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The biopharmaceutical industry is evolving with a shift in focus from recombinant proteins and antibodies towards more complex cell and gene therapies. To be competitive globally, biomanufacturers need to focus on aligning with global standards with regard to drug quality, reducing manufacturing failures and delivering drugs to market quickly. Building these capabilities requires a multifaceted approach that includes improvements in operations, quality compliance, and control strategies. To address these needs, the US Pharmacopeia (USP), the Department of Biotechnology (DBT) India, and the Confederation of Indian Industry (CII) held a symposium to discuss the requirements and gaps in the biotechnology and pharmaceutical sectors in India and other developing countries. A panel of experts from academia, manufacturing, and governmental agencies identified several drivers needed for capability building, including a skilled workforce, public–private partnerships, advanced manufacturing technologies, novel biologics, and favorable policies. This article summarizes the recommendations put forward by this panel.

Introduction. The publication is devoted to the role of laboratory research in ensuring the quality of domestic medicines and is a review and analysis of regulatory documents and current publications on this topic.Text. A number of different types of laboratories are involved in Drug life cycle and ensuring their effectiveness and safety. Today there are a large number of regulations governing laboratory research. Common to all types of laboratories and regulatory documents is the need to organize an effective quality management system (QMS) for the drug life cycle laboratories. The aim of this review is to analyze approaches to regulating the quality of laboratory research of domestic drugs and to consider the most effective QMS model, which is fundamental for all types of laboratories in the life cycle of drugs.Conclusion. The laboratory research quality system serves as a basic tool for achieving the ultimate goal - the clinical value of drugs and is designed to ensure that risks for patients are minimized. At the same time, each stage of the drug life cycle provides a solution to a specific problem on the way to this goal, which must be taken into account when building a QMS in each type of laboratory. The range of regulatory documents and external assessment systems (accreditation, certification, inspection control, etc.) in the field of domestic laboratory research is quite diverse. In this regard, it is advisable for the laboratory to build a harmonious QMS based on priorities in accordance with the goals and objectives. The most effective method for building such a system is an integrated management system model.

Ciprofloxacin is a fluoroquinolone antibiotic employed to treat infections. There are over three hundred registered generic brands of ciprofloxacin in Nigeria. There has been an observed marked variation in therapeutic or clinical outcome with change in brands by health professionals and patients. In a previous study of six (6) brands we had reported a high degree of inequivalence. In this study, twenty-nine (29) brands of ciprofloxacin were extensively evaluated against compendia requirements. Microbial sensitivity against two test organisms was conducted. In-vitro drug release and in-vivo simulation were established. Analysis of the data generated indicated that all brands passed qualitative test using TLC and disintegration test, six failed hardness test, one failed friability, nine failed antimicrobial assay and six failed percentage content assay. Conclusions drawn from the study for evidence-based clinical decisionwould include the fact that three brands only were found to be bioequivalent to the innovator brand, Ciproxin; while eight brands were bio-inequivalent using the three models of similarity factor (f2), and difference factor (f1) in two media and dissolution efficiency (DE) in pH 4.5. The three brands (Cipro-All, Cifran And Ciprogem) may confidently be used interchangeably with the innovator brand Keywords: Bioequivalence; Ciprofloxacin Drug quality; Generic substitution; Post-marketing surveillance

Drug management is the most important management in pharmaceutical services at the pharmacy. Drug storage is an inseparable part of all pharmaceutical activities. Pharmacies including pharmacy service facilities, therefore they must be responsible for drug inventory, maintaining drug supplies to avoid damage and maintaining drug quality. Medicines distributed at pharmacies are the same as drugs distributed in hospitals, therefore a good drug storage system at the pharmacy is the same as storing good medicine in hospitals. This type of research is descriptive research with the main purpose of making an objective picture. Data collection is retrospective by observing and reviewing documents following the drug storage indicators by Pudjaningsih. The population of the study were all medicines. Samples were taken based on the total sampling technique. The research instrument is a stock card and the document resulting from stock opname. The conclusion of this research is an overview of drug storage at Melawai Kemang Pharmacy with indicators suitability of stock card is 97,16 %, percentage of drugs expired and or damaged.

This article examines the evolution of Indian pharmaceutical manufacturer Cipla toward producing drugs that met the quality standards of European and U.S. regulators. It employs new research in both Cipla's corporate archives and a wide range of oral histories. The article argues that, along with a long-standing corporate culture of self-reliance rooted in nationalism starting from the company's inception in 1935, major factors in Cipla's strategy from the 1960s through the early 2000s included the early adoption and continued use of quality-control technology, along with efforts to create global goodwill for affordable high-quality generic drugs during the HIV/AIDS epidemic of the early 2000s.

Introduction. Quantitative assessment of the active substance is necessary and perhaps the most significant part of the drug quality control. Validation of the analytical methods of quantitative assessment ensures their compliance with high requirements. The present study describes the development and validation of a spectrophotometry method for the quantitative evaluation of the active substance in the drug form of the national antitumor and antiangiogenic drug «Dimeric macrocyclic tannin (DMT) lyophilizate for solution for injection, 100 mg».Aim. The development and validation of the assay method for the standardization of «DMT lyophilizate for solution for injection, 100 mg».Materials and metods. The study used «DMT lyophilizate for solution for injection, 100 mg» and the active substance DMT. Method – spectrophotometry.Results and discussion. The methodof the quantitative assessment of the active substance in the DMT lyophilized drug by direct UV spectrophotometry was developed and the validation characteristics of the method were defined as a result of the study.Conclusion. The validation results showed that the assay method of DMT in the drug form has the appropriate accuracy, precision and linearity. The obtained results correspond to the approved criteria that allow the use of the developed methodology for evaluating the quality of the drug.

An informational-analytical review of alternative microbiological methods for quality testing of pharmaceutical products is presented. The expediency and peculiarities of implementing these methods in pharmacy practice for routine testing are considered. General approaches to validation of new methods are described. The new methods are compared with classical methods in all implementation stages. Foreign regulations on the selection of validation parameters and their acceptance criteria are analyzed.

