Recent drug regulatory affair and CTD module progress review for submission of pharmaceuticals product

Regulatory Affairs (RA), also known as government affairs, is a relatively new profession that arose from governments' desire to protect public health by regulating the safety and efficacy of products such as pharmaceuticals, medical devices, pesticides, veterinary medicines, cosmetics, agrochemicals, and complementary medicines. Pharmaceutical regulatory affairs is concerned with the registration of pharmaceutical goods. All regulatory elements and guidelines connected to product filing are summarized in this evaluation. This study covers the whole CTD and eCTD submission process, as well as the modules that go with it. It also focuses on the key regulatory bodies across the world. Various roles of DRA departments, drug regulatory affairs professionals, the importance of drug affairs in pharmacy curriculum, emerging trends affecting regulatory strategy, regulatory affairs in product management, clinical trials, R&D and the drug approval process in the US, EU, and ROW market trends are discussed.

A model-guided pipeline for drug cardiotoxicity screening with human stem-cell derived cardiomyocytes

ABSTRACTNew therapeutic compounds go through a preclinical drug cardiotoxicity screening process that is overly conservative and provides limited mechanistic insight, leading to the misclassification of potentially beneficial drugs as proarrhythmic. There is a need to develop a screening paradigm that maintains this high sensitivity, while ensuring non-cardiotoxic compounds pass this phase of the drug approval process. In this study, we develop an in vitro-in silico pipeline using human induced stem-cell derived cardiomyocytes (iPSC-CMs) to address this problem. The pipeline includes a model-guided optimization that produces a voltage-clamp (VC) protocol to determine drug block of seven cardiac ion channels. Such VC data, along with action potential (AP) recordings, were acquired from iPSC-CMs before and after treatment with a control solution or a low-, intermediate-, or high-risk drug. We identified significant AP prolongation (a proarrhythmia indicator) in two high-risk drugs and, from the VC data, determined strong ion channel blocks that led to the AP changes. The VC data also uncovered an undocumented funny current (If) block by quinine, which we confirmed with experiments using a HEK-293 expression line. We present a new approach to cardiotoxicity screening that simultaneously evaluates proarrhythmia risk (e.g. AP prolongation) and mechanism (e.g. channel block) from iPSC-CMs.

QPHAR: quantitative pharmacophore activity relationship: method and validation

QSAR methods are widely applied in the drug discovery process, both in the hit‐to‐lead and lead optimization phase, as well as in the drug-approval process. Most QSAR algorithms are limited to using molecules as input and disregard pharmacophores or pharmacophoric features entirely. However, due to the high level of abstraction, pharmacophore representations provide some advantageous properties for building quantitative SAR models. The abstract depiction of molecular interactions avoids a bias towards overrepresented functional groups in small datasets. Furthermore, a well‐crafted quantitative pharmacophore model can generalise to underrepresented or even missing molecular features in the training set by using pharmacophoric interaction patterns only. This paper presents a novel method to construct quantitative pharmacophore models and demonstrates its applicability and robustness on more than 250 diverse datasets. fivefold cross-validation on these datasets with default settings yielded an average RMSE of 0.62, with an average standard deviation of 0.18. Additional cross-validation studies on datasets with 15–20 training samples showed that robust quantitative pharmacophore models could be obtained. These low requirements for dataset sizes render quantitative pharmacophores a viable go-tomethod for medicinal chemists, especially in the lead-optimisation stage of drug discovery projects.

Regulatory advances and prospects of variation filing for the registered parenteral products in USA and Europe

Drug Regulatory Affairs (DRA) is a vital unit in a pharmaceutical company. It is concern about the healthcare product lifecycle, it provide strategic, tactical and operational direction and support for working within regulations to expedite the development and delivery of safety and efficacy in pharmaceuticals, veterinary medicines, medical devices, cosmetics and complementary medicines, healthcare products to individuals around the world. Regulatory affairs (RA) professionals are employed in pharmaceutical industry, government, academic research and clinical institutions. As India is growing very rapidly in pharmaceutical sector, there is a need of regulatory affairs professionals to cater the current needs of industries for the global competition. Regulatory affairs professionals are the link between pharmaceutical industries and worldwide regulatory agencies. A regulatory affair is a somewhat new profession which has developed from the desire of governments to defend public health. Substantial documentation and data are required in these types of submissions, resulting in large, complex applications. Today 35 member countries along with 11 candidate countries and 4 international agencies have joined together to create the Pharmaceutical Inspection Cooperation Scheme (PIC/S) to promote a globally accepted GMP. Current constrain of Regulatory Affairs reveals diverse countries need to follow different regulatory requirements for marketing authorization Application (MAA) approval of new drugs. In this present exertion, study expresses the drug approval process and regulatory requirements according to US Food and Drug Administration (UDFDA), European Medical Agency (EMA) and Central Drug Standard Control Organization (CDSCO).

