Product Withdrawal Research Articles

Peculiarities of effective management of products assortment depending on different sizes of pharmacy chains

The aim of the work is to study the features of effective management of product's assortment in small, medium and large pharmacy chains.
 Materials and methods. The study of the features of the assortment policy of pharmacies that are part of pharmacy chains of different sizes was conducted using a questionnaire of 421 heads of pharmacies. The relationship between the size of the pharmacy chain and the approaches used to form the product's assortment is studied and the presence of the procedure of product's assortment formation in pharmacies is analyzed using Pearson's criteria c2 and c2 maximum likelihood (M-L c2). The importance of the influence of the size of the pharmacy network on the scores of the efficiency of the business process of forming the product range, as well as its width and intensity of updating using non-parametric analysis of variance Kraskal-Wallis; Manfer-Whitney test with Bonferroni correction for pairwise comparisons of pharmacy network clusters and correlation analysis. The presence of drugs in treatment protocols was analyzed using the Z-test to compare the frequency of drug administration. Peculiarities of introduction and withdrawal of drugs and medical products to the range of different size pharmacy chains criteria c2 Pearson's and maximum likelihood (M-L c2) are determined. System and logical analysis is used to systematize the existing approaches to product's assortment management in pharmacy chains of different sizes.
 Results. It is established that with the increase in the size of pharmacy chains the tendency to use a centralized approach to the analysis and formation of the range in chains increases, when the list of assortment items is fully created and approved at the head office of the chain. The importance of the relationship between the breadth of the assortment of pharmacies and the size of the chain, which includes a pharmacy. Thus, large and mega-chains support the assortment, which on average includes up to 8.5 thousand items of medicines and medical devices, medium - 4-5 thousand assortment's items, and in half of the establishments of small pharmacy chains the range may include from 2,5 to 3 thousand names of medicines and medical devices. It is established that regardless of the size of the pharmacy chain, the inclusion of medicines / medical products in the range of pharmacies most often takes into account the factor of seasonality of demand and taking into account the core range, i.e. the list of 100-150 most popular items in the pharmaceutical market. When withdrawing medicines or medical products from the assortment of pharmacies from all three clusters are often guided by indicators of low profitability of sales and lack of orders for goods for more than three months.
 Conclusions. The analysis of the assortment policy of pharmacy chains of different sizes showed that in most of the studied institutions it is quite effective. The obtained results allow us to conclude that the effectiveness of the formation and analysis of the assortment is achieved through the use of different approaches to the centralization of this business process depending on the size of the pharmacy chain

Evaluating the impact of single exit pricing (SEP) on medicine product withdrawal from the private healthcare market in South Africa.

The introduction of medicine pricing policies in South Africa (SA) in the form of single exit pricing (SEP) provided a mechanism to improve medicine price transparency and reduce the medicine price and inflation. However, regulation of medicine prices may have further unforeseen effects on the availability of medicine. This research presents the impact of SEP on discontinuation of medicine products on the private healthcare market in SA. To evaluate the impact of SEP legislation on the availability of medicines in the SA private health sector in terms of withdrawal of medicines from the market. A descriptive, quantitative analysis of all registered medicines on the SA market by stock-keeping units (SKUs) was done to establish medicine products that were withdrawn from the market by SKUs during a 14-year period (2001 - 2014). A total of 152 manufacturers discontinued 3 691 SKUs between 2001 and 2014. The mean number of discontinuations per generic manufacturer was 22.34 (standard deviation (SD) 58.11), while innovator manufacturers discontinued a mean of 27.61 (41.89). The largest number of SKUs were commercially withdrawn in 2002 (n=603), followed by discontinuations in 2003 (n=463) and 2004 (n=407). There was a negative correlation between number of discontinued SKUs per year and SEP increase (Pearson's correlation coefficient r ‒0.414; p=0.14). The results showed that SEP and a transparent pricing policy may have had an impact on SKU withdrawal from the market prior to SEP implementation. The result of reduced product availability on the market and its impact on the cost and quality of healthcare to the patient need to be regularly monitored and evaluated to ascertain if direct price regulations achieve the intended outcomes. Other intended or unintended effects on pharmaceutical market dynamics should also be evaluated.

