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The present article analyzes the formation of the first pharmaceutical care policies implemented by the Brazilian Federal Government between 1968 and 1974, during the civil-military dictatorship. It examines a set of measures adopted by the Costa e Silva and Médici governments to contain a continuous rise in the prices of raw materials and pharmaceutical specialties, with this context being essential to the creation of the Medicines Center (CEME) in 1971. The core argument of the article is that CEME represented, at the federal level, the consolidation of a policy carried out at the National Institute of Social Security (Instituto Nacional da Previdência Social - INPS) between 1968 and 1970, based on the production of inputs and medicines in public laboratories. Ended in 1970, this policy was resumed the following year with broad participation of military personnel and laboratories of the Armed Forces. The originality of this article lies in its explanation of how such support influenced the establishment of CEME in its early years. Until 1974, military members were the majority in the Board of Directors of CEME, with some of the agency's early missions being the supplier for Civil-Social Actions of the Armed Forces.

This article proceeds the topic of the article "The development of regulation of the circulation of medicines in the EU and the USA in 1992-2020." The history of development of European pharmaceutical legislation in 2001-2020 is considered. The acts of indirect action adopted by EU Parliament at first stage of development of legislation concerning medications failed to fully harmonize normative base of the EU Member States in pharmaceutical market. Since 2000, the EU Parliament and the EU Council adopt laws of direct action - the Regulations. Alongside with the pharmaceutical Code, the Regulations for single segments of pharmaceutical market constituted set of laws related to turn-over of medications. The legislators, at developing EU laws, took into account the US regulatory standards. Despite differences in history, legislative traditions and structure, regulatory systems of the USA and the EU concerning medications turn-over were basically harmonized.

In the history of Russian pharmaceutical market, the year of 1993 became the year of both formation of rules of market relations and alteration of market landscape for changed conditions. The significant segment of state centralized purchases moved under responsibility of regional authorities and their health authorities. At that, authorizations of former three state organizations occupied with import purchases were distributed between new state companies of the Ministry of Health Care and commercial organizations and firms that entered pharmaceutical market. Pretty soon, this diversity gave rise both to competition for budget funds and Government experiments with market regulation. The traces of these clashes and attempts to make market manageable are found in the Ministry of Health Care archives and journal publications.The Report II uses informational potential of medications prices to decode rules of play in Russian pharmaceutical market with purpose to analyze distributions of power at playing table.

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the history of the Russian pharmaceutical market the year of 1993 became the year of formation of rules of market relations and changing under them of market landscape. The significant segment of state-centralized purchases moved under responsibility of regional authorities and their health care authorities. At that, powers of three former state organizations being occupied with purchases of imported medications were distributed between new state companies of Ministry of Health and commercial organizations and firms that entered pharmaceutical market. This diversity rather soon gave rise to competitive fight for budget funds and experiments of Government with market regulation. The traces of these clashes and attempts to make market regulated can be found in Ministry of Health archives and journal publications. The Report I reveals circumstances of entrance of Ministry of Health into market relationships and its acquisition of market player identity.

Competing Interests: Competing interests: None declared.

Rational prescribing of medicines requires evidence from clinical trials on efficacy, safety and the dose to be prescribed, based on clinical trials. Regulatory authorities assess these data and information is included in the approved summary of product characteristics. Regulatory guidelines on clinical investigation of medicinal products in the paediatric population generally propose that studies are done in defined age groups but advise that any classification of the paediatric population into age categories is to some extent arbitrary or that the age groups are intended only as a guide. The pharmaceutical companies tend to plan their studies using age groups the regulatory guidelines suggest, to avoid problems when applying for marketing authorisation. These age bands end up in the paediatric label, and consequently into national paediatric formularies. The age bands of the most commonly used age-subsets: neonates, infant/toddlers, children and adolescents, are more historical than based on physiology or normal development of children. Particularly problematic are the age bands for neonates and adolescents. The age of 12 years separating children from adolescents, and the upper limit of the adolescents set by the definition of paediatric age in healthcare, which varies according to the region, are particularly questionable. Modern pharmacometric methods (modelling and simulation) are being increasingly used in paediatric drug development and may allow assessment of growth and/or development as continuous covariables. Maybe time has come to reconsider the rational of the currently used age bands., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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 čuvaru ( 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.