This review addresses the history of the creation of standard samples (SS) around the world and in Russia, along with studies of the current condition of the state system for standardization of medicinal products (MP) based on the use of SS. Standardization in the area of drugs is directed to guaranteeing the quality of the items standardized, which includes products (raw materials, other materials, ready MP, etc.), services, and processes. The continuing development of manufacturing technologies and the discovery of novel MP increases the need for standard samples, as drug quality control involves the use of complex, highly effective, specific, and precise physicochemical and biological analysis methods.

Quality is the lifeline for all pharmaceuticals. Process analytical technology (PAT), introduced by FDA in 2004, providing significant opportunities for improving pharmaceutical development, manufacturing, and quality assurance. Therefore, in this review various PAT tools were introduced for solid oral dosage manufacture quality monitor and control. Throughout this review, we would like to provide more information to both researchers and manufacturers in order to improve the drug quality.

With proliferating efforts to regulate the quality of cannabis on legalized markets, and recent discussions about drug quality assessment by darknet buyers, it seems timely to explore definitions of the quality of cannabis among consumers. An inductive analysis of in-depth interviews with people who had used cannabis in the past 12 months was conducted, which focused on the respondents’ subjective definitions and assessments of the quality of cannabis. The data are drawn from convenience samples in four localities (Florida [United States], Czechia, Spain, and New South Wales [Australia]) where cannabis was illegal or decriminalized. The findings suggest that the respondents across all four localities used a range of visual and sensory indicators to assess the quality of cannabis. For many respondents, these were independent indicators of the quality of cannabis suggesting that cannabis was not merely an “experience” good. For others, visual and sensory assessments were used as indirect indicators of quality in that they represented the effect of the cannabis. The desired effect was more complex than simple potency (strength) and several respondents preferred mild and not-sedating cannabis. Across the four localities, the respondents also included “proxy” indicators of the safety of cannabis in their definitions of quality. In other words, high-quality cannabis was defined as not causing excessive intoxication or physical harm. Altogether, cannabis was a specific “credence” good when its quality was seen as a result of cultivation techniques, production location, or producers’ (profit) motivations - depending on the locality. These findings suggest that cannabis policies that regulate the cultivation process can be relevant to people who use cannabis. Given that consumers take the safety of cannabis into consideration when assessing its quality, their involvement in the development of quality standards is warranted. Consumer-led self-regulation should also be considered in policies that seek to regulate cannabis supply.

The study related to pharmaceutical packaging has come to attention for its importance to the quality of drugs and compliance achievement. The aims of this study is to provide a conceptual view of producing a new model of pharmaceutical drug packaging design to overcome existing problems. The proposed methods for this research is to use the process mining techniques to support the construction of a new model for pharmaceutical packaging design process improvement. A case study method was selected for the methodology of the research resulted the flow of packaging design process in pharmaceutical company. The study lengthens the knowledge of drug packaging design process and concludes the importance of drug packaging design process to be investigated for compliance fulfilment purposes. This study is significant to the strong implication of drug quality and safety outcomes for the patients.

The implementation of integrated analytical techniques to meet stringent requirements in the life sciences requires a well-developed analytical capacity. New technology in analytical equipment for the analysis of large and small molecules is continuously being developed. However, developing countries frequently struggle to keep pace with technological advancements. Hence, it is of utmost importance to better invest in optimizing existing and proven methodologies to tackle life-saving challenges in developing countries. In this regard, capillary electrophoresis is a promising candidate for solving multiple analytical problems compared to its chromatographic and spectroscopic counterparts due to its fast analytical response time and notable cost efficiency. In the following, we summarize various issues and opportunities for capillary electrophoresis to be the technique of choice for the unresolved bottlenecks in analytical equipment in developing countries for drug quality control. This perspective demonstrates that the ongoing quest for the design of new, impactful analytical techniques is a dynamic and rapidly developing research area and mentions some directions and opportunities that have arisen during the recent pandemic.

Generic medicines are clinically equivalent and can be used interchangeably for their intended use. Globally, the usage of generic medicines is highly recommended because of their affordability and accessibility. However, consumers hold a negative perception and attitude of using generic medicine as they consider it poor and having inferior quality compared to branded medicines. This study was conducted to assess the consumers’ general view of generic medicines and in vitro evaluation of a locally produced generic medicine, paracetamol. An analytical and cross-sectional study was conducted in three selected hospitals, and in vitro quality control evaluation was done in National Drug Quality Control Laboratory between October 26 and November 21, 2017, in Asmara, Eritrea. A systematic random sampling design was employed, and the data was collected using a questionnaire and a check-list for recording the quality control parameters of paracetamol tablets. A total of 403 respondents were included in the study. The majority of the study participants were females (61.8%). Generally, about half (49.1%) of the respondents choose locally manufactured paracetamol over the imported ones. More than half (68.5%) of the respondents did not believe expensive medicines are of better quality. The main reason consumers prefer the local paracetamol (Azemol) tablet to the imported one was due to their good experience (62.1%). About three-fourths (78.1%) of the consumers also believed that medicines manufactured abroad confer higher quality. At the multivariate level, having educational backgrounds such as elementary ( AOR = 4.19 , 95% CI: 1.251, 14.035) and junior ( AOR = 2.4 , 95% CI: 1.146, 5.028) was associated with preferability to local paracetamol as a pain killer over the brand ones. The in vitro test of the local paracetamol met the standard specification for the identification test, weight variation test, pharmacopeial test, friability test, disintegration test, and dissolution test. In conclusion, the majority of the consumers considered local paracetamol as having an inferior quality when compared with brand paracetamol. However, the reality revealed that the local paracetamol was of the same quality as the brand ones. To facilitate widespread use of generic medicines, healthcare professionals should educate consumers on the advantages of these medicines.

