RESUMO
Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of selected medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI 5.7-14.6) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. This study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.
Assuntos
Medicamentos Genéricos/química , Bangladesh , Comércio , Contaminação de Medicamentos/economia , Contaminação de Medicamentos/legislação & jurisprudência , Contaminação de Medicamentos/estatística & dados numéricos , Embalagem de Medicamentos/economia , Embalagem de Medicamentos/normas , Medicamentos Genéricos/economia , Medicamentos Genéricos/normas , Controle de QualidadeAssuntos
Dimetilnitrosamina/análise , Contaminação de Medicamentos/legislação & jurisprudência , Ranitidina/efeitos adversos , Retirada de Medicamento Baseada em Segurança/legislação & jurisprudência , Humanos , Ranitidina/química , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudênciaRESUMO
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.
Assuntos
Composição de Medicamentos/história , Contaminação de Medicamentos/legislação & jurisprudência , Contaminação de Medicamentos/estatística & dados numéricos , Indústria Farmacêutica/história , Indústria Farmacêutica/legislação & jurisprudência , Legislação de Medicamentos/história , Preparações Farmacêuticas/história , História do Século XX , História do Século XXI , Humanos , Estados UnidosRESUMO
RATIONALE: The screening for illegal adulteration of glucocorticoids (GCs) in cosmetics is challenging due to the vast variety of potential GCs that are present to improve the declared effects. An effective analytical method to screen illegally added GCs in cosmetics is vital to protect consumers. METHODS: An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method using precursor ion scanning (PIS) acquisition mode was developed to screen GCs in cosmetics. Forty-seven GCs were investigated to identify their common product ions formed by collision-induced dissociation. Cosmetic samples spiked with GCs were extracted using solid-phase extraction. RESULTS: Four common positive product ions, m/z 121, 135, 147, and 171, were selected for PIS analysis. Limits of detection (LODs) were established for all 47 GCs. The method was validated on spiked samples to ensure its effectiveness in terms of sensitivity and selectivity. Sixty samples were analyzed. Seven GCs were detected in six samples. CONCLUSIONS: An effective screening method using UPLC/MS/MS with PIS acquisition mode was developed and successfully applied to screen for targeted and untargeted GCs in cosmetic samples.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cosméticos/análise , Glucocorticoides/análise , Espectrometria de Massas em Tandem/métodos , Qualidade de Produtos para o Consumidor , Contaminação de Medicamentos/legislação & jurisprudência , Humanos , Limite de DetecçãoRESUMO
Nitrosamines are known carcinogens which have been recently discovered in several angiotensin receptor blockers (ARBs). This led to the recall of valsartan in the United States in 2018, and afterward, the recall of other ARBs as well as unrelated medications (e.g., ranitidine). The presence of nitrosamine in ARBs was likely a result of changes in the manufacturing process, although nitrosamine contamination is believed to occur by different mechanisms with other medications. The United States Food and Drug Administration has since taken steps to identify products affected by nitrosamine contamination and mitigate this concern going forward. Despite the contamination of some drug products, studies estimate that the overall risk to patients is low enough to not necessitate changes in prescribing patterns at this time.
Assuntos
Antagonistas de Receptores de Angiotensina , Composição de Medicamentos , Contaminação de Medicamentos , Recall de Medicamento , Nitrosaminas , Antagonistas de Receptores de Angiotensina/classificação , Antagonistas de Receptores de Angiotensina/farmacologia , Antiácidos/farmacologia , Carcinógenos/análise , Carcinógenos/química , Carcinógenos/toxicidade , Composição de Medicamentos/métodos , Composição de Medicamentos/normas , Contaminação de Medicamentos/legislação & jurisprudência , Contaminação de Medicamentos/prevenção & controle , Recall de Medicamento/métodos , Recall de Medicamento/organização & administração , Humanos , Nitrosaminas/análise , Nitrosaminas/química , Nitrosaminas/toxicidade , Farmacovigilância , Ranitidina/farmacologia , Retirada de Medicamento Baseada em Segurança/legislação & jurisprudência , Estados Unidos , United States Food and Drug AdministrationRESUMO
Plants and medicinal herbs that are available on the market do not always meet quality and safety standards. One particular concern is the risk of contamination with mycotoxins. Aflatoxins and ochratoxin A are the most frequently described mycotoxins in herbal products and have repeatedly been reported to occur at concentrations which exceed regulatory levels set by the European Union (EU). Possible solutions include enforcing existing limits, and for the new materials, establishing tighter limits and mandate the growth of medicinal plants in EU member countries under more strict conditions.
