Report of a collaborative study to establish the first Indian Pharmacopoeia reference standard for teriparatide.

A collaborative study was conducted to establish the first Indian Pharmacopoeia Reference Standard (IPRS) for teriparatide to be used in quality control testing of marketed products in compliance with the Indian Pharmacopoeia (IP) monograph. The study objective was to evaluate the candidate standard in terms of the WHO International Standard (IS) to assign its content in mg per vial terms. This study involved four laboratories from India and the candidate standard was calibrated against the WHO IS by each participant laboratory using high-performance liquid chromatography (HPLC) assay method per IP monograph. Direct calibration of the candidate standard resulted in an assigned content of 1.02 mg per vial. Based on the study results the candidate standard was judged suitable to serve as the first IPRS for teriparatide for identification and assay by HPLC.

Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data.

Filgrastim, a biopharmaceutical listed on WHO model list of essential medicines, was approved in USA in 1991 for patients with non-myeloid malignancies associated with severe neutropenia and fever. Several filgrastim biosimilars have now been approved in USA, Europe and elsewhere since 2008, based on the reference product which has lost patent exclusivity; however their immunogenicity and safety is controversial. We conducted a retrospective, post market study between 1991 and May 2018 using VigiBase®. The study included all adverse events with case reports ≥150. Overall, 11,183 adverse drugs reaction reports were identified during observation period; of which 5764; 51.5% reports concerned to Neupogen®, the originator, and rest consists of Leucostim® (N = 680), Zarzio® (N = 622), Grasin® (N = 545), Nivestim® (N = 359) and Tevagrastim® (N = 152) biosimilars. When compared with the originator, Grasin® was associated with higher reporting of pyrexia (11.5% vs 7.9%, ROR 1.52, IC025 1.12), myalgia (37% vs 2.2%, ROR 25.94, IC025 2.11) and back pain (11.3% vs 4%, ROR 3.09, IC025 2.32). Zarzio® was associated with increased reporting of arthralgia (4.5% vs 2.9%, ROR 1.59, IC025 1.25) and neutropenia (11.4% vs 4%, ROR 2.59, IC025 3.07). Bone pain was reported more often with Nivestim® (14.4% vs 8.3%, ROR 1.87, IC025 5.30). Drug ineffectiveness was reported in cases with Zarzio® (35.9%), Nivestim® (19.4%) and Tevagrastim® (42.2%). Authors observed significant differences among originator and biosimilars in particular to efficacy, adverse events reported and time to onset of occurrences. Large epidemiologic studies are needed to further confirm these finding and provide additional insights.

Implementation of adverse event reporting for medical devices, India.

PROBLEM: Rapid growth in the use of medical devices has drawn attention to gaps in the systematic monitoring of medical device-associated adverse events in India. APPROACH: Implementation of national regulations on medical devices started in January 2018. Supported by a nationwide network of monitoring centres, the Indian Pharmacopoeia Commission coordinates adverse event reports from manufacturers, legal representatives and patients or users. The commission follows-up and reviews reports with subject expert groups and sends recommendations on necessary action to the national regulatory authority. LOCAL SETTING: Before 2015, no systematic structure was in place to collate adverse events associated with medical devices. Several reports of deaths and hospitalization due to faulty hip implants, cardiac stents and poor-quality devices prompted the health ministry to launch the materiovigilance programme. RELEVANT CHANGES: From July 2015 to October 2019, the commission received 1931 adverse event reports, mostly from marketing authorization holders; 1277 were serious events. Reporting increased markedly after 2017. Cardiac stents were the most reported device (926 events; 47.95%). To encourage a culture of reporting, the commission has raised awareness about the programme among stakeholders, developed user-friendly reporting tools and guidelines, and conducted training for hospital personnel on medical device adverse event reporting. LESSONS LEARNT: Regular training to stakeholders develops a sense of responsibility towards reporting medical device adverse events and ensures quality data reporting. Reporters must be assured that reporting adverse events does not have any legal implications for them and given acknowledgement of their role in high-quality device associated adverse event reporting.

"ADR PvPI" Android mobile app: Report adverse drug reaction at any time anywhere in India.

BACKGROUND: To improve the public health and promote instant adverse drug reaction (ADR) reporting, a need to develop an ADR Pharmacovigilance Programme of India (PvPI) mobile app was identified by the National Coordination CentrePvPI (NCCPvPI) to serve the Pan India ADR reporting. The objective of this study was to develop an indigenous Googlebased Android mobile application known as "ADR PvPI" and to analyze the ADRrelated data reported through this mobile application on pilot basis. MATERIALS AND METHODS: The ADR PvPI mobile application was indigenously developed by NCCPvPI officials within 6 months. The study of spontaneous ADR reporting was carried out between September 2017 and September 2018. This article provides an overview of the salient features of ADR PvPI mobile application, guides on how to fillin ADRs, reporting trends of ADR, types of ADR as per System Organ Class and pharmacological classes of drugs. RESULTS: Till date, >5500 users have downloaded the app with an average rating of 4.26. In that tenure, 262 reports have been received through ADR PvPI mobile app. During the year 2017, 3.55% of reports were received through ADR PvPI mobile app and the percentage of reports received by 2018 was 96.45%. CONCLUSION: The frequency of ADR reporting has significantly increased over the past 1 year and should be promoted further through awareness and training programs.

