WHO shapes priorities for medicines? An analysis of the applicants and decision makers within the historical evolution of the WHO Model Lists of Essential Medicines.

WHO recently announced a process to review and potentially update the procedures for selecting essential medicines. This announcement presents an opportunity to reflect on the evolution of the WHO Model Lists of Essential Medicines (EML), including the composition of the stakeholders that shape priorities. We contextualised our findings within the broader history of the WHO EML to support future reforms to improve access to essential medicines. The current system allows individuals to propose a medicine for the WHO EML. This makes the EML reactive to applicant priorities. Almost all medicines (687/700; 98·1%) proposed to the WHO EML between 2003 and 2023 came from applicants in high-income countries. Most applications (210/700; 30·0%) were submitted by universities and research institutions, followed by non-governmental organisations (159/700; 22·7%), the UN system (158/700; 22·6%), professional associations (98/700; 14·0%), and the pharmaceutical industry (75/700; 10·7%). Between 1977 and 2023, over half of the Expert Committee members were from low-income and middle-income countries, with an increasing proportion in recent EML updates. Mainly, UN agencies acted as observers between 1977 and 2023. One central question emerges when evaluating whether applicants' geographical distribution translates to the WHO EML's intended purpose: for whom is the EML intended? Over the years, the geographical applicability has blurred. Defining a strategic vision for the WHO EML, including articulating a target audience and structured selection process, would strengthen decision-making processes by providing additional clarity, including to those implementing the guidance, mostly in low-income and middle-income countries.

Drug Development Failure: How GLP-1 Development Was Abandoned in 1990.

Many factors determine whether and when a class of therapeutic agents will be successfully developed and brought to market, and historians of science, entrepreneurs, drug developers, and clinicians should be interested in accounts of both successes and failures. Successes induce many participants and observers to document them, whereas failed efforts are often lost to history, in part because involved parties are typically unmotivated to document their failures. The GLP-1 class of drugs for diabetes and obesity have emerged over the past decade as clinical and financial blockbusters, perhaps soon becoming the highest single source of revenue for the pharmaceutical industry (Berk 2023). In that context, it is instructive to tell the story of the first commercial effort to develop this class of drugs for metabolic disease, and how, despite remarkable early success, the work was abandoned in 1990. Told by a key participant in the effort, this story documents history that would otherwise be lost and suggests a number of lessons about drug development that remain relevant today.

Accelerated Development of Pharmaceuticals Past, Present, and Future.

This paper reviews the accelerated development of pharmaceuticals, exploring past, present, and future perspectives. It provides a historical overview of early strategies used to expedite development, beginning with initiatives from the 1990s. The work of Gardner and Byrn in accelerated development analysis during this era is highlighted. The narrative progresses to the 2000s, discussing the emergence of PK/PD in accelerating pharmaceutical development. The paper further examines case studies in the accelerated development field, including the INDIGO and Chorus programs. It concludes with an analysis of the current state of the field, referencing the NIPTE conference, which focused on the industrial perspective of accelerated development. Additionally, the paper outlines strategies for the rapid development of Solid Lipid Nanoparticle manufacturing and vaccine production.

Opposed to Pain: Antikamnia Chemical Company.

The Antikamnia (AK) Chemical Company founded in 1890, which eventually was renamed The Antikamnia Remedy Company in 1819, was an important medicine company that thrived prior to passage of the 1906 Food and Drug act using smart worldwide marketing. As dangerous as the AK products were, success continued after 1906 by pursuing methods to flout regulations and stick to the marketing methods and legal maneuvering that kept AK sales strong. This article describes the tumultuous history of one of the most successful drug companies between 1890 and well into the 1920s.

The Origins of "Confidential Commercial Information" at the FDA.

This Viewpoint reviews regulations regarding FDA's handing of confidential commercial information, explains how these regulations serve as a barrier to disclosure of information in the interest of public health, and suggests how information could be carefully shared to improve health outcomes and advance research.

[The participation of the USSR in development of penicillin industry in the Eastern Europe].

