Food And Drug Administration Guidelines Research Articles

Validation of rapid detection methods for Salmonella enterica in green chile.

The objective of this study is to validate the US Food and Drug Administration (FDA) rea-time polymerase chain reaction (qPCR) assay, the Neogen Amplified Nucleic Single Temperature Reaction (ANSR) assay, and the Vitek ImmunoDiagnostic Assay System (VIDAS) SLM procedure against the FDA cultural procedure for Salmonella detection in green chile pepper. Green chile was artificially contaminated with Salmonella according to the FDA guidelines (FDA. Guidelines for the Validation of Microbiological Methods for the FDA Foods Program, 3rd Edition. 2019. www.fda.gov/media/83812/download?attachment (17 March 2024, date last accessed)) at a fractional recovery level (where 50%-25% tests positive and at a level+1 log greater for each organism tested). Enriched samples were tested directly by the ANSR Salmonella test and by qPCR, and were subcultured into Rappaport-Vassiliadis and tetrathionate brilliant green broth for cultural detection and qPCR. For the VIDAS-SLM assay, the selective enrichments were further cultured in M broth before testing. Presumptive salmonellae were confirmed with biochemical tests, serology, and qPCR. All three rapid assays were compared favorably with the FDA-BAM (Bacteriological Analytical Manual) method. No significant differences at P<.05 were found between the procedures using McNemar's χ2 test. The three procedures were found to be rapid and reliable alternatives to cultural detection of Salmonella enterica in green chile.

Development and validation of a UPLC-MS/MS method to investigate the plasma pharmacokinetics of a KCa 2.2/KCa 2.3 positive allosteric modulator in mice.

There is currently no treatment for spinocerebellar ataxias (SCAs), which are a group of genetic disorders that often cause a lack of coordination, difficulty walking, slurred speech, tremors, and eventually death. Activation of KCa 2.2/KCa 2.3 channels reportedly exerts beneficial effects in SCAs. Here, we report the development and validation of an analytical method for quantitating a recently-developed positive allosteric modulator of KCa 2.2/KCa 2.3 channels (compound 2q) in mouse plasma. Mouse plasma samples (10 μL) containing various concentrations of 2q were subjected to protein precipitation in the presence of a structurally similar internal standard (IS). Subsequently, the analytes were separated on a C18 UPLC column and detected by a tandem mass spectrometer. The method was validated using FDA guidelines. Finally, the validated assay was applied to the measurement of the plasma concentrations of 2q in plasma samples taken from mice after single intravenous doses of 2 mg/kg of 2q, and the pharmacokinetic parameters of 2q were determined. The calibration standards were linear (r2 ≥ 0.99) in the range of 1.56 - 200 nM of 2q with intra- and inter-run accuracy and precision values within the FDA guidelines. The lower limit of quantitation of the assay was 1.56 nM (0.258 pg on the column). The recoveries of 2q and IS from plasma were > 94%, with no appreciable matrix effect. The assay showed no significant carryover, and the plasma samples stored at -80o C or the processed samples stored in the autosampler at 10o C were stable for at least three weeks and 36 h, respectively. After intravenous injection, 2q showed a bi-exponential decline pattern in the mouse plasma, with a clearance of 30 mL/min/kg, a terminal volume of distribution of 1.93 mL/kg, and a terminal half-life of 45 min. The developed assay is suitable for preclinical pharmacokinetic-pharmacodynamic studies of 2q as a potential drug candidate for ataxias.

Assessment, Complications, and Surveillance of Breast Implants: Making Sense of 2022 FDA Breast Implant Guidance.

As more information about the potential risks and complications related to breast implants has become available, the United States Food and Drug Administration (FDA) has responded by implementing changes to improve patient education, recalling certain devices and updating the recommendations for screening for silicone implant rupture. In addition to staying up-to-date with FDA actions and guidance, radiologists need to maintain awareness about the types of implants they may see, breast reconstruction techniques including the use of acellular dermal matrix, and the multimodality imaging of implants and their complications. Radiologists should also be familiar with some key differences between the updated FDA guidelines for implant screening and the imaging recommendations from the American College of Radiology Appropriateness Criteria. The addition of US as an acceptable screening exam for silicone implant rupture by the FDA is one of the most notable changes that has potentially significant implications.

