Post Marketing Research Articles

Evaluating the impact of a Risk Evaluation and Mitigation Strategy with tolvaptan to monitor liver safety in patients with autosomal dominant polycystic kidney disease.

On approval of JYNARQUE (tolvaptan) for use in patients with autosomal dominant polycystic kidney disease (ADPKD) at risk for rapid progression, the US Food and Drug Administration required a Risk Evaluation and Mitigation Strategy (REMS) from the sponsor, which includes collection of post marketing liver safety data. This is a retrospective interim analysis of the ongoing REMS. The period evaluated was from REMS implementation (14 May 2018) at tolvaptan commercialization to the analysis cutoff date (23 February 2021). Patients were previously tolvaptan-naïve and initiated tolvaptan in the post marketing setting. Reports of possible severe drug-induced liver injury (DILI) were evaluated for severity based on the evidence obtained (e.g. liver enzyme levels, symptoms, diagnostic tests and event outcomes). The incidence of DILI was compared between the REMS and tolvaptan clinical trials in ADPKD. Among 6711 REMS patients, 60 (0.9%) cases of possible severe DILI were reported, 4 of which were confirmed as serious and potentially fatal by the sponsor. One of these four patients met Hy's law criteria. In all four patients, liver enzymes normalized after tolvaptan discontinuation. The duration of tolvaptan exposure in the REMS is currently shorter than in completed clinical trials, but within this limitation, the incidence of possible severe DILI was lower in the REMS than in clinical trials (incidence rate ratio 0.587; P = .000411). In interim data on >6000 tolvaptan REMS patients, <1% experienced possible severe DILI. Monthly monitoring, as described in the tolvaptan prescribing information, enables the prompt detection of liver enzyme abnormalities and appropriate drug discontinuation.

458 Pulsed Electromagnetic Fields (PEMF) Used in Cervical Spine Fusion for Patients with Risk Factors for Non-Union

INTRODUCTION: A post market prospective study was conducted to examine the effect of the adjunctive use of a pulsed electromagnetic field (PEMF) device on cervical fusion rate in subjects with risk factors for non-union. PEMF has been shown to stimulate bone healing and can be a valuable tool to help overcome biological deficiencies in patients at risk for non-union. METHODS: Patients undergoing cervical fusion surgery were identified for enrollment from 11 investigator sites based on being classified as having one or more risk factors for non-union. Subjects were those having a multi-level (2 or more) fusion, prior cervical spine fusion, diabetes, osteoporosis, or smokers. Subjects were required to wear the PEMF device for 4 hours/day for 6 months. Compliance was measured based on usage data downloaded from the device. The primary outcome measure was fusion status at 12 month follow-up period as indicated by x-ray and CT. Fusion status was determined by the site investigator using A/P, lateral, and flexion/extension radiographs in addition to CT (without contrast). RESULTS: Out of 152 subjects, 138 (90.8%) were graded as fused (all levels) at the 12 month visit About half of the subjects (49.3%) had 3 or more levels fused. Fusion success for subjects with 2 or more risk factors was 88.5%, and was 94.4% for subjects with a single risk factor. On average, compliance rates (minutes using device/minutes prescribed) were 83.8% and 74.9% for the 3 and 6 month visit, respectively. The followup rate at the 12 month visit was 97%. CONCLUSION: The results of our study suggest that adjunctive use of PEMF is effective in cervical spine fusion patients with factors associated with non-union. Favorable fusion rates were obtained with patients having elevated comorbidity and/or complex surgeries. Further research is planned to include a control group in a real world setting to better assess the impact of the PEMF device in this population.

The HEV Ventilator: at the interface between particle physics and biomedical engineering.

A high-quality, low-cost ventilator, dubbed HEV, has been developed by the particle physics community working together with biomedical engineers and physicians around the world. The HEV design is suitable for use both in and out of hospital intensive care units, provides a variety of modes and is capable of supporting spontaneous breathing and supplying oxygen-enriched air. An external air supply can be combined with the unit for use in situations where compressed air is not readily available. HEV supports remote training and post market surveillance via a Web interface and data logging to complement standard touch screen operation, making it suitable for a wide range of geographical deployment. The HEV design places emphasis on the ventilation performance, especially the quality and accuracy of the pressure curves, reactivity of the trigger, measurement of delivered volume and control of oxygen mixing, delivering a global performance which will be applicable to ventilator needs beyond the COVID-19 pandemic. This article describes the conceptual design and presents the prototype units together with a performance evaluation.