Background Anti-malarial drugs play a critical role in reducing malaria morbidity and mortality, but their role is mediated by their effectiveness. Effectiveness is defined as the probability that an anti-malarial drug will successfully treat an individual infected with malaria parasites under routine health care delivery system. Anti-malarial drug effectiveness (AmE) is influenced by drug resistance, drug quality, health system quality, and patient adherence to drug use; its influence on malaria burden varies through space and time. Methods This study uses data from 232 efficacy trials comprised of 86,776 infected individuals to estimate the artemisinin-based and non-artemisinin-based AmE for treating falciparum malaria between 1991 and 2019. Bayesian spatiotemporal models were fitted and used to predict effectiveness at the pixel-level (5 km × 5 km). The median and interquartile ranges (IQR) of AmE are presented for all malaria-endemic countries. Results The global effectiveness of artemisinin-based drugs was 67.4% (IQR: 33.3–75.8), 70.1% (43.6–76.0) and 71.8% (46.9–76.4) for the 1991–2000, 2006–2010, and 2016–2019 periods, respectively. Countries in central Africa, a few in South America, and in the Asian region faced the challenge of lower effectiveness of artemisinin-based anti-malarials. However, improvements were seen after 2016, leaving only a few hotspots in Southeast Asia where resistance to artemisinin and partner drugs is currently problematic and in the central Africa where socio-demographic challenges limit effectiveness. The use of artemisinin-based combination therapy (ACT) with a competent partner drug and having multiple ACT as first-line treatment choice sustained high levels of effectiveness. High levels of access to healthcare, human resource capacity, education, and proximity to cities were associated with increased effectiveness. Effectiveness of non-artemisinin-based drugs was much lower than that of artemisinin-based with no improvement over time: 52.3% (17.9–74.9) for 1991–2000 and 55.5% (27.1–73.4) for 2011–2015. Overall, AmE for artemisinin-based and non-artemisinin-based drugs were, respectively, 29.6 and 36% below clinical efficacy as measured in anti-malarial drug trials. Conclusions This study provides evidence that health system performance, drug quality and patient adherence influence the effectiveness of anti-malarials used in treating uncomplicated falciparum malaria. These results provide guidance to countries’ treatment practises and are critical inputs for malaria prevalence and incidence models used to estimate national level malaria burden.

Background The Drug Quality and Security Act passed in 2013 created a new voluntary category of compounders, referred to as outsourcing facilities. The regulatory landscape allows these facilities to compound on a larger scale in comparison with the typical compounding pharmacies, which positions them to potentially serve a role in overcoming drug shortages. Objective The purpose of this article is to identify the number of drug products on shortage as reported by the Food and Drug Administration (FDA) that were also compounded by outsourcing facilities. Methods All current and resolved drug shortages through January 27, 2020, as reported by FDA, were compared with the 503B product reports from July 2018 through June 2019 submitted to FDA by outsourcing facilities. The active pharmaceutical ingredient (API) and dosage form for each product on shortage were compared with the 503B product reports to identify similarities. Results There were 344 unique APIs on the FDA drug shortage list and 774 unique APIs on the 503B product reports. After comparison of the APIs on the drug shortage list with those on the product reports, 27% of unique APIs (74 of 272) were included on both lists, and of these, 18% (50 of 272) of the APIs on the drug shortage list were compounded by outsourcing facilities in the same dosage form as what was on shortage. Conclusion The regulatory landscape positions outsourcing facilities to play an important role in providing access to medications while on shortage. However, when comparing the drugs on shortage as reported by FDA with the 503B product reports, there was minimal overlap. Additional research into why outsourcing facilities are not taking on a larger role in overcoming drug shortages should be explored.

This study examines the effect of chain store entry on drug quality and prices in India. In contrast to prevailing mom-and-pop pharmacies, chains exploit scale economies in distribution and signaling to offer high-quality drugs at lower cost. We show that chain entry leads to a 5% improvement in drug quality and a 2% decrease in prices at incumbent retailers. Effects are larger for locally distributed drug brands but do not depend on consumer SES. Our findings suggest that in markets with asymmetric information, organizational technologies such as chains can play an important role translating market expansion into higher quality.

Based on the survey data from questionnaire of Quality Management of Pharmaceutical Production Enterprises in Anhui Province, this research examines the relationship between the change frequency of production director and GMP inspection results of pharmaceutical manufacturers by adopting OLS model and Logit model. We find that director of manufacturing management plays a direct role in enterprise production management as senior administrator. If director of manufacturing management changes more times, the enterprise’s drug production management will lose persistent stability. As a result, the quality of drug production is affected. Without ability to produce high-quality drugs, the GMP inspection results of pharmaceutical enterprises are poor. Thus, this paper suggests that in daily drug quality supervision, enterprises that frequently change director of manufacturing management should be paid more attention to, and we should increase the frequency of examination, so as to reasonably allocate regulatory resources and carry out targeted supervision.

ObjectiveB-type natriuretic peptide (BNP) has favourable effects on left ventricular remodelling, including antifibrotic and antiapoptotic properties. We tested the hypothesis that infusion of BNP after an acute myocardial infarction would reduce left ventricular systolic and diastolic volumes and improve left ventricular ejection fraction compared with placebo.MethodsA total of 58 patients who underwent successful revascularisation for an acute ST elevation anterior myocardial infarction were randomised to receive 72-hour infusion of BNP at 0.006 µg/kg/min or placebo. Left ventricular end diastolic and systolic volumes and left ventricular ejection fraction were measured at baseline and at 30 days by multigated acquisition scan. Left ventricular infarction size was measured by cardiac MRI.ResultsBNP infusion led to significantly higher BNP levels and plasma cyclic guanosine monophosphate at 72 hours. No significant difference in change of left ventricular volumes or ejection fraction from baseline to 30 days was observed between groups. Although left ventricular infarction size measured by cardiac MRI was not significantly different between BNP infusion versus placebo (p=0.39), there was a trend towards reduced infarction size in patients with a baseline ejection fraction of ConclusionsInfusion of BNP in patients with an anterior myocardial infarction did not affect parameters of left ventricular remodelling. Patients treated with BNP who had a baseline left ventricular ejection fraction of Trial registration numberNCT00573144.