This paper reports a pioneering study of an unknown historical drug formulation preserved in the Spezieria of Santa Maria della Scala in Rome, founded at the end of the seventeenth century by the Discalced Carmelites. Due to limited literature related to pharmaceutical remedies and drugs of the Early Modern Era (between the XV and XVIII centuries) and the complexity in their formulations, the study of these drugs represents a great challenge. The untargeted nature of the selected drug required a multi-analytical approach with complementary techniques to formulate a compositional hypothesis: FT-IR spectroscopy, gas chromatography-associated/mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) were successfully employed to identify different organic compounds. Systematic archaeobotanical research was performed as well, allowing us to acquire data related to the possible genus of plants from which these natural compounds derive and their geographical origin. The unknown drug formulation turned out to be a complex mixture used as an ointment with an anti-inflammatory purpose. It mainly contains a mixture of Venetian turpentine; a Pine resin (colophony) from the Pinaceae family; an exudate of a plant from South America, whose identified components are triterpenic compounds such as alpha- and beta-amyrins, betulin and lupeol; and saturated fatty acids which act as carriers and/or to reduce the viscosity of abovementioned exudates and resins. The study of historical drugs is important not only in order to know the practices handed down by the speziali in the past but also to reconstruct historical recipes, which can inspire new dermatological, cosmetic, hygienic and current healing products.Graphical abstract.

The first portable medicine chests appeared in Serbia immediately after liberation from Ottoman rule around 1830. The network of portable medicine chests grew very quickly and became the first effective public health method of supplying medicines and medical items to people living in cities without community pharmacies and to the rural population in villages. According to their purposes, three categories of portable medicine chests could be identified: Portable medicine chests owned by physicians or veterinarians in the cities, portable medicine chests established by the Department of Workers Health Insurance, and portable medicine chests of the Health Cooperatives that operated in the villages This paper analyzes all three types of portable medicine chests. We specifically examine the regulations concerning the management of portable medicine chests, their content, and supply chains of medicines from the third decade of the 19 th century through the first half of the 20 th century. We conclude that portable medicine chests represent a specific type of pharmacy in the territory of Serbia that provided very effective medical service. The medicines in these pharmacies were handled and dispensed to patients by physicians not by pharmacists. Patent medicines, compounded medicines, sanitary items and bandage materials were dispensed as well. Future research is needed to ascertain if physicians who owned or worked with the portable medicine chests actually prepared and compounded simple preparations as they were specified in the laws.

This review presents the early history, the motivation, the research and some of the backstories behind the discovery and development of sulfobutylether-β-cyclodextrin as a novel parenterally safe solubilizer and stabilizer. A specific sulfobutylether-β-cyclodextrin with an average degree of 6.5 sulfobutyl-groups variably substituted on the 2-, 3- and 6-hydroxyls of the seven glucopyranose (dextrose) units of β-cyclodextrin, is known by its commercial name, Captisol®. Today it is in 13 FDA approved injectables and numerous clinical candidates. It is also an example of a novel product discovered and initially preclinically developed at an academic institution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests that could have appeared to influence the work reported in this paper. Professor Stella has consulted for both Gilead and Ligand in the past., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Chemistry as experimental science began in the seventeenth century, when it began moving away from being one of the alchemical doctrines and toward analyzing matter and its transformations using scientific methods. Previously, the ancient Pre-Socratic philosophy through observation of nature was concerned with the laws that govern the natural world and the property of matter. Later, the Hellenistic Alexandrian culture took possession of the Hermetic doctrines of the Egyptians, mixing them with pre-Socratic thought and Gnosticism. At this historical moment, therefore, there was a fusion of the Greek philosophical patrimony and the Hellenistic and Alexandrian influences on medicine. The Hermetic gnosis evolved over time to become alchemy and then to usher in the birth of chemical science. Many doctors were wandering philosophers who dealt with cosmogony to understand the body and diseases and to discover new healing drugs for treatment, and thus they were the first chemist therapists., Methods: The influence of ancient physicians through the pre-Socratic philosophy for these prochemical theories and practice has been researched through ancient texts, so these texts have been referenced to determine the legacy of paleo-chemicals doctrines., Results: The study of various texts in particular from the Pre-Socratic age and the eminent physicians underline that, despite a different approach to the cosmogonic concepts of nature and the matter, the medicine of that age had an important influence on chemistry as an experimental science, especially concerning therapy with drugs., Conclusion: The Pre-Socratic philosophers have influenced the medical practice and guided it toward the concept of the properties of matter for medical treatment and an understanding of the causes of diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the late nineteenth century, as in other regions of Argentina and Latin America, the Santa Fe press featured a growing number of offers of health products such as tonics, pills and syrups. Aimed at a lay audience, these claimed to cure a series of conditions defined as belonging to "modern life." This article analyzes the discursive dimension of the advertisements printed between 1890 and 1918: how they organized meanings associated with these conditions, an issue that is inscribed within a broad line of research aimed at analyzing social representations of health and disease, and how they participated in the different social spheres in the constitution of modern-day Argentina.

