Central Drugs Standard Control Organization Research Articles

Assessment of Lung Health Status by Analyzing Cough Sound Using Swaasa Artificial Intelligence Technology

ABSTRACT Introduction: The crucial function of the respiratory system is the facilitation of blood gas exchange process. Spirometry is the diagnostic tool to detect and differentiate obstructive and restrictive respiratory diseases that impair this vital function. The need for a clinical setup, technical expertise, and patient compliance are certain limitations for utilizing spirometry in remote areas. Swaasa® artificial intelligence (AI) platform, which has a Class B manufacturing license from India’s Central Drugs Standard Control Organization, is a validated “software as a medical device,” which aids in screening and diagnosis of respiratory diseases, unbounded by location, equipment and technical expertise. Objectives: The objectives of the study were to determine the “lung health index” and the “pattern of lung health” conditions among nursing students. Materials and Methods: A cross-sectional study was conducted utilizing the Swaasa® AI platform among students of a nursing college in Central Karnataka in June 2023. Based on audiometric analysis of cough sounds, parameters such as underlying respiratory condition, cough count values, and respiratory symptoms experienced, ‘Swaasa’ AI platform derives pattern of respiratory condition (normal/obstructive/restrictive/mixed), ‘Lung Health Index,’ and presence or absence of lung health risk. Data collected in the Swaasa app were downloaded and analyzed using SPSS.v. 20. Results: Lung health risk was present in 58.2% of participants. Abnormal lung pattern was noted in 21.3% of participants (obstructive: 14.8%, restrictive: 2.5%, and mixed pattern: 4.1%). Conclusion: The Swaasa AI platform was utilized in this study to self-test lung health in real time without the need for a clinical setting. A high lung health index was found among 18% of participants. Studies adopting such cough sound analysis involving a larger population from wider geographic areas have to be conducted to detect and monitor respiratory diseases to increase its usage among the medical community in everyday clinical practice and also in remote areas.

A review on the pharmacology of cariprazine and its role in the treatment of negative symptoms of schizophrenia.

Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India's Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-life make cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia.

Prescribing patterns and analyzing the usage of corticosteroid therapy at tertiary care hospital

Corticosteroids are used extensively in treating inflammation. They provide short-term symptomatic relief in abnormalities of conditions like Auto immune diseases, Dermatological and Respiratory diseases. Adverse effects of Corticosteroids include Cushing’s syndrome, Skin atrophy, contact dermatitis, tachyphylaxis, Myelosuppression, Diabetes mellitus, Hypertension, pleural effusion. As per the sources available from the regulatory authority of Central Drugs Standard Control organization, inappropriate use of Corticosteroids is more commonly practiced in India almost all the drugs are prescribed rationally. The Pharmacist can promote better patient care and drug safety. Most of the Physician is recommending the drugs are mostly branded names. Our study suggests provide it in generic names. Clinical Pharmacists in associations with clinicians must play a crucial role in minimizing the problems associated with irrational usage of corticosteriods.

Regulatory requirement for Medical Devices

The safety and regulatory compliance of a widely used medical device have become a growing concern among a significant population. This has raised questions about the assessment of risks, monitoring of adverse drug reactions (ADR), and overall product safety. The efficacy and safety of such medical devices heavily rely on the regulations and guidelines set forth by regulatory agencies (RAs).
 In the pharmaceutical industry, regulatory affairs (RA) professionals play a crucial role in overseeing the lifecycle of healthcare products. They provide strategic, tactical, and operational guidance to ensure compliance with regulations, facilitating the efficient development and delivery of safe and effective healthcare products worldwide. Evaluating adherence to regulations requires a combination of expertise from the business, legal, and pharmaceutical domains.
 Regulatory authorities must thoroughly monitor medical device design, development, and manufacturing processes to guarantee that the products reaching the market are safe and effective. The certification process is intricate, involving multiple steps and the assessment of materials by competent authorities. In the United States, manufacturers must seek marketing authorization from the United States Food and Drug Administration (USFDA) through two primary application types: 510(k) and Pre-Market Application (PMA). In the European Union (EU), national authorities grant permission for the sale of medical devices, employing a third-party compliance system where notified bodies ensure quality assurance pre- and post-approval. In India, the Central Drug Standard Control Organization (CDSCO) licenses devices for sale and import under the CLAA framework.
 Conclusion
 Pharmaceutical regulatory affairs experts play a critical role in ensuring compliance with industry requirements for all pharmaceutical products. This review provides an overview of how medical devices are regulated and monitored in the EU, India, and the USA, emphasizing the importance of regulatory affairs in maintaining the safety and efficacy of healthcare products.