The article considers on the basis of analysis of archival documents issue of rendering assistance by the Soviet Union to the countries of Eastern Europe to organize production of penicillin. It is established that by the mid of 1950s, modern powerful plants were launched in Bulgaria, Romania and Czechoslovakia by the forces of Soviet engineers . Their construction was carried out on preferential terms for countries-customers. The mutually beneficial cooperation in sphere of production of antibiotics carried out and with other countries of this region. It is demonstrated that the USSR, performing task of enormous humanitarian significance in conditions of the Cold War, simultaneously implemented another goal - formation of loyalty of population of these countries and organization of coalition of friendly states on its Western borders.

Pharmacy services in Mongolia: Historical background and current situation

Over a long history, the pharmacy was developed in close connection with Traditional Mongolian Medicine (TMM) as one part of it. TMM was Mongolia's only available healthcare method before Western medicine was introduced in the 19th century. The pharmaceutical sector, founded in 1923, played an essential role in the health system of Mongolia over the last hundred years. During the socialist time, the pharmaceutical sector was state-owned, and privatization started in 1990 when Mongolia transitioned to a market economy from a centrally planned economy. Mongolian current pharmaceutical sector is fully privatized except for public hospital pharmacies, and as of the end of 2021, 2822 pharmaceutical facilities were operating in Mongolia. Before the transition to the market economy, the functions of the pharmaceutical sector were mainly focused on the production, supply, compounding, and dispensing of drugs. Still, since 1990, the scope of pharmaceutical care services has changed. The pharmaceutical care service has been transferring from product-oriented to patient-centered care since the mid-1990s (AU)

Premios Nobel Chain y Schatz evalúan la producción de penicilina en Chile en los años sesenta / Nobel Prize winners Chain and Schwartz evaluate the production of penicillin in Chile in the sixties

En los años sesenta el antiguo Instituto Bacteriológico de Chile obtuvo de la Universidad de Chile la ayuda de Albert Schatz, descubridor de la estreptomicina, para mejorar su producción de penicilina. Esta asesoría no fue aprovechada y la situación empeoró, hasta la llegada de Mario Miranda como Director, quien trajo a Sir Ernst Chain, Premio Nobel por el desarrollo de la penicilina, para que hiciese una evaluación de la planta de producción antes de decidir su cierre. El autor de estas líneas, quien puso fin a la producción en 1973, relata las visitas y las conclusiones de ambos asesores.

In the sixties the ancient Bacteriological Institute of Chile obtained from the University of Chile the transfer of Albert Schatz, discoverer of streptomycin, to improve its penicillin production. This advisory was wasted and the situation worsened until the arrival of Mario Miranda as the new Director, who brought Sir Ernst Chain, Nobel Prize for the development of penicillin, to make an evaluation of the production plant before deciding to continue or close it. The author of these lines, who ended production in 1973, recounts the visits and the conclusions of both advisors.

Russell Earl Marker and the Beginning of the Steroidal Pharmaceutical Industry.

A biographical essay is presented on the chemical research of Russell E. Marker (1902-1995). The biography begins in 1925 with Marker's decision to forgo a Ph.D. in chemistry because he did not wish to complete the course requirements at the University of Maryland. Marker then took a position at the Ethyl Gasoline Company where he helped develop the octane rating for gasoline. He then moved to the Rockefeller Institute where he studied the Walden inversion, and then to Penn State College where his already prolific publication record soared to even greater heights. In the 1930s, Marker became fascinated with steroids and their potential as pharmaceuticals and collected specimens from plants in the southwest US and Mexico, discovering many sources of steroidal sapogenins. With his students at Penn State College, where he rose to full professor, he discovered the structure of these sapogenins and invented the "Marker degradation" that converted diosgenin and other sapogenins into progesterone. Together with Emeric Somlo and Federico Lehmann, he co-founded Syntex and began the manufacture of progesterone. Shortly thereafter, he left Syntex, began another pharmaceutical company in Mexico, then quit chemistry altogether. A discussion of Marker's legacies and the ironies in his professional career is provided.

