scholarly journals A Broadly Accessible Liquid Chromatography Method for Quantification of Six Nitrosamine Compounds and N,N-Dimethylformamide in Metformin Drug Products Using High Resolution Mass Spectrometry

2020 ◽  
Author(s):  
Qian Wu ◽  
Evgenia Kvitko ◽  
Nicola Zenzola ◽  
Kaury Kucera ◽  
David Light
Keyword(s):  
High Resolution Mass Spectrometry ◽  
The United States ◽  
High Mass ◽  
Chromatography Method ◽  
Drug Products ◽  
Regulatory Guidance ◽  
High Mass Resolution ◽  
United States Food ◽  
States Food ◽  
Liquid Chromatography Method

N-nitrosodimethylamine (NDMA) and the industrial solvent, N,N-dimethylformamide (DMF), are both probable human carcinogens that have been detected in pharmaceutical drug products like metformin, which is used to treat type II diabetes. Some lots of metformin drug products have exceeded the United States Food and Drug Administration (FDA) daily allowable intake limit for NDMA, while the presence of DMF has been detected at several orders of magnitude higher than NDMA. A recent study found that a low abundance isotope of DMF interferes with NDMA quantification by using a unique subset of LC-MS instruments capable of high mass resolution. In this study, an LC-HRMS method is developed that chromatographically separates NDMA from DMF in metformin drug products to eliminate interference. The method can detect nitrosamines and DMF under the current regulatory guidance for industry and provides a solution for simultaneously quantifying nitrosamines and DMF for a broad range of LC-MS instruments.

scholarly journals A Broadly Accessible Liquid Chromatography Method for Quantification of Six Nitrosamine Compounds and N,N-Dimethylformamide in Metformin Drug Products Using High Resolution Mass Spectrometry

2020 ◽  
Author(s):  
Qian Wu ◽  
Evgenia Kvitko ◽  
Nicola Zenzola ◽  
Kaury Kucera ◽  
David Light
Keyword(s):  
High Resolution Mass Spectrometry ◽  
The United States ◽  
High Mass ◽  
Chromatography Method ◽  
Drug Products ◽  
Regulatory Guidance ◽  
High Mass Resolution ◽  
United States Food ◽  
States Food ◽  
Liquid Chromatography Method

N-nitrosodimethylamine (NDMA) and the industrial solvent, N,N-dimethylformamide (DMF), are both probable human carcinogens that have been detected in pharmaceutical drug products like metformin, which is used to treat type II diabetes. Some lots of metformin drug products have exceeded the United States Food and Drug Administration (FDA) daily allowable intake limit for NDMA, while the presence of DMF has been detected at several orders of magnitude higher than NDMA. A recent study found that a low abundance isotope of DMF interferes with NDMA quantification by using a unique subset of LC-MS instruments capable of high mass resolution. In this study, an LC-HRMS method is developed that chromatographically separates NDMA from DMF in metformin drug products to eliminate interference. The method can detect nitrosamines and DMF under the current regulatory guidance for industry and provides a solution for simultaneously quantifying nitrosamines and DMF for a broad range of LC-MS instruments.

scholarly journals Analysis of Crowdsourced Metformin Tablets from Individuals Reveals Widespread Contamination with N-Nitrosodimethylamine (NDMA) in the United States

2020 ◽  
Author(s):  
Qian Wu ◽  
Evgenia Kvitko ◽  
Amber Jessop ◽  
Shannon Williams ◽  
Ryan C. Costantino ◽  
...  
Keyword(s):  
United States ◽  
High Resolution Mass Spectrometry ◽  
Daily Intake ◽  
The United States ◽  
Product Recalls ◽  
Acceptable Daily Intake ◽  
Drug Products ◽  
Post Market ◽  
United States Food ◽  
States Food

AbstractRecent reports of metformin drug products contaminated with unacceptable levels of the probable human carcinogen N-Nitrosodimethylamine (NDMA) prompted a national sampling of post-market metformin drug products. To most broadly sample the market and minimize supply chain bias, metformin medication samples were crowdsourced directly from individuals across many states in the United States. 128 samples were received, and liquid chromatography-high resolution mass spectrometry tests for a panel of nitrosamines revealed significant levels of NDMA that trend with labeling company. 42% of all medication samples contained detectable levels of NDMA and, when scaled to maximum daily tablet dose, 36% of all medication samples contained NDMA levels exceeding the FDA daily acceptable intake limit. The highest NDMA detection from the tested samples was 1565 ng per tablet, which, when commonly taken four times a day, is 65 times the United States Food and Drug Administration (FDA) acceptable daily intake limit. Results underscore the need for immediate product recalls of tainted medications and an overall investigation of metformin manufacturing practices.