A Review of Herbal Regulations and Approval Process in India and Europe

The main suppliers of herbal plants and medications are India and Europe. People prefer using plants and herbs as remedies over synthetic ones since they have fewer adverse effects. In India, AYUSH, CDSCO (Central Drugs Standard Control Organization), AND D&C Act 1940 & 1945(amendment) all control herbal medications. In India, AYUSH systems have been developed to house almost 8000 herbal medications. While in Europe, the European Medicines Agency (EMA) and the Herbal Medicinal Products Committee (HMPC) are in charge of overseeing herbal medications. The regulation of herbal goods in India and Europe is the subject of this essay.

Regulatory requirements in the preparation CTD and ECTD as Per CDSCO comparison with Brazil

Stringent regulatory standards apply to the creation of Common Technical Documents (CTD) and Electronic Common Technical Documents (eCTD) for regulatory submissions in India, which are overseen by the Central Drugs Standard Control Organization (CDSCO). The essential regulatory considerations affecting the creation of CTD and eCTD submissions in accordance with CDSCO criteria are summarized in this abstract. It emphasizes how crucial adherence to these rules is to ensure the prompt and effective registration of pharmaceutical goods in India. The advantages of eCTD in simplifying the regulatory process are also briefly covered in the abstract, along with the changing environment of electronic submissions. For pharmaceutical businesses seeking market authorisation in India and for regulators striving to maintain the highest standards, understanding and adherence to CDSCO's regulatory requirements are essential.

Development of Pharmacovigilance System in India and Paradigm of Pharmacovigilance Research: An Overview.

The drugs are projected to cure, prevent and treat diseases; however, there are also chances of mild or severe adverse drug reactions (ADRs) in the patients. Pharmacovigilance (PV) enhances the approach to safe medicines and healthcare, but integration into public healthcare remains a challenge in many countries. The Pharmacovigilance Programme of India (PvPI) is a nationwide programme launched by the Ministry of Health and Family Welfare (MoHFW), Government of India, on 14 July 2010. It is currently run by the Indian Pharmacopoeia Commission (IPC). Presently, 567 ADR Monitoring Centres (AMC) are functioning under PvPI across India. The Central Drugs Standard Control Organization (CDSCO), under the Directorate General of Health Services (DGHS), and the Ministry of Health, Family & Welfare (MoHFW) Government of India is the National Regulatory Authority (NRA) of India. This review aims to trace the development of PV in India and its status among the top ADR reporting countries, with a focus on the current status of the studied ADR in different regions in India. Among the top 20 countries enthusiastic about sending ICSR per million population between 2015 and 2020, India shares 2% of the total ICSRs in VigiBase. India is now being recognized as a hub of global clinical trials and clinical research studies. Hence, it is the need of the hour in India to have a dynamic PV network system with an efficient and prudent operation method. Nevertheless, in India, PV programs are at an early stage on par with other countries, and only because of underreporting of ADRs. However, in the future, PvPI may appear as a big dashboard for ADR reporting culture in India as it continuously works hard to improve patients and drug safety.

Challenges in development and management of orphan drugs—a case study of Prussian blue insoluble

Prussian blue insoluble (PB) is an antidote for decorporation of radioactive and non-radioactive isotopes of thallium and cesium. Its dosage in the form of capsules, Radiogardase-Cs, is a United States Food and Drug Administration approved formulation since 2003. In India and many other countries, this drug is not available and in case of requirement it is imported from US or Europe. The author has worked extensively to make PB capsules available in India. The drug was recently approved by the Indian drug regulatory agency, Central Drugs Standard Control Organisation and is now available commercially in India. However this drug needs special attention as it is an orphan drug with limited requirement. The post-approval phase of this drug poses a different set of challenges and the author has highlighted some key issues with probable approaches for post-approval product management.

