Pharmaceutical Regulation Research Articles

COVID-19 off-label uses of medicines: the role of civil liability and regulation.

Physicians can prescribe medicines for different indications than the tested and authorised ones. Such 'off-label' uses expand therapeutic options but also create uncertainties. The COVID-19 pandemic triggered new off-label uses and, despite issues being reported in the literature, these have not resulted in substantial personal injury litigation in the EU. Against this backdrop, this article argues that civil liability plays, in fact, a limited role in off-label uses. In particular, civil liability may incentivise health actors to follow and react to the development of the evidence basis for off-label uses. However, it is ultimately unable to incentivise the conduct of additional research on off-label uses. This is problematic, as off-label research is key to protecting patients and is recommended by international medical ethics. The article concludes by critically discussing proposed mechanisms to incentivise off-label research. It argues that extending civil liability for unknown risks may have undesired effects on insurability and innovation, and most regulatory proposals seem ineffective. Building on the 2014 Italian reform of off-label uses, the article proposes the establishment of a fund financed by mandatory contributions from the industry, which should be used by pharmaceutical regulators to promote off-label research and develop guidelines for prescribers.

Antimicrobial resistance in Democratic Republic of Congo: the way forward

Antimicrobial resistance in Democratic Republic of Congo: the way forward

Maternal migraine and risk of pediatric cancers.

Maternal migraine has been linked to adverse birth outcomes including low birth weight and preterm birth, as well as congenital anomalies in offspring. It has been speculated that this may be due to the use of medications in pregnancy, but lifestyle, genetic, hormonal, and neurochemical factors could also play a role. There is evidence for varying cancer incidences among adults with migraine. Here, we utilized data from national registries in Denmark to examine associations between maternal diagnoses of migraine and risk for cancer in offspring. We linked several national registries in Denmark to identify cases from the Cancer Registry among children less than 20years (diagnoses 1996-2016) and controls from the Central Population Register, matched to cases by birth year and sex (25:1 matching rate). Migraine diagnoses were identified from the National Patient Register using International Classification of Diseases, versions 8 and 10 codes and migraine-specific acute or prophylactic treatment recorded in the National Pharmaceutical Register. We used logistic regression to estimate the risk of childhood cancers associated with maternal migraine. Maternal migraine was positively associated with risk for non-Hodgkin lymphoma (odds ratio [OR]=1.70, 95% confidence interval [CI]: 1.01-2.86), central nervous system tumors ([OR=1.31, 95% CI: 1.02-1.68], particularly glioma [OR=1.64, 95% CI: 1.12-2.40]), neuroblastoma (OR=1.75, 95% CI: 1.00-3.08), and osteosarcoma (OR=2.60, 95% CI: 1.18-5.76). Associations with maternal migraine were observed for several childhood cancers, including neuronal tumors. Our findings raise questions about the role of lifestyle factors, sex hormones, genetic, and neurochemical factors in the relationship between migraine and childhood cancers.

What condition leads to an unreasonable pharmaceutical price? Impact research on the effect of medical service provision on pharmaceutical price regulation based on fuss-set QCA.

Given that the pharmaceutical market has experienced severe market failures, it is necessary that we regulate pharmaceutical prices for many countries. Toward ensuring that pharmaceutical price regulation is efficient, this study investigated the antecedents that lead to an unreasonable pharmaceutical price. Based on 33 case-study countries, this study utilized QCA to analyze the conditional configuration of unreasonable pharmaceutical prices from the perspective of medical service provision. The results showed that the causes of unreasonable pharmaceutical prices are configured by medical service provision, especially cost compensation systems and payment mechanism. This study's conclusions contribute to the research on pharmaceutical price regulation and the institution of medical service provision.

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

BackgroundIn 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.MethodsUsing 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.ResultsRegistration 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.ConclusionUnderstanding 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.

English

To some Cannabis is antisocial anathema, to others it is a harmless sedative-hypnotic, or narcotic analgesic and to others it occupies a cultural position as religious sacrament. Some fear its use leads to psychosis and addiction; to others still it is a legal anomaly and should be decriminalized. Whatever the case may be, in Africa where Cannabis is a recreational drug. It is caught in a bizarrely legal and regulatory maze. Regulations are changing internationally and the Cannabis industry is growing. African, National Medicines Regulatory Authorities, NMRs, have to catch up. But unfortunately some lack competent professionals who require to understand regulatory science, RS, in general, and in particular as it pertains to cannabis products with complex pharmacology. RS is “a range of scientific disciplines that are applied - intellectually and practically - to the quality, safety and efficacy assessment of medical products and that inform regulatory decision making, throughout the life cycle of a medical/health product”. RS helps to answer the following questions: Is there a pathway that will lead cannabis to mainstream medicine in Africa? Will cannabis as a botanical agent have to follow the same time-honoured process that any pharmaceutical must attain to receive regulatory approval? There is no doubt the cannabis and regulatory sciences are going to influence the future shaping and implementation of pharmaceutical medicine laws and regulations in Africa. The aim of the article is to highlight the key regulatory science challenges, in Africa, that belong to either a societal or a biomedical sphere regarding Cannabis for adult use or medicinal purposes or nutrition. Key words:  Cannabis, regulatory science, challenges, Africa.

