Pharmaceutical Industry in Uganda: A Review of the Common GMP Non-conformances during Regulatory Inspections

The prevalence of substandard medicines in Africa is high but not well documented. Low and Middle-Income Countries (LMICs) are likely to face considerable challenges with substandard medications. Africa faces inadequate drug regulatory practices, and in general, compliance with Good Manufacturing Practices (GMP) in most of the pharmaceutical industries is lacking. The majority of pharmaceutical manufacturers in developing countries are often overwhelmed by the GMP requirements and therefore are unable to operate in line with internationally acceptable standards. Non-conformances observed during regulatory inspections provide the status of the compliance to GMP requirements. The study aimed to identify the GMP non-conformances during regulatory inspections and gaps in the production of pharmaceuticals locally manufactured in Uganda by review of the available 50 GMP reports of 21 local pharmaceutical companies in Uganda from 2016. The binary logistic generalized estimating equations (GEE) model was applied to estimate the association between odds of a company failing to comply with the GMP requirements and non-conformances under each GMP inspection parameter. Analysis using dummy estimation to linear regression included determination of the relationship that existed between the selected variables (GMP inspection parameters) and the production capacity of the local pharmaceutical industry. Oral liquids, external liquid preparations, powders, creams, and ointments were the main categories of products manufactured locally. The results indicated that 86% of the non-conformances were major, 11% were minor, and 3% critical. The majority of the non-conformances were related to production (30.1%), documentation (24.5%), and quality control (17.6%). Regression results indicated that for every non-conformance under premises, equipment, and utilities, there was a 7-fold likelihood of the manufacturer failing to comply with the GMP standards (aOR=6.81, P=0.001). The results showed that major non-conformances were significantly higher in industries of small scale (B=6.77, P=0.02) and medium scale (B=8.40, P=0.04), as compared to those of large scale. This study highlights the failures in quality assurance systems and stagnated GMP improvements in these industries that need to be addressed by the manufacturers with support from the regulator. The addition of risk assessment to critical production and quality control operations and establishment of appropriate corrective and preventive actions as part of quality management systems are required to ensure that quality pharmaceuticals are manufactured locally

Knowledge Sharing in Organisations: Finding a Best-fit Model for a Regulatory Authority in East Africa

Knowledge is an essential organisational asset that contributes to organisational effectiveness when carefully managed. Knowledge sharing (KS) is a vital component of knowledge management that allows individuals to engage in new knowledge creation. Until it’s shared, knowledge is considered useless since it resides within the human brain. Public organisations specifically, are more involved in providing and developing knowledge and hence can be classified as knowledge-intensive organisations. Scholarly research conducted on KS has proposed a number of models to help understand the KS process between individuals but none of these models is specifically for a public organisation. Moreover, to really reap the benefits that KS brings to an organization, it’s imperative to apply a model that is attributable to the unique characteristics of that organisation. This study reviews literature from electronic databases that discuss models of KS between individuals. Factors that influence KS under each model were isolated and the extent of each of their influence on KS in a public organization context, were critically analysed. The result of this analysis gave rise to factors that were thought to be most critical in understanding KS process in a public sector setting. These factors were then used to develop a KS model by categorizing them into themes including organisational culture, motivation to share and opportunity to share. From these themes, a KS model was developed and proposed for KS in a medicines regulatory authority in East Africa. The project recommends that an empirical study be conducted to validate the applicability of the proposed KS model at a medicines regulatory authority in East Africa

Quality of Sample Testing in the Laboratory Unit: Current Situation and Strategies for Improvement