Alternative biosimilar drugs impact on Global COVID-19 Pandemic and Regulatory approval Repurposed in Emergency periods (2020-2022)

Corona Virus (Covid-19) infection was developed from the SARS-CoV-2 virus. People have infected by the virus in all around the world with moderate issues on the respiratory system. As well the recovery has successful without taken any special treatment. As per the world record, illness and death have the serious medical attention on the chronic diseases; maximum infected people belongs to the diabetes (Type I and Type II), Cardio vascular issues, asthma, respiratory illness, more immunity disorder and cancer etc. In Indian, CDSCO board (Central Drugs Standard Control Organization), Ministry of Health and Family Welfare, India, DBT (Dept. of Biotechnology), Ministry of Science and Technology, Indian council of Medical Research (ICMR) has published the notification to the public section with the NDCT (New Drugs Clinical Trials) rules. In addition, various other rules were applicable for the designing the COVID-19 drugs such as Drugs and Cosmetics Act and Rules, on Similar Biologics with the Regulatory aspects to make the market authorization in India. Biosimilar drug has designing with rules and regulation of COVID-19 repurposed medicines (drugs) were approval in emergency aspects during the COVID-19 infection in India around March 2020 to till date. In this study, we have emphasize the pandemic COVID -19 situation i) biosimilar drugs used in emergency aspects; ii) the list of biosimilar drugs under Govt. of India approval regulatory aspects; iii) the list of biosimilar repurposed drugs doses, time period, sources of the respective drugs and the applications with the successful rate were optimized in the COVID -19 emergencies period.

A descriptive study of new drug approvals during 2017-2021 and disease morbidity and mortality patterns in India.

Studies show the presence of a mismatch between drug research and disease burden. A study conducted in the European Union found that new drug development was restricted to certain diseases. A study of biosimilar approvals in India found that 87% of drugs were for treating noncommunicable diseases. This study aimed to determine the new drugs approved in India from 2017 to 2021 and the top ten causes of morbidity and mortality and detect the presence of any discordance between these. A descriptive study was conducted using data on new drug approvals accessed from the Central Drugs Standard Control Organization website. The top ten causes of mortality and morbidity in India from 2015 to 2019 were identified from the Global Burden of Diseases database. Descriptive statistics were used to compare the drug approvals and the leading diseases. One hundred twenty-six drugs were approved during the study period. Antineoplastic drugs constituted 19.84% of the approvals, antimicrobials 18.25%, and cardiovascular drugs 9.52%. Ischemic heart disease and chronic obstructive pulmonary disease were the two leading causes of morbidity and mortality. Diarrheal diseases, lower respiratory tract infection, and drug-susceptible tuberculosis were among the top ten causes. Ten antibacterials, including four antitubercular drugs, were approved during this period. Two drugs were approved for rare diseases. Our study showed that the drugs approved were largely in line with the prevalent disease burden, and there was no significant discordance observed. Some diseases, such as ischemic stroke/intracranial hemorrhage, require further efforts in bringing forth newer pharmacotherapy options.

ADVERSE DRUG REACTIONS (ADRS) OF CISPLATIN IN PULMONARY CANCER PATIENTS- ONE YEAR PROSPECTIVE STUDY

Background: A cross sectional prospective observational study evaluated the trends and patterns of Adverse drug reactions of cisplatin in pulmonary cancer patients . Methods:Pulmonary cancer patients, who received cisplatin as chemotherapy regimen, were monitored for adverse reactions. New and old diagnosed cases of pulmonary cancer patients belonging to either gender and of all ages, who were receiving cisplatin under any standard regimen, were included for the study. Any ADR due to poisoning, over dosage were excluded from the study. The ADRs were recorded in Central Drugs Standard Control Organization forms. Casuality was assessed by the WHO Casuality Assessment Scale and Naranjos Alograthim. Results:A total number of 98 patients were reported during the study period, wherein a total number of 114 ADR cases were observed.The majority of patients were in the age group of 61-80 (n=45), followed by 41 -60 years (n=41, 41.83%) .Out of the total ADRs, most frequently reported one was vomiting 18 (15.78%) followed by anemia 16 (14.03%), nausea 13(11.40%) and hair loss 12 (10.52 %) which together constituted 51.73 % of the total ADRs. The other commonly encountered ADRs were diarrhea 8 (7.01%), thrombocytopenia 6 (5.26%), constipation 6 (5.26%) neutropenia 5(4.38) and neuropathy 5(4.38%).According to WHO-UMC scale, 37(37.75%) of reports to be certain,33(33.67%) of reports to be possible and 28(28.57%) of reports to be probable where there was no case recorded as unclassified or inaccessible.Naranjos scale which classified 65 (66.32%) to be probable and remaining 33 (33.67%) to be possible. Conclusion:Cisplatin has high potential for adverse effects. There is a need to improve the management of adverse effects. This study also emphasizes the need to improve pharmacovigilance awareness among physicians in order to improve the pharmacovigilance in India.