Construction of a Zinc Oxide Nanorod-Modified Coated Wire Electrode for Potentiometric Determination of Levocetirizine Dihydrochloride in Its Pure and Combined Form.

Coated wire electrodes (CWEs) are considered the most effective and selective type of ion- selective electrodes because of the electroactive materials which are used in surface modification. This study aims to construct the first potentiometric method for analysis of levocetirizine (LVZ) in its combination form with montelukast (MON) drug. A novel potentiometric sensor which consists of a silver wire coated with zinc oxide (ZnO) nanorod modified with a polymeric membrane (combining β-cyclodextrin and tetraphenyl borate, and plasticized with di-butyl phthalate) was constructed for the determination of LVZ·2HCl in its pure form and its combination dosage form. The fabricated sensor exhibited a linearity range of 5 × 10-6-1 × 10-2 mol/L with a Nernstian slope 57.88 mV/decade over the pH range 2-4.5. The effect of temperature on the constructed sensor was studied and it was found that the electrode worked effectively over 10-50°C. The electrode showed a fast response time and the lifetime of the electrode was found to be 72 days without significant change in the Nernstian slope value. The selectivity of the electrode toward LVZ was estimated in the presence of some obstructive ions. The method was validated according to International Council for Harmonisation of Technical Requirments for Registration of Pharmaceuticals for Human Use (ICH) rules and applied to the determination of LVZ in its pure and combined pharmaceutical dosage forms. This article introduces the synthesis of the first coated wire electrode modified with zinc oxide (ZnO) nanorods for the determination of the drug levocetirizine. The results demonstrate the ability of electrochemical methods to analyze drugs in combination. The presented method excels over the other analytical methods in terms of sensitivity, selectivity, and simplicity.

Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography Methods

Dapagliflozin is a novel sodium-glucose cotransporter type 2 inhibitor. This work aims to develop a new validated sensitive RP-HPLC coupled with a mass detector method for the determination of dapagliflozin, its alpha isomer, and starting material in the presence of dapagliflozin major degradation products and an internal standard (empagliflozin). The separation was achieved on BDS Hypersil column (length of 250mm, internal diameter of 4.6 mm and 5-μm particle size) at a temperature of 35℃. Water and acetonitrile were used as mobile phase A and B by gradient mode at a flow rate of 1 mL/min. A wavelength of 224nm was selected to perform detection using a photo diode array detector. The method met the requirement of the International Conference on Harmonisation for Registration of Pharmaceuticals for Human Use (ICH) for validation. The molecular weight of impurities and degradation products was estimated using positive ESI-MS. Fifteen impurities were detected during the analysis of dapagliflozin APIs and the brand Farxiga ® and some generic products. Three of fifteen detected impurities (H, J and K) exceeded the impurities acceptable limits 0.1%. Those impurities were isolated using new preparative chromatography then characterized using elemental analysis, FTIR and NMR.

Against Evidential Pluralism in Pharmaceutical Regulation

AbstractWe examine arguments regarding the use of mechanistic evidence in assessing treatment efficacy and find that advocates and critics of EBM+ have largely been talking past each other due to a difference in focus. We explore aducanumab for the treatment of Alzheimer’s disease as a case that may speak to the role of EBM+ in pharmaceutical regulation. The case suggests the debate may be more fruitful if philosophers confine debates to particular domains of medicine and weigh in prospectively instead of relying on historical cases in which outcomes are known and that are susceptible to hindsight bias.

Pharmaceutical regulation under market integration through parallel trade

AbstractIn this paper, I study the effect of parallel trade (cross‐border resale of goods without the authorization of the manufacturer) on pharmaceutical regulation. Governments may restrict prices directly (price caps) or limit third‐party payer reimbursement for the drug (reimbursement limits). I find that parallel trade may relax regulation in the source country of parallel imports under both instruments and intensify regulation in the destination country under a reimbursement limit. I also find that parallel trade may change regulatory preferences: under no parallel trade, both the source and destination country set price caps, and under parallel trade, the source country sets a price cap but the destination country sets a reimbursement limit, thereby enforcing a higher price cap in the South. This implies that drug prices are higher under parallel trade in both source and destination countries.