It is time to celebrate the 125th anniversary of the first successful attempt to develop and use a specific high-titer antitoxic serum for treating diphtheria, a deadly infectious disease. This was followed by major advances in passive immunotherapy 75 years ago (production of pooled human IgG for subcutaneous injection) and 50 years ago (widespread technology for producing immunoglobulin preparations for intravenous administration). More than 200 tons of pooled human IgG are produced per year worldwide. The preparation is used primarily for IgG substitution in patients with primary and secondary immunodeficiencies, as well as for an immunomodulating treatment of a growing number of autoimmune and inflammatory diseases. These preparations contain the pooled IgG antibody repertoire of a large population of healthy plasma donors. This repertoire includes antibodies that neutralize pathogens and their factors of virulence, anti-idiotypic antibodies, and antibodies to other foreign and own proteins, as well as to carbohydrate antigens. Naturally polyspecific antibodies that are present in all healthy individuals play an important role as a first-line defense against bacteria and viruses. After exposure to protein-modifying agents, some IgG molecules can acquire the ability to bind novel structurally unrelated antigens. This phenomenon is referred to as induced polyspecificity. The list of these protein-modifying molecules was shown to include low-pH buffers, free heme, pro-oxidative ferrous ions, reactive oxygen species, etc. Such modified antibody preparations may have a therapeutic potential, since their administration to animals with experimental sepsis or aseptic systemic response syndromes significantly improved survival rates, while the same dose of the native preparation had no effect. We also hypothesize that the aggressive protein-modifying molecules released in sites of inflammation and tissue damage could also modify the antigen-binding behavior of surface immunoglobulin B cell receptors and the structurally related T cell receptors. This "specificity editing" of both types of receptors may play a major role in the body's defense mechanisms.

This article provides a history of three pharmaceuticals in the making of modern South Africa. Borrowing and adapting Arthur Daemmrich's term 'pharmacopolitics', we examine how forms of pharmaceutical governance became integral to the creation and institutional practices of this state. Through case studies of three medicaments: opium (late 19th to early 20th century), thalidomide (late 1950s to early 1960s) and contraception (1970s to 2010s), we explore the intertwining of pharmaceutical regulation, provision and consumption. Our focus is on the modernist imperative towards the rationalisation of pharmaceutical oversight, as an extension of the state's bureaucratic and ideological objectives, and, importantly, as its obligation. We also explore adaptive and illicit uses of medicines, both by purveyors of pharmaceuticals, and among consumers. The historical sweep of our study allows for an analysis of continuities and changes in pharmaceutical governance. The focus on South Africa highlights how the concept of pharmacopolitics can usefully be extended to transnational-as well as local-medical histories. Through the diversity of our sources, and the breadth of their chronology, we aim to historicise modern pharmaceutical practices in South Africa, from the late colonial era to the Post-Apartheid present., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The standard of weights and measures of medicines in the Han Dynasty has always been an important topic in the study of the ancient Chinese medical history. However, the difference of titles and systems of measurement units recorded in different literature are quite diverse and short of material evidences for a long time, leading to a long debate on the research of ancient measuring system of medicines. The titles in the newly announcing inscriptions of a series of the measuring system of dosages of Eastern Han Dynasty, carried on the 4 containers are ge, yue, cuo and dao gui, confirming the measuring system of the Han Dynasty for the first time. Through actual measurement, the numerical values of ge, yue, cuo, dao gui are 20ml, 10ml, 2ml, and 0.5 ml respectively, and the calculating equation are: 1 ge = 2 yue, 1 yue = 5 cuo, 1 cuo = 4 dao gui . These values were basically the same as the official measuring containers of the Han Dynasty, demonstrating that the official weights and measures system for medicines was adopted by the Eastern Han Dynasty. The appearance of the new measuring tool, fang cun bi (square-inch-spoon), reveals its actual morphology which is frequently mentioned in the Han-Tang's classical recipes yet unable to witness this actual object. This measuring system is significant to the studies of ancient weights and measures of medicines.

