scholarly journals Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria

2019 ◽  
Vol 10 ◽  
pp. 204062071987472 ◽  
Author(s):  
Robert M. Stern ◽  
Nathan T. Connell
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Phase Iii ◽  
The European Union ◽  
Regulatory Review ◽  
Dosing Schedule ◽  
The Us ◽  
United States Food ◽  
States Food ◽  
Us Fda

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis. Until recently, the complement inhibitor, eculizumab, was the only United States Food and Drug Administration (US FDA)-approved therapy for the treatment of PNH. Although effective, eculizumab requires a frequent dosing schedule that can be burdensome for some patients and increases the risk of breakthrough intravascular hemolysis. Ravulizumab, an eculizumab-like monoclonal antibody engineered to have a longer half-life, is intended to provide the same benefits as eculizumab but with a more convenient and effective dosing schedule. In two recently published phase III non-inferiority trials, ravulizumab was found to be non-inferior to eculizumab both in efficacy and safety for the treatment of patients with PNH. Based on these results, ravulizumab was approved by the US FDA on 21 December 2018 and is currently under regulatory review in both the European Union and Japan.

scholarly journals Differentiation between the Regulatory paths placed on Mouthwashes in the US and EU

2018 ◽  
Vol 6 (2) ◽  
pp. 8-13
Author(s):  
Philip Saddik ◽  
John Pappan
Keyword(s):  
United States ◽  
The United States ◽  
The European Union ◽  
Oral Diseases ◽  
External Appearance ◽  
Regulatory Systems ◽  
The Us ◽  
United States Food ◽  
States Food ◽  
Therapeutic Properties

Regulating oral rinses has been and still is a topic of debate and confusion. Oral rinses are products that are mainly used for cleaning, perfuming and changing the appearance of the teeth, which in turn improves the individual’s external appearance. Adding medicinal ingredients to these rinses, it can then be used for the elimination and/or prevention of some oral diseases, an example being gingivitis. The United States Food and Drug Administration placed guidelines which state that mouthwashes with possible therapeutic properties should be registered as drugs rather than cosmetics. Meanwhile, on a different continent, Germany along with the other members of the European Union decided not to categorize mouthwashes as drugs, but rather as cosmetics, using its sole purpose of cleaning and beautifying the teeth as the excuse. The following research will thoroughly differentiate between the diverse regulatory systems forced upon mouthwashes across the two countries—the United States and Germany.

Implementation of Question-based Review in support of Quality by Design streamlining the US FDA’s review process

2018 ◽  
Vol 14 (3) ◽  
pp. 129-134
Author(s):  
Alisha Desai ◽  
Jayanta Kumar Maji ◽  
Kanhoba Walavalkar ◽  
Priti J Mehta
Keyword(s):  
Quality By Design ◽  
Review Process ◽  
Critical Material ◽  
Technical Requirements ◽  
The Us ◽  
Product Profile ◽  
United States Food ◽  
Critical Material Attributes ◽  
States Food ◽  
Us Fda

Question-based Review (QbR) is a format proposed by United States Food and Drug Administration (US FDA) enhancing the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use's Common Technical Document (ICH CTD) format to streamline the submission process. It is a question–answer format applied to Quality Overall Summary section of the submission. The format includes putting up questions under every section, so the applicant can submit precise and accurate data for approval of the respective application. The QbR format can be applied to NDA, ANDA, and Type II DMF applications. The companion document available with Manual of Policy and Procedures 5015.10 (MaPP 5015.10) allows the reviewer to inspect the critical information in the data provided. It encourages applicants to encompass Quality by Design (QbD) in their development process. QbR gives a structure through which the data collected by applying QbD can be presented. For effective application of QbR format, the submission should be backed with thorough scientific knowledge, risk assessment data, and data integrity. The questions asked compel the applicant to provide justification for the various decisions made in the development phase. Also, questions regarding quality target product profile, critical quality attributes, critical material attributes, critical process parameters and design of experiment are covered under the QbR format. MaPP 5015.10 finalized by US FDA in 2014 clarifies the concept of QbR. There is MicroQbR available which includes questions confirming the sterility of the product. QbR is a step towards speeding up the review process with an intention to motivate the applicants to implement QbD to the project.

An audit of Black Box Warnings (BBWs) in the United States Food and Drug Administration (US-FDA) database - a five-year analysis

2021 ◽  
Vol 16 ◽  
Author(s):  
Debdipta Bose ◽  
Nithya Gogtay ◽  
Tejusv Goel ◽  
Mahanjit Konwar
Keyword(s):  
The United States ◽  
Black Box ◽  
Primary Objective ◽  
Molecular Entity ◽  
Therapeutic Class ◽  
The Us ◽  
United States Food ◽  
Black Box Warnings ◽  
States Food ◽  
Us Fda

Background: The black-box warning (BBW) is the most serious warning that US-FDA can ask for on a drug’s labelling. BBWs represent key safety concerns uncovered either during dossier review or post-approval. We have conducted the present study with the primary objective of assessing BBWs issued by the US-FDA. Methods: BBW’s were identified on US-FDA’s website from 1st January 2015 to 31st December 2019. Prescribing information was used to identify and characterize BBWs into new and minor/major update on a previous BBW. The therapeutic class of the drug, nature [Biological/New Molecular entity (NME)], formulation type, expected duration of use along with the year of first approval of the molecule with BBWs were evaluated. Results: A total of n = 167 BBWs were issued by FDA of which 53 (31.7%) had major updates, 57(34.1%) had minor updates and 57(34.1%) were new BBWs. A total of 137(82%) of BBWs were with NME’s whereas 30(18%) were with biologics. Drugs for neurology 40(25.5%)had the highest number of BBWs followed by oncology 38(24.2%). Among type of BBWs, cardiovascular risk 31 (15%) were the highest. Conclusion: Practicing physicians need to understand that benefit-risk of a drug is dynamic and keep abreast of new data related to it.