Desert Endemic Plants in Algeria: A Review on Traditional Uses, Phytochemistry, Polyphenolic Compounds and Pharmacological Activities

Due to their robust antioxidant capabilities, potential health benefits, wide variety of biological activities, and strong antioxidant qualities, phenolic compounds are substances that have drawn considerable attention in recent years. The main goal of the review is to draw attention to saharian Algerian medicinal plants and the determination of their bioactivity (antioxidant, anti-cancer, and anti-inflammatory importance), and to present their chemical composition as well as in vivo and in vitro studies, clinical studies, and other studies confirming their real impact on human health. Research results have revealed a rich variety of medicinal plants used to treat various disease states in this region. Based on in vivo and in vitro studies, biological activity, and clinical studies, a list of 34 species of desert plants, belonging to 20 botanical families, useful both in preventive actions and in the treatment of neoplastic diseases has been established, and polyphenolic compounds have been identified as key to the health potential of endemic diseases and desert plants. It has been shown that people who follow a diet rich in polyphenols are less prone to the risk of many cancers and chronic diseases, such as obesity and diabetes. In view of the increasing antioxidant potential of these plant species, as well as the increasing trade in herbal products from the Sahara region, phytosanitary and pharmaceutical regulations must change in this respect and should be in line with Trade Related Aspects of Intellectual Property Rights (TRIPS), and the sustainable use and development of plant products must be addressed at the same time.

Role of innovation in pharmaceutical regulation: A proposal for principles to evaluate EU General Pharmaceutical Legislation from the innovator perspective

Because the EU General Pharmaceutical Legislation is under review, the EFPIA Innovation Board developed evaluation principles for the policy proposals and key considerations on how the regulatory framework can support innovation while ensuring only safe, efficacious and quality medicines are authorized. The evaluation principles are anchored on actions to promote: agile adoption of new methodologies with soft law tools; continued emphasis on regulatory science to inform policies; a cost/benefit assessment of the new regulation to ensure they have an overall positive impact; and mitigation of any negative externalities or unintended effects for any type of innovation or products. The evaluation principles are intended to guide the impact assessment of the pharmaceutical legislation in the EU but the principles can be applied globally.

The Prevalence of Acceptable Quality of Women Herbal Products Sold Online in Malaysia

The aim of this study is to determine the prevalence of quality herbal products sold online in Malaysia. The quality of herbal products focuses on two specific issues which are the legality of the labelling on herbal products and microbial contamination in herbal products. Using keywords such as‘herbal products’, ‘jamu’, and ‘women herbal products’in Malaysian online stores, a total of 110herbal products were selected. Their labels were observed and analyzed. 90.1% of the selected products are registered and fulfilled the labelling guidelines as required by National Pharmaceutical Registration Authority (NPRA).We obtained 10 samples of the herbal products found for bacterial contamination analysis. Our results show thatall of the products contains gram-negative bacteria, but with anacceptablenumber of colony forming unit (CFU <107). It is also worth noting thatnone was contaminated with Escherichia coli, Salmonellasp.and Staphylococcusaureus.

An Updated Review on Drug Regulatory Affairs

The field of regulatory affairs (RA) serves as a link between the global pharmaceutical sector and regulators. It was created in response to governments’ desire to safeguard the public’s health by regulating the efficacy and safety of pharmaceuticals, veterinary drugs, medical equipment, pesticides, agricultural chemicals, cosmetics, and other goods. Companies that are in charge of the development, manufacture, testing, and sale of these products aim to guarantee that they deliver safe and efficient goods for the welfare of the general public. Different registration criteria for pharmaceutical products are covered by pharmaceutical drug regulatory affairs. As a result of the demand for superior quality medicine that includes safety and efficacy in the areas of not only pharmacy but also veterinary medicine, medical devices, insecticides, pesticides, agrochemicals, cosmetic, and supplementary medicine, a new profession called pharmacy was created. Additionally, it created a connection between the pharmaceutical corporation and the regulating bodies. Maintaining the appropriateness and accuracy of the product information is another duty assigned to it. And its primary responsibility is to serve as a point of contact for regulatory agencies, providing expertise and regulatory intelligence in translating regulatory requirements into realistic, workable plans, and advising the company on regulatory aspects and the regulatory environment that would affect their proposed projects..

Application of QbD based approach in development and validation of RP-HPLC method for simultaneous estimation of methotrexate and baicalin in dual-drug-loaded liposomes.

