The Regulatory Review Process in South Africa: Challenges and Opportunities for a New Improved System.

BACKGROUND: The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures to ensure consistency, transparency, timeliness, and predictability in the review process; and to provide recommendations for enhanced regulatory practices. METHODS: A questionnaire was completed by the Medicines Control Council (MCC) to describe the organization of the authority, record key milestones and timelines in the review process and to identify good review practices (GRevPs). RESULTS: Currently, the MCC conducts a full assessment of quality, efficacy, and safety data in the review of all applications. The overall regulatory median approval time decreased by 14% in 2017 (1411 calendar days) compared with that of 2016, despite the 27% increase in the number of applications. However, the MCC has no target for overall approval time of new active substance applications and no targets for key review milestones. Guidelines, standard operating procedures, and review templates are in place, while the formal implementation of GRevPs and the application of an electronic document management system are planned for the near future. CONCLUSIONS: As the MCC transitions to the newly established South Africa Health Products Regulatory Authority, it would be crucial for the authority to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance. It is hoped that resource constraints may then be alleviated and capacity developed to meet target timelines.Peer reviewedFinal Published versio

Retinopathy of prematurity in infants with birth weight above 1500 grams

Objective: To identify the rate and prognosis of retinopathy of prematurity (ROP) among newborn infants of birthweight of above 1500 grams, and the possible risk factors associated with the disease.Design: A prospective cohort study.Setting: Neonatal unit at Maternity Hospital, Kuwait city, Kuwait.Methods: All low birth weight infants were examined for the presence of ROP in the period between January 1996 to December 1997. Prospective collection of data on babies who were above 1500 grams was done to find an association between the disease in these babies and some of the maternal and neonatal risk factors.Results: A total of 68 babies of birth weight above 1500 grams were screened for ROP out of which 13 (19.1%) had different stages of the disease. None of the patients had threshold disease requiring surgery. Among the risk factors chosen, oxygen therapy, presence ofhypotension at birth and the non-use of surfactant were the only risk factors to be associated with disease. However, with logistic regression analysis, none of these were independently associated with ROP.Conclusion: ROP may occur in newborn infants of larger birthweight but with good prognosis, and oxygen therapy seems to predispose to the disease

Optimum conditions for Inulinase production by Aspergillus niger using solid state fermentation

Thirty local fungal isolates according to Aspergillus niger were screened for Inulinase production on synthetic solid medium depending on inulin hydrolysis appear as clear zone around fungal colony. Semi-quantitative screening was performed to select the most efficient isolate for inulinase production. the most efficient isolate was AN20. The optimum condition for enzyme production from A. niger isolate was determined by busing a medium composed of sugar cane moisten with corn steep liquor 5;5 (v/w) at initial pH 5.0 for 96 hours at 30 0C . Enzyme productivity was tested for each of the yeast Kluyveromyces marxianus, the fungus A. niger AN20 and for a mixed culture of A. niger and K. marxianus. The productivity of A. niger gave the highest specific activity of 153 U/mg, as compared with K. marxianus which gave 86 U/mg

The role of TNF-? in the pathogenesis of multiple myeloma “a study in Iraqi patients”

During recent years, there has been an increasing interest in the investigation of the cytokines roles in pathogenesis of cancer, thus the study aimed at evaluating the level of tumor necrosis factor-alpha(TNF-?) in sera of Iraqi multiple myeloma (MM) patients. Beta 2-microglobulion (?2-m) was assessed to determine if there was any association between this cytokine and the level of ?2- m, as the latter is related to the stage of the disease. In addition, the age and gender were also taken into consideration. Furthermore, we investigated the relationship between IgG and TNF-? in sera of patients. 49 Iraqi patients (27 males and 22 females).The patients were also divided into two groups: the first group included (17) patients who were recently diagnosed and not received any treatment at the time of collecting samples while the second group included (32) patients who received treatment. A further group was also investigated which included (12) apparently healthy individuals (9 males and 3 females), who were regarded as a control group. Serum TNF-? and ?2- m were determined using enzyme-linked immunosorbent assay (ELISA).while the concentration of IgG was measured by radial immune diffusion plates The study reached to the following results: TNF-? levels were not significantly elevated in the patients with MM compared to control group (5.98 ± 8.47 SD vs. 4.85 ± 12.1 SD) and no significant differences (P > 0.05) were observed in the mean (6.02 ±8.1SD vs 5.9 ±9.4SD) concentration of TNF-? in patients with MM who received treatment, when compared with those who did not take the treatment .In addition, there are positive significant correlations between TNF-? and ? 2 Microglobulin (r = 0.316, P = 0 .027), and no relationship between IgG and TNF-? (r = - 0.032, P = 0.829).Furthermore, the study observed that, there was no correlation between TNF-? on the one hand and factors of age and gender on the other hand

Evaluating molecular study of the association of Glutathione S – Transferase GST (T1 , M1) genetic polymorphism in Iraqi Arab Femals with Type 2 Diabetes Mellitus and Coronary Artery Disease