Abbreviated New Drug Application Process: A Gift for The Industry and The Patients

2021 ◽  
pp. 331-335
Author(s):  
Hindustan Abdul Ahad ◽  
Haranath Chinthaginjala ◽  
Gangireddy Jayasimha Reddy ◽  
Pasupuleti Dheeraj Krishna ◽  
Syed Rahamathulla ◽  
...  
Keyword(s):  
Drug Application ◽  
The United States ◽  
New Drugs ◽  
Brand Name ◽  
Application Process ◽  
Drug Products ◽  
Federal Food ◽  
United States Food ◽  
States Food ◽  
New Drug Application

The United States Food and Drug Administration (USFDA) is one of the main regulated agencies wherein the submission and approval of the new drugs is done. This review is based on the process of submission to the ANDA as per FDA norms as described in paragraph IV submission in Federal Food, Drug, and Cosmetic Act (FD and C Act). No drug would exist in the market until it gets accepted by regulatory authorities. The ANDA submission is for those firms seeking to copy branded drugs before running out of patents to get profit on them. A generic applicant must provide in its application a "certification" that a patent submitted to FDA by the brand-name drug's sponsor and scheduled in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (the Orange Book). A Generic Product must meet the standards recognized by FDA in Reference listed drugs (RLD). This study concludes the process of ANDA submission to FDA and acts correlated to the submission in paragraph IV, the details of ANDA filling in the eCTD format and overview of the review process the checklist to the applicant.

The Scope and Challenges of Vesicular Carrier-Mediated Delivery of Docetaxel for the Management of Cancer

2020 ◽  
Vol 17 (10) ◽  
pp. 874-884
Author(s):  
Charu Misra ◽  
Kaisar Raza ◽  
Amit Kumar Goyal
Keyword(s):  
The United States ◽  
Drug Products ◽  
Cancer Management ◽  
Vesicular Carriers ◽  
The Us ◽  
United States Food ◽  
Potential Benefits ◽  
States Food ◽  
Us Fda ◽  
Novel Drug

Since the discovery of liposomes, these vesicular carriers have attracted the researchers from all the vistas of the biomedical domain to explore and harness the potential benefits. Many novel drug delivery-based products have been approved by the United States Food and Drug Administration (USFDA) and other federal agencies of the globe, out of which the major share is of the liposomes and related carriers. Taking cognizance of it, the US-FDA has recently come up with ‘Guidance for Industry on Liposome Drug Products’. In cancer management, chemotherapy is the most frequently employed approach which is still not devoid of untoward challenges and side effects. In chemotherapy, the taxanes, esp. Docetaxel shares a huge percentage in the prescription pattern. Also, the first marketed liposomal product was encasing one drug of this category. Henceforth, the present review will highlight the advances in the delivery of taxanes, in particular docetaxel, with an emphasis on the need, success and pharmacoeconomic aspects of such vesicular-carrier mediated docetaxel delivery.

scholarly journals Performance evaluation of a prescription medication image classification model: an observational cohort

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Corey A. Lester ◽  
Jiazhao Li ◽  
Yuting Ding ◽  
Brigid Rowell ◽  
Jessie ‘Xi’ Yang ◽  
...  
Keyword(s):  
Prescription Medication ◽  
The United States ◽  
Machine Intelligence ◽  
Classification Model ◽  
Drug Products ◽  
National Drug ◽  
Physical Form ◽  
United States Food ◽  
Observational Cohort ◽  
States Food

AbstractTechnology assistance of pharmacist verification tasks through the use of machine intelligence has the potential to detect dangerous and costly pharmacy dispensing errors. National Drug Codes (NDC) are unique numeric identifiers of prescription drug products for the United States Food and Drug Administration. The physical form of the medication, often tablets and capsules, captures the unique features of the NDC product to help ensure patients receive the same medication product inside their prescription bottle as is found on the label from a pharmacy. We report and evaluate using an automated check to predict the shape, color, and NDC for images showing a pile of pills inside a prescription bottle. In a test set containing 65,274 images of 345 NDC classes, overall macro-average precision was 98.5%. Patterns of incorrect NDC predictions based on similar colors, shapes, and imprints of pills were identified and recommendations to improve the model are provided.

scholarly journals Insight on PMDA Regulatory Procedures, Key Stages, Timing, and CMC Requirements for Bio-Therapeutic Products in Japan

2021 ◽  
pp. 1-13
Author(s):  
SEEMA SINGH ◽  
Keyword(s):  
The United States ◽  
Drug Products ◽  
Regulatory Systems ◽  
The Us ◽  
United States Food ◽  
States Food ◽  
Human Use ◽  
Us Fda ◽  
Data Requirements ◽  
Device Agency

The purpose of this manuscript is to provide a basic understanding of legal regulatory systems, marketing authorization application, the Pharmaceutical and Medical Device Agency (PMDA) review process, key stages and timing and CMC (Chemistry, Manufacturing and Controls) requirements in Japan, with a focus on biotherapeutic/biological drug products for human use. The PMDA has some stringent CMC data requirements, which make Japan unique. Japan’s regulatory environment is significantly more complicated than any other country. The level of accuracy and details required by the Japanese regulatory authority is sometimes even greater than the US FDA (the United States Food and Drug Administration), the EMA (the European Medicine Agency) or any other pharmaceutical regulatory agency

