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.

The ethnomedicinal plants used for human ailments at Mojana Wodera District, central Ethiopia

Abebe M. 2021. The ethnomedicinal plants used for human ailments at Mojana Wodera District, central Ethiopia. Biodiversitas 22: 4676-4686. An ethnobotanical study was carried out from March 2020 to February 2021 in selected sites of Mojana Wodera District to assess, identifying, and document medicinal plants to treat human ailments. Purposely and volunteer sampling techniques were applied to select 73 practitioners. Of those, 10 practitioners were key informants. Data was collected from informants using semi-structured interviews, focus group discussions, participant observation, and walk-in-the-word. The collected data were entered into an excel spreadsheet for statistical analysis. ANOVA and t-test were applied to compare the knowledge of the informants in different groups. ICF and FL values were calculated to identify the most common human ailments and heal the potential of medicinal plants. The result showed that a higher average (p< 0.05) was recorded for crucial informants, illiterate and higher aged group. Still, there was a significant difference between male and female informants (p=0.032) on knowledge of medicinal plants. A total of 45 medicinal plant species (41 genera and 27 families) were identified to treat 35 types of ailments. From this total, 15.6% were endemic for Ethiopia. Family Euphorbiaceae was dominant (11.1%) for this study. In the finding, the leaf was the most widely plant part which is used to prepare remedies (29.79%), followed by root (28.72%), and the most popular remedy preparation was pounding (31.18%). A higher ICF value (0.78) was recorded for dermatological category ailments, and the highest FL (94.12%) occurred for Laggera tomentosa, which was under the therapeutic category of the throat and respiratory.

Terretonins from Aspergillus Genus: Structures, Biosynthesis, Bioactivities, and Structural Elucidation

: Fungi are considered as a prosperous pool of microbial bio-metabolites. Terretonins are meroterpenoids that are reported mainly from Aspergillus genus. They exhibited unique tetracyclic core skeletons and various bioactivities. The current review summarizes the published researches on the source, biosynthesis, isolation, structural characterization, and bioactivities of terretonins that have been reported from Aspergillus species, as well as from synthetic sources. A literature search on the published studies was conducted over different databases: Web of Science, MedLine (PubMed), Scopus, SpringerLink, Google Scholar, SciFinder, Wiley, and ACS Publications up to 2020. In this work, 18 compounds from Aspergillus species and synthetic sources are depicted. They have unrivaled and diversified skeletons as well as various bioactivities. Moreover, 37 references are included. Terretonins form a class of fungal bio-metabolites that attain all the characters for becoming lead compounds in their particular therapeutic category.

Analysis of patients’ request to switch from a generic drug to the original drug in external prescriptions

Background Generic drugs are heavily promoted in Japan. The aim of this retrospective single-center study was to clarify whether the frequency and reason that patients request a switch from a generic drug to the original drug differ according to therapeutic category and dosage form. Methods This study was performed at Chiba University Hospital. Prescription inquiries about 121 generic drugs from community pharmacies over a 3-year period (from July 2014 to June 2017) were analyzed. Results Approximately 30% of the requests were related to the efficacy, safety, and comfort of the generic drug. The most cited motive was “patient’s desire with no reason given” at 44.5%. According to multiple logistic regression analysis, therapeutic categories and dosage forms were associated with the requests. The median request frequency differed according to therapeutic category and dosage form. The frequency was highest for “agents affecting the central nervous system” and “tablets and capsules”, respectively. Among the therapeutic categories, “agents affecting the central nervous system” had the highest median number of requests related to “decreased effectiveness”; “cardiovascular agents” had the highest median number of requests related to “physician’s instruction”; and “agents for the epidermis” had the highest median number of requests related to “uncomfortable to use”. Among dosage forms, the odds ratio for patients’ original drug request for “liniment and patch” was about 1.5 times that for “tablets and capsules”. “Liniment and patch” had the highest median frequency of requests related to “decreased effectiveness”, “uncomfortable to use”, and “patient’s desire with no reason given”. Conclusions The request frequency and reason differed according to therapeutic category and dosage form. Pharmacists should advise each patient properly about the choice and switching of drug brands, taking into account the therapeutic category and dosage form, especially liniments and patches.

Precision of VerifyNow P2Y12 Assessment of Clopidogrel Response in Patients Undergoing Cerebral Aneurysm Flow Diversion

Background Dual antiplatelet therapy (DAT), most commonly with aspirin and Clopidogrel, is the standard of care for intracranial stenting, including flow diversion. Clopidogrel response varies by individual. Objective To investigate the real-world precision of VerifyNow P2Y12 assessment (Accumetrics, San Diego, California) of Clopidogrel response. Methods Using a prospectively-collected, IRB-approved cerebral aneurysm database 643 patients were identified who were treated with the Pipeline embolization device from 2011 to 2017. Patients with multiple P2Y12 assays drawn within a 24-h window were identified. A single patient could contribute multiple, independent sets. Levels drawn before a 5-d course of DAT and patients who received alternative antiplatelet agents were excluded. Therapeutic range was defined as platelet reaction units (PRU) 60–200. Results A total of 1586 P2Y12 measurements were recorded; 293 (46%) patients had more than one assay. One hundred forty (22%) patients had multiple P2Y12 measurements within 24 h. These patients accounted for 230 independent 24-h sets. The average P2Y12 fluctuation across all sets was 35 points; the 25th, 50th, and 75th percentiles were 12, 26, and 48 points, respectively. Of the 230 24-h sets of P2Y12 assays, 76% remained within their original therapeutic category: 100 (43%) all therapeutic, 54 (23%) all hypo-responsive, and 21 (9%) all hyper-responsive. Twenty-four percent of patients fluctuated between therapeutic categories when multiple P2Y12 assessments were drawn within a 24-h period: 29 (13%) between hypo-response and therapeutic, 23 (10%) between hyper-response and therapeutic, and 3 (1%) between hypo-response and hyper-response. CONCLUSION Our experience suggests P2Y12 is an often-imprecise measure, and this should be considered when utilizing P2Y12 levels for clinical decisions.