Assuntos
Contaminação de Medicamentos/prevenção & controle , Contaminação de Alimentos/prevenção & controle , Micotoxinas/análise , Preparações de Plantas/normas , Plantas Medicinais/microbiologia , Contaminação de Medicamentos/legislação & jurisprudência , União Europeia , Contaminação de Alimentos/legislação & jurisprudência , Regulamentação Governamental , Legislação de Medicamentos , Plantas Medicinais/crescimento & desenvolvimento , Estados Unidos , United States Food and Drug AdministrationRESUMO
Chemical synthesis is a science and an art. Rooted in laboratory or large-scale manufacture, it results in certain side products, eventually compromising the integrity of the final products. Such "impurities" occur in small amounts and, within chemistry itself, are of little concern. In pharmacy, in contrast, impurities increase the potential for toxicity, side effects, and serious implications for human health and the environment. The pharmaceutical regulatory agencies have therefore developed regulatory and strategic systems to minimize the chemical presence or biological impact of such substances. Here, pharmaceuticals are turned from impure into more defined materials as part of a complex socio-technological system revolving around and constantly evolving its specific rules and regulations. Whilst modern analytical methods indicate the presence of impurities, the interpretations of corresponding results are gated by risk management and agreed thresholds. Ironically, this allows for entities with no identified chemical structures, and hence epistemologically outside chemistry, to be regulated in pharmaceutical products. We will refer to such substances which are not, epistemologically speaking, "chemicals" as Xpurities, in order to distinguish them from recognized and identified impurities. The presence of such Xpurities is surprisingly common and constitutes a major issue in pharmaceutical research and practice. We propose a Space of Information to deal with such impurities based on values regarding the presence, chemical identities, and biological activities. It is anticipated that this may enable pharmacists to handle such Xpurities more efficiently.
Assuntos
Contaminação de Medicamentos , Contaminação de Medicamentos/legislação & jurisprudência , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Legislação de MedicamentosRESUMO
Abuse of recreational drugs (i.e., synthetic chemicals with the structure or expected neurotropic effects, or both, similar to those of controlled substances) is a serious and continuous social harm. Designer drugs are often manufactured or synthesized in small-scale clandestine laboratories with impure starting materials, poor handling skills and inferior storage conditions. Therefore, in addition to the objective compound, diverse impurities may be present, for example, from the starting material, intermediates, catalytic metals formed during chemical synthesis, and materials from the environment. Impurity profiling of drug seizures is a useful scientific tool to obtain information on the clandestine manufacturers and drug trafficking networks. 1-Phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP), a novel psychoactive substance of the cathinone type that is banned in many countries, is still supplied and distributed within the illicit drug market. By using GC-MS and ICP-MS, we identified and estimated the relative contents of organic and inorganic impurities in the bulk powder of 15 batches of α-PVP. We then conducted multivariate data analyses to reveal characteristic patterns of the profiles. Hierarchical cluster analysis of both the organic and inorganic impurities revealed two groups that showed similar impurity profiles, which suggested that the batches in these groups were synthesized in similar routes under similar synthetic environments. The initial groups revealed by the organic impurities were further divided when combined with the data from the inorganic impurities. The present study, therefore, demonstrated the effectiveness of integrated analyses of organic and inorganic impurities for the accurate clustering of designer drugs, to provide precise information to drug investigation authorities.
