A four-year assessment of the characteristics of Rwandan FDA drug recalls.

BACKGROUND: A drug recall is an act of removing products from the market and/or returning them to the manufacturer for disposal or correction when they violate safety laws. Action can be initiated by the manufacturing company or by the order of a regulatory body. This study aimed to assess the characteristics of Rwanda FDA drug recall and determine the association between classes of recall and recall characteristics. METHODOLOGY: This was a retrospective descriptive cross-sectional study. Data about recalled drugs were collected from the official website of the Rwanda FDA in the section assigned to "Safety alerts". The search included data reported between February 2019 and February 2023 covering four years. Data cleaning was conducted in Microsoft Excel to address missing data and inconsistencies, followed by importation into STATA/SE software version 17.0 for further cleaning and subsequent analysis. Descriptive statistics were computed for independent variables. Categorical variables were described in terms of counts and relative frequencies. Bivariate analyses used Pearson's chi-square test to illustrate the associations between categorical independent variables and recall classes. RESULTS: The study revealed that a large proportion (33.0%) of the recalled products belonged to Class I. Antibiotics constituted 35.8% of the recalled products, with contamination emerging as a leading cause and responsible for 26.4% of the recalls. India was the leading manufacturing country for the recalled products (29.2%), followed by France (17.9%), China (17.0%), Kenya (13.2%), and Russia (6.6%). An association was found between the class of recall and several recall characteristics, including the year of recall, drug category, safety issues, reporter, and manufacturing country. CONCLUSION: This study provides a comprehensive overview of the characteristics of drug recalls in Rwanda. The insights gained contribute to a nuanced understanding of recall dynamics and provide evidence-based strategies to enhance drug quality, safety, efficacy, regulatory compliance, and patient welfare.

A retrospective regulatory analysis of FDA recalls carried out by pharmaceutical companies from 2012 to 2023.

To introduce products in the US market, pharmaceutical companies must first obtain FDA clearance. Manufacturers might recall a product if it poses a risk of damage or violates FDA regulations. This study investigates the types, causes and consequences of recalls, as well as FDA participation and suitable recall strategies. We relied on the FDA website to gather recall data sets from 2012 to 2023, collecting information on the date of issuance, company and type of violation. The most frequent causes for recalls were sterility issues and inadequate compliance with current good manufacturing practices (cGMP). An examination of sterility recalls revealed two primary causes: a lack of assurance in sterility (accounting for 48% of recalls) and instances of non-sterility (making up 45% of recalls). A thorough examination of cGMP recalls revealed five primary types of violations: process control issues, inadequate storage practices, manufacturing problems, the presence of nitroso-amine impurities and concerns regarding stability. The findings demonstrate that sterility and cGMP compliance are FDA priorities. Pharmaceutical companies must, therefore, enhance quality compliance and create effective quality management systems that oversee the manufacturing process, quality control, personnel training and documentation to avoid these recalls. Companies should establish an internal compliance checklist and be prepared for the rectification process.

Human Medicines Recall Announcements in Saudi Arabia Between 2017 and 2022: An Analysis of Saudi Food and Drug Authority (SFDA) Reports.

PURPOSE: This study aims to explore the characteristics of drug recall announcements issued over six years by the SFDA in Saudi Arabia. Additionally, to examine the patterns of voluntary drug recall requests by pharmaceutical companies (both innovator and generic) in response to product defects. METHODS: A retrospective data analysis was conducted on drug recall announcements issued by the SFDA between 2017 and December 2022. The study included recalls of registered and unregistered drugs posted on the SFDA Drugs Circulars and Withdrawal webpage. Descriptive analysis was performed on relevant variables: recall year, therapeutic class, recall type, pharmaceutical company type, recall reasons and voluntary or involuntary product defect reports. RESULTS: During the study period, a total of 371 products were recalled, with the majority being involuntary recalls (82.4%). About two-thirds of the recalls (66.0%) were related to registered products. The most common reasons for recalls were non-compliance with the manufacturer's specifications (33.2%), contamination (23.7%), and violations (20.5%). A total of 109 pharmaceutical companies were associated with the recalled products, with (85.3%) being generic pharmaceutical companies. The majority of innovator pharmaceutical companies (68.8%) requested voluntary drug recalls of defective products. Innovator pharmaceutical companies requested voluntary recalls more often than generic pharmaceutical companies. CONCLUSION: The study findings highlight the most frequent causes of drug recalls and the patterns of voluntary recall requests by pharmaceutical companies. Non-compliance with manufacturer's specifications was the most common reason for recalls. Significantly, more innovative pharmaceutical companies request voluntary recalls for product defects compared to generic pharmaceutical companies.