The new guideline for evaluating effects of psychotropic drugs on the performance to drive a motor vehicle in Japan: Comparison with US FDA guideline.

In December 2022, the new guideline for evaluating the effect of psychotropic drugs on the performance to drive a motor vehicle was issued by the Ministry of Health, Labour and Welfare (MHLW) and implemented in Japan. Of the safety information, information on the influence of medications on driving performance is particularly important because it can be relevant to the social functioning of patients. In principle, the package inserts of medications are designed based on evidence and provide precautions regarding the operation of heavy machinery such as automobiles in Japan, the United States, and Europe. The effects of medications on driving performance are generally evaluated in a tiered approach involving nonclinical and clinical studies. Because of the wide variety of functional domains involved in automobile driving, the selection of evaluation methods for a given medication depends on their characteristics, which is a complicated method. Therefore, to evaluate the effects of psychotropic drugs on driving performance efficiently and appropriately, we developed the MHLW guideline that specifically defines the evaluation methods used in pharmacological studies, the neuropsychological tests used in pharmacodynamic studies, and the situations in which driving studies are necessary. Regarding the planning of appropriate drug development strategies, we review the background of the MHLW guideline and its differences from the US Food and Drug Administration (FDA) guideline.

What is the weight of expectation bias in oncology trials?

What is the weight of expectation bias in oncology trials?

Determination of Amygdalin in Apricot Kernels and Almonds Using LC-MS/MS.

Cyanogenic glycosides are secondary metabolites in plants. In almonds and apricot kernels, amygdalin is an abundant cyanogenic glycoside. Upon consumption, amygdalin is enzymatically metabolized into hydrogen cyanide. Depending on the number of kernels consumed and the amygdalin concentration, ingestion of amygdalin-containing kernels may result in adverse effects. To better understand the US marketplace, the development and validation of analytical methods to reliably measure amygdalin in apricot kernels and almonds is needed to support the collection of occurrence and consumption data in retail products. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitation of amygdalin in apricot kernels and almonds following the U.S. Food and Drug Administration (FDA). Foods Program Guidelines for the Validation of Chemical Methods, 3rd Edition. Apricot kernels and almonds were cryogenically homogenized and extracted using methanol containing an internal standard (IS), geniposide, followed by filtration, dilution, and LC-MS/MS analysis. Matrix effects were minimized using dilution. Quantitation was achieved using an external, solvent-based calibration. The amygdalin response was linear (r2 > 0.99) over a range of 0.05-50 µg/mL. The recovery of amygdalin spiked at 10-10 000 µg/g in sweet apricot kernels, raw almond, and dry-roasted almond ranged from 90 to 107% with RSDs ≤6%. The method limit of detection and limit of quantitation was 0.8 and 2.5 ng/g, respectively. Amygdalin concentrations in 18 market samples ranged from 2 to 24 000 µg/g. Corresponding estimates of cyanide concentration ranged from 0.2 to 1420 µg/g. Method performance meets the acceptance criteria defined by FDA guidelines and is fit for purpose for the analysis of amygdalin in apricot kernels and almonds. An LC-MS/MS method is developed for the quantification of amygdalin in apricot kernels and almonds.

Development and Validation of an LC-MS/MS Method to Quantify Gilteritinib and Its Clinical Application in Patients With FLT3 Mutation-Positive Acute Myelogenous Leukemia.

