Applied Clinical Research, Clinical Trials and Regulatory Affairs - Volume 7, Issue 1, 2020

Periodic safety update report (PSUR) is now known as the Periodic Benefit-Risk Evaluation Report (PBRER). In July 2012, as per the new European Legislation, 16 Good Pharmacovigilance Practices (GVP) modules came into effect by replacing Vol 9A guidelines. GVP module VII provides the guidance for the preparation, submission and assessment of PSURs. There are twice as many sections to the new PSUR as compared to ICH E2C (R1) document and Volume 9A PSUR guidelines. The new legislation mainly focuses on benefit-risk assessment of medicinal product and promises much more, but after more than 6 years, how much new lesiglation is able to deliver is still unclear. In the literature, various articles have been published regarding the new Legislation module VII but none of them have highlighted the differences between old and new Legislation, How successful are we? What challenges are we facing? Understanding of all these points is the need of the hour for Pharmacovigilance audience which will be helpful to implement the Pharmacovigilance (PV) in a more efficient and effective way. Thus, in this article, we have explained the differences between new and old legislation and when they come into play. Finally, this article provides a brief examination of current challenges and future perspectives of periodic safety update reporting.

Background: Biological products are the chemicals in the form of medicines that are prepared from the living cells through highly intricate manufacturing techniques that should be handled and managed under favorable conditions. The regulation of the biosimilar products consists of significant challenges, since they are part of the growing sector of the pharmaceutical industry and normally used by human beings. The regulatory framework and the technical requirements of the US biosimilars program involve a stepwise approach that relies heavily on analytical methods to demonstrate through a “totality of the evidence” that a proposed product is biosimilar to its reference product. By integrating analytical, pharmacological, and clinical data, each of which has limitations, a high level of confidence can be reached regarding clinical performance. The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the health reform (Affordable Care Act). Objective: The current manuscript will provide the information regarding the regulation of Biosimilars products with the detail of biosimilar USER fees structure and the list of approved biosimilar by FDA from 2015- 2018. Conclusion: Research is continually developing more biological products that will help treat medical conditions or add some innovation to the existing treatment options. Biosimilars and reference products are generated in the living cells and require trained expertise as well as technology for biologics being usually highly effective compared to small molecule drugs. These are usually specific against the respective target, which generally produces lesser side effects and low toxicity. FDA’s regulatory authority for the approval of biologics is under PHS (Public Health Service Act) which are also suggested to regulate under the Federal Food, Drug and Cosmetics Act (FD). Biosimilars can help expand access to high-quality treatment options for doctors and patients, as well as reduce costs for the healthcare system.

Haemovigilance is an organized and effective process of monitoring, identifying, reporting, investigating and analyzing adverse events and reactions in case of blood transfusion and during the manufacturing process of blood products. This system ensures the quality and safety aspects of blood transfusion, that bring out corrective and preventing actions and advancement in the transfusion system. Nowadays, most of the developed countries have implemented Haemovigilance in order to monitor adverse reactions and events associated with blood donation and transfusion. This review article is about steps that are required to be taken for the implementation of Haemovigilance on a National level as an Indian perspective.

Background: Literature review suggested that regulatory guidelines should be harmonized for better processing of applications and for the upliftment of the regulatory field. Therefore it was thought worthwhile to compare the guidelines for countries where there is requirement of harmonization. Kosovo, Ukraine and Serbia were selected because of being European countries and still they are not a part of EU. Introduction: Kosovo, Ukraine and Serbia are small countries of Europe but they are not members of European Union. They have their own guidelines for the submission of MAA for marketing of pharmaceuticals and medical devices. They are trying to obtain the EU membership and therefore it was worthwhile to compare the guidelines of these countries. Methods: The registration process of pharmaceuticals in Kosovo, Ukraine and Serbia was studied throughly. Along with it, the guidelines for European Union were also studied. A comparison of guidelines of all the three countries with the guidelines of European Union for pharmaceuticals was carried out. Results: The comparison of guidelines showed that there are still some changes needed in the guidelines of Kosovo, Ukraine and Serbia before they can merge with the guidelines of European Union. Some of the points in the guidelines are very different from the guidelines of EU. Conclusion: It was worthwhile to study the regulatory requirements of pharmaceuticals in Non- European Union Member States such as Kosovo, Ukraine and Serbia.