Abstract ES6-1: Approving New Therapies for Early Breast Cancer

Abstract The approval of a therapy by the US Food and Drug Administration (FDA) for the treatment of early breast cancer (EBC) requires substantial evidence of efficacy and an acceptable benefit-to risk evaluation from adequate and well-controlled investigations. There are two different regulatory pathways by which the FDA may approve drugs and biologics for the treatment of cancer. Regular or traditional approvals are based on the demonstration of direct clinical benefit, such as an improvement in survival or disease-related symptoms, or an improvement in an established surrogate. Examples of endpoints used for regular approval in EBC include invasive disease-free survival (IDFS) and event free survival (EFS). In 1992, new regulations were implemented, allowing for the accelerated approval (AA) of drugs for serious or life-threatening diseases in which the drugs seem to provide benefit over available therapy. AA is based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. A post marketing requirement to confirm the effect on a direct clinical benefit is required. An example of an endpoint used for AA in EBC is pathologic complete response (pCR). Pertuzumab, neratinib, ado-trastuzumab emtansine and pembrolizumab have all received approvals for treatment of breast cancer in the neo/adjuvant setting over the last decade. Some of these approvals will be discussed to highlight various efficacy endpoints and clinical trial design features that may be used in the early breast cancer setting. Citation Format: S Wedam. Approving New Therapies for Early Breast Cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES6-1.

Measure of Value: FDA in the Age of COVID

The US Food and Drug Administration (FDA) is the institutional regulatory gateway through which healthcare business sectors gain access to commercial markets in pharmaceuticals, biologicals, vaccines, medical devices, diagnostic test kits and persona protective equipment. The unfolding of events for the COVID-19 pandemic serve as a case study for understanding, in real time, how FDA has contributed value to the healthcare sector. Federal regulatory agencies, such as FDA, require strong processes to provide fair and consistent outcomes to retain the trust of the stakeholder community. These processes include statutes and regulations, internal manual of standard operating procedures and policies, guidance documents, external advisory committees and the Office of Inspector General. These processes cover the following activities: product development conditions, regulatory pathways, types of approvals, manufacturing quality, and post marketing safety. Together, the institutional experiences that led to and shaped these processes prepared FDA for the challenges associated with COVID-19. The sum of twelve decades of experience comes down to the following goals that provide value to the degree with which each is successful: 1) The manufacturing process must meet standards of quality and be secured. 2) Medical products must be shown, through scientific evidence and based on evidentiary standards, to be safe and effective for human use. 3) Identified risks must be mitigated, by labeling at a minimum, with additional strategies as necessary. 4) Provisions must exist for extraordinary circumstances of limited unmet medical needs and of threats to public health and national security. https://doi.org/10.21423/jrs-v10i1beninger

Voriconazole-Induced Hepatotoxicity Concise up-to-date review

Voriconazole is a wide spectrum antifungal used primarily for invasive aspergillosis, an invasive mold infection occurs mostly in immunocompromised patients. Hepatotoxicity is the most common voriconazole-related adverse reaction that leads to treatment discontinuation. Even though reported incidence of hepatic adverse reactions during phase 2 and 3 clinical trials were less than 10%, observational studies in post marketing phase revealed much higher incidence reaching up to 69%. Therefore, the burden caused by hepatotoxicity and interruption of antifungal therapy put immunocompromised patients at serious risk.&#x0D; Currently, there is no biomarker in routine clinical use that can clearly predict susceptibility to voriconazole-induced hepatotoxicity. In effort to identify a predictor, plasma concentrations of voriconazole and cytochrome (CYP) 2C19 genotype/phenotype, which is responsible from substantial inter-individual changes in voriconazole pharmacokinetics, are the most studied subjects. Hepatotoxicity tends to occur at higher concentrations (&gt;4 mg/L), but so far, no significant association has identified in this matter. Although CYP2C19 genotype is strongly associated with voriconazole plasma concentration, current data is insufficient to define a causal relationship between CYP2C19 genotype and voriconazole-induced hepatotoxicity.&#x0D; This article reviews the epidemiology, mechanism, laboratory features of voriconazole-induced hepatotoxicity and current literature investigating the influence of voriconazole plasma concentration and CYP2C19 genetics on voriconazole-induced hepatotoxicity.