The whole system of drug quality standards is based on the national Pharmacopoeias, which regulate the basic requirements to quality of the certain dosage form, including ophthalmic drugs. The development of pharmaceutical science requires constant improvement and updating of drug quality standards. Among a number of other measures, this is ensured by introducing the necessary innovations and changes in existing national Pharmacopoeias. Recently, the general article for ophthalmic drugs included at the list of reviewed articles by leading world Pharmacopoeias. Aim. Research and modern changes evaluation of the quality requirements to ophthalmic dosage form in Pharmacopeias of Ukraine, Europe andUSA compared to their previous versions. Results. At the article is shown that in recent years there have been no significant changes in the European Pharmacopoeia general article for eye drugs; the changes in the State Pharmacopoeia of Ukraine general article for eye drugs concerned the national part; and more significant changes in the monographs associated with eye drugs occurred in United States Pharmacopeia (USP) that are bound with the structure improvement of the general article for pharmaceutical dosage form and, as a consequence, the introduction of the new separate general articles for ophthalmic drugs. The updated general article includes: the description and the routes of administration of ophthalmic products; all dosage forms that can be applied in the eye from the traditionally used to new that have emerged due to the development and improvement of modern technologies of ophthalmic drugs; quality and efficacy in vitro indexes of ophthalmic drugs. Conclusions. The leading world Pharmacopoeias are not hardened dogmas. They constantly undergo modernization and improvement, taking into account the current level of knowledge, including the structure and the function of the human eye so as the new ophthalmic dosage forms, and make appropriate changes to the quality requirements. More detailed specification of the quality indexes of ophthalmic dosage forms with the acceptance criteria are given in USP, which enables developers to create the products that will allow patients to receive safe, effective and quality drugs. It has been expressed a view to take into account such changes in the national part of the domestic Pharmacopoeia.

Проведение лабораторных исследований по апробации методов и методик, заложенных в проектах общих фармакопейных статей и фармакопейных статей, является актуальной задачей отечественной фармакопейной науки и практики. Данные исследования являются основанием для утверждения государственных фармакопейных стандартов качества лекарственных средств. Они позволяют как производителю, так и органам контроля качества фармацевтических субстанций и лекарственных препаратов осуществлять независимую проверку качества лекарственных средств для медицинского применения, способствуя охране здоровья населения.

Changes of manufacturing processes are common. It is required by the regulatory agencies that manufacturers establish adequate and appropriate comparability between pre-change and post-change products. The goals of comparability assessments are to demonstrate the comparability and consistency of product quality before and after change and to demonstrate that the changes do not have an adverse effect on safety and efficacy of the drug products. Accelerated or stressed stability studies may shed light on drug quality under stressed environmental conditions and on product differences in the degradation pathways. Comparability of accelerated stability data may provide further evidence on the impact of process change. Equivalence test has been recommended to demonstrate the comparability of stability profiles for accelerated stability studies. Selection of appropriate acceptance criteria for determining comparability is one of the most challenging steps in the comparability studies. Because of the inherent heterogeneity of biologics, the stability profiles may vary considerably from batch to batch. It is more challenging to set the acceptance criteria for comparing the accelerated stability data for biologics. In this article, we present an approach for determining the acceptance criteria and necessary sample sizes for accelerated comparability studies for biologics.

Introduction: Various pharmaceutical preparations are widely used for clinical treatment. Elucidation of the mechanisms of drug release and evaluation of drug efficacy in biological samples are important in drug design and drug quality control.Areas covered: This review classifies recent applications of Fourier transform infrared (FTIR) spectroscopy in the field of medicine to comprehend drug release and diffusion. Drug release is affected by many factors of preparations, such as drug delivery system and microstructure polymorphism. The applications of FTIR imaging and nano-FTIR technique in biological samples lay a foundation for studying drug mechanism in vivo.Expert opinion: FTIR spectroscopy meets the research needs on preparations to understand the processes and mechanisms underlying drug release. The combination of attenuated total reflectance-FTIR imaging and nano-FTIR accompanied by chemometrics is a potent tool to overcome the deficiency of conventional infrared detection. FTIR shows an enormous potential in drug characterization, drug quality control, and bio-sample detection.

PURPOSE A postmarket evaluation of chemotherapy dosage forms in Ethiopia was conducted to test the accuracy of the chemoPAD, a paper analytical device for drug quality screening. MATERIALS AND METHODS In September of 2018 in Addis Ababa, Ethiopia, 41 anticancer drug dosage forms (representing 4 active ingredients, 5 brands, and 7 lot numbers) were collected and were rapidly screened for quality using a chemotherapy paper analytical device (chemoPAD). Confirmatory analysis via high performance liquid chromatography was conducted. RESULTS The chemoPAD showed that the correct active pharmaceutical ingredient was present in doxorubicin, methotrexate, and oxaliplatin injectable dosage forms. However, 11 of 20 cisplatin samples failed the screening test. Confirmatory assay by high-performance liquid chromatography showed that all 20 cisplatin samples—comprising three lot numbers of a product stated to be Cisteen—were substandard, containing on average 54% ± 6% of the stated cisplatin content. Inductively coupled plasma optical emission spectroscopy analysis of five representative samples found 57% to 71% of the platinum that should have been present. The sensitivity of the chemoPAD for detection of falsified products could not be measured (as none were present in these samples), but the selectivity was 100% (no false positives). The sensitivity for detection of substandard products was 55%, and the selectivity was 100% (no false positives). CONCLUSION Although instrumental analysis by pharmacopeia methods must remain the gold standard for assessing overall drug quality, these methods are time consuming and patients could be exposed to a bad-quality drug while clinical workers wait for testing to be performed. The chemoPAD technology could allow clinicians to check at the point of use for serious problems in the quality of chemotherapy drugs on a weekly or monthly schedule.

