Applied Clinical Research, Clinical Trials and Regulatory Affairs - Volume 7, Issue 3, 2020

Ranitidine is a well known H2 blocker antihistaminic drug used for symptomatic relief of heartburn, indigestion, acid indigestion, peptic ulcer and hyperacidity. However, On 13th September 2019, the United States Food and Drug Administration (USFDA) has given an alerting statement regarding the presence of nitrosamine impurity called N-nitrosodimethylamine (NDMA) in ranitidine containing products. Recently, some pharmaceutical companies have also recalled their ranitidine containing products from the market. Thus, there is a need to understand about these impurities in ranitidine containing products. The first part of this article highlights the mechanism of action of ranitidine in established therapeutic indications along with its adverse drug reactions and contraindications. Further, the introduction of genotoxic impurities in pharmaceutical products along with its types and mechanism of toxicity of ranitidine containing genotoxic impurity have been discussed.

Background: The CIS region has a potential market for India. The registration of the drug products in CIS regions is a challenging task because these countries have no harmonized regulatory organization. The CIS region includes 12 countries such as Russia, Kyrgyzstan, Ukraine, Uzbekistan, Kazakhstan, Tajikistan, Turkmenistan, Armenia, Azerbaijan, Belarus, Georgia and Moldova, which require different regulatory guidelines for medicinal product registration as per their FDA guidelines. The different guidelines for the same region become a challenging task for the manufacturer and exporter. The registration of the same product for different countries of CIS is not possible with the same dossier due to the lack of their regulatory harmonization. These countries obey their country-specific dossier format, so to target these market manufacturers and exporters needs to submit different dossier documents for different countries. But Ukraine and Kazakhstan have harmonization and it varies in Uzbekistan and Tajikistan. Ukraine and Kazakhstan are also imposing strict rules and expecting USFDA level documents for approval. Conclusion: The overall conclusion is that harmonization in CIS is highly imbalanced, which affects both time and cost for product registration. Harmonization is the need of the era for easy product registration, and it will be beneficial for the manufacturer, regulator, importer, exporter, and to access medicines of high public health value.

The nutraceutical industry has three main segments, including herbal/- natural products, dietary supplements and functional foods. The dietary supplements market is preliminarily driven by the paradigm shift towards preventive health management practices, amid rising healthcare costs and increasing burden of lifestyle diseases. Rise in healthcare expenditure, increased usage of nutraceuticals product as a substitute to prescription and OTC drugs and augmented demand for the nutritional diet are the major factors driving the global nutraceuticals market. Many individual laws were devised to govern its manufacturing and sale. However, increasing regulatory formalities from multiple agencies and laws, complicate the development, testing and marketing of these substances and hamper the growth of the nutraceutical market. Globally, the regulatory authorities are aware of the changing needs of consumers and proactively protect consumers by amending existing laws to accommodate changes. Market entry requirements of nutraceuticals, functional foods and supplements vary from country to country. The global regulatory guidelines aim at regulating various aspects of the nutraceutical and dietary supplements market, focusing on its manufacture, testing, labeling, sale and registration to assure safety and quality of the product. The major change that was introduced was the ban on marketing Nutraceuticals as medicinal products. This review has been performed to provide a comprehensive understanding of the global regulatory requirements with critical analysis of the Indian regulatory guidelines to explore the lacunae and suggest the need of further amendments in the form of recommendations that can be incorporated into regulatory body guidelines to make it more competitive for national & international trade.

In pharmaceuticals, raw data management is a tedious process that comprises of obtaining the data, affirming the validity, and preserving the required data to make certain of the quality, accuracy, and timeliness of the one who is using the data. Raw data management makes processing, validation, and other essential functions simpler and less time intensive. It provides actual information, i.e., the information which has not undergone any processing either manually or through an automated system. Raw data are managed by looking into integrity issues, such as document falsification, failure to provide adequate controls, and taking appropriate measures for its prevention. Also, access to the computer system should be restricted to authorized personnel only. There should be shared just-read client accounts that will stop the sharing of important data to personnel other than the authorized one. Prevention and management include training, good documentation practice, self-inspection, management strategy, and global corrective and preventive actions. Also, a good moral practice should be taught to the employees who are into documentation work.