Materiovigilance Programme of India: Current status and way forward.

Postmarketing vigilance system for medical devices in India is not as vigorous as of drugs. W Materiovigilance involves post marketing surveillance of adverse events caused by medical devices. As per directive of WHO, many countries including India have established their own post marketing surveillance system. In India it is known as Materiovigilance Programme of India (MvPI). This article reviews the current state of MvPI, compares it with developed countries, identifies gaps, and recommends specific measure to strengthen the existing program.

Comparative Study of Medical Devices in USA, Europe and India

Any medical equipment must get a marketing authorisation from a regulatory authority before it can be sold. Obtaining authorization is a lengthy, multi-step process that requires relevant authorities to review material. After analyzing the information given by the Manufacturer, the concerned Regulatory authority provides marketing authorization. Manufacturers in the United States must apply to the US Food and Drug Administration for Marketing Authorization (USFDA). There are two types of applications in the United States: 510(k) and Pre-Market Application (PMA). The marketing of medical devices is permitted by national authorities in the EU. Notified Bodies (Third Parties) ensure Quality Assurance both before and after approval via third-party compliance. The sale and import of medical devices are approved by India’s Central Drugs Standard Control Organization (CDSCO). The CLAA scheme regulates medical devices. The central licensing authority for medical devices in India is the Drug Controller General of India (DCGI). This study aims to collect information on medical device regulations in three regions: the United States, the European Union, and India, and compare market authorization provisions in each region, as well as make this complex subject easier to understand for the readers. The medical device sector is made up of several different sorts of items that are used for a variety of purposes. Medical devices must be governed by tight rules according to the different risk categories since their safety and effectiveness are critical to human health. A common framework for medical device regulations is a comprehensive product life cycle regulatory system that includes product design, manufacture, premarket gatekeeping, and post market monitoring. Medical gadgets, on the other hand, are diverse and inventive, putting current regulatory systems to the test. As a result, competent authorities in charge of medical devices around the world are constantly updating their regulatory systems to ensure that medical devices are safe and effective. The goal of this study is to provide an overview of the regulatory regimes for medical devices in the United States.

Safety and effectiveness of thymoglobulin: Results of seven Japanese post marketing surveillances

Safety and effectiveness of thymoglobulin: Results of seven Japanese post marketing surveillances

A questionnaire-based study on knowledge and awareness about clinical trials among medical students

Background: Clinical trials (CTs) play a significant role in timely enhancement of health-care quality. It aids us to find an effective and safe treatment. Clinical research is rapidly developing in India and more graduates from medical, paramedical, and other scientific fields are enrolling for clinical research training. Aims and Objectives: The aims of this study were to know the knowledge and awareness of CT among undergraduate medical students. Materials and Methods: This was a cross-sectional and questionnaire-based study conducted among medical students at a tertiary care hospital in South India from January to February 2022. These questions were designed for assessing knowledge and awareness about CT. After validation, students were administered the questionnaire through the Google form. The data were recorded and analyzed using Microsoft Excel (2019 version) and the results are explained in frequency and percentage. Results: A total of 296 students were sent Google form-based questionnaire, out of which 278 responded with completely filled up questionnaire, giving a response rate of 94%. About 82% reported correctly that healthy normal human volunteers participate in phase 1 of CT. Majority of the students (95%) were aware what is informed consent. Only 98 (35%) students were aware that the request for authorization to conduct CT is given in form 44 as per drugs and cosmetics act. Around 43.16% responded correctly about the time period taken for completion of CT, majority of the students (90%) knew who is responsible for conduction of CT. One hundred and seventy (61.15%) reported correctly that adverse drug effects and new indication or use of the drug is studied in phase 4 and majority were aware that phase 4 is also known as post marketing surveillance. In the study, 204 (73.4%) students were aware that innovatory company of a new drug has to take approval from Institutional Review Board or Institutional Ethics Committee before phase 0 of clinical trial. Majority 240 (86.33%) of the students were aware what is pharmacovigilance. The last question in our study was to assess student’s interest in taking up clinical research in future, only 41% of students showed interest in choosing clinical research as a career option. Conclusion: In the present study, undergraduate medical students’ knowledge regarding clinical trial was average and limited number of students expressed their interest in conduct of CT. A scientifically conducted research helps in evidence-based medicine, which, in turn, improves the patient care and promotes health. A great number of medical students may pursue research in future; hence, it is crucial for medical students to be knowledgeable about clinical research. Therefore, formal, educative, and regular training of medical students is required for choosing clinical research as a career option and conduct high-quality research.