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 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

scholarly journals Bevacizumab use in the frontline, maintenance and recurrent settings for ovarian cancer

2020 ◽  
Vol 16 (7) ◽  
pp. 225-246 ◽  
Author(s):  
Carolyn E Haunschild ◽  
Krishnansu S Tewari
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Double Blind ◽  
Free Survival ◽  
Platinum Sensitive ◽  
The Us ◽  
Us Fda

On 13 June 2018, Genentech, Inc. issued a press release announcing that the US FDA had approved the antiangiogenesis drug, bevacizumab, in combination with chemotherapy for frontline and maintenance therapy for women with newly diagnosed ovarian cancer. Regulatory approval was based on the National Cancer Institute-sponsored Gynecologic Oncology Group (GOG) protocol 0218, the Phase III, randomized, placebo-controlled, double-blind, multi-center and multi-national clinical trial that met its primary end point, progression-free survival. Bevacizumab is now approved in the frontline, platinum-sensitive recurrent and platinum-resistant recurrent settings for epithelial ovarian cancer. This review will address the broad range of clinical trials addressing the efficacy of bevacizumab use in ovarian cancer.

Optimization and validation of a microcolony multiplexed opsonophagocytic killing assay for 15 pneumococcal serotypes

Bioanalysis ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 1003-1020 ◽  
Author(s):  
Katrina M Nolan ◽  
Marie E Bonhomme ◽  
Christina J Schier ◽  
Tina Green ◽  
Joseph M Antonello ◽  
...  
Keyword(s):  
Phase Iii ◽  
Killing Assay ◽  
Assay Performance ◽  
Consensus Values ◽  
The Us ◽  
Functional Antibodies ◽  
Us Fda ◽  
Clinical Trial Program ◽  
Opsonophagocytic Killing ◽  
Validation Experiments

Background: To streamline and improve throughput, the agar-based multiplexed opsonophagocytic killing assay (MOPA) was optimized and validated on a microcolony platform for use in the Phase III clinical trial program for V114, an MSD 15-valent pneumococcal conjugate vaccine candidate. Results & methodology: The precision, dilutional linearity and specificity of the microcolony MOPA (mMOPA) were assessed for each serotype in validation experiments. All prespecified acceptance criteria on assay performance were satisfied. Accuracy was assessed by testing 007sp and the US FDA reference panel and comparing to consensus values. The mMOPA produced comparable results to other opsonophagocytic killing assays/MOPAs. Conclusion: The mMOPA is suitable for measuring functional antibodies in adult and pediatric samples. Benefits include throughput, reduced analyst-to-analyst variability and automation potential.

Improving immune-related adverse event management in a thoracic clinic.

2017 ◽  
Vol 35 (8_suppl) ◽  
pp. 74-74
Author(s):  
Meghan Shea ◽  
Deepa Rangachari ◽  
Daniel Botelho Costa ◽  
Aya Sato-DiLorenzo ◽  
Jessica A. Zerillo
Keyword(s):  
Adverse Events ◽  
Response Rate ◽  
Package Insert ◽  
Retrospective Chart Review ◽  
High Response Rate ◽  
Event Management ◽  
Metastatic Nsclc ◽  
United States Food ◽  
States Food ◽  
Us Fda

74 Background: Widespread use of immunotherapeutic agents has transformed the profile of adverse events associated with systemic cancer therapy. Management of immune-related adverse events (IRAEs) is contingent upon grading severity using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Nivolumab and Pembrolizumab were recently approved for metastatic non-small cell lung cancer (NSCLC). United States Food and Drug Administration (US FDA)-approved package label inserts provide guidance on IRAE management and are predicated on CTCAE grade, including when to discontinue drug. Currently, clinicians in the thoracic oncology group are documenting CTCAE grade of IRAEs infrequently, and management is varied. Methods: A retrospective chart review of baseline data revealed 45 patients (8 on Pembrolizumab, 37 on Nivolumab) who initiated immunotherapy for metastatic NSCLC between March 2015 and August 2016. A team of clinicians developed a process map from diagnosis of IRAE to initiation of toxicity management. Physicians were surveyed. The team’s aim is by February 1, 2017, at least 50% of patients who develop an IRAE on immunotherapy for metastatic NSCLC have documentation of toxicity grade using the CTCAE criteria. Results: The physician survey response rate was 12 of 16 (75%). Physicians reported not using grade to guide management of IRAEs over two thirds (67%) of the time. Time to look up CTCAE criteria and knowing that grade is needed ranked as the top barriers. At baseline, 18 of 45 (40%) patients had 22 IRAEs, of which 6 IRAEs (27%) had grading documented; all graded IRAEs (100%) were managed according to guidelines in the drug-specific package insert. IRAEs included hypothyroidism, pneumonitis, hepatitis, dermatitis, adrenal insufficiency, colitis, and encephalitis. Conclusions: Education on toxicity grading and ease of accessibility to information regarding management of IRAEs are needed. Because clinicians were engaged, a survey to evaluate the current process succeeded with a high response rate. At baseline, there are significant gaps and variability in current practice. Interventions are underway to standardize documentation of grade and management of patients experiencing IRAEs.

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