Coronary artery disease (CAD) is a major health concern and leading of death in individuals with type 2 diabetes mellitus (T2DM). Glutathione S – Transferase(GST) are known for their broad range of detoxification and in the metabolism of xenobiotics . The role of functional variants of these genes in the development of various disorder is proven. We investigated the possible role of these variants in the development of CAD in T2DM patients. In this case – control study a total of 60 patients (T2DM = 30 ; T2DM – CAD = 30) and 30 controls were included. Serum lipid profiles were measured and DNA was extracted from the blood samples. Multiplex PCR for GSTT1/M1 (present / null) polymorphism, were performed for genotyping of study participants. Gene frequency and lipid profiles were statistically analyzed for disease association. Regression analysis showed that, there was no significant difference of the frequency of GSTT1 (positive /null) genotype and GSTM1 (positive /null) genotype in the 3 study groups . GSTT1 – positive genotype is associated with a 0.51 fold increased ( OR = 0.51 ; 95%CI = 2- 0.1 ;P = 0.321 ) , while the GSTM1 – positive genotype was associated with a 3 fold increase ( OR = 3.06 ; 95%CI=1- 9.7 ; P = 0.055) .We conclude GSTT1 positive genotype considered to be a protective risk from CAD in T2DM patients . The GSTM1 – positive genotype it was considered to be a risk factor of the CAD in T2DM patients

Optimising surface roughness and density in titanium fabrication via laser powder bed fusion

The Ti6Al4V alloy has many advantages, such as being lightweight, formal, and resistant to corrosion. This makes it highly desirable for various applications, especially in the aerospace industry. Laser Powder Bed Fusion (LPBF) is a technique that allows for the production of detailed and unique parts with great flexibility in design. However, there are challenges when it comes to achieving high-quality surfaces and porosity formation in the material, which limits the wider use of LPBF. To tackle these challenges, this study uses statistical techniques called Design of Experiments (DoE) and Analysis of Variance (ANOVA) to investigate and optimise the process parameters of LPBF for making Ti6Al4V components with improved density and surface finish. The parameters examined in this study are laser power, laser scan speed, and hatch space. The optimisation study results show that using specific laser settings, like a laser power of 175 W, a laser scan speed of 1914 mm/s, and a hatch space of 53 µm, produces Ti6Al4V parts with a high relative density of 99.54% and low top and side surface roughness of 2.6 µm and 4.3 µm, respectively. This promising outcome demonstrates the practicality of optimising Ti6Al4V and other metal materials for a wide range of applications, thereby overcoming existing limitations and further expanding the potential of LPBF while minimising inherent process issues

Multi stages toolpath optimisation of single point incremental forming process

Single point incremental forming (SPIF) is a flexible technology that can form a wide range of sheet metal products without the need for using punch and die sets. As a relatively cheap and die-less process, this technology is preferable for small and medium customised production. However, the SPIF technology has drawbacks, such as the geometrical inaccuracy and the thickness uniformity of the shaped part. This research aims to optimise the formed part geometric accuracy and reduce the processing time of a two-stage forming strategy of SPIF. Finite element analysis (FEA) was initially used and validated using experimental literature data. Furthermore, the design of experiments (DoE) statistical approach was used to optimise the proposed two-stage SPIF technique. Mass scaling technique was applied during the finite element analysis to minimise the computational time. The results showed that the step size during forming stage two have significantly affected the geometrical accuracy of the part, whereas the forming depth during stage one was insignificant to the part quality. It was also revealed that the geometrical improvement had taken place along the base and the wall regions. However, the areas near the clamp system showed minor improvements. The optimised two-stage strategy had successfully decreased both the geometrical inaccuracy and processing time. After optimisation, the average values of the geometrical deviation and forming time were reduced by 25% and 55.56%, respectively

Hybrid finite element–smoothed particle hydrodynamics modelling for optimizing cutting parameters in CFRP composites

Carbon-fibre-reinforced plastic (CFRP) is increasingly being used in various applications including aerospace, automotive, wind energy, sports, and robotics, which makes the precision modelling of its machining operations a critical research area. However, the classic finite element modelling (FEM) approach has limitations in capturing the complexity of machining, particularly with regard to the interaction between the fibre–matrix interface and the cutting edge. To overcome this limitation, a hybrid approach that integrates smoothed particle hydrodynamics (SPHs) with FEM was developed and tested in this study. The hybrid FEM-SPH approach was compared with the classic FEM approach and validated with experimental measurements that took into account the cutting tool’s round edge. The results showed that the hybrid FEM-SPH approach outperformed the classic FEM approach in predicting the thrust force and bounce back of CFRP machining due to the integrated cohesive model and the element conversion after failure in the developed approach. The accurate representation of the fibre–matrix interface in the FEM-SPH approach resulted in predicting precise chip formation in terms of direction and morphology. Nonetheless, the computing time of the FEM-SPH approach is higher than the classic FEM. The developed hybrid FEM-SPH model is promising for improving the accuracy of simulation in machining processes, combining the benefits of both techniques