Anesthesiologists and intensivists are modern professionals who provide conscious sedation and respiratory care and prescribe medicines with potential toxicity. Similarly, ninjas, covert agent soldiers who carried out special operations in medieval Japan, also had ample knowledge of toxicology, psychology, human consciousness and respiration. Although the extent of their knowledge remains largely unknown, that which has been described in the literature appears to be practical and scientifically explainable from the standpoint of modern medical science., (Copyright © 2018 Elsevier Inc. All rights reserved.)

New drugs introduced to the market every year represent privileged structures for particular biological targets. These new chemical entities provide insight into molecular recognition while serving as leads for designing future new drugs. This annual review describes the most likely process-scale synthetic approaches to 19 new chemical entities that were approved for the first time in 2016.

This article retraces the history of an old medicine chest, used at the beginning of the 19th century, but probably designed earlier. Possibly made in A ustria, with a two-headed eagle lining the bottom of the lid, this first-aid kit belongs to a small group of related chests. It should be noted that these chests were used for a wide variety of different purposes over time. Also named a «droguier» in French, this light chest, made of walnut, and, according to family lore, found in Normandy, would have belonged to a doctor, as confirmed by a short invoice found among numerous documents. The identity of the supplier of numerous old medicines is shown on the labels on the flasks (many of which are intact) and other boxes (containing, in particular, herbal drugs) : «Clément, Apothicaire. Rue St Onge N°. 42. près le Bd. du Temple A Paris», whose history is recounted here step by step.

JBA Chevallier is first known for his publication in 1850 of his book on falsifications. But he had also a major role for the opening of the pharmacy world to toxicological and Public Health issues, through the founding in 1825, and the management for more than 50 years, of the Journal de chimie médicale, de pharmacie et de toxicologie (Journal of Medical Chemistry, of Pharmacy and of Toxicology). The purpose of the present study has been to look at the evolution of that publication over the years and to compare its content with the reference pharmaceutical journal at that time : the Journal de pharmacie et de chimie (Journal of Pharmacy and Chemistry). One can observe that the editorial lines of both journals will progressively diverge from each other, but Chevallier remained strongly connected with pharmacy, his journal merging finally in 1876 with the Répertoire de pharmacie (Index of Pharmacy).

This article examines traditions of testing drugs (as substances) and trying cures (on patients) in medieval and early modern Europe. It argues that the history of drug testing needs to be a more central story to overall histories of scientific experiment. The practice of conducting thoughtful-and sometimes contrived-tests on drugs has a rich and varied tradition dating back to antiquity, which expanded in the Middle Ages and early modern period. Learned physicians paired text-based knowledge (reason) with hands-on testing (experience or experiment) in order to make claims about drugs' properties or effects on humans. Lay practitioners similarly used hands-on testing to gain knowledge of pharmaceutical effects. Although drug testing practices expanded in scale, actors, and sites, therpublished a work extolling the virtues of drugs froe was significant continuity from the Middle Ages to the eighteenth century.

Among Galenic texts attracting attention circa 1300 was De complexionibus, which described a crude protocol for determining the qualitative character and intensity of any given medicine. This caught the attention of physicians at Montpellier, where three generations of writers made it into a carefully structured test procedure for identifying by a via experimenti the nature of a drug's effect on healthful function: they introduced a null point as the referent for their measurements, identified a range of contingent factors that had to be controlled for, and devised ways to standardize the sample being tested. Their protocol was certainly designed to be used, but in practice they seemed to have preferred an alternative via rationis that inferred the effect of a medicine from sensory attributes like taste and color, acknowledging that taste tests were coarser and less certain than a structured experimental procedure, but were easier and quicker to perform than the elaborate alternative.

This article explores the role of testing in the allocation of royal monopoly privileges for drugs in eighteenth-century France by following the multi-generational fortunes of a single "secret remedy" from 1713 to 1776: the poudre fébrifuge of the Chevalier de Guiller. On at least five occasions, this drug was tested on patients in order to decide whether it should be protected by a privilege and whether or not its vendors should be awarded lucrative contracts to supply it in bulk to the French military. Although efforts were made early in the century to test the drug through large-scale hospital trials and to relegate privilege granting to a bureaucratic commission, the case of the poudre fébrifuge instead suggests that military expediency and relatively small-scale trials administered personally by royal practitioners remained decisive in determining whether or not a drug received a monopoly privilege or a military contract.