Regulatory approaches: Global medical device tracking advancement in USA, EU and India

Advancement in science & technology of medical industry is coming up with innovations. Medical devices play a vital role. Real Time Location System (RTLS) which includes Radio Frequency Identification (RFID) device, Wi-Fi technology that helps to look after adverse events and recall products when required, thereby, prevent theft by keeping regular check on their movement with location sensors. In 19th century two products of United States faced product withdrawal. After that, US felt the need to develop system for product record management and tracking. In 2004, FDA introduced Unique Device Identifier (UDI) for medical device tracking. With time, GHTF came up with UDI working groups and in 2013, new version of UDI guidelines for globally harmonized use was generated. In this article study about various countries has been done. It was found that countries like United States and Europe have introduced medical device tracking system and by 2022 this will be implemented in India.

Primum non nocere: In silico prediction of adverse drug reactions of antidepressant drugs

Early and accurate prediction of adverse drug reactions (ADRs) by computer-aided methods is extremely important for decreasing health threats, along with preventing product withdrawal after clinical trials which need long time and high cost. In this study, we built a model to predict 329 known ADRs of 27 approved antidepressant drugs, and we examined three machine learning algorithms (multilayer perceptron, k-nearest neighbour and support vector machine) in order to find which one is better for this duty. We integrated the known ADRs of a drug with the drug’s chemical structures and biological properties, including drug targets, enzymes and transporters for prediction of ADR in our predictive model. In addition, 329 known ADRs were grouped according to their system organ classes (SOCs) and compared the performances of ADR predictions. This assessment, based on a ten-fold cross-validation, showed that the multilayer perceptron (MLP) algorithm surpassed the others. 248 out of 329 ADRs were successfully predicted. The best performing attribute group was the chemical plus biological, followed by the chemical and biological. The mean AUC values are 0.623, 0.676, and 0.695 for the feature groups of chemical, biological, and chemical plus biological, respectively. Among ADRs of the 21 SOCs, only ADRs belonging to 5 SOCs were predicted successfully by chemical, biological or combined attributes. Also, the ADRs related to withdrawal of indalpine, pheniprazine, medifoxamine, zimelidine and amineptine were successfully predicted by our model constructed using MLP with the CfsSubsetEval and BestFirst, based on chemical properties of the approved antidepressants. The results showed the external validity of our approach, predicting satisfactory amount of previously known ADRs from the literature. In conclusion, the proposed approach is an efficient and promising tool for predicting ADRs of antidepressants.

ДОСЛІДЖЕННЯ СПОЖИВАЧІВ У ПРОЦЕСІ СТВОРЕННЯ ТА РОЗПОВСЮДЖЕННЯ ІННОВАЦІЙНИХ ТОВАРІВ

The motivated consumer innovativeness in the creation and distribution of innovation products are considered. The process of determining the consumer preferences of innovative products based on its attributes is investigated. The target audience selection mechanism for the marketing communication complex formation considering the consumer motivation is developed. One of the ways of maintaining the competitiveness of the enterprise, the development of new market segments is the withdrawal of innovative products. This process is always quite risky, even when an innovative product has obvious benefits for consumers. The results of many studies have shown that more than 30% of consumer goods and about 20% of industrial goods suffer market failures. This is due to the fact that innovative products are mainly created only on the basis of new knowledge, without taking into account the real needs of the market. Under these conditions, the key factor in the market success of the product is the marketing research of consumers at the stage of creating an innovative product. Communication impact on consumer categories "innovators" and "early followers" leads to a faster perception of innovative products by the entire target audience. The impact on different categories of consumers through different sets of marketing communication tools corresponds to an approach based on the motivation of consumers of innovative products. The development of a set of marketing communication tools should take into account the needs that meet the innovative products or the relative advantages that they possess.

Consequences to patients, clinicians, and manufacturers when very serious adverse drug reactions are identified (1997-2019): A qualitative analysis from the Southern Network on Adverse Reactions (SONAR).