Gilteritinib, a novel oral tyrosine kinase inhibitor, is used to treat acute myeloid leukemia (AML) with FMS-like tyrosine kinase-3 (FLT3) mutations. Therapeutic drug monitoring (TDM) of gilteritinib is important for improving clinical outcomes and ensuring safety. Therefore, this study aimed to develop a simplified method for quantifying gilteritinib in human plasma using liquid chromatography-tandem mass spectrometry. Liquid chromatography was performed by using an Acquity BEH C18 column (50 mm × 2.1 mm, 1.7 μm) and a gradient elution with 0.1% formic acid in water (A) and acetonitrile (B). Detection was performed by using a Shimadzu tandem mass spectrometer through multiple reaction monitoring in the positive-ion mode. The developed method enabled quantification of gilteritinib in 4 minutes and was validated by evaluating selectivity, calibration curve (10-1000 ng/mL, r 2 > 0.99), a lower limit of quantification (LLOQ), accuracy (overall bias -4.2% to 1.9%), precision (intraday CV ≤ 7.9%; interday CV ≤ 13.6%), carryover, recovery, matrix effect, dilution integrity, and stability according to the US Food and Drug Administration (FDA) guidelines. This method was successfully applied to the TDM of gilteritinib trough concentrations in 3 patients with AML. The developed method fulfilled the FDA guideline criteria and can easily be implemented to facilitate TDM in patients receiving gilteritinib in a clinical setting.

Relaxation of the criteria for entry to the UK Clozapine Central Non-Rechallenge Database: a modelling study

Clozapine is uniquely effective in treatment-resistant psychosis. In the UK, patients must discontinue clozapine indefinitely if they are placed on the Central Non-Rechallenge Database (CNRD) after their haematological parameters fall below particular thresholds. Under exceptional circumstances, patients can be rechallenged on clozapine under an off-licence agreement. In the USA in 2015, restrictive practice was discontinued to allow greater flexibility for clozapine maintenance. The absolute neutrophil count leading to treatment interruption was lowered from less than 1·5 × 109/L to less than 1·0 × 109/L and platelet and white cell count monitoring were ceased. We aimed to investigate the implications of a similar policy change on clozapine use in the UK. This was a modelling study of all patients registered on the UK CNRD. First, we determined the proportion of patients placed on the database in the UK who would have had to discontinue clozapine treatment under the US Food and Drug Administration (FDA) criteria. Second, we compared the haematological characteristics of patients who did or did not meet FDA criteria for discontinuing clozapine, including the time to registration from clozapine initiation and the proportion of cases of severe neutropenia at registration. Third, we investigated the success rates of clozapine re-challenge for patients that had been placed on the CNRD. Successful rechallenge was defined as no recurrence of CNRD registration. Between May 2, 2002 and March 1, 2021, 3731 patients were placed on the CNRD, with a mean age of 47 years (SD 15), including 1420 (38%) women and 2311 (62%) men, of whom 3089 (83%) were White, 360 (10%) were Black, 190 (5%) were Asian, and 92 (2%) were classified as other. 566 (15%) of 3731 patients met the equivalent criteria for clozapine discontinuation under the FDA guidelines. The median time to CNRD registration from clozapine initiation was 1·6 years (IQR 0·2-4·9). Data for 519 rechallenged patients were examined; 419 (81%) were successful. Clozapine rechallenge success rates were broadly similar between individuals who did not meet the US CNRD registration criteria (36 [78%] of 46) and those who did meet the criteria (383 [81%] of 473). Implementing the revised FDA monitoring criteria in the UK would substantially reduce clozapine discontinuation for haematological reasons, which would greatly improve the mental health outcomes of these patients without having a major effect on their physical health. None.

Validation of an LC-MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma.

Silmitasertib (CX-4945) is currently being investigated in clinical trials against various types of cancer. The U.S. Food and Drug Administration (FDA) has already granted orphan drug designation to the compound for the treatment of advanced cholangiocarcinoma, medulloblastoma, and biliary tract cancer. Silmitasertib inhibits the serine/threonine protein kinase CK2, which exerts a proliferation-promoting and anti-apoptotic effect on cancer cells. In view of current and future applications, the measurement of silmitasertib levels in plasma is expected to play an important role in the evaluation of therapeutic and toxic concentrations in cancer patients. In the present work, we therefore present an LC–MS/MS method for the quantification of silmitasertib in human plasma. Using a simple liquid–liquid extraction with ethyl acetate and a mixture of n-hexane and ethyl acetate, this method can be performed in any laboratory with mass spectrometry. The validation was carried out according to the FDA guideline.

