A Review on Carcinogenic Impurities Found in Marketed Drugs and Strategies for its Determination by Analytical Methods

2021 ◽  
pp. 159-169
Author(s):  
Amitkumar J. Vyas ◽  
Jayshree P. Godhaniya ◽  
Ajay I. Patel ◽  
Ashok B. Patel ◽  
Nilesh K. Patel ◽  
...  
Keyword(s):  
Analytical Methods ◽  
Raw Materials ◽  
Drug Product ◽  
Pharmaceutical Products ◽  
Carcinogenic Risk ◽  
European Medicines Agency ◽  
International Agency ◽  
Angiotensin Ii Receptor Blocker ◽  
Product Recalls ◽  
Angiotensin Ii Receptor

The control of potentially mutagenic and carcinogenic impurities in pharmaceutical products is key importance in evaluating carcinogenic risk to humans. The recent discovery of nitrosamine impurities in some marketed pharmaceuticals has increased the risk of their mutagenic and carcinogenic potential. According to the International Agency for Research on Cancer (IARC), nitrosamine is the chemical classified as a probable human carcinogen. Nitrosamine impurities are known to be mutagenic and carcinogenic, very small exposure of these impurities can lead to cancer. These impurities may be produced and get incorporated into drug substances or drug products by a reagent, catalyst, solvent, or raw materials used in the process of manufacturing. The presence of nitrosamine impurities in angiotensin II receptor blocker (ARB) drugs containing tetrazole ring has caused worldwide product recalls. The various regulatory authorities have published the press release or notice regarding the control of these impurities with the interim limit. In 2007, the European medicines agency (EMA) suspended the marketing authorization of Viracept, because of the presence of elevated levels of ethyl methane sulfonate, in the drug product. Validated analytical methods are used to identify and quantify these impurities to the trace level at a given interim limit.

scholarly journals Nitrosamines in Drug Substance and Drug Product-A Regulatory Challenge

2020 ◽  
Vol 11 (2) ◽  
pp. 2123-2130
Author(s):  
Prasannakumar P Bhat ◽  
Balamuralidhara V ◽  
Gowrav M P ◽  
Venkatesh M P
Keyword(s):  
Drug Product ◽  
Human Cancer ◽  
Carcinogenic Risk ◽  
Drug Substance ◽  
International Agency ◽  
Angiotensin Receptor ◽  
Synthetic Compound ◽  
Treatment Of Hypertension ◽  
And Control ◽  
Regulatory Challenge

Nitrosamine is the class of synthetic compound which is a potent genotoxic agent and considered as probable plausible human cancer-causing agents by the International Agency for Research on Cancer (IARC).N nitroso mixes are known as the potent carcinogenic and a global worry according to the various authorities and also from ICH M7, Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. Before June 2018, the presence of nitrosamine in the drug substance and also product was not known, however in June 2018, USFDA identified the presence of Nitrosamine impurities in one of the API producers of valsartan which is recognized as NDMA (N-Nitroso dimethylamine). Valsartan is a medication which is utilized for the treatment of hypertension, cardiovascular breakdown and diabetic kidney damage. From that point forward, FDA has discovered that different kinds of nitrosamine mixes, e.g., N-Nitrosodiethylamine (NDEA), are available at unsuitable levels in APIs from various API makers of valsartan and different medications in the ARB class. (Angiotensin receptor blocker). Then the Regulatory Authorities has stepped forward for educating the health care professional, manufacturers and also public about the adverse effect(carcinogenic)of the NDMA and NDEA consumption.

scholarly journals QUALITY BY DESIGN APPROACH: REGULATORY NEED, CURRENT, AND FUTURE PERSPECTIVE

2021 ◽  
pp. 29-35
Author(s):  
AAYUSHI RAJORA ◽  
GURMEET CHHABRA
Keyword(s):  
Quality By Design ◽  
Raw Materials ◽  
Drug Product ◽  
Active Pharmaceutical Ingredient ◽  
Pharmaceutical Products ◽  
Future Perspective ◽  
Development Methodology ◽  
Unit Of Measurement ◽  
The Impact ◽  
Analytical Technology

Quality by design (QbD) is utilized in the event of pharmaceutical processes to create certain predefined product quality. QbD ideas unit of measurement explained in International Conference on Harmonization (ICH) pointers Q8 (R1) (Pharmaceutical development), Q9 (Quality risk management [QRM]), and Q10 (Pharmaceutical quality system). ICH Q8 (R1) guideline defines QbD as “a systematic approach to develop that begins with predefined objectives and emphasizes product and methodology, understanding, and methodology management, supported sound science and QRM.” QbD approach studied the implications of various input variables (e.g. methodology parameters, and materials) of the merchandise development methodology, on the final word product (active pharmaceutical ingredient or drug product). The late QbD approach integrates the principles of QRM, and methodology analytical technology (PAT). QbD combined with methodology analytical technology (PAT) tools modify methodology management and increase assurance that the merchandise quality attributes unit of measurement achieved consistently. An integrated and risk-based approach for review of the merchandise development methodology is also a future need of the QbD plan. Although implementing the QbD approach is not a restrictive demand, restrictive agencies to supply flexibility in their pointers for producing that unit of measurement developed by the QbD approach. Rising trends embody the growing interest in quantifying and managing the impact of raw materials’ attributes variability of methodology and product, what is more, as a result of the event of retrospective QbD approaches in complement to simple QbD. Thus, the QbD approach is also a tool for developing worth effective and quality pharmaceutical products.

