing of pharmaceuticals.

Following the European Commission decision to develop a roadmap to phase out animal testing and the signing of the US Modernisation Act, there is additional pressure on regulators and the pharmaceutical industry to abandon animal experimentation in safety testing. Often, endeavours already made by governments, regulators, trade associations, and industry to replace, reduce and refine animal experimentation (3Rs) are unnoticed. Herein, we review such endeavours to promote wider application and acceptance of 3Rs. ICH guidelines have stated 3Rs objectives and have enjoyed many successes driven by global consensus. Initiatives driven by US and European regulators such as the removal of the Abnormal Toxicity Test are neutralised by reticent regional regulators. Stream-lined testing requirements have been proposed for new modalities, oncology, impurity management and animal pharmacokinetics/metabolism. Use of virtual controls, value of the second toxicity species, information sharing and expectations for life-threatening diseases, human specific or well-characterised targets are currently being scrutinised. Despite much effort, progress falls short of the ambitious intent of decisionmakers. From a clinical safety and litigation perspective pharmaceutical companies and regulators are reluctant to step away from current paradigms unless replacement approaches are validated and globally accepted. Such consensus has historically been best achieved through ICH initiatives.

Federal Trade Commission Actions on Prescription Drugs, 2000-2022.

Importance: The Federal Trade Commission's (FTC) oversight role in the pharmaceutical market is critical to the health of patients and the health care system. This study characterized the FTC's policy on the pharmaceutical market in recent decades, identifying the types of actions it has favored, barriers it has faced, and authorities that remain untested. Objective: To review FTC legal actions in the pharmaceutical market from 2000-2022. Evidence Review: Legal actions were determined through manual review of search results from the FTC's online Legal Library as well as a 2023 FTC report on pharmaceutical actions. The alleged misconduct, type of legal action taken, timing, and outcome were collected from press releases, complaints, orders, and other legal documents. Findings: From 2000-2022, the FTC challenged 62 mergers, brought 22 enforcement actions against allegedly unlawful business practices, and made 1 rule related to pharmaceuticals. Alleged misconduct in enforcement actions involved anticompetitive settlements in patent litigation (n = 11), unilateral actions by brand manufacturers to delay generic competition (n = 6), noncompete agreements (n = 4), and monopolization (n = 3), with 10 outcomes involving monetary payment, totaling $1.6 billion. Of the 62 mergers the FTC challenged, 61 were allowed to continue, 58 after divesting certain drugs to third-party competitors. The FTC's reliance on drug divestitures decreased from 18 drugs per year from 2000-2017 to 4.3 per year from 2017-2023. Conclusions and Relevance: The FTC brought about 1 enforcement action and 3 merger actions per year against pharmaceutical manufacturers from 2000-2022, pursuing a small fraction of the estimated misconduct and consolidation in the pharmaceutical marketplace. Although the FTC faces substantial legal and practical limitations, important tools remain untested, including a rule defining "unfair methods of competition," that may allow it to more effectively prevent repetitive patterns of anticompetitive behavior.

Availability of medical abortion medicines in eight countries: a descriptive analysis of key findings and opportunities.

BACKGROUND: In recent years a growing number of manufacturers and medical abortion products have entered country markets and health systems, with varying degrees of quality and accessibility. An interplay of factors including pharmaceutical regulations, abortion laws, government policies and service delivery guidelines and provider's knowledge and practices influence the availability of medical abortion medicines. We assessed the availability of medical abortion in eight countries to increase understanding among policymakers of the need to improve availability and affordability of quality-assured medical abortion products at regional and national levels. METHODS: Using a national assessment protocol and an availability framework, we assessed the availability of medical abortion medicines in Bangladesh, Liberia, Malawi, Nepal, Nigeria, Rwanda, Sierra Leone and South Africa between September 2019 and January 2020. RESULTS: Registration of abortion medicines-misoprostol or a combination of mifepristone and misoprostol-was established in all countries assessed, except Rwanda. Mifepristone and misoprostol regimen for medical abortion was identified on the national essential medicines list/standard treatment guidelines for South Africa as well as in specific abortion care service and delivery guidelines for Bangladesh, Nepal, Nigeria, and Rwanda. In Liberia, Malawi, and Sierra Leone-countries with highly restrictive abortion laws and no abortion service delivery guidelines or training curricula-no government-supported training on medical abortion for public sector providers had occurred. Instead, training on medical abortion was either limited in scope to select private sector providers and pharmacists or prohibited. Community awareness activities on medical abortion have been limited in scope across the countries assessed and where abortion is broadly legal, most women do not know that it is an option. CONCLUSION: Understanding the factors that influence the availability of medical abortion medicines is important to support policymakers improve availability of these medicines. The landscape assessments documented that medical abortion commodities can be uniquely impacted by the laws, policies, values, and degree of restrictions placed on service delivery programs. Results of the assessments can guide actions to improve access.