International audience; Objective Drug quality in medical devices is not evaluated during the marketing authorization of radiopharmaceuticals. Therefore, the extemporaneous change of packaging made for preparation of patient unit doses in a syringe is the responsibility of radiopharmacists. The present study aimed to determine the impact of packaging and storage in a polypropylene syringe on the quality of hydrophilic drugs [99mTc]Tc-EDDA/HYNIC-TOC (Tektrotyd) and [68Ga]Ga-DOTA-TOC (Somakit-TOC).Methods Appearance, pH, radiochemical purity, sterility, and endotoxin tests were performed according the current European Pharmacopoeia. Subvisible and visible particles tests of the European Pharmacopoeia were adapted due to limited preparation volume (

The efficacy, availability, tolerable side effects and relative affordability of praziquantel makes it the drug of choice in the treatment and various control programmes of schistosomiasis in the endemic areas with excellent outcomes. However, there are reports of low cure rate with praziquantel observed by clinicians with various speculations on the likely causes. This study explored poor drug quality as a possible cause of praziquantel treatment failure in schistosomiasis. On the spot sampling of twelve different samples of praziquantel tablets from various patent medicine shops in Kano metropolis were assayed for active ingredient using British Pharmacopeia methods. Only 6 out of 12 (50%) of the praziquantel tablets studied were found to be acceptable of quality. Cost and number of months before expiry date were not found to be significantly associated with the quality of the drug. Poor quality praziquantel currently in the market may possibly explain failure of standard dose of the drug in the treatment of schistosomiasis. Therefore, it is recommended that additional vigilance by regulatory agencies is required to ensure quality drugs in the market.Keywords: Efficacy, Kano, praziquantel, quality, schistosomiasis

This chapter develops the theme of faith being put in technology over community to consider the differences between automatic trust systems and users’ and vendors’ own judgements when it comes to drug quality. The chapter explores the different kinds of knowledge that are employed to assess and ensure drug quality. Some of this knowledge can be reflected in published market ratings but much has to be developed and shared between users. Drug quality is not a single attribute that can be measured by one metric. It is a multivariate element that changes depending on the purpose for which it is being used and the context in which it is being taken.

This chapter examines the possible benefits that cryptomarkets have for harm reduction. The cryptomarket ecosystem is claimed as being transparent about drug quality and therefore benefiting both harm-reduction in illicit drug use and the establishment of a model for a legalised drug market. To that end, many market players seek to promote a rational, risk-reducing consumer-orientation to their actions. This chapter explores the significance for peer-supported harm-reduction. As with drug quality, risk and health are not agreed-on standards, but are dependent on how the drug is used. Some users do not seek to reduce their risk to the lowest possible level. Instead harm is expected and anticipated as a ‘necessary’ cost of drug use.

For over a century, researchers have focused on how to optimize drug delivery. Systemic administration means that the drug becomes dilute and has the potential to diffuse to all tissues, which is only until the immune system steps in and rapidly clears it from blood circulation. Drug carriers are the solution for amplifying the intended effect and diminishing side effects. With drug carriers, tissue-specific drug delivery and controlled drug release is possible. Thus far, both synthetic and non-synthetic carriers exist. However, due to the numerous limitations of synthetic carriers, science has begun to concentrate on using live cells and cell-derivatives as drug carriers. The most problematic shortcomings of synthetic carriers are their limited biocompatibility and biodegradability. Most synthetic carriers are cytotoxic or induce immune responses. Moreover, synthetic carriers typically depend on passive diffusion and risk phagocytosis, further reducing their impact. On the other hand, live-cell carriers and their derivatives usually have a targeting mechanism and drug release is controlled, increasing the efficiency with which a drug accumulates and acts on a tissue. Still, both types of carriers face similar problems, including achieving high loading capacity, maintaining drug quality, efficiently accumulating in the target tissue, and minimizing side effects. This review aims to elucidate the advantages and disadvantages of each popular cell or cell-derived carrier and to spotlight novel solutions. Keywords: Drug delivery, Immune cells, Red blood cells, Stem cells, Biomimetics, Exosomes

Panama, like most Latin American countries, has insufficient regulatory safeguards to ensure the safety and efficacy of all pharmaceutical products in the market, a situation that results in a two-tier system, where affluent citizens can afford innovator products while poor citizens must consume 'generics' of uncertain quality. Given that one lot of each drug product is analyzed every five years during registration while commercial lots are not, and since most products are not bioequivalent but simply copies or similars, there is a concern that commercial and registration lots of these 'generics' may not be of the same quality. The objective of this study was to assess the ability of various in vitro quality control tests to detect difference among five amlodipine products available in the Panamanian market: four 'generics', made in various countries, and the innovator, made in Germany and used as reference listed drug in Panama (Pan-RLD). The innovator manufactured in the United States (US-RLD) was used to compare the two RLDs. The Content Uniformity test, 30-min Dissolution test and multiple-pH Dissolution Profiles did not show any difference among the products. However, the in vitro dissolution absorption system 1 (IDAS1) showed a statistically significant difference in the amount dissolved between Pan-RLD and three out of the four 'generics', and significantly lower permeated amount for all the 'generics' compared with Pan-RLD; only US-RLD was similar to Pan-RLD. Thus, IDAS1 showed promise as a potential tool that authorities in weakly regulated markets can use to monitor for possible lot-to-lot product changes, which can help improve the quality of pharmaceutical products available to their entire populations. The significance of the similarity between the innovators made in Germany and the United States and their difference from the 'generics' (manufactured in other countries) is not known but deserves investigation.