The attitudes of physicians and drug manufacturers in the US toward patenting pharmaceuticals changed dramatically from the mid-nineteenth century to the mid-twentieth. Formerly, physicians and reputable manufacturers argued that pharmaceutical patents prioritized profit over the advancement of medical science. Reputable manufactures refused to patent their goods and most physicians shunned patented products. However, moving into the early twentieth century, physicians and drug manufacturers grew increasingly comfortable with the idea of pharmaceutical patents. In 1912, for example, the American Medical Association dropped the prohibition on physicians holding medical patents. Shifts in wider patenting cultures therefore transformed the ethical sensibilities of physicians.

At the end of the Middle Ages, in 1492, the Hôtel-Dieu de Paris was still and establishment of charity intended to receive thepoor which came there to find a shelter and some food. Three centuries later, just before the French Revolution, it became an establishment of care mainly destined to receive the patients, to feed them, take care of them and if possible cure them. This medicalization of the Hôtel-Dieu de Paris is related to the progressive emergence of the medical function, which resulted in the creation and the development of a doctor's and surgeon's profession, but also in the development of the apothecary and its drugs. In this context, the diet plays a central part, because it happens to supplies. It would not be until the eve of the French Revolution that it would be integrated in the doctor's prescription and became a dietetic item.

Considered by many to be the most learned Portuguese physician who lived in Goa during the sixteenth century, Garcia de Orta (c. 1500-1568) was the author of CoIoquios dos Simples, e Dro gas he cousas medicinais da India [Colloquies on the Simples and Drugs of India] (Goa, 1563). Devoted entirely to the description of Asian natural resour ces, very little is known about how this treatise came into existence. Publish ed at the edges of the Portuguese empire, and a hostage to technical, structural and human constraints, the princeps edition had a limited circulation. The diffusion around Europe of the novelties described in Col6quios dos Simples owed in part to the efforts of Clusius (1526-1609), one of the leading botanists of the time. This scholar promptly published Aromatum et Simplicium (Antwerp, 1567), a Latin epitome of Coloquios dos Simples. This complete reframing of Orta's treatise guaranteed the wide dissemination of the new knowledge about Asian plants, fruits and drugs validated by the Portuguese physician on the periphery of the empire. In this essay I analyse the background to the publication of the Portuguese treatise and demonstrate that, especially due to structural constraints, the princeps edition had a limited circulation. I show that the wide diffusion of the novelties about the natural resources of the Indies was dependent on the technical equipment, artistic skills and editorial criteria dictated and managed by European academics, artists and printers. I propose that the appropriation of local knowledge collected and validated in the Iberian Empires by imperial agents challenged European academics and typographers to create innovative treatises about the Indies' natural resources that assured the widespread circulation of an entirely new natural knowledge.

Historically, pharmaceutical industry regulatory guidelines have assigned certain active pharmaceutical ingredients (APIs) to various categories of concern, such as "cytotoxic", "hormones", and "steroids". These categories have been used to identify APIs requiring segregation or dedication in order to prevent cross-contamination and protect the quality and safety of drug products. Since these terms were never defined by regulatory authorities, and many novel pharmacological mechanisms challenge these categories, there is a recognized need to modify the historical use of these terms. The application of a risk-based approach using a health-based limit, such as an acceptable daily exposure (ADE), is more appropriate for the development of a Quality Risk Management Program (QRMP) than the use of categories of concern. The toxicological and pharmacological characteristics of these categories are discussed to help identify and prioritize compounds requiring special attention. Controlling airborne concentrations and the contamination of product contact surfaces in accordance with values derived from quantitative risk assessments can prevent adverse effects in workers and patients, regardless of specific categorical designations to which these APIs have been assigned. The authors acknowledge the movement away from placing compounds into categories and, while not yet universal, the importance of basing QRMPs on compound-specific ADEs and risk assessments. Based on the results of a risk assessment, segregation and dedication may also be required for some compounds to prevent cross contamination during manufacture of APIs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This manuscript discusses the different historical and more recent default approaches that have been used to derive an acceptable daily exposure (ADE). While it is preferable to derive a health-based ADE based on a complete nonclinical and clinical data package, this is not always possible. For instance, for drug candidates in early development there may be no or limited nonclinical or clinical trial data. Alternative approaches that can support decision making with less complete data packages represent a variety of methods that rely on default assumptions or data inputs where chemical-specific data on health effects are lacking. A variety of default approaches are used including those based on certain toxicity estimates, a fraction of the therapeutic dose, cleaning-based limits, the threshold of toxicological concern (TTC), and application of hazard banding tools such as occupational exposure banding (OEB). Each of these default approaches is discussed in this manuscript, including their derivation, application, strengths, and limitations. In order to ensure patient safety when faced with toxicological and clinical data-gaps, default ADE methods should be purposefully as or more protective than ADEs derived from full data packages. Reliance on the subset of default approaches (e.g., TTC or OEB) that are based on toxicological data is preferred over other methods for establishing ADEs in early development while toxicology and clinical data are still being collected., (Copyright © 2016. Published by Elsevier Inc.)