Landscape of Combination Therapy – Which Way Forward? Proceedings of the Satellite Symposium Held at the ESH European Meeting on Hypertension and Cardiovascular Protection, 27 April 2012, London

2012 ◽  
Vol 8 (3) ◽  
pp. 192
Author(s):  
Patricia Fonseca ◽  
Anna F Dominiczak ◽  
Stephen Harrap ◽  
◽  
◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Risk ◽  
Combination Therapy ◽  
Enzyme Inhibitor ◽  
Synergistic Effects ◽  
Term Treatment ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Hypertensive Patients ◽  
Long Term Treatment

Early combination therapy is more effective for hypertension control in high-risk patients than monotherapy, and current guidelines recommend the use of either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) for first-line therapy in patients younger than 55 years. Recent evidence shows that ACEIs reduce mortality, whereas ARBs show no apparent benefit despite their blood pressure lowering action. However, it is important to consider which blood pressure parameters should be targeted given that different drugs have distinct effects on key parameters. Remarkably, a high percentage of hypertensive patients whose treatment has brought these parameters within target ranges still remain at high risk of cardiovascular disease due to additional risk factors. Combination therapy with synergistic effects on blood pressure and metabolic control should thus be considered for the long-term treatment of hypertensive patients with co-morbid conditions.

Analytical Methods Practiced to Quantitation of Rifampicin: A Captious Survey

2020 ◽  
Vol 16 ◽  
Author(s):  
Rajendra Muljibhai Kotadiya ◽  
Foram Narottambhai Patel
Keyword(s):  
Thin Layer ◽  
Thin Layer Chromatography ◽  
Analytical Methods ◽  
Bacterial Infections ◽  
High Performance ◽  
Drug Product ◽  
Extensive Literature ◽  
Legionnaires Disease ◽  
Instrumental Methods ◽  
Layer Chromatography

Background: Rifampicin (RIF), also known as rifampin, a bactericidal antibiotic having broad antibacterial activity against various gram-positive and gram-negative bacteria act by inhibiting DNA dependent RNA polymerase. RIF has been administered in different dosage forms like tablets, capsules, injections, oral suspension, powder etc. for the treatment of several types of bacterial infections, including tuberculosis, Mycobacterium avium complex, leprosy and Legionnaires’ disease. Introduction: To ensure the quality, efficacy, safety and effectiveness of RIF drug product, effective and reliable analytical methods are utmost important. To quantify RIF for quality control or pharmacokinetic purposes, alternative analytical methods have been developed along with the official compendial methods. Method: In this review paper, an extensive literature survey was done to gather information on various analytical instrumental methods used so far for RIF. Result: These methods were high-performance liquid chromatography (42%), hyphenated techniques (18%), spectroscopy (15%), high-performance thin-layer chromatography or thin-layer chromatography (7%) and miscellaneous (18%). Conclusion: All these methods were selective and specific for the RIF analysis.

PP469 From Theory To Practice: Which Value Framework Is Applied For Onco-Hematology Therapies In Italy? A 5-year Retrospective Analysis

2020 ◽  
Vol 36 (S1) ◽  
pp. 37-37
Author(s):  
Americo Cicchetti ◽  
Rossella Di Bidino ◽  
Entela Xoxi ◽  
Irene Luccarini ◽  
Alessia Brigido
Keyword(s):  
Real World ◽  
Ad Hoc ◽  
Grey Literature ◽  
National Level ◽  
Pharmaceutical Products ◽  
European Medicines Agency ◽  
The Real ◽  
R Process ◽  
The One ◽  
The Impact

IntroductionDifferent value frameworks (VFs) have been proposed in order to translate available evidence on risk-benefit profiles of new treatments into Pricing & Reimbursement (P&R) decisions. However limited evidence is available on the impact of their implementation. It's relevant to distinguish among VFs proposed by scientific societies and providers, which usually are applicable to all treatments, and VFs elaborated by regulatory agencies and health technology assessment (HTA), which focused on specific therapeutic areas. Such heterogeneity in VFs has significant implications in terms of value dimension considered and criteria adopted to define or support a price decision.MethodsA literature research was conducted to identify already proposed or adopted VF for onco-hematology treatments. Both scientific and grey literature were investigated. Then, an ad hoc data collection was conducted for multiple myeloma; breast, prostate and urothelial cancer; and Non Small Cell Lung Cancer (NSCLC) therapies. Pharmaceutical products authorized by European Medicines Agency from January 2014 till December 2019 were identified. Primary sources of data were European Public Assessment Reports and P&R decision taken by the Italian Medicines Agency (AIFA) till September 2019.ResultsThe analysis allowed to define a taxonomy to distinguish categories of VF relevant to onco-hematological treatments. We identified the “real-world” VF that emerged given past P&R decisions taken at the Italian level. Data was collected both for clinical and economical outcomes/indicators, as well as decisions taken on innovativeness of therapies. Relevant differences emerge between the real world value framework and the one that should be applied given the normative framework of the Italian Health System.ConclusionsThe value framework that emerged from the analysis addressed issues of specific aspects of onco-hematological treatments which emerged during an ad hoc analysis conducted on treatment authorized in the last 5 years. The perspective adopted to elaborate the VF was the one of an HTA agency responsible for P&R decisions at a national level. Furthermore, comparing a real-world value framework with the one based on the general criteria defined by the national legislation, our analysis allowed identification of the most critical point of the current national P&R process in terms ofsustainability of current and future therapies as advance therapies and agnostic-tumor therapies.

scholarly journals Efficacy and Mechanism of Angiotensin II Receptor Blocker Treatment in Experimental Abdominal Aortic Aneurysms

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e49642 ◽  
Author(s):  
Yasunori Iida ◽  
Baohui Xu ◽  
Geoffrey M. Schultz ◽  
Vinca Chow ◽  
Julie J. White ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Receptor Blocker ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Abdominal Aortic
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