Pharmacovigilance in generic Indian pharmaceutical industries - Need of the moment

Introduction: The pharmacovigilance department is liable for monitoring the safety of medicines during clinical trials and normal clinical use. The necessity of the pharmacovigilance department is an utmost requirement for effective regulations of the drug approval process and conscious pre and post-approval vigilance of the undesired effects, especially in India. Methods: In the light of the regulatory notification GSR 287(E) dated on 8th march 2016 by CDCSO, it has become clear that it is necessary to take measures to set up and improve the operation of the pharmacovigilance of medicinal products for human use in pharmaceutical companies. Results: The regulators have also developed and posted Guidance document for marketing authorization holders (MAH) for Indian marketers and made clear that the MAH should be responsible for continuously monitoring the safety of its medicinal products for human use, for updating the health authorities of any changes related to the drug, and for ensuring that the product information is kept up-to-date. MAH should record all suspected adverse reactions occurring in the country, and which are brought to their attention spontaneously by the patients or their health care, or occurring in the context of the post-authorization study. Conclusions: According to the Regulatory Guidance document, MAH is also responsible for the submission of the information on suspected adverse reactions of a newly approved drug or applicable product, in form of periodic safety update reports (PSURs), to the competent authorities.

QPhAR – Quantitative Pharmacophore Activity Relationship: Method and Validation

QSAR methods are widely applied in the drug discovery process, both in the hit‑to‑lead and lead optimization phase, as well as in the drug-approval process. Most QSAR algorithms are limited to using molecules as input and disregard pharmacophores or pharmacophoric features entirely. However, due to the high level of abstraction, pharmacophore representations provide some advantageous properties for building quantitative SAR models. The abstract depiction of molecular interactions avoids a bias towards overrepresented functional groups in small datasets. Furthermore, a well‑crafted quantitative pharmacophore model can generalise to underrepresented or even missing molecular features in the training set by using pharmacophoric interaction patterns only. This paper presents a novel method to construct quantitative pharmacophore models and demonstrates its applicability and robustness on more than 250 diverse datasets. 5‑fold cross-validation on these datasets with default settings yielded an average RMSE of 0.62, with an average standard deviation of 0.18. Additional cross-validation studies on datasets with 15-20 training samples showed that robust quantitative pharmacophore models could be obtained. These low requirements for dataset sizes renders quantitative pharmacophores a viable go-to method for medicinal chemists, especially in the lead-optimisation stage of drug discovery projects.

Regulatory Approval process for marketing drug in Japan

For the development of new drug, it requires a greater amount of research work in chemistry, Manufacturing, control, Preclinical and clinical trials. The drug approval process in all regulatory market carrying responsibilities on multiple factors such as data, safety, efficacy to public health in a country. Current constrain of affairs reveals diverse countries need to follow different regulatory requirements for Regulatory approval process for marketing drug in the different regulatory market of the country to ensure safety and efficacy of the product. In order to conduct a regulatory process for approval of a drug, every country has their unique regulation, guidelines, legislation and respective regulatory authority. Japan has its own regulatory authority for drug and medical device called the Ministry of Health, Labour, and Welfare (MHLW), Pharmaceuticals and Medical Devices Agency (PMDA), respectively. In the Japan Ministry of Health, Labour, and Welfare are overseeing the approval procedure of New drug, Generic Drug and Orphan Drug also. In that regard, the Drug Approval process followed in Japan ensures that every company has adhered to specific guideline available in their respective website. The drug comes to market with safety, efficacy to enhance the health of people in Japan by scrutinised process. It results into the longevity of human, which is so apparent in their demographic chart of Japan's Population.