We study the long-run welfare effects of parallel trade (PT) in pharmaceuticals. We develop a two-country model of PT with endogenous quality, where the pharmaceutical firm negotiates the price of the drug with the government in the foreign country. We show that, even though the foreign government does not consider global R&D costs, (the threat of) PT improves the quality of the drug as long as the foreign consumers’ valuation of quality is high enough. We find that the firm’s short-run profit may be higher when PT is allowed. Nonetheless, this is neither necessary nor sufficient for improving drug quality in the long run. We also show that improving drug quality is a sufficient condition for PT to increase global welfare. Finally, we show that, when PT is allowed, drug quality may be higher with than without price controls.

Pharmaceutical technology is an indispensable and important link in drug research and development, which plays a key role in drug research and development quality. In the background of science and technology development, pharmaceutical technology has been greatly developed, but also to promote the quality of drug research and development, to provide more guarantee for people’s health. In the new era, how to achieve pharmaceutical technology innovation, so as to further improve the quality of drug research and development, is an important research topic in the current related industries. This paper mainly revolves around quality of pharmaceutical technology development of a series of exploration, in the traditional drug development based on a better control of drug quality, the future of smart pharmaceutical green pharmaceutical development direction, aims to further enhance the pharmaceutical technology, promote the quality of research and development to promote the comprehensive, promote the steady development of the pharmaceutical industry as a whole.

The use of biosimilar drugs for multiple sclerosis (MS) has become widespread in Latin America, with the goal of reducing costs of treatments, promoting the sustainability of healthcare systems, and improving patient access to these therapies. There is currently a need to define and comply with requirements to guarantee the efficacy, safety, and quality of these drugs. Thus, the objective of the present study was to compile up-to-date information from each Latin American country assessed on (a) approval of biosimilar drugs by regulatory agencies; (b) use of biosimilar drugs, pharmacovigilance plans, risk management; and (c) update in the knowledge on different molecules. To do so, a group of experts from Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, Panama, Peru, Uruguay, and Venezuela met to discuss the current situation regarding good practices and risks associated with the use of biosimilar drugs in their respective countries. Regulation, risk management plans, and pharmacovigilance in the whole continent must guide the strategies on the commercialization and access of biosimilar drugs and copies of complex molecules. Current regulations must be implemented for the registration of biosimilar drug products and complex molecules. It is paramount to ensure that new products follow the best quality standards at all stages beyond being safe and efficient. Uncontrolled interchangeability between original biological and biosimilar should be avoided. Latin America requires the implementation and full use of strong pharmacovigilance programs. National and multinational clinical studies are required to demonstrate the similarity in safety, efficacy, and immunogenicity profiles of complex molecules, as well as biological and biosimilar products. Plain Language Summary Plain language summary available for this article.

International audience; ObjectiveEpilepsy is a major public health issue in low‐ and middle‐income countries, where the availability and accessibility of quality treatment remain important issues, the severity of which may be aggravated by poor quality antiepileptic drugs (AEDs). The primary objective of this study was to measure the quality of AEDs in rural and urban areas in 3 African countries. MethodsThis cross‐sectional study was carried out in Gabon, Kenya, and Madagascar. Both official and unofficial supply chains in urban and rural areas were investigated. Samples of oral AEDs were collected in areas where a patient could buy or obtain them. Pharmacological analytical procedures and Medicine Quality Assessment Reporting Guidelines were used to assess quality. ResultsIn total, 102 batches, representing 3782 units of AEDs, were sampled. Overall, 32.3% of the tablets were of poor quality, but no significant difference was observed across sites: 26.5% in Gabon, 37.0% in Kenya, and 34.1% in Madagascar (P = .7). The highest proportions of substandard medications were found in the carbamazepine (38.7%; 95% confidence interval [CI] 21.8‐57.8) and phenytoin (83.3%; 95% CI 35.8‐99.5) batches, which were mainly flawed by their failure to dissolve. Sodium valproate was the AED with the poorest quality (32.1%; 95% CI 15.8‐42.3). The phenobarbital (94.1%; 95% CI 80.3‐99.2) and diazepam (100.0%) batches were of better quality. The prevalence of substandard quality medications increased in samples supplied by public facilities (odds ratio [OR] 9.9; 95% CI 1.2‐84.1; P < .04) and manufacturers located in China (OR 119.8; 95% CI 8.7‐1651.9; P < .001). The prevalence of AEDs of bad quality increased when they were stored improperly (OR 5.4; 95% CI 1.2‐24.1; P < .03). SignificanceNo counterfeiting was observed. However, inadequate AED storage conditions are likely to lead to ineffective and possibly dangerous AEDs, even when good‐quality AEDs are initially imported.

Background: Cryptomarkets – online, anonymous marketplaces for illicit goods and services that mostly specialise in drugs – account for a small but rapidly growing share of the illicit drug market in many countries. Policy responses so far are generally based on the assumption that their rise will only increase drug harms. In this contribution for debate, we question this assumption.Methods: We provide a narrative review of the emerging literature connected to drug cryptomarkets. We use MacCoun and Reuter’s formula to understand the effect of population- level increases in use on total harm as depending on the level of harm associated with each unit of use. We then consider the potential for cryptomarkets to increase or decrease the harms and benefits related to each unit of drug use, with specific attention to the quality of drugs sold and the non-drug related harms and benefits for customers.Results: We suggest it is likely that cryptomarkets will increase both the amount and the range of substances that are sold. But we argue that the effects on harms will depend on whether cryptomarkets also increase the quality and safety of products that are sold, provide harm- reducing information to consumers, and reduce transactional conflict involved in drug purchasing.Conclusions: We alert readers to an emerging and rapidly growing evidence base connected to the macro and micro harms and benefits of cryptomarkets for drug users. We point out the importance for future researchers of using appropriately matched comparative designs to more firmly establish the differential harms and benefits of sourcing drugs online and offline. We conclude that while it is unlikely that the online drug trade can be completely eradicated; cryptomarkets will respond to regulation and enforcement in ways that have complex, and sometimes unanticipated, effects on both harms and benefits.