Unsafe abortion is a leading cause of death and disability among women of reproductive age. Medical management of abortion with mifepristone and misoprostol pills, or just misoprostol, is a safe and effective way to end a pregnancy. Owing to an increase in the number of medical abortion products that have entered country health systems, we examined access to these medicines from supply to demand in selected countries. The overarching goal of the national landscape assessments was to produce evidence to support advocacy efforts and policymaking for improved access to quality medical abortion products that is appropriate to the needs of the country. This paper aims to describe key findings across eight country settings on the availability of medical abortion medicines and identify key opportunities to improve access to them across countries.

Surviving in the Valley of Death: Opportunities and Challenges in Translating Academic Drug Discoveries.

With pharmaceutical companies shrinking their research departments and exiting out of efforts related to unprofitable diseases, society has become increasingly dependent on academic institutions to perform drug discovery and early-stage translational research. Academic drug discovery and translational research programs assist in shepherding promising therapeutic opportunities through the so-called valley of death in the hope that a successful new drug will result in saved lives, improved health, economic growth, and financial return. We have interviewed directors of 16 such academic programs in the United States and found that these programs and the projects therein face numerous challenges in reaching the clinic, including limited funding, lack of know-how, and lack of a regional drug development ecosystem. If these issues can be addressed through novel industry partnerships, the revision of government policies, and expanded programs in translational education, more effective new therapies are more likely to reach patients in need.

Probiotics and the Microbiome-How Can We Help Patients Make Sense of Probiotics?

The notion of probiotics as microbes that confer health benefits has its origins in the speculative ideas that are more than a century old, yet remain largely unsubstantiated by scientific evidence. The recent advances in microbiome science have highlighted the importance of intestinal microbes in human physiology and disease pathogenesis. These developments have provided a boost to the probiotics industry, which continues to experience exponential growth driven mainly by creative marketing. Consumers, patients, and most health care providers are not able to discern the underlying science or differentiate the permitted claims that promise vague health benefits from disease-specific claims reserved for drugs. No probiotic product has been able to satisfy the regulatory requirements to be categorized as a drug, a substance intended to cure, mitigate, or prevent disease. However, patients take probiotic products in the belief that they will help to treat their intestinal or systemic diseases. Thus far, the regulators have failed to create policies that would assist to inform the public in this area. In fact, the existing regulatory regime actually creates formidable barriers to research that could provide evidence for clinical efficacy of probiotic products. We propose a potential solution to this vexing problem, where a committee created through a partnership of academia, professional organizations, and industry, but free of potential conflicts of interest, would be charged with rigorous evaluation of specific probiotic products and the evidence in support of their different claims. Companies that would submit to this process would earn the trust of consumers and healthcare providers, as well as a distinction in the marketplace.

The current use and evolving landscape of nutraceuticals.

The nutraceutical market is currently a high-impact multi-billion-dollar industry, and it is anticipated to grow rapidly over the next decade. Nutraceuticals comprise diverse food-derived product categories that have become widespread due to increased consumer awareness of potential health benefits and the need for improved wellness. This targeted review is designed to identify the current global trends, market opportunities, and regulations that drive the nutraceutical industry. Safety and efficacy concerns are also explored with a view to highlighting areas that necessitate further research and oversight. Key drivers of the nutraceutical market include aging populations, consumer awareness, consumer lifestyle, increasing cost of healthcare, and marketing channels. Although some nutraceuticals hold promising preventive and therapeutic opportunities, there is a lack of a universal definition and regulatory framework among countries. Moreover, there is a lack of adequate evidence for their efficacy, safety, and effectiveness, which was even further highlighted during the ongoing coronavirus pandemic. Future prospective epidemiological studies can delineate the health impact of nutraceuticals and help set the scientific basis and rationale foundation for clinical trials, reducing the time and cost of trials themselves. Together, an understanding of the key drivers of the nutraceutical market alongside a consistent and well-defined regulatory framework will provide further opportunities for growth, expansion, and segmentation of nutraceuticals applications.