Poor aqueous solubility, oral bioavailability, inter, and inter-subject variability, and physical stability have always been a concern for pharmaceutical formulation scientists while formulating an oral dosage form. Self-Emulsifying Drug Delivery System (SEDDS) is a promising new approach to mitigating those potential problems. The main advantages of SEDDS are that it increases the solubility and decreases the bio-degradation of lipophilic drugs. Mostly BCS II & IV Class drugs are preferable. SEDDS is an admixture of drugs, oil, surfactants, cosolvents, and stabilizers. With little energy input, they form (o/w) microemulsion within the G.I. lumen. The present review discusses the various formulations of SEDDS, selection criteria for surfactants, oils, Patentable SEDDS dosage forms, solidification technique, characterization, and future approaches.

Background: The outlook on “Nano-materials, products, medicine and technology' lacks a consensus on the definition to be considered by regulatory bodies all over the world. Engineered nanoparticles, the formulated products containing nanomaterials, are not subject to any precise regulation pertaining to production, handling and labeling till now. Also, nano medicines holding an immense potential involved in treatment and diagnosis with emerging research, yet, lag behind with unnoticed concerns regarding their safety and toxicity. Therefore, a regulatory framework focused on specific guidelines for products with the application of nanotechnology is being designed for extending the immense benefits of nanomedicines to humanity. Regulatory bodies have taken the forefront in dealing with the risks associated with nanomedicines, including the United States Environment Protection Agency (EPA) and the US Food and Drug Administration (USFDA), and the Health and Consumer Protection Directorate of the European Commission (EC). Objective: The study aimed to depict the current status and suggest future perspectives of nanomedicine, by compiling the guidance of different regulatory bodies, thereby, eliminating the vagueness of nanotechnology in regulatory terms. Conclusion: Ambiguity continues to prevail considering the regulations and safety of nanomaterials. Therefore, it becomes vital to facilitate the harmonization of assessment practices for nanomaterials with a unanimous opinion. On global level, OECD and its Working Party are currently dealing with manufactured nanomaterials.

IVDR is the new regulatory basis for placing IVDs in the market, making them available and putting them into service in the European market. EU IVDR regulation is much bigger than the impact of EU IVDD, which is a bold statement to make, considering the significant industry- wide impact as it presents challenges to the manufacturer. Rather, it is largely a revision that contains guidance on how to fulfill the existing IVDD requirements. IVDR focused on the IVD-specific provisions therein regarding classification, performance evaluations, clinical data, conformity assessments and notified bodies. IVDR presents enormous change to the IVD industry, not only because it needs a significant change in technical documentation and Quality management system, but also because it changes the relationship with the economic operator and their responsibilities.

Background: Cesarean section (CS) done before the onset of labor is called an elective and done during labor is called an emergency CS. During labor, CS may be needed in early(1st) or late(2nd) stages. Earlier studies have shown more maternal and fetal complications when a cesarean is done for the first time in the late stages. Objective: Our objective was to find out whether the maternal and fetal outcomes differ when primary CS is done in the first stage of labor compared to the second stage of labor for various indications and how. Methods: This was a retrospective observational study on women who underwent primary CS during active labor and to link the maternal and fetal outcomes related to the stages of labor. The study population was patients admitted to the Labor ward of Saqr hospital, Ras Al Khaimah, UAE, between 1st January 2017 till 31st December 2017, but had to undergo primary CS during labor for various indications at 1st and 2nd stages of labor. Data was collected from maternal and neonatal electronic case records. Results: A total of 135 case records were studied. Most cesarean sections were in the early stage of labor. The most common indications were fetal distress and prolonged labor. The maternal and fetal complications were higher in 2nd stage of labor than in 1st stage which includes uterine atonia (p=.001), postpartum hemorrhage (p=.006), postoperative hematuria(RR=3.46), problems with breastfeeding (p=0.001) and fetal injuries (p<.001). Conclusion: Primary CS in late labor is associated with increased maternal and neonatal complications compared to CS in early labor.