Guidance on the need for contraception related to use of pharmaceuticals: the Japan Agency for Medical Research and Development Study Group for providing information on the proper use of pharmaceuticals in patients with reproductive potential

BackgroundThe U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have published guidelines on the use of cancer treatments in young people of reproductive potential. However, no such guideline is available in Japan. Therefore, this project aimed to gather relevant data and draft a respective guidance paper.MethodsFrom April 2019 to March 2021, the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential at the Japan Agency for Medical Research and Development gathered opinions from experts in reproductive medicine, toxicology, and drug safety measures. The group considered these opinions, the FDA and EMA guidelines, and relevant Japanese guidelines and prepared a guidance paper, which they sent to 19 related organizations for comment.ResultsBy November 2020, the draft guidance paper was completed and sent to the related organizations, 17 of which provided a total of 156 comments. The study group finalized the guidance paper in March 2021.ConclusionsThe “Guidance on the Need for Contraception Related to Use of Pharmaceuticals” (The report of the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential, Research on Regulatory Science of Pharmaceuticals and Medical Devices, Japan Agency for Medical Research and Development: JP20mk0101139) is expected to help Japanese healthcare professionals provide fertility-related care and advice to adolescents, and young adults with cancer and their families.

Abstract P043: A Framework For The Evaluation Of Digital Tools

Digital health tools encompass a wide range of technologies that have been used in healthcare services including mobile applications, health information technology, smart wearable devices, remote monitoring and treatment, and health platforms. These tools walk a fine line between lifestyle consumer products and medical devices. Sleep applications can be used by consumers as a fun gadget to track sleep, but it may also be used as a medical tool to collect information concerning serious sleep disorders. The fast proliferation of these tools has put pressure on concerned stakeholders to make sense of this group of technologies. Various questions have been raised within this realm: What counts as medical as opposed to a lifestyle device? Which devices require regulation and under what standards? Which devices are allowed to be used in the medical context? And which are not? And under what conditions? Social scientists have highlighted the complexity of digital health tools that (include both medical and lifestyle characteristics and the difficulties accompanied with classifying these tools for regulatory purposes. In an attempt to do so, several regulatory bodies including the US Food and Drug Administration (FDA) have revised their existing standards to accommodate the regulation of digital health tools. As such, the FDA published a guidance document on Mobile Medical Applications; this led to various concerns questioning the boundaries between lifestyle and medical digital technologies that were defined by the FDA guidelines, which left a significant number of technologies that were considered to be low-risk, completely out of the FDA oversight and with no required compliance/quality control/effectiveness checks. This prompted many companies to develop hundreds of products that belong to the low-risk category, granting them the ability to ignore FDA regulations. Consequently, there remains considerable concern regarding the quality and safety of these digital health technologies that are being used within the medical context. Clear and well-defined regulation processes are needed to control the development and design of these tools, especially that many lack scientific evidence and data privacy. The framework ought to include a risk-based approach to classify devices for regulation in a way to ensure the safety and effectiveness of all digital health tools throughout their life cycle, even those classified as low-risk. The framework and regulatory process also need to take into consideration the rapid change in digital product development, as processes that extend for a long period of time may become obsolete in supporting decisions about these tools. As these digital health tools become more sophisticated, accessible, widespread, and cheaper, the need for classifying and regulating the sector becomes important, especially with the rapid evolution of these technologies.

Pilot implementation of opioid stewardship measures using the national surgical quality improvement program-pediatric platform