Assuntos
Drogas Desenhadas/química , Contaminação de Medicamentos/legislação & jurisprudência , Compostos Inorgânicos/análise , Compostos Orgânicos/análise , Pentanonas/química , Pirrolidinas/química , Análise por Conglomerados , Controle de Medicamentos e Entorpecentes/métodosRESUMO
Aluminum has no known biological function; however, it is a contaminant present in most foods and medications. Aluminum is excreted by the renal system, and patients with renal diseases should avoid aluminum-containing medications. Studies demonstrating long-term toxicity from the aluminum content in parenteral nutrition components led the US Food and Drug Administration to implement rules for these solutions. Large-volume ingredients were required to reduce the aluminum concentration, and small-volume components were required to be labeled with the aluminum concentration. Despite these rules, the total aluminum concentration from some components continues to be above the recommended final concentration. The concerns about toxicity from the aluminum present in infant formulas and antiperspirants have not been substantiated but require more research. Aluminum is one of the most effective adjuvants used in vaccines, and a large number of studies have documented minimal adverse effects from this use. Long-term, high-concentration exposure to aluminum has been linked in meta-analyses with the development of Alzheimer disease.
Assuntos
Alumínio/efeitos adversos , Soluções/química , Adjuvantes Farmacêuticos/química , Alumínio/análise , Alumínio/farmacocinética , Doença de Alzheimer , Antiperspirantes/química , Criança , Soluções para Diálise/química , Contaminação de Medicamentos/legislação & jurisprudência , Rotulagem de Medicamentos/legislação & jurisprudência , Regulamentação Governamental , Humanos , Lactente , Fórmulas Infantis/química , Recém-Nascido , Recém-Nascido Prematuro , Rim/metabolismo , Nefropatias/metabolismo , Nutrição Parenteral , Soluções/normas , Estados Unidos , United States Food and Drug Administration , Vacinas/químicaRESUMO
The pharmaceuticals may generate impurities at various stages of development, transportation and storage which make them risky to be administered. Thus, it is essential that these impurities must be detected and quantified. However, their presence as impurities in finished products is virtually unavoidable, even under GMP conditions. Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to control based on permitted daily exposures in drug products. Within the pharmaceutical community, there is uncertainty regarding the impact of these changes on manufactures of drug products. This uncertainty is fueled due to lack of publicly available information on elemental impurity levels in common pharmaceutical excipients. The present compilation gives an account of updated information about elemental impurities and reviews the regulatory aspects for such impurities in active pharmaceutical ingredients/drug formulations. In addition, the aim of this article is to review and discuss the currently used quantitative analytical method, which is used for quality control of elemental impurities in pharmaceutical products.
Assuntos
Contaminação de Medicamentos , Metais/análise , Preparações Farmacêuticas/análise , Animais , Contaminação de Medicamentos/legislação & jurisprudência , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Legislação de Medicamentos , Metais/toxicidade , Controle de QualidadeRESUMO
For the handling of active pharmaceutical ingredients (APIs) and production of medicinal products in shared facilities, the European Medicines Agency (EMA) has introduced the determination of permitted daily exposure (PDE) values to provide limits for cross-contamination. APIs have a desired pharmacological effect in the patient who intendedly uses a certain medicinal product. However, this effect is undesired in a patient that receives this API unintendedly as a cross-contamination of another medicinal product. In particular, for approved APIs for human use, a multitude of data is available on the pharmacological activity as well as adverse effects, which have to be taken into account in PDE setting. Thus, the setting of PDEs for APIs needs a structured scientific evaluation of all properties and identification of the most critical effect, which is the basis for PDE calculation. In this publication, we provide guidance on points for consideration when setting PDEs for APIs, or when evaluating the quality of documents describing the derivation of PDEs received, e.g. by third parties.