Future of TABST and LABST in the Indian Pharmacopoeia Monographs A Humane Society International/India Workshop Report

Humane Society International India (HSI India) organized and facilitated a workshop on the ‘Future of Target Animal Batch Safety Test (TABST) and Laboratory Animal Batch Safety Test (LABST) in the Indian Pharmacopoeia (IP) Monographs’. The workshop hosted key Indian regulators from the Indian Pharmacopoeia Commission (IPC) and the Central Drugs Standard Control Organization (CDSCO), industry representatives from the Indian Federation of Animal Health Companies (INFAH), Asian Animal Health Association (AAHA), and international experts representing the European Directorate for the Quality of Medicines (EDQM), the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), and multinational veterinary products manufacturers. The workshop was organized to encourage a bidirectional flow of information and to discuss the deletion of TABST and LABST from the veterinary vaccine monographs in the IP. This workshop was built from the symposium held by Humane Society International on the ‘Global Harmonization of Vaccine Testing Requirements’ held in 2019. This report details the outcomes of the workshop with proposed activities to be taken up as part of the next steps for the elimination or waiving of these tests.

A Review on Approval Process and Regulation of Medical Devices as per US FDA and CDSCO

Regulatory affairs play a significant role in the pharmaceutical industry, it is “the process of gathering, reviewing, and monitoring the existing regulatory environment and creating regulatory plans and gaining a competitive edge for securing regulatory approvals required more than just acquiring facts”. A medical device is a treatment instrument that "does not work on or in the human body in a way that is primarily intended by pharmacological, immunological, or metabolic mechanisms”. In other words, a medical device is essentially any medical product, not a medicine or biological product. By the Drugs and Cosmetics Act, Central Drugs Standard Control Organization (CDSCO) oversees approving drugs, conducting clinical trials, setting standards for drugs, monitoring the quality of drugs imported into the nation, and coordinating the efforts of state drug control organizations by offering professional advice to ensure uniformity in the application of the Drugs and Cosmetics Act. The US Food and Drug Administration (FDA), a single agency, oversees the regulation of a trillion dollars’ worth of goods, or about 25 cents of every dollar spent, including 80 percent of the food supply in the US, all medical devices, and prescription drugs, animal products, cosmetics, and even the production of tobacco products. The FDA's Center for Devices and Radiological Health regulates companies that produce, repackage, re-label, and/or import medical devices sold in the United States (CDRH). Also, CDRH is in charge of overseeing the regulation of lasers, x-ray machines, ultrasound equipment, microwave ovens, and color televisions, among other electronic gadgets that generate radiation for both medical and non-medical purposes. The IMDR, which was published in January 2017 and became effective in January 2018, was produced by the Medical Devices and Diagnostics Division of CDSCO and is a set of structured regulations for medical devices. In February 2020, the "Medical Devices (Amendment) Regulations, 2020" were established, and they became effective in April 2020. The 2020 amendment now includes a new clause called "registration of specific medical equipment."

Fixed dose combinations in India- what a way to go!

