Applied Clinical Research, Clinical Trials and Regulatory Affairs - Volume 4, Issue 3, 2017

Background: The Government of India regulates medical devices through a specialized division called, Medical Device and Diagnostics Division, CDSCO, Min of Health and Family Welfare. Earlier, only 14 categories of Medical Devices, called Notified Devices were regulated under CLAA scheme for the purpose Manufacture, Import, Sale and Distribution. On 17th October 2016, a draft of rules, called Medical Device Rules, was published by Ministry of Health and Family Welfare, in Official Gazette, for feedback from industry. Objective: In this paper we would examine the provisions for import of Medical Devices under CLAA scheme and Medical Device Rules, 2017 and make easier to grasp the regulatory system of India for any manufacturer who wishes to enter Indian Market. Discussion: After due consideration, the Medical Device Rules, 2017 were passed and set for implementation by 1st January 2018. This will create a separate registration and oversight system for drugs and medical devices. Drug Controller General of India would remain the Licensing Authority for Import of devices under the new system. Indian Medical Device Industry is primarily import oriented. Indian Market presently offers tremendous opportunities for high-end sophisticated device manufacturers as most of the high end innovative products are imported into the country. The import of medical devices for the year 2016, stood at $208,230.65 million.

Background: India presents a peculiar case for Drug Eluting Stents (DES). 85% of India's stent need is met through imports which enjoy perception premium in terms of quality. Recently, drug eluting stents' prices were capped to INR 30,000 in India by National Pharmaceutical Pricing Authority (NPPA) of DES to curb soaring high prices. Indian Market offers tremendous opportunities for stent makers. The total market for stents in India is estimated to be of US$ 531 mn by 2016 end and is expected to expand at a CAGR of 14.0% from 2016-2026) [1]. Objective: This paper attempts to study and compare marketing authorization provisions and regulatory standards that need to be met to obtain marketing approval for Drug Eluting Stents in the three regions and provide recommendations for Indian regulatory system. Discussion: Regulatory authorities of developed countries outline their data expectation in the form of non-binding guidance document for industry; however, there are no such equivalent documents in India. Technical data ranging from specification of "stent platform " "eluting drug " and the "finished product " is furnished to the Regulatory authority prior to grant of marketing authorization. Data in application include both Clinical and Non-Clinical (Bench Tests) information obtained during the course of device development. In USA, a Premarket Application (PMA) should be submitted to FDA. In EU, an application dossier is to be submitted to the Competent Authority and in India marketing authorization application is to be made to the CDSCO. Regulatory authorities of developed countries outline their data expectation in the form of non-binding guidance document for industry however, there are no such equivalent documents in India. Conclusion: This article enlists and provides a comparative grid of Regulatory requirements of Drug Eluting Stents in the said regions. Any organization involved in regulatory affairs of DES could use this article as point of reference on the subject.