Los orígenes de Zeltia / The origins of Zeltia

Se presentan en este trabajo los orígenes del proceso que culminó en la creación de la empresa Zeltia S.A., buque insignia de la industria farmacéutica gallega. Sus antecedentes aparecen en la constitución formal en Vigo del Instituto Bio-Químico Miguel Servet, en abril de 1936, si bien el farmacéutico Rubira y el médico Obella habían estado trabajando en el proyecto al menos desde 1929. El levantamiento militar del 36 impacta directamente en las primeras etapas del laboratorio. Mientras unos socios se posicionan a favor del levantamiento, a otros les afectan seriamente las medidas represivas del nuevo régimen. En cualquier caso, entre unos y otros se establecen lazos de cooperación y se crean lealtades. Incluso, durante la Guerra Civil, se incorporan al laboratorio profesionales y técnicos represaliados por su ideología política. Finalizada la contienda, cuando las circunstancias predecían el comienzo de un periodo de mayor estabilidad para el desarrollo del negocio, se produce una grave crisis en el accionariado, relacionada en gran medida con la influencia que tenía en Vigo el colectivo alemán y la fractura social existente frente a los germanófilos. En estas circunstancias se fragmenta la sociedad. Rubira continua al frente del Servet, al que terminaría incorporándose el alemán Boehme, con el que ya compartía previamente otros negocios, mientras Obella buscaba nuevos socios, con mayor afinidad ideológica, para fundar Zeltia S.A. en agosto de 1939. (AU)

The origins of the process that culminated in the creation of the company Zeltia S.A., flagship of the Galician pharmaceutical industry, are presented in this paper. Its precedents appear in the formal constitution in Vigo of the Miguel Servet Biochemical Institute, in April 1936, although the pharmacist Rubira and the doctor Obella had been working on the project since at least 1929. The military uprising of 1936 had a direct impact on the early stages of the laboratory. While some partners are positioned in favor of the uprising, others are seriously affected by the repressive measures of the new regime. In any case, between one and the other, bonds of cooperation are established and loyalties are created. Even during the Civil War, professionals and technicians retaliated for their political ideology joined the laboratory. At the end of the fight, when the circumstances predicted the beginning of a period of greater stability for the development of the business, a serious crisis occurred in the shareholding, largely related to the influence that the German collective had in Vigo and the existing social fracture. against the Germanophiles. In these circumstances society is fragmented. Rubira continues to lead the Servetus, which the German Boehme would end up joining, with whom he had previously shared other businesses, while Obella was looking for new partners, with greater ideological affinity, to found Zeltia S.A. in August 1939. (AU)

The Pharmaceutical Industry in 2021. An Analysis of FDA Drug Approvals from the Perspective of Molecules.

Similar to last year, 2021 will be remembered for the COVID-19 pandemic. Although five vaccines have been approved by the two most important drug regulatory agencies, namely the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the pandemic has still not been brought under control. However, despite the context of a global pandemic, 2021 has been an excellent year with respect to drug approvals by the FDA. In 2021, 50 drugs have been authorized, making it the fourth-best year after 2018 (59 drugs) and 1996 and 2020 (53 each). Regarding biologics, 2021 has been the third-best year to date, with 14 approvals, and it has also witnessed the authorization of 36 small molecules. Of note, nine peptides, eight monoclonal antibodies, two antibody-drug conjugates, and two oligonucleotides have been approved this year. From them, five of the molecules are pegylated and three of them highly pegylated. The presence of nitrogen aromatic heterocycles and/or fluorine atoms are once again predominant among the so-called small molecules. This report analyzes the 50 new drugs approved in 2021 from a chemical perspective, as it did for those authorized in the previous five years. On the basis of chemical structure alone, the drugs that received approval in 2021 are classified as the following: biologics (antibodies, antibody-drug conjugates, enzymes, and pegylated proteins); TIDES (peptide and oligonucleotides); combined drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

Medicamentos órfãos em Portugal no contexto internacional (séculos XX-XXI) / Orphan drugs in Portugal in the international context (XX-XXI centuries)