Fixed dose combinations (FDCs) are generally considered desirable options in chronic diseases such as tuberculosis, cardiovascular diseases & diabetes, tropical diseases such as malaria & in HIV and in Cancer. FDCs are useful in chronic conditions especially when multiple disorders often co-exist The advantages of the FDC are basically patients compliance, simple dosage schedule, better efficacy, cheaper shipment & packaging activities. The drawbacks of FDCs are (a) Pharmacodynamic mismatch between the two ingredients, one drug having additive/antagonistic effect leading to reduced efficacy or enhanced side effects, (b) Pharmacokinetic disparity having peak efficacy at different time zone, (c) Chemical non compatibility leading to decreased shelf life, (d) Drug interactions due to common metabolizing pathways, and (e) limitations of dose titration of individual ingredients. As per Rule 122 E of Drugs and Cosmetics Act 1940, the FDCs are considered as New Drugs where the Central Drugs Standard Control Organization (CDSCO), ensures proper clinical data is submitted for the approval into the market. Appendix VI of Schedule Y (Drugs & Cosmetics Rules 1945) mentions the requirements for marketing approval of various types of FDCs.

Emergency use authorization of medicines: History and ethical dilemma.

The regulatory approval process of the United States Food and Drug Administration and European Union is the most demanding and challenging worldwide. They have the provision of the expedited approval pathways, i.e., "Emergency use authorizations" and "Conditional marketing authorizations," respectively, to give approval to novel therapeutics agents during emergency situations. India, firstly formalized the accelerated pathway named "Accelerated Approval Process" as per the New Drugs and Clinical Trials rule 2019 to address unmet medical needs that was implemented by the Central Drug Standard Control Organization to approve the novel therapeutics agents during COVID-19. Hence, our aim is to understand and compare the different emergency approval processes in the world, their underlined claims and conditions with the list of approved products under this concept. All the information collected and analyzed from different official websites of regulatory bodies. In this review, we have enlightened on all these processes with their few approved products.

Investigator knowledge, awareness, and registrations of academic clinical trials with the Clinical Trial Registry of India: An observational study.

In 2019, the Central Drugs Standard Control Organization (CDSCO) introduced the New Drugs and Clinical Trials Rules 2019 (NDCTR), which separated the research guidelines for "Clinical Trials" and "Biomedical and Health Research." As a result, guidelines issued by Indian Council of Medical Research were stated to apply to academic clinical trials (ACTs). This change is important because academic studies are crucial for scientific advancement and repurposing of approved drugs in health-care industry. However, conducting an ACT can pose challenges. We assessed the level of awareness, knowledge, and challenges faced by investigators. Our aim is to overcome some of these challenges and encourage more academic studies for the betterment of healthcare and scientific knowledge in India. The study was conducted in two phases after obtaining approval from the Institutional Ethics Committee (EC) of three tertiary care hospitals in Mumbai. In the first phase, the number of ACTs was assessed from the clinical trial registry India website, while the number of registered and re-registered ECs were assessed from the CDSCO website. The second phase involved assessing investigator awareness and knowledge about ACTs using a prevalidated questionnaire with a content validity index score of 0.93. In 2020, the highest numbers of studies were registered, with the highest numbers of registered and re-registered ECs from Maharashtra. All participants completed the questionnaire and were aware of the need to follow guidelines for clinical trials. Sixty-seven percent of participants knew that the guidelines for ACTs differed from those of sponsored clinical trials, but only 58% were aware of the exact definition of an ACT as per NDCTR, 2019. Eighty-five percent of participants knew who could initiate an ACT, but only 27% knew about the applicability of results of an ACT and 33% had in-depth knowledge about the required approvals, while only 10% knew the archival period. Although 71% of participants had knowledge about serious adverse event reporting, few answered in-depth questions correctly. Only 31 participants reported facing varied challenges. To conduct ACTs effectively and contribute to healthcare and scientific advancement, it is crucial to enhance investigators' existing knowledge about ACTs.

NANOTEX BONE Graft along with Fibula Flap in the Reconstruction of Segmental Mandibular Defect: Protocol for Pilot Clinical Trial.

