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.

Management of validation of HPLC method for determination of acetylsalicylic acid impurities in a new pharmaceutical product

The work mainly focused on a validation of the method for determining the content of salicylic acid and individual unknown impurities in new pharmaceutical product—tablets containing: 75, 100 or 150 mg of acetylsalicylic acid and glycine in the amount of 40 mg for each dosage. The separation of the components was carried out by means of HPLC, using a Waters Symmetry C18 column (4.6 × 250 mm, 5 μm) as the stationary phase. The mobile phase consisted of a mixture of 85% orthophosphoric acid, acetonitrile and purified water (2:400:600 V/V/V). Detection was carried out at a wavelength of 237 nm, with a constant flow rate of 1.0 ml min−1. In order to verify the method, linearity, precision (repeatability and reproducibility), accuracy, specificity, range, robustness, system precision, stability of the test and standard solution, limit of quantification and forced degradation were determined. Validation tests were performed in accordance with ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) guidelines. The method was validated successfully. It was confirmed that the method in a tested range of 0.005–0.40% salicylic acid with respect to acetylsalicylic acid content is linear, precise and accurate.

Recruiting for Resilience

Bringing a safe and effective pharmaceutical product or medical device to market requires an astonishing amount of time and money. This research features interviews with the Chief Executive Officers (CEOs), Chief Scientific Officers (CSOs) and Chief Medical Officers (CMOs) of many of the most successful life science firms in the USA with the goal of to capturing their thoughts on the recruitment of new hires. The executives screened candidates for emotional commitment as an essential quality to complete the long process of bench science, regulatory clearance and product positioning in the market. They sought to hire experienced team members who thought of set-backs as problems to be solved on the way to providing life-altering options for patients. These C-suite leaders needed to create a productive workplace culture, enhanced by a diverse group of professionals with a variety of experiences and temperaments. Participants noted that shared vision and resilience played a greater role in predicting performance than any particular skill-set discernible from a resume.

The Effectiveness Test Of Wound Healing Daun Gatal (Laportea Decumana) Against Mice (Mus Musculus L)

Daun Gatal (Laportea spp) is one of the shrubs that are widely distributed in Papua from the coast to the mountains. Daun Gatal (Laportea spp) has been used for generations by the Papuan people as painkillers. Daun Gatal (Laportea spp) contains compounds monoxide, tryptophan, histidine, alkaloids, flavonoids, formic acid, and anthraquinones. This content is called "antacid" because it gives a sensation like being bitten by an ant. There are many itchy leaves in the village but often they are just left to dry, wither, die, and even be thrown away. The value of this leaf is very large if it is developed not only as an itchy leaf sheet but as a pharmaceutical product. (Simaremare, et al, 2019). This is supported by several research results stating that itchy leaf extract contains compounds of the alkaloid group, glycosides, steroids (Simaremare, 2014), also contains triterpenoid compounds and formic acid (Chrystomo, et al., 2016) and (Krisna and Santanina, 2019) which states that itchy leaves provide antibacterial activity. The type of research used is experimental research. The research design used was a randomized control group pretest and posttest design. The population in this study was white mice. The samples used in this study were white mice that had met the following inclusion and exclusion criteria. Inclusion criteria were female mice, bodyweight 20-30grams, age 2-4 months while the exclusion criteria. Included in the exclusion criteria in this study were mice that were sick or died in the study conditions. The results of the Extraction of Daun Gatal (Laportea Decumana), namely the itchy leaf sample that has been weighed at a concentration of 25% obtained from a mixture of itching leaf extract (25 grams) added with water (30 ml) produces 18.5 ml. Itchy leaf extract at a concentration of 50 % was obtained from a mixture of itchy leaf extract (50 grams) added with water (30 ml) to produce 20.1 ml. Gatak leaf extract at a concentration of 75% was obtained from a mixture of itching leaf extract (75 grams) added with water (30 ml) to produce 24.3 ml. The extraction method used is extracting the extract of itchy leaves. This method was chosen because the process is simple and does not involve heating so that it can prevent damage to chemical compounds that are not resistant to heating, especially flavonoids contained in itchy leaves. Based on the results of the data on the difference in wound diameter of mice, it showed that Treatment Group 1 with 25% itching leaf extract and Treatment Group 2 with 50% itching leaf extract almost had the same healing rate. Meanwhile, Treatment Group 3 with 75% itching leaf extract had the fastest healing rate among other concentrations. In contrast to Treatment Group 3, the control group had a much longer healing rate among other concentrations.

Stability Testing of Pharmaceutical Products

Stability studies must be carried out according to the guidelines provided by the International Conference of Harmonization, World Health Organization, and other agencies in a scheduled manner. The pharmaceutical product’s stability can be defined as the ability, within its physical, chemical, microbiological, toxicology, protective, and informational requirements of a particular formulation in a specific container-closure system. It also guarantees that the performance, safety, and efficacy are maintained throughout the shelf life of any pharmaceutical product which is considered as pre-requisite for acceptance and approval. Different stability test methods have originated with the need for constant monitoring of drugs and products for their quality and purity. In this review, we have included the types of stability of drugs substances, the relevance of different methods used to test the stability of the pharmaceutical product, guidelines issued to test the stability of pharmaceuticals, stability testing protocols which describes the main components of a well-controlled and regulated stability test and other aspects of stability.