Impact of Drug Recalls on Patients in The Netherlands: A 5-Year Retrospective Data Analysis.

Drug recalls occur frequently and have the potential to impact considerable numbers of patients and healthcare providers. However, in the absence of a comprehensive overview the extent of conducted recalls and their impact on patients remains unknown. To address this, we developed a comprehensive overview of drug recalls affecting patients. We compiled this overview based on the drug recall registrations from the Jeroen Bosch Hospital (JBZ), the University Medical Center Utrecht (UMCU), and the Royal Dutch Pharmacists Association (KNMP). A retrospective data analysis was conducted to identify drug recalls that affected patients. Specifically, we defined these as drug recalls that required patients to actively switch their drug to a different batch or brand of the same drug or to switch to a drug within the same or a different class of drugs. To quantify the impact, we used real-world drug dispensing data. Between January 1, 2017, and December 31, 2021, we identified 48 drug recalls that necessitated patients to make active changes to their medications an estimated 855,000 times. Most of the affected patients (292,000) were required to switch to a different brand of the same drug, whereas in 95,000 cases patients had to switch to a drug from another drug class. Our study suggests that a significant number of patients are affected by drug recalls. Future efforts are needed to elucidate patients' experiences and preferences regarding drug recalls, which could provide valuable insights to aid decision-making by relevant (national) authorities concerning drug recalls.

Descripción de una serie de pacientes con miastenia gravis refractaria / A series of patients with refractory myasthenia gravis

Introducción: Los avances en el tratamiento de la miastenia gravis (MG) han conseguido mejoría en la calidad de vida y el pronóstico de la mayoría de los pacientes. Sin embargo, un 10-20% presenta la denominada MG refractaria sin alcanzar mejoría, con frecuentes recaídas e importante repercusión funcional. Pacientes y métodos: Se seleccionó a pacientes con MG refractaria a partir de una cohorte de pacientes con MG diagnosticados desde enero del 2008 hasta junio del 2019. Se definió MG refractaria como falta de respuesta al tratamiento con prednisona y al menos 2 inmunosupresores o imposibilidad para la retirada del tratamiento sin recaídas en los últimos 12 meses o intolerancia al mismo con graves efectos secundarios. Resultados: Se registraron 84 pacientes con MG, 11 cumplían los criterios de MG refractaria (13%), con una edad media de 47 ± 18 años; un 64% los pacientes con MG refractaria fueron clasificados como miastenia generalizada de comienzo precoz (p < 0,01) con una mayor proporción de mujeres (p < 0,01). La gravedad de la enfermedad al diagnóstico, así como en el momento del análisis de los datos, fue superior en el grupo de MG refractaria con un mayor número de recaídas en el seguimiento. En el modelo de regresión logística se obtuvo una asociación independiente entre MG-R y el número de reagudizaciones graves. Conclusiones: El porcentaje de pacientes con MG refractaria en nuestra serie (13%) es similar al descrito en estudios previos, con frecuencia mujeres con inicio precoz, formas graves de inicio y reiteradas reagudizaciones con ingreso hospitalario en el seguimiento.(AU)