BackgroundAdverse drug/device reactions (ADRs) can result in severe patient harm. We define very serious ADRs as being associated with severe toxicity, as measured on the Common Toxicity Criteria Adverse Events (CTCAE)) scale, following use of drugs or devices with large sales, large financial settlements, and large numbers of injured persons. We report on impacts on patients, clinicians, and manufacturers following very serious ADR reporting.MethodsWe reviewed clinician identified very serious ADRs published between 1997 and 2019. Drugs and devices associated with reports of very serious ADRs were identified. Included drugs or devices had market removal discussed at Food and Drug Advisory (FDA) Advisory Committee meetings, were published by clinicians, had sales > $1 billion, were associated with CTCAE Grade 4 or 5 toxicity effects, and had either >$1 billion in settlements or >1,000 injured patients. Data sources included journals, Congressional transcripts, and news reports. We reviewed data on: 1) timing of ADR reports, Boxed warnings, and product withdrawals, and 2) patient, clinician, and manufacturer impacts. Binomial analysis was used to compare sales pre- and post-FDA Advisory Committee meetings.FindingsTwenty very serious ADRs involved fifteen drugs and one device. Legal settlements totaled $38.4 billion for 753,900 injured persons. Eleven of 18 clinicians (61%) reported harms, including verbal threats from manufacturer (five) and loss of a faculty position (one). Annual sales decreased 94% from $29.1 billion pre-FDA meeting to $4.9 billion afterwards (p<0.0018). Manufacturers of four drugs paid $1.7 billion total in criminal fines for failing to inform the FDA and physicians about very serious ADRs. Following FDA approval, the median time to ADR reporting was 7.5 years (Interquartile range 3,13 years). Twelve drugs received Box warnings and one drug received a warning (median, 7.5 years following ADR reporting (IQR 5,11 years). Six drugs and 1 device were withdrawn from marketing (median, 5 years after ADR reporting (IQR 4,6 years)).InterpretationBecause very serious ADRs impacts are so large, policy makers should consider developing independently funded pharmacovigilance centers of excellence to assist with clinician investigations.FundingThis work received support from the National Cancer Institute (1R01 CA102713 (CLB), https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci; and two Pilot Project grants from the American Cancer Society's Institutional Grant Award to the University of South Carolina (IRG-13–043–01) https://www.cancer.org/ (SH; BS).

Consequences to Patients, Clinicians, and Manufacturers When Titanic Adverse Drug Reactions are Identified (1997- 2019): A Report from the Southern Network on Adverse Reactions (SONAR)

Introduction: Adverse drug/device reactions (ADRs) can result in severe patient harm. We operationally define titanic ADRs as Common Toxicity Criteria Adverse Events grade 4 or 5 that follow use of drugs or devices that have large sales, large safety financial settlements, and affect large numbers of persons. We report on the impact of titanic ADRs identified between 1997 and 2019. Methods: We reviewed clinician reported titanic ADRs. Data sources included Food and Drug Advisory (FDA) Advisory Committee transcripts, news reports, and medical journals. We reviewed data on timing of titanic ADR reports, Boxed warnings, product withdrawals, and impacts on patients, clinicians, and manufacturers. Results: Overall, twenty titanic ADRs involved 15 drugs and 1 device. Legal settlements totaled $38.4 billion for 874,000 persons reportedly developing titanic ADRs. Five clinicians reported receiving threats from manufacturers’ employees, one clinician lost a university faculty position, and five clinicians were not invited to FDA meetings where their safety findings were discussed. Annual sales for 9 still patented drugs and 1 device decreased 78% from $21.3 billion pre-ADR report to $3.9 billion afterwards. Following FDA approval, the median time to titanic ADRs reporting was 7.5 years. Fourteen drugs received Box warnings a median of 7.5 years following titanic ADR reporting. Six drugs and 1 device were withdrawn from marketing (median of 5 years after titanic ADR reporting). Conclusion: Overall, 874,000 persons were purportedly injured by fifteen drugs and one device that caused titanic ADRs, reputational harms were reported by eleven clinicians , and $38.4 billion in legal settlements were paid . Because titanic ADRs impacts are so large, and investigative processes not always transparent, policy makers should develop an independently funded drug safety board. Funding Statement: This work received support from the National Cancer Institute (1R01 A102713 (CLB), https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci; the American Cancer Society (IRG-13-043-01), https://www.cancer.org/; and an unrestricted grant from Doris Levkoff Meddin. Declaration of Interests: The authors have declared that no competing interests exist.