IntroductionData surrounding optimal pediatric postoperative opioid prescribing are incomplete. The objective of this study was to leverage the American College of Surgeons (ACS) National Surgical Quality Improvement Program-Pediatric (NSQIP-P) and assess feasibility of added data collection surrounding pediatric perioperative pain management practices including opioid prescribing at discharge. MethodsNineteen (19) novel data elements were added to NSQIP-P data collection of selected patients, ages 5–18 years, who had undergone surgery at a single, free-standing children's hospital. Metrics around data abstraction and completion of variables were collected. Univariate analyses (using Chi-square or Wilcoxon Rank Sum tests) and multiple logistic regressions were performed to describe predictors of opioid prescribing at discharge and to monitor adherence to Food and Drug Administration (FDA) prescribing recommendations. ResultsMedian abstraction time of the novel variables decreased from 12 to 5 min per patient over 13 months with 94% variable completion rate. Of 878 patients, 302 (36.4%) were prescribed opioids at discharge. Factors associated with an opioid prescription included older age (p < 0.001), white race (p < 0.05), undergoing an orthopedic surgery (p < 0.001), and receiving a regional block perioperatively (p < 0.001). All opioid prescriptions met FDA guidelines with no patients receiving codeine, and 98% of patients receiving opioid prescriptions < 50 morphine milli-equivalents per day. ConclusionCollecting data on current pain management practices, opioid prescribing, and adherence to safety recommendations is feasible using the NSQIP-P with little added burden. Further expansion of data collection is needed to develop generalizable optimal prescribing practices for post-discharge pain management for children.

Ocular Ultrasound: Review of Bioeffects and Safety, Including Fetal and Point of Care Perspective: Review of Bioeffects and Safety, Including Fetal and Point-of-Care Perspective.

Ocular ultrasound is an invaluable tool for the evaluation of the eye and orbit. However, the eye and orbit are potentially sensitive to the thermal and mechanical effects of ultrasound. When performing B-mode imaging, dedicated ocular settings should be used. If these settings are not available, limiting the acoustic output to Food and Drug Administration (FDA) recommended maximum levels is strongly advised. Especially important is the acoustic output in spectral (pulsed) and color Doppler modes, which can exceed the FDA's maximum recommended levels for the eye. Adjusting settings to decrease acoustic output and limiting the time of the examination should be done when performing a Doppler examination. The acoustic output of shear wave elastography is significantly higher than FDA guidelines for the eye and should be considered experimental.

Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs.

The statistical procedures as outlined by the European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) guidelines for bioequivalence testing of highly variable drugs (HVDs) are complex. Additionally, the sample size is affected by clinical study designs or practical real-world problems, such as dropout rate or study budget. To overcome these difficulties, we propose a model-based approach for the selection of a study design with a sample size that satisfies the bioequivalence criteria using simulation studies based on a pharmacokinetic (PK) model. The designed approach was implemented using a simulation procedure considering some conventionally measured factors, such as geometric mean ratio and within-subject coefficient of variation, with various PK information important in determining bioequivalence. All simulation results were assessed according to the EMA and FDA guidelines. Furthermore, power calculations from simulation results were interpreted with regard to PK characteristics and compared among 2 × 2, 3 × 3, and 2 × 4 crossover designs to determine the efficient design considering appropriate sample size and duration of the clinical study. The proposed approach can be applied to bioequivalence studies of all drugs. However, the current study was targeted at HVDs, which are highly likely to require detailed decision making for sample size and study design.

Why are US military personnel prescribed transdermal fentanyl patches?

IntroductionTransdermal fentanyl is a continuous release opioid delivery system intended for use in opioid-tolerant patients requiring around-the-clock opioid therapy. The purpose of this study is to identify the most common...

Analysis of docosanol using GC/MS: Method development, validation, and application to ex vivo human skin permeation studies

Docosanol is the only US Food and Drug Administration (FDA) approved over-the-counter topical product for treating recurrent oral-facial herpes simplex labialis. Validated analytical methods for docosanol are required to demonstrate the bioequivalence of docosanol topical products. A gas chromatography/selected ion monitoring mode mass spectrometry (GC/SIM-MS) method was developed and validated for docosanol determination in biological samples. Docosanol and isopropyl palmitate (internal standard) were separated on a high-polarity GC capillary column with (88% cyanopropy)aryl-polysiloxane employed as the stationary phase. The ions of m/z 83 and 256 were selected to monitor docosanol and isopropyl palmitate, respectively; the total run time was 20 min. The GC/SIM-MS method was validated in accordance with US FDA guidelines, and the results met the US FDA acceptance criteria. The docosanol calibration standards were linear in the 100–10000 ng/mL concentration range (R2>0.994). The recoveries for docosanol from the receptor fluid and skin homogenates were >93.2% and >95.8%, respectively. The validated method was successfully applied to analyze ex vivo human cadaver skin permeation samples. On applying Abreva® cream tube and Abreva® cream pump, the amount of docosanol that penetrated human cadaver skin at 48 h was 21.5 ± 7.01 and 24.0 ± 6.95 ng/mg, respectively. Accordingly, we concluded that the validated GC/SIM-MS was sensitive, specific, and suitable for quantifying docosanol as a quality control tool. This method can be used for routine analysis as a cost-effective alternative to other techniques.