Global safety monitoring of COVID-19 vaccines: how pharmacovigilance rose to the challenge.

Pharmacovigilance (PV) came suddenly into the spotlight when several new vaccines, developed as a response to the COVID-19 pandemic, received emergency authorisation and were rolled out on a large scale in late 2020. The vaccines underwent stringent clinical trials and evaluation from regulatory authorities, but with the use of novel technology and an anticipated rapid and vast deployment of the vaccines, the importance of a well-functioning international post marketing safety surveillance system was stressed. International PV stakeholders were faced with several challenges due to the extent of the global vaccination campaign. The unprecedented volume of reports of suspected adverse events following immunization has led to the development and use of new tools. Furthermore, the collaboration between various PV stakeholders was encouraged and strengthened. PV rose to the challenges posed by the currently ongoing global COVID-19 vaccination campaign and successful adaptations were made in a short period of time. However, the pandemic has not ended yet, the vaccination campaign is far from being completed, and further challenges are anticipated. Advances made during the pandemic will be important to strengthen PV in future and ensure to advance medicines’ safety together.Plain Language Summary Global safety monitoring of the COVID-19 vaccines: challenges, preparations, and outlooks Pharmacovigilance (PV) is the umbrella term for all sciences and activities relating to the detection, assessment, understanding, and prevention of adverse effects relating to medicines or vaccines. PV came into the spotlight when several new vaccines were authorised and rolled out as a response to the COVID-19 pandemic.The anticipated extent of the global vaccine rollout stressed the importance of a well-functioning safety surveillance system and international collaborations between patients, health care workers, vaccine producers, regulatory authorities, and PV centres.The identification and communication of potential safety concerns showed that adaptations to PV processes made in a short period of time as well as international collaborations were successful. However, it is important to learn from experiences made so far and to make sure the positive advances are maintained in the future to advance medicines’ safety together.

THE INFLUENCE OF THE REGULATORY SYSTEM ON THE STUDY DESIGN AND DATA MANAGEMENT PRACTICES IN CLINICAL TRIALS.

The aim: To review real-life regulatory-dependent study design and data management practices of post marketing multicenter studies of medical devices conducted in 2021 in Ukraine and Poland. Materials and methods: This article presents the case study of 4 post marketing multicenter studies of medical devices conducted in 2021 in Ukraine and European Union. Results: The case study presented effective cross-border cooperation between Ukrainian and European actors. Despite the gaps in Ukrainian legislative framework on medical devices, complex solutions on employment of the most stringent regulatory provisions led to appropriate study design. Usage of the highly compliant electronic data capture led to fast-track study start-up and solid clinical data collection. Conclusions: Publications on real-life regulatory-dependent clinical trials conduct might be essential to innovate the regulatory system in Ukraine. The cross-border cooperation might assist the advancement of clinical trials industry in Ukraine. Gaps in medical devices regulations in Ukraine impede the context-specific clinical trials solutions for biotech industry in Ukraine. The regulatory framework and practice in Ukraine may be perceived as externally driven due to gaps in medical devices regulations, lack of capacities of domestic notified bodies and business interests of Sponsors.

Pharmacovigilance – possible career journey for pharmacists

After graduating from the Pharmacy School, there are several career paths that a young professionals can follow. One of the many opportunities to start the career is working for a pharmaceutical company, in the Department of Pharmacovigilance, that has the main goal the patient‘s safety. There are different types of activities that make up a highly effective pharmacovigilance system which supports the medicine throughout its lifecycle, from the first human studies to the post marketing phase. The aim of this article is to describe a personal experience after nine years of working in the field of pharmacovigilance of several pharmaceutical companies, to raise awareness among healthcare professionals regarding the importance of reporting of the adverse events and to share how pharmaceutical companies use this information to continuously monitor the safety of their medicines.