Platform Venture Capital Investments and the Introduction and Withdrawal of Complementary Products

Many platform providers are involved in corporate venturing. Increasingly, platform providers stake out minority equity investments in complementors from their own platform ecosystem as an act of ecosystem governance, a practice that we refer to as platform venture capital (PVC). We study how other complementors respond to such investments, as it pertains to their decisions to introduce and withdraw complementary products. Building upon the triadic exchange structure and contingent adoption nature that are characteristic for platforms, we advance theoretical arguments that position PVC as a powerful proxy for customer demand in the platform ecosystem. We explore the implications of PVC for complementary product introduction and withdrawal by assessing the consequences of 24 PVC investments in the context of Salesforce’s platform ecosystem. Consistent with our theoretical arguments, we show that complementors tend to view PVC as a signal of opportunity rather than as a potential threat, such that they are more likely to introduce and less likely to withdraw complementary products in product categories affected by PVC. We also show that these effects are weaker for complementors with greater platform ecosystem experience and multihoming complementors that are better positioned to access information on the preference of platform customers.

Development of engineering decisions to reduce technological exposure to the environmental environment of oil flower

The way of neutralization of waste of oil-processing industry of receiving valuable secondary raw materials is developed for use in the construction industry.Optimization of process of interaction of withdrawal of production of additive (DF-11) with waste of the ground is performed. The method of liquidation of the map of viscous production wastes of additives is developed. The special collector of waste is developed for selection of waste from the card.The regression equation establishing connection between the number of the absorbed petrowaste and content in initial mix OPP, GP and KEKA, allowing to optimize composition of mix is received. The optimum maintenance of the components entering mix is defined.

The Impact of Routine Skin Care on the Quality of Life

Importance: Consumers purchase a wide variety of consumer products and come into contact with these products on a daily basis. Manufacturers invest deeply in developing new products or improving existing products, in order to produce a positive impact on the lives of consumers. Objective: The goal of this study was to determine the impact of over-the-counter skin care products on the quality of life (QoL) of female consumers. Design and Measures: A QoL instrument developed for consumer products (the Farage QoL with an added Skin Care Module) was used to assess the impact of a 28-day facial skin care regimen using commercially available products formulated to improve elasticity, firmness and hydration, and to correct age- and sun-related skin color. Responses were collected prior to study commencement, at completion of the product usage stage, and after a period of withdrawal of the product with reversion to a basic skin care regimen. Participants: Two main study groups from Australia included 89 new mothers, i.e., women with children 2 years and under (mean age ± SD was 34 ± 4.8), and a national representative sample of 91 women (45 ± 12). An additional test group from China consisted of 40 younger cosmetic users (25 ± 4.3). The Skin Care Module was not included in the instrument for the third group. Results: After 28-days of usage, both test groups in the main study showed significant improvement in three of five items in the Skin Care Module (improved feelings of empowerment, happiness and self-esteem). Improvements persisted after 2 weeks of product withdrawal. In the main QoL instrument, the New Mothers group showed significant improvement in the Well-Being domain, driven by improvements in the Self-Image and Self Competence subdomains. The National Representative group showed improvements in the Energy and Vitality domain, driven by improvements in the Personal Pleasure, Physical State and Routine Activity subdomains. The additional group in the China study showed results similar to the New Mothers group. Conclusions and Relevance: A quality and efficacious skin care regimen can have a positive impact on the QoL of consumers. Differences in responses of the test groups were likely related to differences in the mean age and differences in time available to look after themselves.

Media coverage of the 2019 United States Food and Drug Administration ordered withdrawal of vaginal mesh products for pelvic organ prolapse.

