Content analysis of drug recall announcements in Saudi Arabia: Between 2016 and 2022

doi:10.21203/rs.3.rs-3137976/v1

Purpose

This study aims to analyze drug recall reports issued by the Saudi Food and Drug Authority (SFDA) in Saudi Arabia over seven years and describe the practice of pharmaceutical companies regarding voluntary drug recalls.

Methods

A retrospective data analysis was conducted on drug recall announcements issued by the SFDA between July 2016 and December 2022. The study included registered and unregistered drug recalls posted on the SFDA Drugs Circulars and Withdrawal webpage. Descriptive analysis was performed on variables such as recall year, report language, number of report items, depth of recall, product name, therapeutic class, product registration status, recall type, pharmaceutical company type, recall reasons, and voluntary or involuntary product defect reports.

Results

During the study period, a total of 375 products were recalled, with the majority being involuntary recalls (82.7%). Over two-thirds of the recalls (66.4%) were related to registered products. The most common reasons for recalls were non-compliance with manufacturer's specifications (33.3%), 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 recall of defective products. Innovator pharmaceutical companies tended to request 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. Innovator pharmaceutical companies were more likely to request voluntary recalls for product defects compared to generic pharmaceutical companies.

Drug recalls

Recalls announcement

SFDA

Pharmaceutical companies

Poor-quality medicines are a significant public health issue, mainly affecting developing countries and impacting their emerging market economies. The World Health Organization (WHO) reports that 1 in 10 substandard medicines is distributed in low- and middle-income countries countries[1]. The availability of falsified and substandard medicines, whether branded or generic, has become a major concern due to their potential impact on patient health. These substandard medicines can lead to treatment failure, adverse drug reactions, and antimicrobial resistance, resulting in serious health crises [2]. In fact, it has been estimated that over 116,000 deaths occur annually in sub-Saharan Africa due to substandard and falsified antimalarials, with economic losses exceeding US$40 million [3].

The widespread presence of substandard medicines can be attributed to inadequate regulation and governance by regulatory authorities, as well as unethical practices by wholesalers and healthcare practitioners [4].In response, drug regulatory authorities and pharmaceutical companies implement drug recalls as a means to mitigate the impact of substandard medications [4].Drug recalls involve the removal or withdrawal of defective drugs from the market and can be initiated either voluntarily by the company or involuntarily by the public, including healthcare professionals and consumers [5].

While the number of drug recalls has been increasing in recent years, with a focus on ensuring the safety and efficacy of drugs and medical products for consumers, there is limited research analyzing the patterns and characteristics of drug recall announcements issued by regulatory authorities [6, 7].Previous studies have explored aspects such as patterns of recalls, distribution of recalls among pharmaceutical firms, and the most common reasons for recalls in specific regions like the United States (U.S) [8].

In Saudi Arabia, there has been a notable increase in drug recall trends, particularly in 2018, compared to the previous decade [9]. However, no studies have specifically investigated the patterns of drug recall requests by manufacturers or the public in the country. Therefore, there is a need for regulatory authorities to understand the drug recall process and the behavior of pharmaceutical companies to ensure the safety of products. The aim of this study is to analyze the content of drug recalls issued over a seven-year period by the Saudi Food and Drug Authority (SFDA) and examine the patterns of voluntary drug recall requests by pharmaceutical companies (both innovator and generic) in response to product defects.

A retrospective data analysis was conducted using drug recall announcements issued by the Saudi Food and Drug Authority (SFDA) between July 2016 and December 2022. Data were collected from the SFDA Drugs Circulars and Withdrawal webpage, which includes registered and unregistered drug recall announcements. The National Pharmacovigilance and Drug Safety Center (NPC) at SFDA provided access to the database for data extraction [7, 8, 10].

The study included all human drugs that were subject to recall. Two researchers extracted relevant information from the recall announcements, which included data such as recall action date, announcement number, announcement language, number of reported items, product name, therapeutic class, product registration status (registered or unregistered), type of recall, company name, issues identified, recall reasons, drug recall class (I, II, and III) [13], and whether the recall was voluntary or involuntary. Definitions of these groups are shown in (Table-1).