The purpose of this study was to understand the status quo of quality sample testing in the laboratory unit. A quantitative research method was used. An extensive laboratory documents (protocol, worksheets, laboratory analytical plan, standard operating procedures and manuals) review was performed and a networking approach to both management and lab staff at all levels was reviewed in order to identify all non-conformities occurred in the past three years. Results identified 36 number of results deviated from reference standards among different test performed, 400 number of samples lost, the number of laboratory personnel who were not sufficiently trained to take the task properly decreased from 16 in 2016 to 6 in 2018 after conducting training on laboratory quality management system, 36 controlled documents including sample management standard operating procedure, bench job aids were missing and 8 customer complains about the delay of results and quality laboratory of services have been identified

Compliance to GMP guidelines for Herbal Manufacturers in East Africa: A Position Paper

With the global increase in the use of traditional and complementary remedies for the prevention and treatment of illness, the quality and safety of these medicines have become a significant concern for all regulatory authorities. Herbal medicines are the most commonly used form of traditional and complementary medicines in the world and the efficacy and safety of herbal medicines, like conventional medicines, largely depends on their quality from planting to harvesting, preprocessing and final processing. Due to the inherent complexity of herbal medicines, often containing an array of active compounds, the primary processing of herbal medicines has a direct influence on their quality. Quality concerns are the reason why the medicines regulatory agencies insist that manufacturers of medicines strictly follow Good Manufacturing Practices since it is an essential tool to prevent instances of contamination, mix-ups, deviations, failures and errors. However, a strict application of GMP requirements is expensive and would drive the prices of the manufactured products up. As a result, a maturity level grading of facilities is proposed as a way of justifying the costs incurred for manufacturers desiring to reach a broader market and investing in continuous improvement. 36 Good Manufacturing Practice (GMP) inspection reports of local herbal manufacturers conducted by National Drug Authority were analyzed to establish the type and extent of deficiencies to GMP requirements for local herbal manufacturers in Uganda. The different GMP chapters and related sub-parameters constituted the variables used for the analysis of conformity to requirements. The primary outcome variable was the conclusion regarding compliance or noncompliance of the inspected local herbal manufacturing facility. GMP parameters that were frequently defaulted by local herbal manufacturers and the corresponding frequencies were identified. The Pearson Chi-square test was applied independently on each category to find the association that existed between conformity and the questions in each category. Only 22% (8) of the 30 inspected facilities were found to comply with GMP requirements, as per National Drug Authority (NDA) guidelines; while the majority of the facilities, 28 (78%), were found not to comply. Of the facilities inspected, 25 were undergoing GMP inspection for the first time. A total of 1,236 deficiency observations were made in the 36 inspection reports reviewed for the study. The mean for all deficiencies was 34.3, and the standard deviation was 15.829. 91.5% of the facilities did not have mechanisms for a record of market complaints; 80.9% did not meet documentation requirements; 78.9% did not have quality control measures in place, and 65.7% did not meet stores requirements. By encouraging a culture of self/voluntary improvement through the introduction of listing of manufacturers based on a maturity level grading, the National Drug Authority will improve the Herbal Medicines sector as per the mandate of improving the herbal medicine industry. Also, increased sensitization of all relevant stakeholders regarding the requirements for GMP should be intensified

Improving Pharmacovigilliance Quality Management System in the Pharmacy and Poisions Board of Kenya