There Is Life After the UK Clozapine Central Non-Rechallenge Database.

In the United Kingdom, patients on clozapine whose hematological parameters fall below certain thresholds are placed on the Central Non-Rechallenge Database (CNRD), meaning that they cannot be prescribed clozapine again except under exceptional circumstances. This practice was discontinued in the United States in 2015 by expanding the hematological monitoring guidelines, allowing more patients to receive clozapine. Our objective was to investigate the implications this policy change would have on clozapine utilization in the United Kingdom. This was an observational, retrospective analysis of patients registered on the CNRD in a large mental health trust. The first objective was to compare the number of patients placed on the CNRD under the United Kingdom and the US Food and Drug Administration (FDA) criteria. The second objective was to explore the hematological and clinical outcomes of CNRD patients. The third objective was to investigate the hematological outcomes of patients rechallenged on clozapine after nonrechallengeable status. One hundred and fifteen patients were placed on CNRD from 2002 to 2019, of whom 7 (6%) met the equivalent criteria for clozapine discontinuation under the FDA guidelines. Clinical outcomes, as measured by the Clinical Global Impression-Severity scale, were worse 3 months after clozapine cessation than on clozapine (t = -7.4862; P < .001). Sixty-two (54%) patients placed on CNRD were rechallenged. Fifty-nine of those (95%) were successfully rechallenged; 3 patients were placed back on CNRD, only one of which would have had to stop clozapine again under FDA criteria. Implementation of the updated FDA's monitoring criteria in the United Kingdom would significantly reduce clozapine discontinuation due to hematological reasons. The evidence suggests an urgent need for revising the UK clozapine monitoring guidelines to improve outcomes in treatment-resistant schizophrenia.

EMA and FDA psychiatric drug trial guidelines: assessment of guideline development and trial design recommendations.

The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) produce guidelines for the design of pivotal psychiatric drug trials used in new drug applications. It is unknown who are involved in the guideline development and what specific trial design recommendations they give. Cross-sectional study of EMA Clinical Efficacy and Safety Guidelines and FDA Guidance Documents. Study outcomes: (1) guideline committee members and declared conflicts of interest; (2) guideline development and organisation of commenting phases; (3) categorisation of stakeholders who comment on draft and final guidelines according to conflicts of interest ('industry', 'not-industry but with industry-related conflicts', 'independent', 'unclear'); and (4) trial design recommendations (trial duration, psychiatric comorbidity, 'enriched design', efficacy outcomes, comparator choice). Protocol registration https://doi.org/10.1101/2020.01.22.20018499 (27 January 2020). We included 13 EMA and five FDA guidelines covering 15 psychiatric indications. Eleven months after submission, the EMA had not processed our request regarding committee member disclosures. FDA offices draft the Guidance Documents, but the Agency is not in possession of employee conflicts of interest declarations because FDA employees generally may not hold financial interests (although some employees may hold interests up to $15,000). The EMA and FDA guideline development phases are similar; drafts and final versions are publicly announced and everybody can submit comments. Seventy stakeholders commented on ten guidelines: 38 (54%) 'industry', 18 (26%) 'not-industry but with industry-related conflicts', six (9%) 'independent' and eight (11%) 'unclear'. They submitted 1014 comments: 640 (68%) 'industry', 243 (26%) 'not-industry but with industry-related conflicts', 44 (5%) 'independent' and 20 (2%) 'unclear' (67 could not be assigned to a specific stakeholder). The recommended designs were generally for trials of short duration; with restricted trial populations; allowing previous exposure to the drug; and often recommending rating scale efficacy outcomes. EMA mainly recommended three arm designs (both placebo and active comparators), whereas FDA mainly recommended placebo-controlled designs. There were also other important differences and FDA's recommendations regarding the exclusion of psychiatric comorbidity seemed less restrictive. The EMA and FDA clinical research guidelines for psychiatric pivotal trials recommend designs that tend to have limited generalisability. Independent and non-conflicted stakeholders are underrepresented in the guideline development. It seems warranted with more active involvement of scientists and independent organisations without conflicts of interest in the guideline development process.