This article analyzes why adulteration became a key trope of the Indian drug market. Adulteration had a pervasive presence, being present in medical discourses, public opinion and debate, and the nationalist claim for government intervention. The article first situates the roots of adulteration in the composite nature of this market, which involved the availability of drugs of different potencies as well as the presence of multiple layers of manufacturers, agents, and distributors. It then shows that such a market witnessed the availability of drugs of diverse potency and strengths, which were understood as elements of adulteration in contemporary medical and official discourse. Although contemporary critics argued that the lack of government legislation and control allowed adulteration to sustain itself, this article establishes that the culture of the dispensation of drugs in India necessarily involved a multitude of manufacturer-retailers, bazaar traders, and medical professionals practicing a range of therapies.

The article series provides a written and pictorial account of the Danish pharmaceutical industry's products from their introduction until about 1950. Part 8 deals with products from Lundbeck. Lundbeck which today is known as a considerable international pharmaceutical company could in 2015 celebrate its 100 years' jubilee. Among the early Danish medicinal companies H. Lundbeck & Co. is in many ways an exception as the company was not originally established as a pharmaceutical company. Not until several years after the foundation the company began to import foreign ready-made medicinal products and later-on to manufacture these medicinal products in own factory and even later to do research and development of own innovative products. When Lundbeck was established in 1915 several Danish medicinal companies, not only the well-known such as Alfred Benzon and Løvens kemiske Fabrik (LEO Pharma), but also Skelskør Frugtplantage, Ferrin and Ferraton, had emerged due to the respective enterprising pharmacy owners who had expanded their traditional pharmacy business and even with commercial success. Other medicinal companies, such as C.R. Evers & Co., Leerbeck & Holms kemiske Fabriker, Chr. F. Petri, Erslevs kemiske Laboratorium, Edward Jacobsen, Th. Fallesen-Schmidt, and yet other companies which were named after the founder had all been established by pharmacists with the primary intention to manufacture and sell medicinal products. Also for the limited companies Medicinalco, Ferrosan, Pharmacia, and GEA the primary task was to manufacture and sell medicinal products, and also in these companies pharmacists were involved in the foundation. Not until 1924, fully 9 years after the foundation, Lundbeck started to be interested in medicinal products and initiated import and sale of foreign medicinal products manufactured by a.o. German and French companies which had not established their own sales companies in Denmark. Almost all contemporary Danish manufacturers of medicinal products could exclusively determine own proprietary names of the articles and could themselves make their own homogeneous and easily recognisable design, a.o. by frequent use of prefixes as Afa, Asa, Gea, Ido, Leo, and Meco which associated to for instance the company name. However, it goes without saying that Lundbeck had to market the articles in commission according to the different contracts with their partners. Consequently their range of products appeared heterogeneously. The international financial crisis and the consequent unemployment in the 1920s and 1930s had in Denmark a.o. resulted in national regulation in order to complicate import of ready-made goods and thus support the domestic manufacture of such articles. This was one of the reasons why Lundbeck decided to initiate its own manufacture of medicinal products in Denmark instead of continuing only with the import business which had been obstructed by the authorities. This article does not mention all Lundbeck's medicinal products which were marketed in Denmark until 1955 where a new Pharmacy Act came into force though undoubtedly a lot of interest can be written about all of them. The products mentioned in this article have been carefully selected, not only because they are representative for Lundbeck's development during the first decades, but also because the Danish Collection of the History of Pharmacy has acquired consumer packages of many of the articles. Several of these packages include patient information leaflets with an instruction for use and/or other information, and especially these leaflets represent a source material which has not previously been given much attention. It does not appear from the available source material whether these earliest medicinal products from Lundbeck were assembled in Danish packages on the production sites, or whether they were repacked in Copenhagen. It is not unlikely that the assembling originally was finalized abroad, and that instructions for the production of packaging material with Danish text were supplied by Lundbeck to the respective manufacturers. However, it is not unlikely either that the currency restrictions which were made after 1932 encouraged Lundbeck, where possible, first of all to import raw materials and bulk products and then manufacture the finished products in Valby. This was the case with Anusol, which Lundbeck certainly emphazised in the advertisement. It has to be pointed out that at that time there were no legal requirements regarding dating, neither of the user instructions nor of advertisements. Thus it is not due to mistakes or omissions made by Lundbeck that these materials are undated. The user instructions which Lundbeck had inserted in the packages were made and distributed at a time where no legal restrictions were in force neither regarding form nor content of such. The user instructions for products marketed after 1932 had probably been