The purpose of this study was to explore ways of improving the pharmacovigilance quality system employed by the Pharmacy and Poisons Board of Kenya. The Pharmacy and Poisons Board of Kenya employs a hybrid system of pharmacovigilance that utilizes an online system of reporting pharmacovigilance incidences and a physical system, where a yellow book is physically filled by the healthcare worker and sent to the Pharmacy and Poisons Board for onward processing. This system, even though it has been relatively effective compared to other systems employed in Africa, has one major flaw. It is a slow and delayed system that captures the data much later after the fact and the agency will always be behind the curve in controlling the adverse incidents and events. This means that the incidences might continue to arise or go out of control. This project attempts to develop a system that would be more proactive in the collection of pharmacovigilance data and more predictive of pharmacovigilance incidences. The pharmacovigilance system should have the capacity to detect and analyze subtle changes in reporting frequencies and in patterns of clinical symptoms and signs that are reported as suspected adverse drug reactions. The method involved carrying out a thorough literature review of the latest trends in pharmacovigilance employed by different regulatory agencies across the world, especially the more stringent regulatory authorities. A review of the system employed by the Pharmacy and Poisons Board of Kenya was also done. Pharmacovigilance data, both primary and secondary, were collected and reviewed. Media reports on adverse drug reactions and poor-quality medicines over the period were also collected and reviewed. An appropriate predictive pharmacovigilance tool was also researched and identified. It was found that the Pharmacy and Poisons Board had a robust system of collecting historical pharmacovigilance data both from the healthcare workers and the general public. However, a more responsive data collection and evaluation system is proposed that will help the agency achieve its pharmacovigilance objectives. On analysis of the data it was found that just above half of all the product complaints, about 55%, involved poor quality medicines; 15% poor performance, 13% presentation, 8% adverse drug reactions, 7% market authorization, 2% expired drugs and 1% adulteration complaints. A regulatory pharmacovigilance prioritization tool was identified, employing a risk impact analysis was proposed for regulatory action

Evaluating and Understanding the Reason for an Increase in Nonconformances in the Laboratory

This is a study of nonconformances experienced by a laboratory of a pharmaceutical manufacturing facility in East Africa. There has been an increase in nonconformances from 216 nonconformances in 2017 to 229 in 2018 and by September 2019, 306 nonconformances were already logged. Increasing nonconformances result in delayed release of tested materials and many resources are wasted (e.g. chemicals, man hours and equipment). Analysts become frustrated, which may result in inexhaustive investigations. Understanding the reason for the increase in nonconformances will enable the facility to derive effective solutions to the identified causes, hence reducing the number of nonconformances and improving the productivity and morale of employees. This quantitative, nonexperimental, longitudinal survey study was intended to evaluate and understand the reason for increasing nonconformances. Trends of the nonconformances, previous investigations, procedure for investigation and the training given to analysts have been reviewed. Laboratory incidences were the most recurring nonconformances; and these were mainly caused by analyst errors. Corrective and Preventive Actions (CAPAs) were derived by cross functional teams whenever root causes were identified. Procedure for investigation of nonconformances refers to investigative tools. Identification of root causes to nonconformances recently became mandatory. Analysts have limited advanced industrial training on investigation of nonconformances. Another study should be carried out to understand the cause of analyst errors. The study can be rolled out to other departments at the manufacturing facility to create similar improvements. Analysts should enroll into advanced courses of industrial pharmacy to gain advanced industrial skills which they can apply in investigations to find root causes to nonconformances

Retrospective Study of Inspectors Competency in the Act of Writing GMP Inspection Report

The research was a retrospective study of twenty-five Good Manufacturing Practice (GMP) inspection reports (from March 2017 through to December 2018) of a national medicine regulatory agency, drug Inspectorate, in West Africa, designed to assess the inspectors’ expertise in the act of inspection report writing. The investigation examined a paper-based tool of thirteen pre-registration Inspection reports and twelve GMP reassessment reports written prior and following an intervention program by external GMP trainers to enhance inspectors’ skill in pharmaceutical cGMP inspection. The study made use of quantitative analysis to investigate each team’s expertise in the act of writing GMP inspection report. Likewise, each report’s compliance with the requirements of three regulatory standards on GMP inspection report writing was ascertained. Impact of intervention program on lead inspectors’ competence was assessed. Lastly, gap in each team writing effectiveness, and lead inspectors’ abilities to deliver an effective report were determined. The results showed one of the inspection team (4.0%) wrote an excellent report. Two (8.0%) of the twenty-five inspection teams penned good inspection reports. Eleven (44.0%) teams drafted needs improvement reports and the remaining eleven teams (44.0%) prepared unacceptable reports. The excellent report and the two good reports had report format that meet expectation. One (50.0%) of the good reports showed the authors possess excellent knowledge of cGMP technical areas. The remain good report (50.0%) revealed the writers’ knowledge.as good. The excellent report showed the authors displayed partial mastery in the use of objective evidence while the two good reports disclosed theirs as having partial and evolving abilities. One of the teams (50.0%) that wrote good reports displayed good use of third person narrative past tense in report writing whereas the other team used the same tense and voice excellently. Generally, a sort of marginal level of performance was prominent among the inspection teams. A gap, if not tackled, will slow down regulatory process through increase report review, litigations that query report factual accuracy (AIHO, 2017) and delay in issuance of marketing authorization. In conclusion, trainings on quality attributes, such as technical content (Quality Management System (QMS) and Site), the use of objective evidence, assignment of risk levels to GMP violations and citing of applicable laws, regulation and guidelines that substantiate GMP observations, were recommended, to enhance knowledge sharing and regulators’ performance in the act of writing inspection report