The paper presents the application of Shewhart control charts in the annual review of medicinal products quality in order to analyze the production process stability and to use the indicators of process capability for the purpose of its enhancement. The authors presented the sequence of applying Shewhart control charts to identify the various states of manufacture processes and calculate reproducibility and suitability indices, enabling to interpret the input data for effective assessment of drug quality and proper management decisions. By example of some solid, liquid, and soft medicinal forms and by means of assessing the statistical characteristics used in drug quality review, we identified the possibilities of optimizing the production process, grounded the required management dicisions, confirmed the production process stability, identified the need for stabilizing the mean value, and established the causes of the production process uncontrollability.

Drug quality in modern market is discussed. There is an increase of a number of drugs that don’t meet to the quality requirements.Most of them are produced by Russian manufacturers, which number has also increased recently. According to official data 6-10%of all medicines are counterfeit. Quality reduction is also connected with a huge number (80%) of reproduced drugs (generics). Considerable part among generics doesn’t pass required evaluation of equivalence with original product. Approved deviations (according to Russian regulative rules) in pharmacological equivalence may reach 5%, and in pharmacokinetic equivalence -25%. Evidences of pharmacodynamic (therapeutic) equivalence are not required at all. At the same time, author advocates the production of qualitative generics that can providemodern and accessible treatment. Generic quality should be confirmed by randomized studies with cross-over designed comparison with original drug in parallel groups. The examples of the generics with such evidences are demonstrated. The requirements to the data about drugs are given to help the physician to make a right independent estimation of its quality.

Aim: To identify the possible risks associated with critical quality attribute of combined eye drops for the treatment of glaucoma using of common risk evaluation methodologies for plannig a drug quality on the stage of pharmaceutical development. Methods: The paper used method of causal analysis. The maximal number of factors has been define to identify potential factors that provide most significant impact on the drug quality and Ishikawa diagram - graphical representation of causes and effects has been built.Results: Analysis allowed to organize the possible factors affecting the drug quality in the generalized categories: quality control methods, medicines and excipients, primary packaging, proper manufacturing conditions and the stage of the process. The most important factors that are carriers of the risk factors and may lead to negative effects have been identified for the generalized categories.Conclusions: Determined at the stage of pharmaceutical development potential critical quality attribute of AFI, excipients and primary packaging, critical parameters of the process, provide a better understanding, reduction and adoption of risk in subsequent stages of the life cycle of the drug

Pharmaceutical products can be of poor quality either because they contain zero correct active ingredient (referred to as “falsified”) or because they contain a nonzero but incorrect amount of the right active ingredient (referred to as “substandard”). Although both types of poor-quality drugs can be dangerous, they differ in health consequence, price, and potential policy remedies. Assessing basic quality of 1437 samples of Ciprofloxacin from 18 low-to-middle- income countries, we aim to understand how price and nonprice signals can help distinguish between falsified, substandard, and passing drugs. Following the Global Pharma Health Fund e.V. Minilab® protocol, we find 9.88% of samples have less than 80% of the correct active ingredient and 41.5% of these failures are falsified. Falsified and substandard drugs tend to differ in two observable attributes: first, falsified drugs are more likely to mimic drugs registered with local drug safety regulators. Second, after controlling for other factors, substandard drugs are on average cheaper than passing generics in the same city but the price of falsified drugs is not significantly different from that of passing drugs on average. These data patterns suggest that careful consumers may have information to suspect a drug is substandard before purchase but substandard drugs can still exist to cater to poor and less-educated population. In contrast, falsified drugs will be more difficult for consumers to identify ex ante because they appear similar to high-quality, locally registered products in both price and packaging

The primary drug quality requirements—safety, efficacy, and reliability—for oral pharmaceutical products in tablet form, translate into bioavailability, tablet weight, and tablet strength. The bioavailability of an oral drug, i.e., the amount of the drug that can reach the systemic circulation, is dependent on the drug permeation rate through the epithelial membrane or on dissolution rate, in the case of bioequivalence. Thus, the critical quality attributes affecting bioavailability can be the dissolution profile, tablet weight, and tablet hardness, which are affected by process conditions and drug product composition, i.e., active pharmaceutical ingredients (APIs) and excipients and their mass fractions. A Mixture Design experiment (DOE) has been carried out for a generic oral drug, with the input factors being the mass fractions of three excipients and the response variables being the dissolution profile, tablet weight, and hardness. While the last two response variables are single-point-value attribute...

Identification is an important step in the quality control of drugs and the research for new drugs. First, this review discusses the identification of bulk drugs and the active ingredients in formulations, based mainly on pharmacopoeial tests. The most important methods for this purpose are infrared (IR) and, to a lesser extent, ultraviolet (UV) spectroscopy, as well as retention matching with standards using high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). The identification of impurities and degradants is based mainly on HPLC-UV, HPLC-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR) spectroscopies. The above methods are also used for identification purposes in drug research. The use of MS and NMR in the research for large-molecule drugs of biotechnological origin and natural products, mainly of plant origin, with special respect to traditional Chinese (and Indian) medicines is also discussed. The review concludes with the identification aspects of the fight against counterfeit drugs.

Capture reagents are critical to affinity-based bioanalytical methods. The potential bias of capture reagents, for or against certain subpopulations of the target of interest, may lead to inaccurate quantitation. This issue is more profound for sensitive measurements, such as post-translational modification (PTM) profiling of therapeutic proteins from complex matrix. Here, a recently developed affinity purification coupled mass spectrometric method was utilized to assess the full sequence of a circulating therapeutic aglycosylated IgG1 (MAB3) in human subject, using two different capture reagents. We monitored all PTMs known to be related to MAB3 drug quality (three representative PTMs are shown in this paper). The results validated the comparability of these two reagents.