Assuntos
Relação Dose-Resposta a Droga , Contaminação de Medicamentos , Legislação de Medicamentos , Contaminação de Medicamentos/legislação & jurisprudência , Indústria Farmacêutica/legislação & jurisprudência , Europa (Continente) , Humanos , Medição de RiscoAssuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Contaminação de Medicamentos/legislação & jurisprudência , Recall de Medicamento , Irbesartana/química , Losartan/química , Nitrosaminas/isolamento & purificação , Valsartana/química , Dimetilnitrosamina/isolamento & purificação , Humanos , Hipertensão/tratamento farmacológico , Estados Unidos , United States Food and Drug AdministrationAssuntos
Anestésicos Locais/administração & dosagem , Anestésicos Locais/normas , Contaminação de Medicamentos/legislação & jurisprudência , Contaminação de Medicamentos/prevenção & controle , Centers for Disease Control and Prevention, U.S./legislação & jurisprudência , Centers for Disease Control and Prevention, U.S./normas , Humanos , Manejo da Dor/métodos , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudênciaRESUMO
A novel method for hierarchical screening of illegal adulterants in Fur seal ginseng pills products was developed by multi-dimensional fingerprint profiling analysis. Fingerprint feature of the samples was acquired by high-performance liquid chromatography analysis of 11 batches of samples with diode array detector and fluorescence detector, and then potential illegal adulterants including phosphodiesterase type-5 inhibitors, androgens, α receptor antagonists and yohimbine, were further separated at multiple wavelengths to reduce or remove interferences from sample matrix for highlight their chromatographic characteristics. Accordingly, a hierarchical screening strategy was designed by first-order and second-order fingerprints combined with spectral examination to achieve high accuracy and reliability. The method was successfully applied to screening of illegal adulterants in real samples, and it also exhibited good quantification performance through validation tests. From 16 batches of samples, three suspected samples were confirmed to be positive, containing 9.37µg/g of testosterone, 18.8 µg/g of tadalafil, and 48.5 µg/g of sildenafil, respectively. The recoveries and relative standard deviations were in the range of 83.6-103.1% and 4.2-6.8%, respectively. The proposed method provided a simple, efficient and promising alternative to monitoring functional foods.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Medicamentos/legislação & jurisprudência , Panax/química , Alimento Funcional/análise , Inibidores da Fosfodiesterase 5/análise , Citrato de Sildenafila/análise , Comprimidos/análise , Tadalafila/análiseRESUMO
Dietary supplements are regulated by the U.S. FDA as a subset of foods. Most botanical dietary ingredients do not have pesticide tolerances, resulting in the enforcement of zero tolerance or general maximum residue limits (GMRL), rather than utilizing science-informed tolerances. In the current study, chemical-specific maximum allowable levels (MALs) were derived for 185 pesticides by converting existing, authoritative-body human health effects criteria. MALs were derived for 96% of pesticides using criteria established by the U.S. EPA. If multiple authoritative-bodies had established human health effects criteria, the most scientifically-defensible criteria was selected, taking into consideration both carcinogenic and non-carcinogenic endpoints. Five pesticides (o-phenylphenol, pirimicarb, oxadixyl, tetradifon, o,p'-DDT), lacking criteria established by the U.S. EPA had criteria established by other authoritative-bodies that were utilized in the derivation of MALs. Two pesticides did not have any established human health effects criteria (o,p'-DDD and o,p'-DDE). In total, MALs were derived from existing criteria for over 98% of the pesticides in the present study. Consequently, it is demonstrated that human health effects criteria derived by authoritative-bodies can be effectively utilized to derive chemical-specific, science-informed MALs applicable to all food commodities, including botanical ingredients, thereby, minimizing reliance on precautionary zero tolerance and GMRLs.