Preventing Prescription Drug Misuse: A Regulatory Perspective in the United States, Europe, and India

Prescription medicines, such as analgesics, stimulants, steroids, anti-depressants, psychotropics, and certain antibiotics are commonly mishandled in a variety of ways, including overdosing, abuse, diversion, and drug trafficking. Because of the considerable risk to public health, they are subject to strict regulatory oversight. The drugs possess abuse potential at specific dose and hence prone to abuse therefore they are categorized as Controlled substances. Therefore, they are subject to constant vigilance over the pharmaceutical supply chain. The complete clinical data as well as post marketing surveillance study of such drugs are critical to be in place as per the regulatory requirements. The countries have kept up with the times by constantly updating the system with regulatory laws and strategies to prevent cases of misuse. The current review will give a quick summary of how prescription medications and prohibited substances are regulated in the United States, Europe, and India. It will also emphasize current trends in drug usage, as well as the issues that these countries face and the preventive policies implemented to manage and prevent drug misuse. It will also make recommendations for new regulatory initiatives to address the current drug- misuse-related concerns. As a result, a review of the regulatory system in various countries will present current challenges and new lessons for countries around the globe.

Real-time CMR guidance for intracardiac and great vessel pressure mapping in patients with congenital heart disease using an MR conditional guidewire-results of 25 patients.

The aim of this study was to test a CE-certified MR-conditional guidewire to facilitate blood pressure measurement in cardiovascular magnetic resonance (CMR) using fluid-filled catheters in patients with congenital heart disease (CHD). The main purpose was to determine procedural success in a post market clinical follow-up (PMCF) for routine procedure in a diagnostic and interventional workflow. Real-time CMR provides high quality imaging without the risk of exposing the patient to X-rays, especially for patients with irregular heart anatomy and patients who are susceptible to radiation and iodinated contrast media. To date, the assessment of blood pressure gradients is not a common feature of CMR, as these gradients cannot be accurately evaluated in routine CMR. Twenty-five CHD patients who were planned for combined clinical CMR and diagnostic and/or interventional catheterization were enrolled in the trial. Prior to inclusion, a specific procedure for catheterization in CMR was defined, encompassing the assessment of pressure and pressure gradients in the heart and great vessels. By the use of an MR-conditional guidewire we successfully measured specific pressure and pressure gradients in up to 92% of cases with liquid-filled catheters which were guided exclusively under CMR guidance. There were no guidewire-related adverse events, and guidewire guidance and manipulation of catheters were successful. Using a MR-conditional guidewire assists in easily reaching targets in the heart and great vessels and makes the catheter itself visible, so that invasive blood pressure assessment by CMR guidance with liquid-filled catheters can be improved. Cardiovascular magnetic resonance (CMR); congenital heart disease (CHD); cardiac catheterization; magnetic resonance; pressure; guidewire.

Longitudinal extensive transverse myelitis with sixth nerve palsy post ChAdOx1 nCov-19 vaccine: A case report and literature review

Concurrently with the quick development of COVID-19 vaccines globally, concerns about vaccination efficacy and safety are rising. Neurological complications such as transverse myelitis (TM) are major worries because they can cause lifelong disabilities, which may require long term care. Here, we report a case of longitudinal extensive transverse myelitis (LETM), with sixth nerve palsy in a young female occurring shortly after ChAdOx1 nCov-19 vaccine. The patient recalled developing strabismus, progressive ascending bilateral lower limb weakness, along with upper extremity paresthesia, abnormal sensation below T6 dermatomes, and difficulty in urination. She presented to the hospital with complete paralysis below the neck associated with urinary retention. Extensive diagnostic studies were performed to rule out alternative etiologies, including but not limited to demyelinating diseases, para-post infectious agents, paraneoplastic syndromes, tumors, and autoimmune diseases. She was treated with corticosteroids and discharged upon clinical improvement. However, the patient clinically deteriorated and intravenous immunoglobulin was administered. Unfortunately, the patient is still suffering from physical impairment. We suggested that LETM could be induced by an autoimmune process triggered molecule mimicry. In conclusion, safety monitoring of the COVID-19 vaccines is of great importance in the post marketing surveillance, particularly for rare adverse events.