Delirium Secondary to Lamotrigine Toxicity

2020 ◽  
Vol 15 (2) ◽  
pp. 156-159 ◽  
Author(s):  
Deborah L. Sanchez ◽  
Adam J. Fusick ◽  
Steven R. Gunther ◽  
Michael J. Hernandez ◽  
Gregory A. Sullivan ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Valproic Acid ◽  
Mental Status ◽  
The United States ◽  
Clinical Correlation ◽  
Medication Regimen ◽  
Medication Effects ◽  
United States Food ◽  
States Food ◽  
Rule Out

Background: Lamotrigine is a phenyltriazine medication that has been approved by the United States Food and Drug Administration as monotherapy and as an adjunctive agent for the treatment of seizure disorder. It was later approved by the FDA for the treatment of bipolar disorder. Lamotrigine is generally well tolerated by patients, but some serious symptoms can occur during treatment. These severe side effects include rashes and multi-organ failure. Lamotrigine has also been associated with the development of mental status changes, frequently when used concurrently with other medications that may impact the metabolism of lamotrigine. Objective: To present the case of a 65-year-old man being treated with lamotrigine and valproic acid who developed mental status changes after the addition of sertraline to his medication regimen, and to compare this case to existing cases reported in the literature. Discussion: Our case adds to the existing literature by demonstrating that patients may experience adverse medication effects despite lamotrigine levels that are normally considered to be in the therapeutic range, highlighting the importance of clinical correlation when obtaining medication levels. Conclusion: Clinicians should use caution interpreting lamotrigine levels when working up delirium, as normal levels may not rule out the development of lamotrigine toxicity.

scholarly journals The Efficacy of Convalescent Plasma Use in Critically Ill COVID-19 Patients

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 257
Author(s):  
Livius Tirnea ◽  
Felix Bratosin ◽  
Iulia Vidican ◽  
Bianca Cerbu ◽  
Mirela Turaiche ◽  
...  
Keyword(s):  
Pilot Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Therapeutic Option ◽  
White Blood Cells ◽  
The United States ◽  
Plasma Therapy ◽  
Reactive Protein ◽  
United States Food ◽  
States Food

Background and Objectives: On 24 March 2020, the United States Food and Drug Administration (FDA) announced the approval of convalescent plasma therapy for critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergency investigational new drug. This pilot study from Romania aimed to determine if convalescent plasma transfusion can be beneficial in the treatment of selected critically ill patients diagnosed with a SARS-CoV-2 infection. Materials and Methods: Donor and receiver eligibility for critically ill coronavirus disease 2019 (COVID-19) patients was based on Romanian guidelines issued at the time of the study. Here, we describe the evolution of a total of five eligible patients diagnosed with COVID-19 who received convalescent plasma (CP) in Romania. Results: In spite of our efforts and convalescent plasma administration, three of the five patients did not survive, while the other two recovered completely. Over the course of our five-day laboratory record, the surviving patients had significantly lower values for C-reactive protein, interleukin-6, and white blood cells. Conclusions: This pilot study provides insufficient evidence to determine the efficacy of convalescent plasma use as a therapeutic option for critically ill COVID-19 patients.

scholarly journals Review of COVID-19 mRNA Vaccines: BNT162b2 and mRNA-1273

2021 ◽  
pp. 089719002110096
Author(s):  
Shyh Poh Teo
Keyword(s):  
Vaccine Development ◽  
Safety Data ◽  
The United States ◽  
Virus Infections ◽  
Phase 3 ◽  
Vaccination Programs ◽  
Safety Surveillance ◽  
Mass Immunization ◽  
United States Food ◽  
States Food

The United States Food and Drug Administration recently issued emergency use authorization for 2 mRNA vaccines for preventing COVID-19 disease caused by SARS-CoV-2 virus infections. BNT162b2 from Pfizer-BioNTech and mRNA-1273 by Moderna are planned for use in mass-immunization programs to curb the pandemic. A brief overview of COVID-19 mRNA vaccines is provided, describing the SARS-CoV-2 RNA, how mRNA vaccines work and the advantages of mRNA over other vaccine platforms. The Pfizer-BioNTech collaboration journey to short-list mRNA vaccine candidates and finally selecting BNT162b2 based on safety data is outlined, followed by the Phase 3 study of BNT162b2 demonstrating 95% efficacy in preventing COVID-19 infections. Studies regarding mRNA-1273 (Moderna) are described, including extended immunogenicity data up to 119 days. The Phase 3 COVE study of mRNA-1273 eventually showed vaccine efficacy of 94.5%. Recommendations for future mRNA vaccine development are provided, including ongoing safety surveillance, evaluation in under-represented groups in previous studies and improving mRNA vaccine thermostability. Finally, further logistical considerations are required for manufacturing, storing, distribution and implementing mass vaccination programs to curb the pandemic.

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