presented to the Pharmacopoeia Commission as this was statutory. It is, however, uncertain whether the Commission has dealt with the contents and the look of the user instructions. The most important task of the Commission was besides of the work with maintaining the Pharmacopoeia to look after the economic interests of the pharmacies so that only new drug substances could be marketed by the pharmaceutical industry, cf. below. In order to find out whether, and if so to which extent, the Pharmacopoeia Commission has been occupied in evaluating the informative and promoting printed matters of the industry, would require studies of the unprinted files of the Commission, and that is outside the scope of this article. At that time it was not against the law to inform in a user instruction that in case of a longer period of treatment, it would be more economical for the patient to buy a larger package. If you look at these patient information leaflets with today's eyes in the light of the present detailed, comprehensive and rigid regulations which the EU Commission has stated regarding patient information leaflets, you will find that Lundbeck's patient information leaflets were both simple and easy to read. On a free sample of Gelonida meant for the prescribing physician Lundbeck stated, besides of indication, dosage and warnings, also that the article was "Manufactured in Denmark". At that time it was not required to print information of production sites on packaging materials, however, it was not unusual to use this sales promoting claim in times of unemployment. In 1949 the original packaging material for Beatin was modified because certain text elements, the therapeutic indications were removed as it appeared that they since 1933 had violated the Pharmacy Act against advertisements for medicinal products aimed at the public. The packaging material for Beatin is a model example of the possibilities to combine practical information about the use of a medicinal product with sales claims in a reliable way. The above text modification and thus the legalisation of the packaging material took place upon request from the company as the violation of the advertising rules of the Pharmacy Act apparently had not resulted in any legal problems. Studies of unpublished files from the National Board of Health may possibly explain the background of this sequence of events, however, that is outside the scope of this article. The paragraph of the Pharmacy Act of 1932, stating that a medicinal product containing a common commodity as the active ingredient could not be marketed as a proprietary medicinal product, was meant to protect the pharmacies against the increasing competition from the industry. At first the paragraph did put a strain on the industry which from then on either had to manufacture own originator products or to copy other originator products without breaking patents. In the long run it has probably caused that not only Lundbeck, but also other Danish pharmaceutical companies became research-oriented and thus have been able to develop a relatively large number of originator products. In this context a product like Lucamid can hardly be regarded as an example of such a compulsory development of an originator product, an acetylsalicylic acid analogue. There were already such products on the market, but the wish to develop a better active ingredient has probably been bigger. From the three first editions of The Tariff of Medicines from 1935, 1937 and 1939 respectively it appears how Lundbeck's business within the area of medicines developed during the last half of the 1930s. In 1935 Lundbeck had placed 36 different medicinal products on the market, and all of them were in-licensing products. 4 years later, in 1939 Lundbeck had placed 40 different medicinal products on the market, and the number of in-licensing products had been reduced to 18 and 22 products were Lundbeck products. However, the increased focus on the development of own new medicinal products as Epicutan and Klianyl did not stop the in-licensing activities. Varex which Lundbeck brought on the market in 1942 came from a German pharmaceutical company with which Lundbeck had not previously collaborated. In Denmark Lundbeck had the intention to market 4 of Goedecke's 6 different medicinal products which all had Gelonida as part of the proprietary name. However, only one of these products got a longer life and with a simplified name, namely Gelonida. The fixed combination with three compounds of acetylsalicylic acid, phenacetin and codeine was without doubt effective, however, already at the end of the 1950s concern was raised about the safety of phenacetin. The Card Index of Medicines is a primary source of knowledge of how Lundbeck marketed the earliest medicinal products to the prescribing physicians. (ABSTRACT TRUNCATED)

For several convergent reasons, 1915 was a key period for the pharmaceutical industry in France. The overall realization that France was dependent on Germany for chemical and pharmaceutical products came from shortages of key drugs but also from massive use of poison gas for which France was not able to face this unexpected event. France's shortage for chemists properly trained to answer the needs of industry, the weak relationship between industry and faculty, the uncomfortable situation of specialty drugs, the regulations on patents and trademarks were many subjects of controversies which will contribute to the analysis of the source of this French dependence to Germany. It will be at the origin of new orientations after the war for the pharmaceutical industry and the French society. The objective was to be independent for drugs and consequently to resolve the identified issues, as well as to have a dynamic industrial research. The creation and development of several pharmaceutical companies after the war was a more or less direct benefit from the considerations starting in 1915.