Utilisation of disease modifying treatment and diversity of treatment pathways in relapsing remitting multiple sclerosis

BackgroundThere is minimal information on the utilisation of Disease Modifying Treatment (DMTs) for multiple sclerosis. The appropriate and safe use of medicines is informed by utilisation studies. Outcomes can inform health interventions to improve appropriate use of medicines and post marketing surveillance activities to improve safety. ObjectiveTo evaluate utilisation and treatment patterns of disease modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS). MethodsA representative sample of the Australian pharmaceutical benefits scheme data were analysed (2006–2016). Demographics of incident users and trends in incident and prevalent users were determined. Individual patient treatment pathways were determined by sequential initiation of medicines in two different periods (2006–2013 and 2014–2019). ResultsThere were 20,660 patients with at least one dispensing of a DMT for RRMS during the study period (median age 41 years, 75% female). Incident and prevalent use increased by 20% and 88%, respectively. The market was responsive to 13 new listings of DMTs over the study period. Sequential treatment was found for 66% of initiators in 2006–2013 and 28.5% of initiators in 2014–2019. Diverse treatment pathways were found, with 278 and 93 unique sequences in 2006–2013 and 2014–2019, respectively. ConclusionThe availability of new DMTs has influenced both initial treatment choice and prevalence of users. Individualised treatment patterns and exposure to multiple medicines over time will challenge traditional pharmacovigilance systems.

Evaluation of efficacy and tolerability of hepameg (probiotics + eicosapentaenoic acid + docosahexaenoic acid + vitamin E) in the management of non-alcoholic fatty liver disease

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) has currently emerged as common liver disorder compared to alcoholic liver disease. Available treatments are associated with certain side-effects. Recently a relation between gut and liver, i.e. gut-liver axis has been studied extensively. Modulation of gut may provide a natural mechanism to improve NAFLD associated complications. Aim: To evaluate the efficacy and tolerability of Hepameg. Patients were given 1 gram Hepameg sachet containing probiotics, omega-3-fatty acids and vitamin E twice a day for 12 weeks. Methods: An open-label, non-comparative post marketing study was conducted in 20 subjects with NAFLD. Physical and biochemical investigations were performed and inflammatory markers were assessed at baseline and after 12 weeks. Primary outcomes were change in scores for Fibrosis-4 (FIB-4) and AST to Platelet Ratio Index (APRI) at baseline and week 12. Secondary outcomes were global assessment of efficacy by physician and patients on a pre-defined 0 to 4 score scale. Results: After 12 weeks of Hepameg therapy, all patients reported significant improvement in FIB-4 and APRI scores. On the predefined scale of global assessment, physicians and patients reported excellent efficacy and tolerability rating for Hepameg. Conclusion: The results of the study showed that Hepameg is clinically effective and safe in the management of NAFLD. Keywords: non-alcoholic fatty liver disease; probiotics; omega-3-fatty acids; vitamin E.

Rare Cases of Infusion-Related Reactions (IRRs) Presenting As Pain Events during or after Crizanlizumab Infusion in Patients (Pts) with Sickle Cell Disease (SCD): A Systematic Evaluation of Post-Marketing (PM) Reports

Rare Cases of Infusion-Related Reactions (IRRs) Presenting As Pain Events during or after Crizanlizumab Infusion in Patients (Pts) with Sickle Cell Disease (SCD): A Systematic Evaluation of Post-Marketing (PM) Reports

Opinion on the re-evaluation of mono- and diglycerides of fatty acids (E 471) as food additive in foods for infants below 16 weeks of age and follow-up of their re-evaluation as food additives for uses in foods for all population groups.

Mono‐ and diglycerides of fatty acids (E 471) was re‐evaluated in 2017 by the former EFSA Panel on Food Additives and Nutrient sources added to Food (ANS). As a follow‐up to this assessment, the Panel on Food Additives and Flavouring was requested to assess mono‐ and diglycerides of fatty acids (E 471) for its use as food additive in food for infants below 16 weeks of age belonging to food categories 13.1.1 (Infant formulae) and 13.1.5.1 (Dietary foods for infants for special medical purposes and special formulae for infants). In addition, the FAF Panel was requested to address the issues already identified during the re‐evaluation of the food additive in 2017 when used in food for the general population. The Panel considered that there is no indication of adverse effects from the available animal studies at the highest dose tested and from the post marketing data. A comparison was made between the daily exposure to the sum of mono‐ and di‐acylglycerols from breast milk and that resulting from the use of E 471 in the infant formula. The Panel noted that the resulting exposures are in the same order of magnitude. Overall, the Panel concluded that there is no reason for a safety concern when E 471 used as food additive in FC 13.1.1 and 13.1.5.1 and according to the Annex III to Regulation (EC) No 1333/2008. The risk assessment for toxic elements and impurities clearly indicated the need to lower the current maximum limits for arsenic, lead, cadmium and mercury and to include limits for glycidyl esters, 3‐monochloropropane diol and erucic acid in the EU specifications of E 471.