Mandible reconstruction with vascularized fibula flap is the standard treatment for segmental mandibulectomy in patients with tumor or trauma. But the height of the fibula graft is insufficient for dental implant placement and prosthetic rehabilitation to replace the missing teeth, which in turn will compromise the functional efficiency and aesthetics of the patient. Although the bone height can be augmented through onlay grafting with iliac crest, it is associated with limitations like donor site morbidity and fast resorbability. This suggests the need for a synthetic biomaterial for vertical bone augmentation in implant dentistry.We have developed a biomimetic, porous, mechanically stable, and biodegradable nanocomposite named "NANOTEX BONE Graft" and its bone regeneration potential was evaluated in pre-clinical animal models. In this clinical trial, the safety as well as the efficacy of NANOTEX to augment new bone over fibula and further its ability to integrate with dental implants will be studied. The study has received the approval of the Ethics Committee of Amrita Institute of Medical Sciences and Central Drugs Standard Control Organization (CDSCO), India. We have designed a prospective, single-center, non-randomized pilot clinical study. Patients with benign tumor or trauma indicated for mandibular reconstruction followed by implant rehabilitation will be included in the study. Eligible patients will be enrolled after obtaining informed consent. The study will be initiated and followed up as per defined timelines. Resection of benign mandibular tumours necessitates surgical removal of jaw bone and adjacent affected areas.The segmental mandibulectomy leaves the patient with functional impairments and aesthetic defects which in turn affect the quality of life.The standard treatment of reconstruction with vascularized fibula flap has challenge in achieving sufficient vertical bone height for implant placement and prosthetic rehabilitation.Alternate surgical techniques cause donor site morbidity and surgical complications.There is need for a synthetic biomaterial to be grafted over fibula for vertical bone augmentation.NANOTEX BONE Graft, a nanofibrous composite scaffold that mimics native bone, promote cell infiltration, neo-angiogenesis and new bone formation.Preclinical studies of NANOTEX in animal models showed bone tissue regeneration, better biodegradation in critical sized defects and efficient integration with dental implants.This clinical study propose to evaluate the safety and efficacy of NANOTEX bone graft augmented over fibula in bone regeneration and Titanium dental implant integration.

A Real-World Study of Safety, Immunogenicity and Efficacy of Bevacizumab in Patients With Solid Malignancies: A Phase IV, Post-Marketing Study in India.

The aim of this study was to evaluate the post-marketing safety, tolerability, immunogenicity and efficacy of Bevacizumab (manufactured by Hetero Biopharma) in a broader population of patients with solid tumors. This phase IV, prospective, multi-centric clinical study was carried out in Indian patients with solid malignancies (metastatic colorectal cancer, non-squamous non-small-cell lung cancer, metastatic renal cell carcinoma) treated with Bevacizumab between April 2018 and July 2019. This study included 203 patients from 16 tertiary care oncology centers across India for safety assessment, of which a subset of 115 patients who have consented were also evaluated for efficacy and immunogenicity. This study was prospectively registered in the Clinical Trial Registry of India (CTRI), and was commenced only after receiving approval from the competent authority (Central Drugs Standard Control Organization, CDSCO). Out of the 203 enrolled patients, 121 (59.6%) patients reported 338 adverse events (AEs) during this study. Of 338 reported AEs, 14 serious adverse events (SAEs) were reported by 13 patients including 6 fatal SAEs, assessed as unrelated to the study medication and 7 non-fatal SAEs, 5 assessed as related, and 3 unrelated to Bevacizumab. Most AEs reported in this study (33.9%) were general disorders and administration site conditions, followed by gastrointestinal disorders (29.1%). The most frequently reported AEs were diarrhea (11.3%), asthenia (10.3%), headache (8.9%), pain (7.4%), vomiting (7.9%), and neutropenia (5.9%). At the end of the study, 2 (1.75%) of 69 patients reported antibodies to Bevacizumab without affecting safety and efficacy. However, at the end of 12 months, no patient had reported antibodies to Bevacizumab. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were reported in 18.3%, 22.6%, 9.6%, and 8.7% of patients, respectively. The overall response rate (CR + PR) was reported in 40.9% of patients at the end of the study. Disease control rate (DCR), also known as the clinical benefit rate (CBR) was reported in 50.4% of patients. Bevacizumab (Cizumab, Hetero Biopharma) was observed to be safe, well tolerated, lacking immunogenicity, and efficacious in the treatment of solid tumors. The findings of this phase IV study of Bevacizumab, primarily as a combination therapy regimen suggest its suitability and rationality for usage in multiple solid malignancies. CTRI/2018/4/13371 [Registered on CTRI http://ctri.nic.in/Clinicaltrials/advsearch.php : 19/04/2018]; Trial Registered Prospectively.