Those sketches, restaured by the French "Institut national de l'audiovisuel", are transcribed and analyzed for the first time. They was probably broadcasted during the summer of 1939 by the private station Radio Gard Nîmes.

Ethnopharmacological Relevance: This paper speaks to the theme of the boundaries of food and medicine as constructed in the Greek and Roman worlds. It examines how physicians developed innovative ways of thinking about the body that did not attribute health and sickness to the intervention of gods. Ancient physicians and natural historians conceived of new potencies for substances and described their impact on the body׳s physiology between the late fifth century BC and the early third century AD. The legacy of these ideas and practices had great traction in the Mediterranean world and survived into Early Modern Times, and until the rise of new forms of science., Materials and Methods: This article analyses texts transmitted from the ancient world and considers how substances were attributed nutritional and medical potency. The texts relevant to this analysis include medical and philosophical treatises as well as cookery books. The article highlights discussions about the nature of food and drugs and the herbs thought to cross the boundaries between them. It interrogates different contexts within which foods were thought good or bad for the body, and the social and moral connotations attached to those perceptions., Conclusion: Much of the analysis is devoted to understanding the flavours that were a key marker in the nutritional potencies attributed to foodstuffs. However there are clear and influential moral boundaries set by Plato in the discourse around food and pleasure. While every physician should be a chef, and many wrote cookery books that have been lost, a chef׳s talent was located in increasing pleasure, and therefore a less valuable skill. However the different literary genres show overlapping terminology and concerns, particularly with the quality of ingredients. Poor taste was not only a culinary concern. With regard to the setting of boundaries between foods and medicines, the transition between one category and another is frequently determined by the preparation and strengthening of a food׳s potency., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The debate on the food-drug continuum could benefit from a historical dimension. This study aims at showing this through one case: the food-drug continuum in Greece in the fifth- and fourth-century BCE. I suggest that at the time the boundary between food and drug - and that between dietetics and pharmacology - was rather blurred., Materials and Methods: I study definitions of 'food' and 'medicine' in texts from the fifth- and fourth-century BCE: the Hippocratic texts, the botanical treatises of Theophrastus and the pseudo-Aristotelian Problems. To illustrate these abstract definitions, I focus on two substances: garlic and silphium., Results and Discussion: The Hippocratics were writing in a context of increased professionalization and masculinization of medicine, a context in which dietetics became the most prestigious branch of medicine, praised above pharmacology and surgery. While medicine was becoming more specialised, professionalised and masculine, it avoided becoming too conspicuously so. The Hippocratic authors sometimes noted that medical discoveries are serendipitous and can be made by anyone, whether medically trained or not. By doing so, they allowed themselves to integrate common knowledge and practice into their writings., Conclusion: In the context of the professionalization of ancient medicine, the Hippocratic authors started to address the difference between food and medicine. They saw, however, some advantage in acknowledging the continuum between food and medicine. Scholars should avoid drawing too strict a boundary between ancient dietetics and pharmacology and should instead adopt a multi-disciplinary approach to the therapeutics of the Hippocratic texts., (Copyright © 2014 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.)

Since Antiquity, oyster is a subject of interest and medical use, as indicated by Oribiase and Galien. From the 17th century, this unique drug was proposed by physicians for various diseases, and more often for (la rage). One could think that that drug disappeared at the 20th and 21st centuries. But we can observe that it was still recommended by several authors as drug. Still today, companies offer oyster under various forms for allopathic and homeopathic treatments, as well as for food supplement. Research are ongoing to discover active substances within oyster and their potential medical interests.

In this article, the author examines the claims of the pharmacist Adolphe René Le Brun, assignee of the trademark "Coricide russe". Litigation and trials are reported. Some hypotheses are studied. But for now, no final award is considered.

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems., (© 2015 The British Pharmacological Society.)