Background: This paper expands on our initial research published in this journal in 2014 which analyzed global trends in biopharmaceutical R clinical trials (BPCT) covering the period 2007 – 2012. In this paper, we have built on this work and used an enhanced and improved methodology (analysis of the Phase II and Phase III BPCT data from ClinicalTrials.gov clinical trial registry with the number of active, rather than just the newly added, clinical trial sites utilized as a surrogate of BPCT activity) to analyze geographic participation of countries and regions in BPCTs during the period 2009-2014. Discussion: Our data demonstrate that the developed clinical BPCT markets North America and Western Europe have been successful to reduce, and to a certain degree reverse, loss of market share to the emerging markets, and keep the market share of developed markets well above the 70% mark. While almost all emerging markets lost market share at a regional level, there were two regional outliers. The first being Central and Eastern Europe (CEE), which as a region managed to protect its market share position amidst the developed markets offensive. In terms of patient accessibility to clinical trials (population-adjusted number of BPCT sites), core Central Europe outperformed Western Europe, and some countries (Bulgaria, Hungary, Czech Republic) also exceeded levels in North America. The other outlier on the opposite end of the spectrum is MENA1 (Middle East and North Africa – excluding Israel), which contributes almost 2% of the global spend on pharmaceuticals, but attracted less than 0.2% of the BPCTs market share. Population-adjusted accessibility to clinical trials of novel compounds in MENA is 200x below US levels, and more than 20x below global average. Conclusion: Patient accessibility to clinical trials in the developed markets is roughly 20x higher than in a majority of the developing markets, however patient accessibility to BPCTs in several countries in CEE, as well as Israel, exceeds the US levels. Our data also demonstrate substantial imbalance between participation in development of new products (expressed as BPCT market share) and consumption of marketed pharmaceuticals (expressed as market share of pharmaceutical sales) across several emerging markets, most notably MENA. Moreover, this strong consumption bias is further increasing over time across a majority of emerging markets, driven by low (and declining across the majority of the emerging markets) BPCT market share. This contrasts the rapid growth of pharmaceutical sales across a majority of the emerging markets, significantly exceeding the rate of growth in the developed countries.

Background: Over the past decade, there has been great development arising in the field of Molecular imaging and Nuclear medicine using innovative Radiopharmaceuticals. The Radiotherapy practices are also expanding due to increasing number of Cancer cases and technological advances. Indian market is also emerging as a foremost country to carry out research for a new drug. There is a need for the implementation of strict guidelines to assess the quality, safety, and efficacy of Radiopharmaceuticals. Discussion: Radiopharmaceuticals have proven its therapeutic potential but it still comes in Schedule K of Drugs & Cosmetic Act 1940 and the rules frames there under. There is a need to provide it a status of the drug. This review aims to highlight the current regulatory challenges faced by Radiopharmaceuticals regarding various issues. Conclusion: These unique issues intensify the concern for stipulated guidelines for conducting preclinical studies, clinical trials, bioavailability and bioequivalence studies of radiopharmaceuticals. It helps in drafting the uniform regulatory framework with respect to the radiopharmaceuticals which are accepted globally by the investigator.

Background: Methamphetamine (METH) dependence becomes the major public health concern for many countries. METH is an abusive stimulant with various psychophysiological effects to its abusers. METH activates the human's brain reward circuitry and addiction, by increasing dopamine (DA) and serotonin (5-HT) levels in the synaptic cleft. Objective: We investigated allelic variants of 5-HTTLPR, 5-HT1A C(-1019)G, 5-HT2A (102 T/C), and DRD2 Taq IA gene polymorphisms. Methods: Subjects were recruited and met the DSM-IV criteria of METH dependence. They were screened with Diagnostic Interview for Genetic Study (DIGS), Family Interview for Genetic Study (FIGS), and a short research questionnaire. Blood samples were collected, and DNA was extracted from leukocytes and PCR-amplified. The PCR products were then digested with enzymes: Hpy CH4IV, MspI, and Taq I restriction enzyme, respectively for 5-HT1A C(-1019)G, 5-HT2A (102 T/C), and DRD2 Taq IA. The genotypes were assigned on agarose gel size fractionation and allele identification. Results: The results indicated that METH-dependent patients were likely to be poly-substance abusers. Genetic results showed that there were no differences between genetic variation of 5-HTTLPR, 5-HT1A C(-1019)G, and DRD2 Taq IA gene polymorphisms and METH dependence. For 5-HT2A 102T/C, T/C genotype was found to be significantly higher in METHdependent patients compared to healthy controls. Additionally, there was a significant difference for T allele of 5-HT2A 102T/C in METH-dependent patients with comorbidity of three prominent psychotic features: METH-induced psychosis, suicidal behaviors, and depressive symptoms. Conclusion: These results suggest that the METH dependence, psychiatric comorbidity, and genetic variation can pose a challenge in the treatment of METH-dependent patients.