Purdue College of Pharmacy's Response to the Hand Sanitizer Shortage during the Pandemic

With the outbreak of Coronavirus Disease 2019 (COVID-19), came struggles and hardships that were not foreseen. One of these struggles was to maintain an adequate supply of medical equipment, medications, and other necessities to help protect individuals and communities. Proper hand hygiene is an important part of the response to COVID-19. Sanitizing and taking steps to prevent contraction of COVID-19 was a high priority and with the high demand, the availability of hand sanitizer was scare. In March 2020, the US Food and Drug Administration (FDA) released a policy allowing pharmacists to temporarily compound alcohol-based hand sanitizer during the public health emergency. This provided the Purdue University Pharmacy the opportunity to provide this essential service to the Purdue and local community. In collaboration with the Purdue University Pharmacy, four pharmacists, two pharmacy technicians, and five pharmacy students compounded a total of 831.36 liters of hand sanitizer (approximately 220 gallons) during March and April 2020. They packaged the product into smaller bottles (i.e., two ounces) and labeled them according to FDA guidelines. This resulted in over 13,000 bottles of hand sanitizer that was safe for human use. Many of the bottles were donated to campus and community agencies including food pantries and transitional housing and shelters to assist those most in need. While the remaining bottles were sold (at cost) to campus and community members, police departments, fire departments, sanitation departments, funeral homes, libraries, and childcare centers, to name just a few. Pharmacy students reflected on the experience and commented that the initiative impacted them both personally and professionally and provided a way to work together and give back to the community during this challenging time. This community outreach initiative helped to protect community members and allowed the pharmacy students to continue to learn during this uncertain time.

Comparative assessment of off-label and unlicensed drug prescription in neonatal intensive care: FDA versus Brazilian guidelines

IntroductionRegulatory agencies are responsible for defining the use of off-label (OL) and unlicensed (UL) drug prescription in neonatal intensive care. However, these regulatory criteria may differ between agencies in different countries. The aim of this study was to establish the frequency of OL and UL drug prescription in a sample of patients in a neonatal intensive care unit applying the criteria of the Food and Drug Administration (FDA) of the United States and the Agência Nacional de Vigilância Sanitária (ANVISA) of Brazil, analysing the differences observed in the results based on the applied criteria. MethodsProspective cohort study in neonates admitted for more than 24h to the NICU of a teaching maternity hospital between August 2017 and July 2018. We obtained information concerning the drugs included in the analysis of OL and UL prescriptions from the DrugDex-Micromedex® and official information on pharmaceutical products in Brazil. We used the kappa correlation coefficient to assess the agreement between the FDA and ANVISA criteria. We defined disagreement as a kappa value of less than 0.200. ResultsWe evaluated 220 neonates admitted to the NICU and 17,421 items prescribed during the study period. We did not find a difference in the proportion of neonates in which at least 1 drug was prescribed under OL conditions applying the FDA versus the ANVISA criteria (96.4% vs. 98.6%). We found differences between the FDA and ANVISA in the OL classification based on the authorized age of use and indications for prescription, mainly in systemic antimicrobials and cardiovascular drugs. When we compared the prescribing information provided by the FDA and the ANVISA, we found that the criteria of the ANVISA were less specific. ConclusionOff-label and unlicensed drug prescription are frequent in neonatal intensive care applying the criteria of either agency, although the FDA has established more detailed criteria in terms of the ages and indications for which prescription is authorized.