Approaches for setting occupational exposure limits in the pharmaceutical industry.

The use of pharmaceutical drugs has provided a cure for many diseases. However, unintended exposure to drugs in the manufacturing workplace can cause significant health hazards to workers. It is important to protect the workforce from these deleterious effects by limiting exposure to an acceptable level, the occupational exposure limit (OEL). OEL is defined as airborne concentrations (expressed as a time-weighted average for a conventional 8-h workday and a 40-h work week) of a substance to which nearly all workers may be repeatedly exposed (for a working lifetime) without adverse effects. Determination of OELs has become very challenging over time, requiring an overall assessment of the preclinical and clinical data of the drug being manufactured. Previously, to derive OEL values, toxicologists used animal no-observed-adverse-effect level (NOAEL) data, which have been replaced with the overall assessment of animal and human data, placing a higher emphasis on human health-based data. A major advantage of working with human pharmaceuticals is that sufficient clinical data are available for them in most cases. The present manuscript reviews the latest knowledge regarding the derivation of occupational exposure limits as health-based exposure limits (HBELs) for pharmaceuticals. We have provided examples of OEL calculations for various drugs including levofloxacin (CAS No. 100986-85-4), dienogest (CAS no. 65928-58-7), and acetylsalicylic acid (ASA, CAS no. 50-78-2) using human data. This report will benefit professionals in the OEL domain in understanding this highly important, growing, and challenging field.

Challenges for biosimilars: focus on rheumatoid arthritis.

Healthcare systems worldwide are struggling to find ways to fund the cost of innovative treatments such as gene therapies, regenerative medicine, and monoclonal antibodies (mAbs). As the world's best known mAbs are close to facing patent expirations, the biosimilars market is poised to grow with the hope of bringing prices down for cancer treatment and autoimmune disorders, however, this has yet to be realized. The development costs of biosimilars are significantly higher than their generic equivalents due to therapeutic equivalence trials and higher manufacturing costs. It is imperative that academics and relevant companies understand the costs and stages associated with biologics processing. This article brings these costs to the forefront with a focus on biosimilars being developed for Rheumatoid Arthritis (RA). mAbs have remarkably changed the treatment landscape, establishing their superior efficacy over traditional small chemicals. Five blockbuster TNFα mAbs, considered as first line biologics against RA, are either at the end of their patent life or have already expired and manufacturers are seeking to capture a significant portion of that market. Although in principle, market-share should be available, withstanding that the challenges regarding the compliance and regulations are being resolved, particularly with regards to variation in the glycosylation patterns and challenges associated with manufacturing. Glycan variants can significantly affect the quality attributes requiring characterization throughout production. Successful penetration of biologics can drive down prices and this will be a welcome change for patients and the healthcare providers. Herein we review the biologic TNFα inhibitors, which are on the market, in development, and the challenges being faced by biosimilar manufacturers.

Regulatory Requirements for the Quality of Allergen Products for Allergen Immunotherapy of Food Allergy.

PURPOSE OF REVIEW: Medicinal products for allergen immunotherapy (AIT) of food allergies have gained enormous momentum in recent years. With this new class of products entering marketing authorization procedures, compliance to regulatory requirements becomes a critical element. Here, an overview is provided on specific requirements and aspects concerning the quality control and manufacturing of these products. RECENT FINDINGS: Recent developments in the field of AIT for food allergies are divers, including products for oral, epicutaneous, and subcutaneous application, most notably targeting egg, milk, and peanut allergy. As the source materials for food AIT product are typically produced for food consumption and not for medicinal purposes, unique challenges arise in the manufacturing processes and controls of these medicinal products. Individual approaches are needed to assure acceptable quality, including control of relevant quantitative and qualitative characteristics. Major characteristics for quality verification include determination of protein content, total allergenic activity, and major allergen content. The applied manufacturing processes need to be established such that relevant process parameters are kept within justified limits and consistency of produced batches is assured. Allergen products for food AIT present specific challenges with respect to quality aspects that differentiate them from other commonly available AIT products. While established regulation is available and provides clear guidance for most aspects, other issues require consideration of new and individual settings relevant here. Consequently, as experience grows, respective amendments to currently available guidance may be needed.