Introduction: Advances in the treatment of myasthenia gravis (MG) have improved quality of life and prognosis for the majority of patients. However, 10%-20% of patients present refractory MG, with frequent relapses and significant functional limitations. Patients and methods: Patients with refractory MG were selected from a cohort of patients diagnosed with MG between January 2008 and June 2019. Refractory MG was defined as lack of response to treatment with prednisone and at least 2 immunosuppressants, inability to withdraw treatment without relapse in the last 12 months, or intolerance to treatment with severe adverse reactions. Results: We identified 84 patients with MG, 11 of whom (13%) met criteria for refractory MG. Mean (standard deviation) age was 47 (18) years; 64% of patients with refractory MG had early-onset generalised myasthenia (as compared to 22% in the group of patients with MG; P<.01), with a higher proportion of women in this group (P<.01). Disease severity at diagnosis and at the time of data analysis was higher among patients with refractory MG, who presented more relapses during follow-up. Logistic regression analysis revealed an independent association between refractory MG and the number of severe relapses. Conclusions: The percentage of patients with refractory MG in our series (13%) is similar to those reported in previous studies; these patients were often women and presented early onset, severe forms of onset, and repeated relapses requiring hospital admission during follow-up.(AU)

Preapproval Promises to Voluntarily Withdraw FDA-Approved Drugs.

This Viewpoint provides recommendations for improvements to strengthen legal obligations and decrease ambiguity for the US Food and Drug Administration regarding their reliance on voluntary preapproval withdrawal pledges.

The FDA Struggle to Withdraw Makena: Problems With the Accelerated Approval Process.

This Viewpoint discusses the controversy surrounding the FDA's efforts to withdraw Makena from the market and the broader implications for the accelerated approval pathway.

Review of drug recalls and quality of pharmaceutical products in Nepal.

OBJECTIVES: To evaluate the pattern of substandard and falsified pharmaceutical products recall in Nepal. SETTING: We analysed drug recall notices issued by the Department of Drug Administration (DDA), Nepal, and systematically reviewed peer-reviewed research articles during January 2010 to December 2020. PARTICIPANTS: This study did not include human participants. However, data were collected from 72 drug recall notices issued by DDA and four research papers. RESULTS: A total of 346 pharmaceutical products were recalled during the reported period. The number of recalled pharmaceutical products has increased significantly over the past decade in Nepal. The most frequently recalled drugs were antimicrobials followed by gastrointestinal medicines, vitamins and supplements and pain and palliative medicines among others. Number of imported recalled drugs were slightly higher (42.2%) than domestic recalled drugs (40.7%). Sixty-two percentage of recalled drugs were substandard, 11% were falsified and remaining 27% were not registered at the DDA. Similarly, higher number of modern drugs (62%) were recalled than traditional ones (35%). Hand sanitisers used to minimise COVID-19 transmission contributed significantly to the list of recalled pharmaceutical products in 2020. Most of these sanitisers contained significant amounts of methanol (as high as 75% v/v) instead of appropriate amount of ethyl or isopropyl alcohol. The peer-reviewed research papers reported issues with labelling, unregistered drugs and drugs failed in several laboratory testing. CONCLUSION: Our analysis showed that number of recalls of substandard and falsified drugs are increasing in Nepal. Since the recall data in this paper did not include number of samples tested and location of samples collected, more studies to understand the prevalence of substandard and falsified drugs in Nepal is recommended.

Vigilância e controle de medicamentos abaixo do padrão, falsificados e não registrados: revisão integrativa

[RESUMO]. Objetivo. Identificar as estratégias de atuação dos sistemas regulatórios na vigilância e controle de medicamentos abaixo do padrão, falsificados e não registrados em nível regional-global, especialmente quanto aos processos de recall. Métodos. Foi realizada uma revisão integrativa da literatura nas bases de dados MEDLINE via PubMed, Embase e SciELO. Foram selecionados estudos publicados no período de 2007 a 2019, em inglês, português e espanhol, que abordavam estratégias desenvolvidas pelos sistemas regulatórios dos países, com foco no recall de medicamentos abaixo do padrão, falsificados e não registrados. Resultados. Dos 483 estudos inicialmente identificados, foram incluídas 21 publicações de alcance global, regional ou nacional. As estratégias de prevenção, detecção e resposta, incluindo o recall, foram agrupadas em dois modelos (passivo-reativo e proativo) de atuação dos sistemas regulatórios na vigilância e controle de medicamentos. Esses modelos parecem combinar estratégias passivas e proativas, complementares ou concorrentes, variando conforme o nível de desenvolvimento dos países e a capacidade regulatória. Embora seja considerado a resposta mais eficaz de proteção da população, o recall não foi implementado de forma uniforme no âmbito dos sistemas regulatórios, segundo os estudos. Conclusões. A complexidade e a magnitude do problema dos medicamentos abaixo do padrão, falsificados e não registrados exigem esforços, investimentos e mudanças profundas na abordagem, nos processos e nas capacidades dos sistemas regulatórios, podendo as estratégias de vigilância e controle do mercado convergir para um modelo híbrido, multisetorial, multidisciplinar, global e sistêmico de proteção da saúde humana.