Herbal Medicines Registration Process for Zimbabwe Overview of the Process

Unregistered traditional medicines pose a huge public health threat as the safety and efficacy of these products is unknown. The issue this study addresses is the inadequate regulatory measures for herbal medicines in Zimbabwe. This project was done to describe the current registration process of traditional medicines in Zimbabwe, and to identify the gaps and opportunities they present to improve the regulatory landscape. Regulations and laws governing the registration of herbal medicines in the country and published research on legislation of herbal medicines were reviewed. Two parallel regulatory bodies both registering and controlling the sale of herbal medicines were identified. The Medicines Control Authority of Zimbabwe (MCAZ) and the Traditional Medical Practitioners Association (TMPA) both derive their authority to regulate from the ministry of health and were established through the act of parliament which gives these authorities power to regulate the quality and sale of traditional medicines without giving a prescriptive way of doing it. The registration process, and product evaluations for the two authorities are different. While the MCAZ has a clearly defined registration process, the TMPA does not. However, MCAZ has not been very successful in registering local products with the majority of the registered herbal products being imports and only 2% of total registered products being local herbs. As a recommendation, there is need for collaboration between the regulatory bodies for consistence in quality of herbal products on the market and to improve registration of local herbal products. Developing monographs for local herbs commonly used in the country will also assist local manufacturer to fulfill the quality requirements and successful compilation of dossiers for product registration

Defects Analysis and Root Cause Robustness of Product Labels of an Acaricide Product in East Africa

This project aimed at investigating online damages of packaging materials generated during production because of imperfectness of production processes. These online damages may lead to upsurge in production cost and/or market returns, causing the company to experience losses and even damage its reputation. Data on online damages were collected for 20ml, 40ml and 100ml labels of an acaricide product for the period between July 2018 and June 2019 and statistically analyzed. Investigation was done on the causes of online damages, then corrective and preventive actions carried out. Analysis of online damages of labels of the three pack sizes revealed a loss of 1.01% on labels alone during the year under analysis. After implementing corrective and preventive actions, there was a reduction of online damages of labels

Resource Modelling for the QC Laboratory at XYZ Pharmaceuticals in Southern Africa

Quality control (QC) laboratories are critical components in drug manufacturing and running them efficiently contributes to better, consistent supply of cost-effective quality products, while also and preventing deaths due to untimely delivery or unavailability of medicines. Having a resource modelling tool to estimate resources needed to handle a particular demand in a given system is essential for efficient running of QC laboratory. This study was done to establish such a model at XYZ Pharmaceuticals. The list of all products manufactured by XYZ Pharmaceuticals Southern Africa was reviewed; and product families for all products were identified. Analysts’ hands on time (HOT) to process one sample of each of the product families was estimated. The number of analysts required to support the workload at XYZ Pharmaceuticals was calculated using the HOTs for the different product families and the Maslaton’s Calculation Model. A baseline resource model was established