Among the insights in commentaries to our article was the valuable suggestion that cryptomarkets serve a particular subpopulation of drug buyers; whatever harm-reducing outcomes they generate may simultaneously reproduce drug-related inequalities. We caution against generalising our arguments to other online purchasing locations and conclude that responses to cryptomarkets that do not acknowledge benefits may be short-sighted.

Alprazolam is a benzodiazepine anxiolytic commonly prescribed as a sleeping aid and for the treatment of anxiety disorders. The current study was undertaken with the aim of analyzing quality of commercially available brands of alprazolam tablets available in Bangladesh. To assess the quality, locally available 0.25 mg alprazolam tablet of seven different manufacturers were selected and certain physico-chemical parameters like weight variation, hardness, friability, disintegration time and dissolution profile etc. were evaluated using in-vitro analytical methods. All the tablet brands met the requirements of British Pharmacopoeia as they showed acceptable weight variation and friability (below 1%). Brands were slightly different in hardness, disintegration time and dissolution profile from each other. The hardness of all the brands was found to be in the range of 1.50±0.18 to 4.21±0.11 kg-ft. In water medium the disintegration time of all brands were found to be 0.57±0.45 to 2.22±0.23 min. Five out of seven brands showed better dissolution profile as they released more than 90% drug in 30 min. The study revealed that most of the marketed alprazolam tablets met the BP standards for physico-chemical properties which are the indicators of drug quality. It can be concluded that drug products should always comply standard quality parameters that are the prerequisites for getting satisfactory clinical effects. DOI: http://dx.doi.org/10.3329/bpj.v16i2.22302 Bangladesh Pharmaceutical Journal 16(2): 185-188, 2013

The emergence and transmission of antimalarial resistance is hampering malaria eradication efforts and is shortening the useful therapeutic life of currently available antimalarials. Drug selection pressure has been identified as a contributing factor to the emergence and transmission of resistance, especially population treatment coverage and sub-therapeutic concentrations of active pharmaceutical ingredient (API) in the bloodstream. Medicine quality can be defined as good quality or poor quality. Poor quality antimalarials can be falsified, substandard or degraded and are estimated to make up between 10 and 50% of the antimalarial market in developing countries, and can be a source of sub-therapeutic doses of antimalarial API(s). The availability and use of poor quality antimalarials and the non-recommended use of quality assured monotherapies have historically been linked to treatment failure and in some cases, have coincided with the emergence and transmission of resistance in regions. We propose and outline the hypotheses that the use of poor quality antimalarial treatments and non-recommended quality assured monotherapies promote the (i) emergence and/or (ii) transmission of antimalarial resistance. Refereed/Peer-reviewed

Poor-quality medicines present a serious public health problem, particularly in emerging economies and developing countries, and may have a significant impact on the national clinical and economic burden. Attention has largely focused on the increasing availability of deliberately falsified drugs, but substandard medicines are also reaching patients because of poor manufacturing and quality-control practices in the production of genuine drugs (either branded or generic). Substandard medicines are widespread and represent a threat to health because they can inadvertently lead to healthcare failures, such as antibiotic resistance and the spread of disease within a community, as well as death or additional illness in individuals. This article reviews the different aspects of substandard drug formulation that can occur (for example, pharmacological variability between drug batches or between generic and originator drugs, incorrect drug quantity and presence of impurities). The possible means of addressing substandard manufacturing practices are also discussed. A concerted effort is required on the part of governments, drug manufacturers, charities and healthcare providers to ensure that only drugs of acceptable quality reach the patient.

Red yeast rice (RYR) is made by fermenting the rice with Monascus. It is commonly used in food colorants, dyeing, and wine making in China and its neighboring countries. Nowadays RYR has two forms on the market: common RYR is used for food products, the other form is functional RYR for medicine. However, some researchers reported that commercial lovastatin (structure is consistent with monacolin K) is illegally added to common RYR to meet drug quality standards, so as to imitate functional RYR and sell the imitation at a higher price. Based on current detection methods, it is impossible to accurately distinguish whether functional RYR is adulterated. Therefore, it is especially important to find a way to authenticate functional RYR. In the current review, the advances in history, applications, components (especially monacolins, monacolins detection methods), quality standards, authentication methods and perspectives for the future study of RYR are systematically reviewed.

Since Akerlof’s theory of lemons, economists have viewed quality uncertainty as an informational advantage for sellers. Drawing on frontier techniques, we propose in this paper a simple method for measuring inefficiency of both sellers and buyers in markets for goods with different levels of quality. We apply a non-parametric robust double-frontier framework to the case of illicit substance markets, which suffer from imperfect information about drug quality for purchasers and to a lesser extent for sellers. We use unique data on cannabis and cocaine transactions collected in France that include information about price, quantity exchanged and purity. We find that transactional inefficiency does not really benefit either dealers or purchasers. Furthermore, information influences the performance of agents during market transactions.

Background Users of darknet markets refer to product quality as one of the motivations for buying drugs there, and vendors present quality as a selling point. However what users understand by quality and how they evaluate it is not clear. This paper investigates how users established and compared drug quality. MethodsWe used a two-stage method for investigating users' assessments. The user forum of a darknet market that we called 'Merkat' was analysed to develop emergent themes. Qualitative interviews with darknet users were conducted, then forum data was analysed again. To enhance the applicability of the findings, the forum was sampled for users who presented as dependent as well as recreational.ResultsQuality could mean reliability, purity, potency, and predictability of effect. We focused on the different kinds of knowledge users drew on to assess quality. These were: embodied; craft; and chemical. Conclusion.Users’ evaluations of quality depended on their experience, the purpose of use, and its context. Market forums are a case of indigenous harm reduction where users share advise and experiences and can be usefully engaged with on these terms.Highlights:• We investigate how darknet market users assess drug quality• Market forums allow users to apply embodied, craft and chemical knowledge to compare the quality of different products• Good quality does not necessarily equate to high chemical purity• Different drugs are assessed with different priorities in mindExpanding the range of knowledge types that users apply to product quality may have positive implications for harm reduction