Recall reasons were categorized into groups, including non-compliance with manufacturer's specifications, packaging defects, failure to demonstrate bioequivalence, contamination, chemical impurities, incorrect therapeutic dose, violations, and adverse reactions. The recalls were further classified based on the World Health Organization's Anatomical Therapeutic Chemical (ATC) Classification System [14].

Descriptive analysis was performed to calculate frequencies and percentages for various data categories, such as the number of drug products, number of recalls reported each year, recall type, product formulation, report classification, reasons for recall, complexity of recalls, registered and unregistered recalls, voluntary and involuntary recalls, therapeutic class, innovator pharmaceutical companies, and generic pharmaceutical companies. Statistical analysis was conducted using SPSS software (version 26.0).

Between July 2016 and December 2022, a total number of 375 products were recalled and analyzed. The highest recall announcements were reported in 2019 [153, (40.8%)] compared to other years (Figuer-1).

The majority of recalls were involuntary [310, (82.7%)], while [65 ,(17.3%)]of recalls were voluntary. The most voluntary recalls were reported in 2022 [17, (%53)] compared to the past six years (Table-2). In addition, two-thirds [249, (66.4%)] of recalls were related to registered products in the SFDA, unregistered products were accounted for the remaining recalls [126, (33.6%)].

In terms of the complexity of the reports, the majority of reports included one product [147, (77%)], while 23% (N: 44) reports included more than one product (Table − 2).

The most common reasons for recalls were as follows: non-compliance with manufacturer's specifications [125, (33.3%)], contamination [89, (23.7%)], violations [77, (20.5%)] and chemical impurities [38, (10.1%)], more details are presented in (Table-3). Most of the recall’s types were identified as batch recall [284, (75.7%)], followed by product recall/ registration suspension [52, (13.9%)], and product recall [30, (8%)] (Table − 2). In terms of product formulations, the majority of recalls were tablets [186, (49.6%)] followed by injectable products [99, (26.4%)] (Table − 2).

Forty-one therapeutic classes were found in the product recalled reports; of those, seven therapeutic classes were highlighted as the highest recall frequency throughout the study period (2016–2022) as shown in (Figure − 2). Antacid was reported as the highest-recalled therapeutic class in three different years (2017, 2019 and 2020).

A total of 109 pharmaceutical companies were involved in the recall reports we reviewed. Of those, 14.7% (N: 16) companies were innovator pharmaceutical companies and 85.3% (N: 93) companies were generic pharmaceutical companies. About 68.8% (N:11) of innovator pharmaceutical companies requested voluntary drug recall of defective products whereas 16% (N: 15) of generic pharmaceutical companies requested voluntarily drug recall (Table-3).

This study aimed to analyze the content of drug recall announcements issued by the SFDA in Saudi Arabia over seven years. The results shed light on the patterns of pharmaceutical companies in requesting voluntary or involuntary drug recalls for defective products and highlight the most frequent causes of drug recalls.

During the study period, the highest number of product recalls was reported in 2019. Furthermore, the most frequently recalled therapeutic classes between 2016 and 2022 were antihypertensives and antacids. While these findings indicate an increase in drug recalls, there is insufficient evidence to explain the root cause of this trend. This study shared some similarities with AlQuadeib et al., which showed that the highest recall happened in 2018, and antihypertensives and antibiotics were the most recalled therapeutic classes in Saudi Arabia [9].

Product recalls have a negative impact on the reputation and economic status of companies, including stock prices and sales of affected products [15]. Interestingly, our results suggest that innovator companies are more likely to voluntarily request a drug recall when a product defect occurs compared to generic companies.

The SFDA plays a vital role in ensuring the safety of pharmaceutical products and publishing warnings related to defective products [16]. In this study, the most common reasons for drug recalls were non-compliance with the manufacturer's specifications (33.3%) and contamination (23.7%). These findings align with previous studies conducted in the United States and Saudi Arabia, highlighting mislabelling and contamination as significant causes of drug recall. Notably, a considerable proportion (33.6%) of the recalled drugs were unregistered. This issue is not unique to Saudi Arabia and has also been observed in other countries. Of relevance, in Nepal, where the analysis of drug recall notices issued by the Department of Drug Administration (DDA) between 2010–2020 showed that most recalled drugs were due to product unregistration (26.8%) [17]. The results indicate that the circulation of unregistered drugs in the market is a serious concern and may be attributed to inadequate monitoring and regulation in certain regions [18]. The SFDA has the authority to initiate drug recalls for unregistered products, which is within its jurisdiction and responsibilities.