The present study delineates the development of a novel, rugged and sensitive stability-indicating risk-based HPLC method for the concurrent estimation of methotrexate (MTX) and baicalin (BCL) in dual-drug-loaded-nanopharmaceuticals based on an analytical quality-by-design approach. Preliminary screening trials along with systemic risk analysis were performed, endeavouring to explicate the critical method attributes, namely pH, percentage of orthophosphoric acid and percentage of acetonitrile, that influence the critical quality attributes. Box-Behnken design was utilized for the optimization of the tailing factor as the response for MTX and BCL in a short run time. The chromatographic conditions were optimized by performing 17 experimental runs using design expert software. The chromatographic conditions were selected after the analysis of the optimized zone within the confines of the design space: water:acetonitrile adjusted to a pH of 3.0 with 0.05% orthophosphoric acid (60:40, %v/v) was the mobile phase, the flow rate was 1.0ml/min and an analytical C18 column was used at an isobestic wavelength of 282 nm. Furthermore, the optimized method was validated in accordance with the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines and was found to be within the prescribed limits. Therefore, the developed reversed-phase-high-performance liquid chromatography method has a high degree of practical utility for synchronous detection of MTX and BCL in pharmaceutical nano-dosage forms such as protein-based nanoparticles, nanocrystals, polymeric nanoparticles and metallic nanoparticles in in vivo and in vitro studies.

Imaginaries of the EU Commission Proposal for New the Pharmaceutical Regulation

Imaginaries of the EU Commission Proposal for New the Pharmaceutical Regulation

Exploration and Practice of Teaching Reform in Pharmaceutical Regulation Courses Based on OBE-CDIO Background

Exploration and Practice of Teaching Reform in Pharmaceutical Regulation Courses Based on OBE-CDIO Background

Do No Harm? Unintended Consequences of Pharmaceutical Price Regulation in India

Do No Harm? Unintended Consequences of Pharmaceutical Price Regulation in India

RATIONAL PHARMACOTHERAPY ON THE BASIS OF PHARMACOECONOMIC JUSTIFICATION AND MARKETING RESEARCH ON THE APPLICATION OF IMMUNOMODULATORY PHYTOPREPARATIONS.

The aim: Pharmacoeconomic substantiation and marketing research of immunoprotective phytopreparations in Ukraine to substantiate rational pharmacotherapy of the effectiveness of immunomodulatory drugs of plant origin and pharmaceutical care of patients to strengthen individual immunity. Materials and methods: Research materials - data from the State Register of Medicinal Products of Ukraine; information content of the Public Health Center of the Ministry of Health of Ukraine; data of the State Register of Wholesale Prices for medicines declared in Ukraine under the international non-proprietary or common name as of 01.01.2023. Research methods: theoretical analysis of scientific sources, systematic, retrospective, descriptive and frequency analysis of information resources of databases; pharmacoeconomic analysis, marketing analysis of positioning in the pharmaceutical market of Ukraine to substantiate rational pharmacotherapy and the effectiveness of immunomodulatory drugs of plant origin to strengthen individual immunity. Results: Theoretical analysis and pharmacoeconomic substantiation of rational pharmacotherapy of efficiency of application of drugs of immunomodulatory action of plant origin and pharmaceutical care for strengthening of individual immunity of patients is carried out. The algorithm of pharmacoeconomic analysis of the use of immunomodulatory phytopreparations to ensure rational pharmacotherapy and pharmaceutical care of outpatients is substantiated. To substantiate the availability of effective immunomodulatory phytopreparations for patients, marketing research on the use of immunomodulatory phytopreparations in Ukraine has been conducted. Conclusions: The theoretical analysis shows that the use of immunomodulatory drugs of plant origin is appropriate in rational pharmacotherapy to strengthen the individual immunity of patients, which is especially relevant in an exacerbation of the epidemic situation caused by the spread of infectious diseases of viral origin. An algorithm of pharmacoeconomic substantiation has been developed, which provides an opportunity to confirm the therapeutic efficacy and pharmacoeconomic feasibility of immunomodulatory phytopreparations for rational pharmacotherapy and pharmaceutical care of patients. The results of marketing research provide an opportunity to determine the availability (positioning and price range) for patients of effective immunomodulatory phytopreparations in Ukraine and outline the prospects for pharmaceutical development and registration on the pharmaceutical market of Ukraine of new effective immunomodulatory drugs of plant origin.

Regulatory pathway for pharmaceutical drug product registration and export in Gulf countries

The Indian pharmaceutical market is the third largest in terms of generic production. It has developed a reputation as a center of industry and research in the international market. India offers some of the costeffective manufacturing facilities globally. The Gulf cooperation council (GCC) region is regarded as a “developing market for pharmaceutical export”. This study assessed the regulatory frameworks of the GCC member countries of Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates (UAE) to build a coordinated approach. GCC regions are exposed to a partially regulated market. Most regulatory changes and developments must be kept up to date by pharmaceutical businesses, and GCC adopted the international council for harmonization common technical document (ICH CTD) format for new product registration. To fulfill the public demand for safe and effective treatments, regulations are needed for pharmaceutical drug products urgently due to rising healthcare costs, R&D expenditures, and other factors. Harmonizing the data on quality, safety, and efficacy reported in the application dossier is a main concern for the ICH committee. This review article provides the regulatory framework of GCC countries for effective control of pharmaceutical products.