Highly Sensitive Amperometric Detection of Hydrogen Peroxide in Saliva Based on N-Doped Graphene Nanoribbons and MnO2 Modified Carbon Paste Electrodes

Four different graphene-based nanomaterials (htGO, N-htGO, htGONR, and N-htGONR) were synthesized, characterized, and used as a modifier of carbon paste electrode (CPE) in order to produce a reliable, precise, and highly sensitive non-enzymatic amperometric hydrogen peroxide sensor for complex matrices. CPE, with their robustness, reliability, and ease of modification, present a convenient starting point for the development of new sensors. Modification of CPE was optimized by systematically changing the type and concentration of materials in the modifier and studying the prepared electrode surface by cyclic voltammetry. N-htGONR in combination with manganese dioxide (1:1 ratio) proved to be the most appropriate material for detection of hydrogen peroxide in pharmaceutical and saliva matrices. The developed sensor exhibited a wide linear range (1.0–300 µM) and an excellent limit of detection (0.08 µM) and reproducibility, as well as high sensitivity and stability. The sensor was successfully applied to real sample analysis, where the recovery values for a commercially obtained pharmaceutical product were between 94.3% and 98.0%. Saliva samples of a user of the pharmaceutical product were also successfully analyzed.

Baseline Assessment of Poultry Production, Pharmaceutical Product Use, and Related Challenges on Commercial Poultry Flocks in Kano and Oyo States of Nigeria

Poultry production is a major component of the livestock sector in Nigeria and continues to expand rapidly; however, it is still constrained by low productivity. A farm survey was conducted to provide a baseline assessment of poultry production (products generated, farm costs, and revenue), pharmaceutical use, and related challenges faced by farmers on 44 commercial poultry farms in Oyo and Kano states of Nigeria. Live spent layers, eggs, and used beddings were the most frequently sold products for revenue. Antibiotic products were widely used, the most reported were Doxygen, Tylosin, and Conflox. Overall, 40% of farms used feed additives (including toxin binders, minerals, and vitamins) and 12% used coccidiostats. Access to pharmaceutical products was a key challenge and appeared to disproportionally affect farmers in the northern part (Kano) of Nigeria. Other challenges included perceived antibiotic ineffectiveness, high cost of drugs, and long distances to pharmaceutical suppliers. Challenges related to vaccine use were unavailability, distance to the supplier, and health issues interfering with the vaccination schedule. Study findings highlight the need for improved access to veterinary pharmaceuticals, particularly in the northern states. Further investigations into the causes of antibiotic ineffectiveness and strategies for distribution of high-quality, effective pharmaceuticals are also necessary.

STUDY OF PHARMACEUTICAL INVENTORY CONTROL SYSTEM IN SEVERAL PHARMACIES IN KARANGASEM, BALI

The control of pharmaceutical products is one of the pharmaceutical services at the Pharmacy that is regulated in Permenkes RI No. 73 of 2016. The pharmacy control of each pharmacy must always apply the principles stated in the Good Pharmacy Practice (GPP) guidelines. GPP is a pharmaceutical practice that responds to the needs of people who use pharmacist services to provide optimal and evidence-based care. This study aims to determine the system of one of the pharmaceutical service standards, namely the control of pharmaceutical products in several pharmacies in Karangasem, Bali. This type of research is observational descriptive. Data retrieval is carried out in a retrospective manner related to the pharmaceutical product control system in the form of an order or procurement, dispensing, and handling system. Most pharmacies are researched to apply the same control system in the procurement and spending of pharmaceutical products. Only the pharmaceutical product system for handling parts has a slight difference in each pharmacy.

Larvicidal activity of granulated pharmaceutical products using Indonesian holy basil leaf extract

<em>Ocimum sanctum</em> Linn, known as holy basil, is a larvicide, which is relatively safe compared to synthetic insecticides. This study investigates the larvicidal activity of a granule formulation of Indonesian holy basil leaf extract against third larval instar of <em>Aedes aegypti</em>. The extract of holy basil leaves was obtained by a maceration process with 96% ethanol. The granule was formulated with various concentrations of holy basil leaf extract, including F1 (2000 ppm), F2 (4000 ppm), and F3 (6000 ppm). The extract contained terpenoid, alkaloid, saponin, flavonoid, and polyphenol compounds. The extract granules had a moisture content of 3.01%, flowability of 1.51 seconds, and dispersion time of 1.09 seconds. The mortality rates of mosquitos treated with the different formulation groups were significantly different from positive control with values of 25.33% (F1), 50.67% (F2), and 90.67% (F3). In conclusion, the granulated formulation of holy basil leaf extract has a larvicidal LC₅₀ of 4405.803 ppm and LC₉₀ of 6080.714 ppm. Therefore, a granulated pharmaceutical product derived from holy basil leaf extract could be developed as a potent larvicide to control dengue fever.

Stability Study of fast Disintegrating tablets of Nisoldipine as per ICH Guidelines

The stability study is a critical parameter to be evaluated in a pharmaceutical product development cycle. A pharmaceutical scientist pays a great deal of heed in testing a product stability. The present research work focused on conducting stability study of fast disintegrating tablet batch of Nisoldipine (NFDT). The various parameters evaluated were weight, hardness, friability, disintegration time, drug content and % drug released. The stability study of optimized fast disintegrating tablet batch NFDT was performed according to ICH guidelines. For the study plan, fast disintegrating tablet batch was placed in a wide mouth air tight containers, which were charged into the stability chamber. The temperature was adjusted at 40°C ± 2°C and relative humidity of 75% ± 5%. The study period was of 6 months. The fast disintegrating tablet batch NFDT did not showed any significant difference in weight, hardness, % friability and disintegration time. The drug content was also reported to be in limits of acceptance. The % drug released at various time intervals was insignificantly changed during its storage period. Hence, the prepared tablets were stable during their storage period.