A consciência científica, clínica e pública da existência das doenças raras tem aumentado nos últimos anos. Os medicamentos denominados de “medicamentos órfãos” são aqueles que são apropriados para o tratamento de doenças raras. As doenças raras, comparadas com outras doenças, apresentam uma baixa incidência demográfica. Por esta razão, e em virtude das condições vigentes de comercialização, as indústrias farmacêuticas não apostam fortemente nos medicamentos órfãos. Os produtores não teriam oportunidade de recuperar o capital investido na investigação e desenvolvimento do medicamento. Neste estudo os autores fazem um historial dos medicamentos órfãos em Portugal tendo como fontes a legislação e regulamentação portuguesas no quadro da legislação e diretivas europeias, o papel das indústrias farmacêuticas em Portugal, a regulamentação e fiscalização realizada pelo INFARMED, IP, bem como o acesso dos doentes aos medicamentos órfãos e o papel fulcral das associações de doentes (AU)

Denaturing and Native Mass Spectrometric Analytics for Biotherapeutic Drug Discovery Research: Historical, Current, and Future Personal Perspectives.

Mass spectrometry (MS) plays a key role throughout all stages of drug development and is now as ubiquitous as other analytical techniques such as surface plasmon resonance, nuclear magnetic resonance, and supercritical fluid chromatography, among others. Herein, we aim to discuss the history of MS, both electrospray and matrix-assisted laser desorption ionization, specifically for the analysis of antibodies, evolving through to denaturing and native-MS analysis of newer biologic moieties such as antibody-drug conjugates, multispecific antibodies, and interfering nucleic acid-based therapies. We discuss challenging therapeutic target characterization such as membrane protein receptors. Importantly, we compare and contrast the MS and hyphenated analytical chromatographic methods used to characterize these therapeutic modalities and targets within biopharmaceutical research and highlight the importance of appropriate MS deconvolution software and its essential contribution to project progression. Finally, we describe emerging applications and MS technologies that are still predominantly within either a development or academic stage of use but are poised to have significant impact on future drug development within the biopharmaceutic industry once matured. The views reflected herein are personal and are not meant to be an exhaustive list of all relevant MS performed within biopharmaceutical research but are what we feel have been historically, are currently, and will be in the future the most impactful for the drug development process.

Adolf Thierry and the first pharmaceutical factory in Southeast Europe.

The paper explores the beginnings of pharmaceutical industry development in Croatia and the establishment of the first pharmaceutical factory in Southeast Europe. Adolf Thierry de Chateauvieux (St. Pölten, 1854 - Pregrada, 1920), a nobleman hailing from France, immigrated to Croatia at the end of the 19 th century. He bought the Angjelu cuvaru ( Guardian Angel ) pharmacy (1892) in the small town of Pregrada and established the first pharmaceutical factory (1894) in this part of Europe. The factory had an equipped laboratory, a production facility, a storage room for raw materials and balsams, a room for packaging and shipping finished products and a commercial office. Production was mainly based on herbal remedies. The most famous were Thierry's Balsam and Thierry's Centifolia Ointment, both registered and patented in London (1900). By virtue of Adolf Thierry's entrepreneurial spirit and skilful product advertisement, his medicinal preparations were distributed across Europe, America, India and Africa, a testament to which is the well-preserved and researched documentation.

The discovery of insulin revisited: lessons for the modern era.

2021 to 2022 marks the one hundredth anniversary of ground-breaking research in Toronto that changed the course of what was, then, a universally fatal disease: type 1 diabetes. Some would argue that insulin's discovery by Banting, Best, Macleod, and Collip was the greatest scientific advance of the 20th century, being one of the first instances in which modern medical science was able to provide lifesaving therapy. As with all scientific discoveries, the work in Toronto built upon important advances of many researchers over the preceding decades. Furthermore, the Toronto work ushered in a century of discovery of the purification, isolation, structural characterization, and genetic sequencing of insulin, all of which influenced ongoing improvements in therapeutic insulin formulations. Here we discuss the body of knowledge prior to 1921 localizing insulin to the pancreas and establishing insulin's role in glucoregulation, and provide our views as to why researchers in Toronto ultimately achieved the purification of pancreatic extracts as a therapy. We discuss the pharmaceutical industry's role in the early days of insulin production and distribution and provide insights into why the discoverers chose not to profit financially from the discovery. This fascinating story of bench-to-beside discovery provides useful considerations for scientists now and in the future.

Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors.

INTRODUCTION: Medications are compounded when a formulation of a medication is needed but not commercially available. Regulatory oversight of compounding is piecemeal and compounding errors have resulted in patient harm. We review compounding in the United States (US), including a history of compounding, a critique of current regulatory oversight, and a systematic review of compounding errors recorded in the literature. METHODS: We gathered reports of compounding errors occurring in the US from 1990 to 2020 from PubMed, Embase, several relevant conference abstracts, and the US Food and Drug Administration "Drug Alerts and Statements" repository. We categorized reports into errors of "contamination," suprapotency," and "subpotency." Errors were also subdivided by whether they resulted in morbidity and mortality. We reported demographic, medication, and outcome data where available. RESULTS: We screened 2155 reports and identified 63 errors. Twenty-one of 63 were errors of concentration, harming 36 patients. Twenty-seven of 63 were contamination errors, harming 1119 patients. Fifteen errors did not result in any identified harm. DISCUSSION: Compounding errors are attributed to contamination or concentration. Concentration errors predominantly result from compounding a prescription for a single patient, and disproportionately affect children. Contamination errors largely occur during bulk distribution of compounded medications for parenteral use, and affect more patients. The burden falls on the government, pharmacy industry, and medical providers to reduce the risk of patient harm caused by compounding errors. CONCLUSION: In the US, drug compounding is important in ensuring access to vital medications, but has the potential to cause patient harm without adequate safeguards.

Pharmacy in Latvia during the occupation regime of Nazi Germany (1941-1945).

The study covers the period of World War II after shift of occupational powers in Latvia when Soviet occupation was replaced by the occupation regime of Nazi Germany in the summer of 1941 and retained until first half of 1945. Due to this shift gradually Latvia, Lithuania, Estonia and Belarus were merged into a single administrative area and designated as "Ostland". Soviet officials left the pharmaceutical industry, which they had tried to apply to the communist ideology from June 1940 to June 1941 creating confusion and chaos. The renewed Pharmacy Board of Latvia had to deal with the restoration of supervision and a partial return from the communist to the capitalist regime. The research provides an insight to adaptation and development of the pharmaceutical industry in Latvia during Nazi Germany occupation regime, highlighting as essential indicators the administrative operation of Pharmacy Board of Latvia and its cooperation with German authorities, the availability of medicines, process of reprivatisation of pharmacies and changes in the number of pharmaceutical employees. The research issue raised is topical, since it is this period that reflects the industry's ability to adapt and perform work in fundamentally different and severe circumstances, which include both resource deficits and the transition from one regime to another. The collected evidence shows the efforts to stabilize the pharmaceutical industry in many terms. One example was the attemptions to ensure the rational dispensing of medical products to the pharmacies and hospitals, with the greatest degree of austerity, because the supply and consumption of medication was extremely complex issue throughout the war.

MEDICINE AND COLONIAL PATENT LAW IN INDIA: A Study of Patent Medicines and the Indian Patents and Designs Act, 1911 in Early- Twentieth-Century India.

This paper investigates the history of drugs sold as "patent medicines" in India in the early twentieth century. The paper investigates their legitimacy as patenting of medicines was forbidden by the Indian Patents and Designs Act, 1911 (IPDA). The paper argues that the instrument of letters patents functioning as the prerogative of the Crown that gave monopolistic rights to grantees to sell any compound without having to disclose its constituents was the reason behind this seemingly conflicting historical relationship between the law and the market. Colonial law-making left sufficient space within the ambit of the IPDA for letters patents to have their ill effects. The colonial state made attempts to address this as a public health issue by incorporating concerns related to this class of medicines within regulations addressed to the drugs market in the 1930s. The currency of patent medicines in the market was further added to by Indian indigenous entrepreneurs fueled by cultural nationalism of Swadeshi ideology in Bengal in the early twentieth century. However, even such indigenous responses or attempts at hybridization of manufacturing and selling practices related to patent medicines were mostly informed by upper-caste/ upper-class interests and not so much by those of consumers of these medicines.