Assuntos
Suplementos Nutricionais/análise , Contaminação de Medicamentos/legislação & jurisprudência , Resíduos de Praguicidas/química , Contaminação de Medicamentos/estatística & dados numéricos , Humanos , Concentração Máxima PermitidaRESUMO
In this contribution, data for 7 elemental impurities originating from quality control analysis of manufacturers of herbal products is evaluated in light of the current requirements of the European Pharmacopoeia (Ph. Eur.) and the European legislative framework. The data shows that the Ph. Eur. limits set for cadmium, lead and mercury in herbal drugs are in principle still appropriate. The probability of herbal drugs exceeding the limits for arsenic, cobalt, nickel and vanadium (based on the ICH Q3D guideline for elemental impurities) appears to be very low, and consequently, it is proposed that general limits for these elements in herbal drugs in the Ph. Eur. are not required. For essential oils, there does not appear to be a risk of heavy metal contamination and a general test on heavy metals is not considered necessary.
Assuntos
Contaminação de Medicamentos/prevenção & controle , Metais Pesados/análise , Óleos Voláteis/análise , Farmacopeias como Assunto/normas , Preparações de Plantas/análise , Contaminação de Medicamentos/legislação & jurisprudência , Europa (Continente) , Legislação de Medicamentos , Óleos Voláteis/normas , Preparações de Plantas/normasAssuntos
Dessensibilização Imunológica/métodos , Composição de Medicamentos/estatística & dados numéricos , Contaminação de Medicamentos/legislação & jurisprudência , Embalagem de Medicamentos , Infecções/epidemiologia , Rinite Alérgica/terapia , Cálculos da Dosagem de Medicamento , Humanos , Controle de Infecções , Rinite Alérgica/epidemiologia , Rinite Alérgica/imunologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Recent deaths of young Australian music festival attendees from 'party-drug' overdoses have sparked debate about the effectiveness of drug policies. Australia is widely lauded for its harm minimisation approach to drugs, and yet, over the last 30 years, it can be argued its policies have been fragmented, sometimes inconsistent and contradictory. The present article examines the root of this inconsistency, using it as a foundation to advocate for drug policy reform. In keeping with the goals of the National Drug Strategy to promote policy innovation, there is an opportunity to learn from international studies which have shown promising findings in the reduction of party-drug use and its harms through application of pill testing. METHOD: This paper evaluates Australia's National Drug Strategy and pill testing through a lens of pragmatism, to determine whether there is space for testing practices in contemporary policy. Specifically, the paper analyses current drug policy literature and research studies, examining a range of key drug use indicators, social and political debate and research evidence. RESULTS: The need for policy reform, attitudinal and cultural shifts and development of stronger cross-sectoral partnerships is highlighted, to ensure a rational and logical approach that genuinely tackles drug policy-making and strategy from a broad public health perspective. CONCLUSIONS: Using a theoretical frame of pragmatism and drawing from national and international research evidence, this paper recommends the integration of pill testing into Australia's harm minimisation strategy.
Assuntos
Contaminação de Medicamentos/legislação & jurisprudência , Contaminação de Medicamentos/prevenção & controle , Política de Saúde/legislação & jurisprudência , Drogas Ilícitas/análise , Drogas Ilícitas/legislação & jurisprudência , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Austrália , Redução do Dano , Conhecimentos, Atitudes e Prática em Saúde , HumanosRESUMO
The pharmaceutical industry is one of the most regulated industries in Switzerland. Though the concept of good manufacturing practises (GMP) was implemented for chemical production in the early 1990s, the rules and regulations for our industry are in constant evolution. In this article we will highlight the impact of these changes to the industry using three recent guideline up-dates as examples: the implementation of ICH Q3D 'Guideline for elemental impurities', the EU-GMP Guideline Part III Chapter 'Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities' from 01. June 2015, and the new guidelines to data integrity such as 'PIC/S 041-1 Good Practices for Data Management and Integrity in regulated GMP/GDP environments'. These examples show how scientific approaches help to modernize the control strategies for our products and increase product quality for a better patient safety. The requirements of data integrity regulations are also of interest to industries and universities not working under GxP requirements as they also support the business to improve data quality (traceability) for patent applications, and reduce risk of data falsification.