[ABSTRACT]. Objective. To identify the strategies employed by regulatory systems for the market surveillance and control of substandard, falsified, and unregistered medicines at the regional-global levels, especially regarding drug recall procedures. Method. An integrative literature review was performed. Searches were performed in MEDLINE via PubMed, Embase, and SciELO to select articles published from 2007 to 2019 in English, Portuguese, and Spanish, covering national regulatory system initiatives, with a focus on the recall of substandard, falsified, and unregistered medicines. Results. Of 483 articles initially identified, 21 global, regional, or national scope studies were selected. Prevention, detection, and response strategies, including drug recall, were grouped according to two broad market surveillance and control models (passive-reactive and proactive) used by regulatory systems. These models seem to combine passive and proactive, complementary or concurring actions that varied according to country development level and regulatory capacity. Although considered the most effective response for protection of populations, medicine recall was not implemented in a uniform manner in different regulatory systems as indicated by the studies. Conclusions. Addressing the complexity and magnitude of the problem of substandard, falsified, and unregistered medicines will demand effort, investment, and profound changes in the approaches, processes, and capacity of regulatory systems, with market surveillance and control strategies possibly converging toward a hybrid, multisectoral, multidisciplinary, global, and systemic model of human health protection.

[RESUMEN]. Objetivo. Identificar las estrategias de actuación de los sistemas regulatorios en la vigilancia y control de los medicamentos subestándar, falsificados y no registrados a nivel regional-mundial, especialmente en lo que se refiere a los procesos de retirada de medicamentos del mercado (recall). Métodos. Se realizó una revisión bibliográfica integral en las bases de datos de MEDLINE a través de Pub- Med, Embase y SciELO. Se seleccionaron los estudios publicados entre 2007 y 2019, en inglés, portugués y español, en los que se abordaban las estrategias elaboradas por los sistemas regulatorios de los países, con énfasis en la retirada de los medicamentos subestándar, falsificados y no registrados. Resultados. De los 483 estudios identificados inicialmente, se incluyeron 21 publicaciones de ámbito nacional, regional o mundial. Las estrategias de prevención, detección y respuesta, incluida la retirada de medicamentos, se agruparon en dos modelos de actuación (pasivo-reactivo y proactivo) de los sistemas de regulación en la vigilancia y el control de los medicamentos. Estos modelos parecen combinar estrategias pasivas y proactivas, complementarias o concurrentes, que varían según el nivel de desarrollo de los países y su capacidad de regulación. Aunque la retirada de productos se considera la respuesta más eficaz para proteger a la población, según los estudios esta no se ha aplicado de manera uniforme en los sistemas de regulación. Conclusiones. La complejidad y la magnitud del problema de los medicamentos subestándar, falsificados y no registrados exigen esfuerzos, inversiones y cambios profundos en el enfoque, los procesos y las capacidades de los sistemas de regulación; y las estrategias de vigilancia y control del mercado pueden converger hacia un modelo híbrido, multisectorial, multidisciplinar, mundial y sistémico de protección de la salud humana.

Categorization and comparisons of drug recalls for manufacturers and compounders.