Dermatological adverse drug reactions with particular reference to Steven-Johnson syndrome and toxic epidermal necrolysis

Background: Drug therapy is an inevitable cause of cutaneous adverse reactions. Aims and Objectives: The primary aim was to identify the incidence and magnitude of various dermatological adverse reactions including Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Moreover, secondary aim was to quantify the risks associated with the use of specific medications. Materials and Methods: A prospective and hospital-based study was conducted in the department of dermatology SMHS hospital on hospitalized cases of cutaneous adverse drug reactions (CADRs). Informed consent was sought and reactions were reported on validated questionnaire based on adverse drug reaction (ADR) monitoring form provided by Central Drug Standard Control organization Ministry of Health and Family Welfare, Government of India. These dermatological reactions were assessed for the clinical pattern, causative agents, and prognosis. The WHO-Uppsala Monitoring centre system for standardized case was used for causality assessment of all cases identified. Results: A total of 101 hospitalized patients with varied dermatological ADRs were reported during the study period. Cases were found more in females (n=75, 74.25%) than in males (n=26, 25.75%). CADRs that were reported in our study were exanthematous rash, fixed drug eruptions, urticarial rashes, SJS, TEN, urticarial vasculitis, anticonvulsant hypersensitivity syndrome, erythema multiforme, contact dermatitis, exfoliative dermatitis, mucosal hyperpigmentation, and nail pigmentation, respectively. After a meticulous drug history, the drugs implicated in causing the cutaneous reactions were anticonvalscents such as phenytoin, carbamazepine, lamotrigine, and phenobarbitone. Other drugs identified were non-steroidal anti-inflammatory drugs such as oxicam, antibiotics such as sulfasalazine, cefixime, cefpodoxime, amoxicillin, fluoroquinolones such as levofloxacin and ciprofloxacin, chemotherapeutic agents such as cyclophosphamide, 5FU, and hydroxurea. Conclusion: The present study concluded that skin is most common target for ADRs. Drug-induced cutaneous reactions can be as simple as a mild rash to rare life-threatening SJS and TEN. Moreover, certain group of patients is at increased risk for developing CADR’s as women are more susceptible than men.

The BRAVO Clinical Study Protocol: Oral Varespladib for Inhibition of Secretory Phospholipase A2 in the Treatment of Snakebite Envenoming.

Snakebite is an urgent, unmet global medical need causing significant morbidity and mortality worldwide. Varespladib is a potent inhibitor of venom secretory phospholipase A2 (sPLA2) that can be administered orally via its prodrug, varespladib-methyl. Extensive preclinical data support clinical evaluation of varespladib as a treatment for snakebite envenoming (SBE). The protocol reported here was designed to evaluate varespladib-methyl for SBE from any snake species in multiple geographies. BRAVO (Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite) is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study to evaluate the safety, tolerability, and efficacy of oral varespladib-methyl plus standard of care (SoC) vs. SoC plus placebo in patients presenting with acute SBE by any venomous snake species. Male and female patients 5 years of age and older who meet eligibility criteria will be randomly assigned 1:1 to varespladib-methyl or placebo. The primary outcome is the Snakebite Severity Score (SSS) that has been modified for international use. This composite outcome is based on the sum of the pulmonary, cardiovascular, nervous, hematologic, and renal systems components of the updated SSS. This protocol was submitted to regulatory authorities in India and the US. A Clinical Trial No Objection Certificate from the India Central Drugs Standard Control Organisation, Drug Controller General-India, and a Notice to Proceed from the US Food and Drug Administration have been obtained. The study protocol was approved by properly constituted, valid institutional review boards or ethics committees at each study site. This study is being conducted in compliance with the April 1996 ICH Guidance for Industry GCP E6, the Integrated Addendum to ICH E6 (R2) of November 2016, and the applicable regulations of the country in which the study is conducted. The trial is registered on Clinical trials.gov, NCT#04996264 and Clinical Trials Registry-India, 2021/07/045079 000062.