On April 16, 2019, the United States Food and Drug Administration announced a withdrawal on sales and distribution of transvaginal mesh products for pelvic organ prolapse. The aim of this study was to asses online user behavior on pelvic-mesh related articles after the withdrawal and to evaluate article accuracy. We used Google Trends© to identify the terms related to pelvic mesh that experienced increased activity after the FDA announcement. The terms were analyzed for worldwide social media engagement (Facebook, Twitter, Pinterest, and Reddit) between April 16-19, 2019. The top ten lay press articles shared for each term were evaluated. We also examined the top ten Google search results for each term on June 6, 2019, in the US to evaluate what information was available after peak interest subsided. During peak activity in April, 30 unique articles were identified after the FDA announcement. Two (6.7%) did not mention the April 2019 FDA announcement. Seven (23%) discussed mesh for stress urinary incontinence. After peak interest on June 6, 2019, Google identified 26 unique articles for the four terms. Seven (27%) did not mention the FDA announcement, and 3 (12%) mentioned mesh for incontinence. Internet search patterns and social media behavior following the April 2019 ordered withdrawal on transvaginal mesh for pelvic organ prolapse reveal that some of the most disseminated information did not accurately or thoroughly distinguish the type of mesh discussed. This could lead to negative consequences for other mesh indications in female pelvic medicine and reconstructive surgery.

Beer spoilage and low pH tolerance is linked to manganese homeostasis in selected Lactobacillus brevis strains.

Beer is a harsh medium for bacteria to survive, however, lactic acid bacteria including Lactobacillus brevis have evolved the ability to grow in beer. Here, the influence of environmental factors such as low pH, ethanol or hop content was assessed. A transcriptomic analysis of two Lact. brevis beer-spoiling strains was performed comparing growth in nutritive media with or without the imposition of a stressor related to the beer environment. This allowed the identification of a manganese transporter encoding gene that contributes to low pH tolerance. We report on the importance of a manganese transporter associated with pH tolerance and beer spoilage in Lact. brevis. The importance of manganese for Lact. brevis growth in a low pH environment was highlighted. Bacterial spoilage of beer may result in product withdrawal with concomitant economic losses for the brewing industry. A limited number of genes involved in beer spoilage have been identified but none of them are universal. It is clear that other molecular players are involved in beer spoilage. The study highlights the complexity of the genetic requirements to facilitate beer spoilage and the role of multiple key players in this process.

ПОВЫШЕНИЕ ПРОЧНОСТИ И МОРОЗОСТОЙКОСТИ КЕРАМИЧЕСКИХ ИЗДЕЛИЙ ПРИ ИСПОЛЬЗОВАНИИ МЕЛАССНОЙ БАРДЫ В КАЧЕСТВЕ ПЛАСТИФИЦИРУЮЩЕЙ ДОБАВКИ

ways of production of ceramic materials with use as the plasticizing additive of the sulphitic and alcohol bards (SAB), the calcium citrate filtrate (CCF) which is liquid withdrawal of production of citric acid in the microbiological way are known. However introduction to raw mix of CoB reduces forming humidity and fall of the formed products insufficiently, and an essential lack of FTsK is the low durability of products on compression with a big volume mass of samples.&#x0D; In work the possibility of use as the plasticizing additive to a clay lot of withdrawal of the spirit industry – melasses bards is investigated. As a part of molasses the remains of amino acids and other organic substances which have the plasticizing effect on clay materials contain. On the example of natural clays of three various fields the plasticizing action melasses bards is proved, and the number of plasticity of the studied clays increases in direct ratio to increase in additive melassny bards in clay raw mix. It is shown that introduction to raw mix melasses bards leads to improvement of appearance of pottery, decrease in jointing, increase in durability for Veselovsky clay for 7%, for the Oryol clay for 67%, for Bessonovskaya – for 23%.&#x0D; Research of the received ceramic samples on frost resistance according to requirements of GOST bards unlike the products which aren’t containing additive bards showed high frost resistance of products with additive melass. Also lowered decrease in durability and loss of mass of the samples containing additive melassny bards is noted

