Common deficiencies found in generic Finished Pharmaceutical Product (FPP) applications submitted for registration to the South African Health Products Regulatory Authority (SAHPRA)

Background The aim of the study was to investigate the common deficiencies observed in the Finished Pharmaceutical Product (FPP) section of generic product applications submitted to SAHPRA. The study was conducted retrospectively over a 7-year period (2011–2017) for products that were finalised by the Pharmaceutical and Analytical pre-registration Unit. Methods There were 3148 finalised products in 2011–2017, 667 of which were sterile while 2089 were non-sterile. In order to attain a representative sample for the study, statistical sampling was conducted. Sample size was obtained using the statistical tables found in literature and confirmed by a sample size calculation with a 95% confidence level. The selection of the products was according to the therapeutic category using the multi-stage sampling method called stratified-systematic sampling. This resulted in the selection of 325 applications for non-sterile products and 244 applications for sterile products. Subsequently, all the deficiencies were collected and categorised according to Common Technical Document (CTD) subsections of the FPP section (3.2.P). Results A total of 3253 deficiencies were collected from 325 non-sterile applications while 2742 deficiencies were collected from 244 sterile applications. The most common deficiencies in the FPP section for non-sterile products were on the following sections: Specifications (15%), Description and Composition (14%), Description of the Manufacturing Process (13%), Stability Data (7.6%) and the Container Closure System (7.3%). The deficiencies applicable to the sterile products were quantified and the subsection, Validation and/or Evaluation (18%) has the most deficiencies. Comparison of the deficiencies with those reported by other agencies such as the USFDA, EMA, TFDA and WHOPQTm are discussed with similarities outlined. Conclusions The overall top five most common deficiencies observed by SAHPRA were extensively discussed for the generic products. The findings provide an overview on the submissions and regulatory considerations for generic applications in South Africa, which is useful for FPP manufacturers in the compilation of their dossiers and will assist in accelerating the registration process.

CAPRISA 018: a phase I/II clinical trial study protocol to assess the safety, acceptability, tolerability and pharmacokinetics of a sustained-release tenofovir alafenamide subdermal implant for HIV prevention in women

IntroductionYoung African women bear a disproportionately high risk for HIV acquisition. HIV technologies that empower women to protect themselves are needed. Safe, potent antiretroviral agents such as tenofovir alafenamide (TAF), formulated as long-acting subdermal implants, offer an innovative solution.Methods and analysisCAPRISA 018 is a phase I/II trial to evaluate the safety, acceptability, tolerability and pharmacokinetics (PKs) of a TAF free base subdermal silicone implant containing 110 mg of TAF with an anticipated 0.25 mg/day release rate.The phase I trial (n=60) will assess the safety of one implant inserted in six participants (Group 1), followed by dose escalation components (Groups 2 and 3) assessing the safety, tolerability and PK of one to four TAF 110 mg implants releasing between 0.25 mg and 1 mg daily in 54 healthy women at low risk for HIV infection. Data from this phase I trial will be used to determine the dosing, implant location and implant replacement interval for the phase II trial.The phase II component (Group 4) will assess extended safety, PK, tolerability and acceptability of the implant in 490 at risk women, randomised in a 1:1 ratio to the TAF implant and placebo tablet or to the placebo implant and an oral pre-exposure prophylaxis tablet. Safety will be assessed by calculating the percentage change in creatinine clearance from baseline at weeks 4, 12, 24, 36, 72, 96 and 120, compared with the percentage change in the control group.Ethics and disseminationThe South African Health Products Regulatory Authority and the University of KwaZulu-Natal’s Biomedical Research Ethics Committee have approved the trial. Results will be disseminated through open access peer reviewed publications, conference presentations, public stakeholder engagement and upload of data into the clinical trials registry.Trial registration numberPACTR201809520959443.

Nutraceutical Properties in Flowers

Flowers are associated with human life since time immemorial. Beside aesthetic beauty, several flowers are used for edible purpose viz., rose, marigold, calendula, hibiscus, hollyhock, carnation, chrysanthemum, nasturtium, lotus, cosmos and pansies etc. These flowers have medicinal as well as nutritional values and are rich source of vitamins, antioxidants and mineral elements. The flowers are enriched with various pigments viz., chlorophyll, flavonoids, xanthophylls, carotenoids, betalains and anthocyanin that are generally used in coloring food, beverage, and textile and paper industries. Edible flowers have anticancer, anti-inflammatory, antitumor, antimicrobial and antimutagenic properties too. The flowers are used as vegetables and other purpose since time immemorial, however, flowers for supplementary health products is comparatively a new concept and therefore needs further research to utilize flowers as nutraceuticals.

Health promoting properties and functions of medicinal and culinary mushrooms for the COVID-19 era. An appraisal: does the “anti” mantra stack up?