BACKGROUND: Ensuring the quality and safety of the pharmaceutical supply chain is a key policy focus vital to protecting the public from harmful or potentially harmful medications. Although the Food and Drug Administration (FDA) reports the number of recalled products per fiscal year and categorizes recalls based on product type and recall classification, these reports do not distinguish between manufactured and compounded products. OBJECTIVES: This research aims to categorize drug recalls based on the reason for recall and then to compare this reason between manufacturers and compounders. METHODS: All publicly available drug recall data were downloaded from the FDA Data Dashboard website on January 24, 2021. Two reviewers independently categorized the recalling firm, distribution pattern, and reason for recall, and a third reviewer resolved all conflicts. Descriptive statistics were reported for recall event classification, distribution, and recall reason for the full sample. Chi-square test of independence was used to assess categorical variables by facility type (manufacturer or compounder) as well as by event classification (class I, II, or III). A subgroup analysis was performed focusing on class I level recalls only, representing the most serious recall, and similar statistical procedures were performed. RESULTS: From June 8, 2012, to January 24, 2021, there were 12,343 drug products recalled; 6771 were from a manufacturer, and 5572 were from a compounder. Most recalls from both compounders and manufacturers were class II recalls with products being distributed to multiple states. Sterility assurance was the predominant reason for recall among compounders, whereas product quality was the most frequent recall reason for manufacturers. There were statistically significant differences in class I recalls between compounders and manufacturers and recall reason compared across recall classification. CONCLUSION: There was a statistically significant difference in the reason for a drug to be recalled, the distribution level, and the product class for manufactured and compounded products.

The plague of unexpected drug recalls and the pandemic of falsified medications in cardiovascular medicine as a threat to patient safety and global public health: A brief review.

Valsartan, losartan, and irbesartan, are widely used in the treatment strategies of cardiovascular medicine diseases, including hypertension and heart failure. Recently, many formulations for the aforementioned diseases contained active pharmaceutical ingredients and had been abruptly recalled from the market due to safety concerns mainly associated with unwanted impurities - nitrosamines, which are highly carcinogenic substances accidentally produced during manufacturing. Along with cardiovascular medications, formulations containing ranitidine were also recalled from the market. This poses a particular threat to public health due to the non-prescription status of these drugs. Regulatory authorities, including the Food and Drug Administration and European Medicines Agency among others, have taken action to minimize patient risk and improve the manufacturing quality as well as re-checking current guidelines and recommendations. While these steps are necessary to avoid further recalls, authorities should remember the growing concerns of patients regarding the safety and efficacy of pharmacotherapy. Apart from the genuine manufacturing mistakes mentioned above, falsified and counterfeit medications should be at the heart of global attention. The lack of a well-accepted definition of falsified/counterfeit medications has impeded political and scientific efforts to mitigate risk of this phenomenon. Falsified Medicines Directive should be considered the most pivotal legislation recently enacted to harmonize international cooperation. In summary, one should remember that only international and direct collaboration between patients, stakeholders, and authorities be considered a remedy for a pandemic of falsified medicines and plague of unexpected recalls due to safety concerns.

The Identification of Quality Risk Factors for Non-biological Complex Drugs and Epilepsy Drugs Using Statistical Analysis of Formulation-Based Recalls in the USA.

Pharmaceutical companies use the quality by design (QbD) approach to build high-quality drug products. A thorough understanding of risk factors is required to successfully employ QbD. In order to better understand risk factors that potentially impact drug product quality and inform future QbD approaches, we hypothesized root causes of drug product recalls based on publicly available data and a retroactive analysis of drug products recalled by the United States Food and Drug Administration (USFDA) from 2012 to 2018. We focused on two categories of drug products that pose unique regulatory challenges and an increased risk of shortage that could hinder the adequate supply of quality medicine to the patient. Knowing the significant risk factors from previous drug product recalls can help inform QbD and avoid future recalls. Quality recall reasons were studied individually to find risk factors associated with each recall category. Logistical regression statistical tests were done in R using a significance level of 0.05 to find correlations between a recalled product and its manufacturing information such as excipients and manufacturing steps. The results showed significant positive and negative correlations, such as products containing magnesium stearate are more likely to be recalled for impurities and degradation. This information could be used in the future to inform the design and manufacturing of drug products, ensuring consumers receive high-quality products with a low risk of recall.

Extent of a valsartan drug shortage and its effect on antihypertensive drug use in the Canadian population: a national cross-sectional study.