This study has several limitations to consider. Firstly, the reliance on retrospective data analysis from drug recall announcements issued by SFDA between July 2016 and December 2022 may introduce potential errors or missing information. The study's analysis focused on recalls reported by the SFDA, leading to potential bias in the selection of recalls. Furthermore, the study did not explicitly investigate the root causes of drug recalls, limiting the understanding of underlying factors.

In conclusion, this study provides insights into the trends of drug recalls in Saudi Arabia, including the highest year of recalls, the most common therapeutic classes affected, and the primary reasons for recalls. Non-compliance with manufacturer's specifications was found to impact the majority of recalled products. Additionally, innovator pharmaceutical companies were more likely to report drug defects voluntarily compared to generic pharmaceutical companies. Further exploration of the drug recall process is recommended to understand different factors that may influence recall strategies and announcements by the SFDA. Additionally, future studies should assess the impact of drug recalls on the patient care system in Saudi Arabia.

Ensuring the control and quality of drug production is becoming increasingly complex. Stringent legislation and inspections of API manufacturing facilities abroad by the SFDA might be necessary. It is advisable for pharmaceutical companies to voluntarily request product recalls as soon as potential threats to public health arise. Moreover, registering all products with the responsible health authorities and encouraging health institutions to exclusively purchase registered products can enhance patient safety.

Author Contributions

All authors contributed to the study conception and design [Malak Almutairi], [ Aljoharah Algabbani], [Ajbaa Al Asiri], [Ali Al Homaidan] and [Amani S. AL Qahtani]. Material preparation, data collection and analysis were performed by [Malak Almutairi] data collection was performed by [Ajbaa Al Asiri]. The first draft of the manuscript was written by [Malak Almutairi], and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding

The authors did not receive support from any organization for the submitted work.

Disclaimer

The views expressed in this paper are those of the author(s) and not do not necessarily reflect those of the SFDA or its stakeholders. Guaranteeing the accuracy and the validity of the data is the sole responsibility of the research team.

Data availability

The datasets generated during and/or analyzed during the current study are available in the SFDA Drugs (Circulars and Withdrawal) from National pharmacovigilance and drug safety center (NPC) at SFDA database.

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Table 2: Characteristics of SFDA drug recalls between 2016 and 2022

Reason of recall	N (%)
Non-compliance with manufacturer's specifications	125 (33.3%)
Contamination	89 (23.7%)
violations	77 (20.5%)
Chemical impurities	38 (10.1%)
Contamination and Non-compliance with manufacturer's specifications	28 (7.5%)
Packaging defects	8 (2.1%)
Failure to demonstrate bioequivalence	4 (1.1%)
Incorrect therapeutic dose	3 (0.8%)
Not available	3 (0.8%)
Type of recall	N (%)
Batch recall	290 (77.3%)
Product recall and registration suspension	52 (13.9%)
Product recall	30 (8%)
Batch recall and registration suspension	2 (0.5%)
Cancel registration of products	1 (0.3%)
Number of products included in one report	N (%)
Reports included one product	147 (77%)
Reports included more than one product	44 (23%)
Product formulations	N (%)
Tablets	186 (49.6%)
Injectables	99 (26.4%)
Syrup	21 (5.6%)
Capsules	16 (4.3%)
Others	16 (4.3%)
Suspension	10 (2.7%)
Cream	7 (1.9%)
Solution	4 (1.1%)
Tablets and Powder	4 (1.1%)
Ointment	4 (1.1%)
Drops	3 (0.8%)
Powder	2 (0.5%)

Table 3: Voluntary and Involuntary drug recall requests for defective products between years 2016 and 2022

Year	Voluntary recalls N (%)	In voluntary recalls N (%)
2016	0	4 (100%)
2017	3 (21.4%)	11(78.6%)
2018	6 (17.1%)	29 (82.9%)
2019	23 (15%)	130 (85%)
2020	7 (14.3%)	42 (85.7%)
2021	10 (11.4%)	78 (88.6%)
2022	15 (46.9%)	17 (53.1%)

Content analysis of drug recall announcements in Saudi Arabia: Between 2016 and 2022

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Abstract

Purpose

Methods

Results

Conclusion

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Introduction

Method

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