Many mushroom species are consumed as food, while significant numbers are also utilised medicinally. Mushrooms are rich in nutrients and bioactive compounds. A growing body of in vitro, in vivo, and human research has revealed their therapeutic potentials. Some of the most notable benefits include such properties as anti-pathogenic, antioxidant, anti-inflammatory, immunomodulatory, gut microbiota enhancement, and angiotensin-converting enzyme 2 specificity. The use of medicinal mushrooms (MMs) as extracts in nutraceuticals and other health products are burgeoning. COVID-19 presents an opportunity to consider how, and if, specific MM compounds might be utilised therapeutically to mitigate associated risk factors, reduce disease severity, and support recovery. As vaccines become a mainstay, MMs may have the potential as an adjunct therapy to enhance immunity. In the context of COVID-19, this review explores current research about MMs to identify the key properties claimed to confer health benefits. Considered also are barriers or limitations that may impact general recommendations on MMs as therapy. It is contended that the extraction method used to isolate bioactive compounds must be a primary consideration for efficacious targeting of physiological endpoints. Mushrooms commonly available for culinary use and obtainable as a dietary supplement for medicinal purposes are included in this review. Specific properties related to these mushrooms have been considered due to their potential mediating effects on human exposure to the SARS CoV-2 virus and the ensuing COVID-19 disease processes.

Effects of Light on Secondary Metabolite Biosynthesis in Medicinal Plants

Secondary metabolites (SMs) found in medicinal plants are one of main sources of drugs, cosmetics, and health products. With the increase in demand for these bioactive compounds, improving the content and yield of SMs in medicinal plants has become increasingly important. The content and distribution of SMs in medicinal plants are closely related to environmental factors, especially light. In recent years, artificial light sources have been used in controlled environments for the production and conservation of medicinal germplasm. Therefore, it is essential to elucidate how light affects the accumulation of SMs in different plant species. Here, we systematically summarize recent advances in our understanding of the regulatory roles of light quality, light intensity, and photoperiod in the biosynthesis of three main types of SMs (polyphenols, alkaloids, and terpenoids), and the underlying mechanisms. This article provides a detailed overview of the role of light signaling pathways in SM biosynthesis, which will further promote the application of artificial light sources in medicinal plant production.

Economic impact of biomaterials for bone regeneration in Brazil during the pandemic

Implantable devices are therapeutic options for oral rehabilitation, with several presentations available in the dental consumption market. The consumption power of health products is a little explored in the literature, particularly in the face of financial crises. The aim of this study was to evaluate the economic impact of biomaterials for bone regeneration in Brazil during the pandemic. A quantitative study was carried out through online document analysis, with publicly accessible secondary data extracted from IBGE and websites for the sale of dental products. Data collection in the second quarter of 2020 and 2021 of absolute values ​​of products, official GDP data and population estimates allowed the generation of a biomaterial/income coefficient. The categories obtained from grafts and membranes were stratified by composition, origin and industry. Statistical analysis used the Shapiro-Wilk test to assess normality, the non-parametric Kruskall-Wallis test to compare the means of variables and the Wilcoxon test for paired samples of medians according to the two periods, considering significant differences if p <0.05. Of 97 products analyzed, a higher frequency of bone grafts than barrier membranes was observed, with an average growth of 18.5% in the price of biomaterials, below 28.7% of GDP in the same period. The highest prevalence of biomaterials was the ceramic composition for bone grafts and resorbable polymeric for membranes, from the xenogenous source and Brazilian industry. There was a chronological decrease in the biomaterial/income coefficient in most categories, with a drop in the general average from 4.67±4.40% to 4.30±3.96%, accompanied by an increase in the median, demonstrating a trend towards homogeneity of this coefficient in the comparison between years. The drop in the coefficient indicates a greater purchasing power of biomaterials by the potential consumer. Market knowledge can contribute for the decision making in clinical planning involving bone regeneration.

Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs

Drug-induced liver injury (DILI) is a common adverse drug reaction (ADR) and a serious threat to health that affects disease treatments. At present, no targeted clinical drugs are available for DILI. Traditional natural medicines have been widely used as health products. Some natural medicines exert specific hepatoprotective effects, with few side effects and significant clinical efficacy. Thus, natural medicines may be a promising direction for DILI treatment. In this review, we summarize the current knowledge, common drugs and mechanisms of DILI, as well as the clinical trials of natural drugs and their bioactive components in anticipation of the future development of potential hepatoprotective drugs.

APPLICATION OF VHI VEGETATION INDICES TO CROP YIELD FORECASTING

The aim of this work is to highlight the algorithm and results of modeling the average regional levels of cereals and legumes yields in some regions of Ukraine (Odessa region for example) using remote data, which used the vegetation index VHI. Methods. Model calculations were performed according to the productivity of cereals and legumes in Odessa region for 2011-2020 and the vegetation index VHI for the same period. VHI products received from NOAA STAR - Global Vegetation Health Products system (4 km resolution, 7-day composite). The relationship between VHI and cereals and legumes yields was assessed by correlation-regression analysis. Results. Statistically significant relationships between VHI and cereals and legumes yields levels in Odessa region with a correlation coefficient of 0.8- 0.9 in the period from April to July were establish. Regression dependences for early forecast of сereals and legumes yields (as of the end of April and May) were established using VHI for 16 and 20 weeks (from the beginning of the year). The correlation coefficient between the actual yield Ufact and the model values is 0.93 for Ufor(16) and 0.89 for Ufor(20). The forecast error did not exceed 10 % for Ufor(16) in 70 % of cases, and for Ufor(20) – in 80 % of cases. Conclusions. The authors established regression dependences for the early forecast (as of the end of April and May) of cereals and legumes yields in Odesa region using the region-averaged vegetation indices VHI for 16 and 20 weeks from the beginning of the year. This algorithm can be used to build model ratios for calculating crop yields for different regions of Ukraine and separately for different crops.