BACKGROUND: Drug shortages represent a growing global problem, with potentially serious consequences to patients and the health care system. Our study investigates the impacts of a major recall and shortage of valsartan, an angiotensin receptor blocker (ARB), in July 2018 in Canada. METHODS: We conducted a time-series analysis of antihypertensive drugs dispensed in Canada between 2015 and 2019 using commercially available retail prescription data. Using autoregressive integrated moving average (ARIMA) modelling, we evaluated the change in valsartan use after the recall. We also measured the overall use of ARBs, angiotensin-converting-enzyme (ACE) inhibitors and other antihypertensive drug classes for the same period. RESULTS: After the recall in July 2018, valsartan use decreased 57.8%, from 362 231 prescriptions dispensed in June 2018 to 152 892 in September 2018 (difference = 209 339, p < 0.0001). Overall use of the ARB drug class decreased 2.0%, from 1 577 509 prescriptions dispensed in June 2018 to 1 545 591 in September 2018 (difference = 31 918, p = 0.0003), but use of non-valsartan ARBs increased 14.6%, from 1 215 278 to 1 392 699 prescriptions dispensed (difference = 177 421, p < 0.0001) in the same time frame. Although use of ACE inhibitors initially declined, this reduction was not sustained. The valsartan recall was not associated with a significant impact on use of other antihypertensive drug classes. INTERPRETATION: Our findings illustrate the impact of a major drug shortage, with the immediate and substantial reduction of valsartan dispensed and cascading effects on other ARBs, though future research is warranted to understand the consequences of such extensive shortages on clinical outcomes and health system costs. Improved policy strategies are needed to address the underlying causes of drug shortages and to mitigate their effects.

Insuficiencia suprarrenal secundaria persistente tras tratamiento prolongado con corticoides / Chronic secondary suprarrenal failure after prolonged corticosteroid treatment

Los glucocorticoides son fármacos frecuentemente usados de forma crónica para el tratamiento de enfermedades autoinmunes, hematológicas y neoplasias avanzadas. Sin embargo, representan una causa común de insuficiencia suprarrenal terciaria. Por lo tanto, la terapia de reemplazo corticoidea puede ser frecuente tras la administración crónica de glucocorticoides. Presentamos el caso clínico de una paciente de 65 años en tratamiento crónico con glucocorticoides debido a una sarcoidosis pulmonar diagnosticada en 2012. A pesar de la reducción gradual del tratamiento, una vez que la patología estaba en remisión, la paciente es diagnosticada de insuficiencia suprarrenal ante la persistencia de clínica de astenia intensa y sudoración profusa y haber descartado una reactivación de su proceso. Se debe sospechar Insuficiencia suprarrenal en todo paciente que ha estado en tratamiento crónico con tratamiento glucocorticoideo. La retirada gradual del tratamiento con glucocorticoides a lo largo de las semanas es una práctica comúnmente extendida que minimiza el riesgo de Insuficiencia suprarrenal pero no lo anula. La determinación del cortisol basal al menos 18 horas de la última dosis de glucocorticoides puede ser útil para evaluar el eje hipofisario-adrenal y retirar con seguridad el tratamiento con glucocorticoides.(AU)

Glucocorticoids are drugs widely used chronically to treat various autoimmune, haematological conditions and advanced malignancies. Nevertheless, glucocorticoids are considered a common cause of tertiary adrenal insufficiency. Therefore, patients may require glucocorticoid replacement therapy after chronic use of glucocorticoids. We report the clinical case of a 65-year-old patient on chronic glucocorticoid treatment due to pulmonary sarcoidosis diagnosed in 2012. Despite gradual tapering of treatment once the main disease was in remission, the patient was diagnosed with adrenal insufficiency due to persistent clinical symptoms of intense asthenia and profuse sweating once reactivation of her disease was ruled out. Adrenal insufficiency should be suspected in every patient on chronic glucocorticoid treatment. Gradual tapering of glucocorticoid treatment over weeks is a common clinical practice that minimizes the risk of adrenal insufficiency but does not eliminate it completely. Determination of basal cortisol at least 18 hours after the last dose of glucocorticoid may be useful to evaluate the pituitary-adrenal axis and safely withdraw glucocorticoid treatment.(AU)