Background: Eperisone hydrochloride possesses short biological half-life due to first pass metabolism resulting in low bioavailability and short duration of response with toxic effects, ultimately limits its utilization for treatment of muscle spasm. Objective: In view of this background, current study was designed for the development of Eperisone hydrochloride-loaded microemulsion and Eperisone hydrochloride-loaded microemulsion based cream for topical delivery and compared it with conventional cream. Methods: Firstly, water-in-oil microemulsion was prepared by spontaneous emulsification method. The concentration of components was found out from existence of microemulsion region by constructing pseudoternary phase diagram. The oil was selected on the basis of drug solubility effect on the drug release, whereas surfactant and cosurfactant were screened on the basis of their efficiency to form microemulsion region. The influence of components on microemulsion formation, drug release capacity, permeation was studied by differential scanning calorimetry, X-ray diffraction, in-vitro release and ex-vivo drug permeation studies respectively. By using microemulsion, the cream was prepared for proving optimum structure for topical application. Microemulsion was evaluated for droplet size, zeta potential, pH, viscosity and conductivity. Besides the cream was characterized for pH, rheology and stability. Permeation of EPE from microemulsion across the rat skin was evaluated and compared with conventional cream. Results: The microemulsion consisting Isopropyl Myristrate/Water/Span 80:Tween 80 (50/8/42% by weight) possessed droplet size of 95.77nm, zeta potential of −5.23 mV with 7.25 pH and conductivity near to zero (<0.05mScm-1). Physical parameters of the cream were satisfactory, also 2.33-fold higher permeation and 1.57-fold higher release observed as compared to conventional cream. Conclusion: It can be concluded that Eperisone hydrochloride-loaded microemulsion and its cream is being effectively used for muscle spasticity by topical route.

Introduction: A randomized clinical trial is known as the best and most effective way to assess the effects of interventions if it is properly planned and implemented. The purpose of this study was to evaluate the quality of clinical trials published in Persian internal journals by Iranian researchers. Methods: In this cross-sectional study, all the clinical trials published by Iranian researchers in the Iranian Journals in 2014, were evaluated according to entry criteria and finally 587 included articles were reviewed and their quality was evaluated by using Consolidated Standards of Reporting Trials (CONSORT) checklist. Results: The results revealed that the mean±SD adherence to the CONSORT checklist’s item in our included articles was 59.61±24.99. The lowest adherence to the items was seen for random allocation (76.1%), description of the sampling method (70.1%) and presenting RCT code registration (60.4%), respectively. The highest adherence was observed for title suitability (96%), appropriate presentation time and place of study (84.2%), a suitable expression of study participants (82.8%) and time duration of the study (82.3%). Conclusion: The adherence to the various items of CONSORT checklist in Iranian Persian language journals was not in satisfactory status. In this regard, the CONSORT checklist needs to be carefully followed for conducting and reporting RCTs by Iranian researchers.

Background: A DMF consists of confidential information, usually related to Chemistry, Manufacturing and Control (CMC) of the drug substance. DMF is prepared and submitted by the pharmaceutical manufacturer solely to the regulatory authority of the respected country where he wants to market. Objective: Compare the regulations of the emerging markets with that of a regulated market and to highlight the stringent requirements imposed by emerging authorities. The similarities and differences of the requirements for filing a DMF in emerging markets are compared against the regulated market. Methods: The method carried out for every single study follows some patterns and certain pathways in order to reach its target. Method begins with scope and objective of regulatory perspective of DMF filing requirements for USA, China, Brazil and Korea. The information was collected from Regulatory authorities, Legislations, Guidelines and Experts opinion. Results: Regulatory requirements for filing a DMF for API registration vary from country to country. Even though a standard ICH-CTD format is available and most widely followed, there are some specific requirements recommended by drug authorities which are mandatory to be provided while filing to that particular country. Conclusion: Based on the current study it is clear that emerging markets possess more stringent requirements for API approval as compared to the regulatory market but the dispute is that the emerging markets do not have harmonized guidelines and are not transparent enough.