Ranitidine Induced Hepatotoxicity: A Review

Background: Ranitidine (RAN) is one of the common drugs associated with idiosyncratic adverse drug reactions (IADRs) in humans. It was found to be associated with severe adverse drug reactions due to the presence of contaminants such as N-Nitrosodimethylamine (NDMA) which is claimed to be carcinogenic. As a consequence, on April 1, 2020, United States Food and Drug Administration (USFDA) had decided to call off all the RAN products from the market. The exact cause of RAN associated idiosyncratic hepatotoxicity is not clear yet. Purpose: To summarize and analyze the reason behind the withdrawal of RAN products from the market and whether ranitidine will be available again in future or will FDA withdraw approvals of ranitidine National Drug Authority (NDA) and an abbreviated new drug application (ANDA)? Methods: We performed a systematic PubMed/MEDLINE search of studies investigating the reason behind the withdrawal of RAN products and explored the possible mechanism associated with RAN induced hepatotoxicity. Conclusion: RAN induced liver injury is difficult to diagnose and study because of its relative rarity and unpredictive occurrence. Recent studies suggest that most of the RAN associated idiosyncratic reactions may lead to hepatocyte damage, followed by a series of events, such as activation of specific T- and B-cells, release of proinflammatory mediators like TNFα, interleukins, various cytokines and chemokines. The exact cause of RAN associated idiosyncratic hepatotoxicity is not clear yet. More studies must be carried out on this to know about the exact reason behind RAN associated hepatotoxicity.

FDA requests market withdrawal of all ranitidine products

FDA requests market withdrawal of all ranitidine products

Bio-absorbable Cardiovascular Implants: Status and Prognosis

There are three major classes of cardiovascular implants that can benefit from biodegradable materials: coronary/peripheral stents, occluders for heart defects, and embolic devices. We review the progress made in these three device classes, and offer our own prognosis for where the technology needs to improve. Although there has been product withdrawals of an approved fully resorbable stent (Absorb BVS), we believe that metallic bioresorbable stents may have a role to play. Likewise, in the area of embolic devices, there is a need for a quick-acting, fully-degradable device that blocks certain blood vessels. Most of the push for bioabsorbable occluders will come from countries where there is a large incidence of heart defects, such as China and India.

Postmarket Modifications of High-risk Plastic Surgery Devices.

Background:In the United States, high-risk medical devices must be cleared through the premarket approval (PMA) pathway, which requires clinical evidence ensuring safety and efficacy. Approved devices can be modified and reintroduced to market without additional study through the PMA supplemental review track. This study characterizes the changes of high-risk plastic surgery devices once they undergo initial clearance.Methods:A retrospective, cross-sectional analysis of the Food and Drug Administration (FDA) PMA database. The following data were extracted from the PMA database (January 1, 1980 to December 31, 2018): initial clearance date, device type, the number and type of supplement, supplement reason, and product withdrawal date. Data from the FDA medical device recall database were also extracted and reported. The median number of device modifications and median lifetime of device-years were calculated.Results:There have been 39 original plastic surgery devices approved by the FDA. There was no significant change with respect to initial clearance dates for original devices over time (r = 0.28; P = 0.084). PMA supplement usage has significantly increased with time (rs = 0.9174, P = 0.000). Overall, approved plastic surgery devices have undergone a median of 11 changes (IQR, 3–35). Breast implant devices collectively underwent the most modifications with a median of 28 modifications per device (IQR, 20.25–33.25).Conclusions:Over the past 2 decades, plastic surgery device manufacturers have significantly increased the use of supplement track review. High-risk plastic surgery devices may undergo frequent minor changes without clinical evidence to support the safety and efficacy of modified versions.

أثر التعرض للسلوک العدائي يف مکان العمل على السلوکيات املناوئة للعمل املوجهة للمنظمة )بالتطبيق على هيئة التمريض بمستشفيات جامعة المنصورة(

امللخص تستهدف هذه الدراسة اختبار تأثير التعرض للسلوک العدائي في مکان العمل على السلوکيات المناوئة للعمل الموجهة للمنظمة لدى هيئة التمرض بمستشفيات جامعة المنصورة، وتم جمع بيانات من 358 . وتوصلت الدراسة إلى وجود ارتباط معنوي بين کل من التعرض للعدوان مفردة وتحليلها إحصائيا النفسي والجسدي في مکان العمل والسلوکيات المناوئة للعمل الموجهة للمنظمة )انحراف اإلنتاج، التخريب، السرقة، االنسحاب(، کما يوجد تأثير معنوي للتعرض للعدوان النفسي في مکان العمل على کل من انحراف اإلنتاج، السرقة، االنسحاب. بينما اليوجد تأثير معنوي للتعرض للعدوان النفسي في مکان العمل على التخريب. کما يوجد تأثير معنوي للتعرض للعدوان الجسدي في مکان العمل على کل من انحراف اإلنتاج، السرقة، التخريب. بينما ال يوجد تأثير معنوي للتعرض للعدوان الجسدي في مکان العمل على االنسحاب. t This study aimed to examine the effect of Workplace aggression exposure on Counterproductive Work Behaviors Directed to the organization, applied to nurses in hospitals of Mansoura University. We collect data From 358 nurse. And the Findings revealed that there is a positive relationship between psychological aggression and Physical aggression exposure and Counterproductive Work Behaviors Directed to the organization. There is also a significant effect of psychological aggression exposure in the workplace on production deviance, theft, and withdrawal. While there was no significant effect of exposure to psychological aggression in the workplace on Sabotage. There is also a significant effect of exposure to physical aggression in the workplace on production devianc, theft, and Sabotage. While there was no significant effect of exposure to physical aggression in the workplace on withdrawal.

A Plasmid-Encoded Putative Glycosyltransferase Is Involved in Hop Tolerance and Beer Spoilage in Lactobacillus brevis.

Lactobacillus brevis beer-spoiling strains harbor plasmids that contain genes such as horA, horC, and hitA which are known to confer hop tolerance. The L. brevis beer-spoiling strain UCCLBBS124, which possesses four plasmids, was treated with novobiocin, resulting in the isolation of UCCLBBS124 derivatives exhibiting hop sensitivity and an inability to grow in beer. One selected derivative was shown to have lost a single plasmid, here designated UCCLBBS124_D, which harbors the UCCLBBS124_pD0015 gene, predicted to encode a glycosyltransferase. Hop tolerance and growth in beer were restored when UCCLBBS124_pD0015 was introduced in one of these hop-sensitive derivatives on a plasmid. We hypothesize that this gene modifies the surface composition of the polysaccharide cell wall, conferring protection against hop compounds. Furthermore, the introduction of this gene in trans in L. brevis UCCLB521, a strain that cannot grow in and spoil beer, was shown to furnish the resulting strain with the ability to grow in beer, while its expression also conferred phage resistance. This study underscores how the acquisition of certain mobile genetic elements plays a role in hop tolerance and beer spoilage for strains of this bacterial species.IMPORTANCELactobacillus brevis is a member of the lactic acid bacteria and is often reported as the causative agent of food or beverage spoilage, in particular, that of beer. Bacterial spoilage of beer may result in product withdrawal or recall, with concomitant economic losses for the brewing industry. A very limited number of genes involved in beer spoilage have been identified and primarily include those involved in hop resistance, such as horA, hitA, and horC However, since none of these genes are universal, it is clear that there are likely (many) other molecular players involved in beer spoilage. Here, we report on the importance of a plasmid-encoded glycosyltransferase associated with beer spoilage by L. brevis that is involved in hop tolerance. The study highlights the complexity of the genetic requirements to facilitate beer spoilage and the role of multiple key players in this process.

Industrial approaches and consideration of clinical relevance in setting impurity level specification for drug substances and drug products

The safety and efficacy of drug substances or products do not solely depend on its active(s). The quantity of impurities present in the product has a significant role in its safety profile. Pharmaceutical impurities are one of the primary reasons for the withdrawal of many approved products from the market. Therefore, the level of impurities in the pharmaceuticals needs to be controlled within a specified safe limit. Nowadays, setting impurity level specification remains a great challenge for pharmaceutical manufacturers. Regulatory guidelines recommend to control the impurity based on the concentration level criteria and provides limits of allowable impurities in pharmaceuticals. However, a single set of impurity limits cannot work for all the drug substances. There are numerous reasons which demand to set the impurity level specification based on safety dominated critical quality attribute principle. In this review, we have discussed the need for the consideration of both concentration based and patient safety-related approaches for setting the impurity level specification. To achieve this goal, it is required to identify the safety limits of the impurities during clinical development and provide a specification for the finished pharmaceutical products before entering the market. However, tremendous challenges faced by pharmaceutical companies to have an appropriate balance amongst the critical factors like safety, efficacy, analytical variability, process knowledge and regulatory requirement. Finally, the specification for API and finished drug product should be established considering both quality and patient safety. Considering all such factors, we have included a systematic and scientific approach that can guide to establish the safe and flexible impurity limit specification for pharmaceuticals.