Peptide-based therapeutics: quality specifications, regulatory considerations, and prospects.

Exquisite selectivity, remarkable efficacy, and minimal toxicity are key attributes inherently assigned to peptides, resulting in increased research interest from the pharmaceutical industry in peptide-based therapeutics (PbTs). Pharmacopoeias develop authoritative standards for PbT by providing standard specifications and test methods. Nevertheless, a lack of harmonization in test procedures adopted for PbT in the latest editions of Pharmacopoeias has been observed. Adoption of a harmonized monograph could increase further the interest of the global pharmaceutical industry in PbTs. Here, we provide an overview of pharmacopoeial methodologies and specifications commonly observed in PbT monographs and highlight the main differences among the pharmacopoeias in terms of the active pharmaceutical ingredients that they focus on. We also address the prospects for PbTs to mature as a new therapeutic niche.

The Unprecedented Role of Gold Nanomaterial in Diabetes Management.

Gold nanoparticles possess unique mechanical, chemical, photo-optical and biological properties and have been an interesting field of research on life sciences. The research studies produced new nanodevices and nanotechnology-based biosensing, diagnostics therapeutics, and targeted drug delivery systems. In this review, the unique potential aspects of gold nanoparticles/ nanoformulations/ or devices related to diabetes management have been discussed together with the recent patent on the gold nanoparticles developed for diabetes management. The first part of this review will focus on recent strategies for the treatment of hyperglycemia and its management with the help of gold nanoparticles and the second part of the review focused on recent patents on gold nanoparticles useful in the diabetes management. Gold nanoparticles have proved themselves useful in diabetes therapeutics and diagnostics. Due to the high surface area, and low toxicity, gold nanoparticles have become a unique aspect of the delivery approach. The main issues that need to be covered are the biopharmaceutics, biocompatibility, and potential clinical applications.

Drug safety alerts of pharmacovigilance programme of India: A scope for targeted spontaneous reporting in India.

BACKGROUND: The National Coordination Centre-Pharmacovigilance Programme of India (NCC-PvPI), Indian Pharmacopoeia Commission works under the aegis of Ministry of Health and Family Welfare, Government of India. It promotes patient safety in India and also supports postmarketing surveillance programs. Currently, almost hundred thousand case reports are submitted to NCC-PvPI each year through its 250 ADR Monitoring Centers (AMCs) located across India, and India is the one of the top ten contributor countries under WHO-Uppsala Monitoring Centre since 2012 and start issuing drug safety alerts from March 2016. AIM: This study aims to highlight the drug safety alerts issued by NCC-PvPI from March 2016 to June 2017 and urgent need for further monitoring by adopting targeted spontaneous reporting (TSR) methodology at AMCs and its impact on the NCC's drug safety database, i.e., VigiFlow in India. METHODOLOGY: A retrospective analysis was done for the reported unlisted ADRs by various AMCs to PvPI through VigiFlow, i.e., individual case safety report (ICSR) management system at NCC, where these unlisted drug-ADR combinations considered and issued as drug safety alerts for further reporting these to NCC, if any detected at healthcare settings during routine clinical practice by healthcare professionals. RESULTS: From July 2011 to June 2017, NCC-PvPI was collated 250,787 ICSRs and contributed to WHO international drug safety database, i.e., VigiBase, from these ICSRs; NCC-PvPI was issued 56 drug safety alerts from March 2016 to June 2017. CONCLUSION: In India, spontaneous reporting of ADRs existed since 1998 under passive surveillance method, but there is an urgent need to initiate TSR, which is a complementary method to spontaneous reporting on these drug safety alerts for further regulatory action by Central Drugs Standard Control Organization.

Current Status of Herbal Drug Standards in the Indian Pharmacopoeia.

The benefits of herbal drugs were well understood way back. They have been used for the promotion of health and medical purposes - in disease conditions. It is a conventional belief that herbal drugs have no side effects, are cheaper and locally available. Among Indian systems of medicines, herbs/herbal formulations are used to a larger extent. The quality control of the marketed herbs/herbal formulations is important for acquiring optimum therapeutic benefit as well as for expanding global outreach. Therefore, herbal drug standards are important. Reference standards, the Indian Pharmacopoeia Reference Substances especially the botanical reference substances and the phytochemical reference substances are required for comparison of quality of herbal drugs. The Indian Pharmacopoeia Commission has initiated the process of providing Indian Pharmacopoeia Reference Substances to the stakeholders. Therefore, this article provides an overview of the history and the status of herbal drug standards in the current and forthcoming issues of Indian Pharmacopoeia. In Indian Pharmacopeia, efforts have been made for the harmonization of standards with international counterparts wherever possible. Copyright © 2017 John Wiley & Sons, Ltd.

Risk of Intussusception with Rotavirus Vaccine.

OBJECTIVE: To study the case series for intussusception associated with the vaccination of rotavirus vaccine in children. METHODS: The study of spontaneous adverse event monitoring such as intussusception due to rotavirus vaccine was carried out from the year 2011 through 2015. The individual case safety reports (ICSRs) of this event were collated, assessed and recorded as per the requirement of Suspected Adverse Drug Reactions Reporting form of Pharmacovigilance Programme of India (PvPI). RESULTS: In the present study, 10 ICSRs of intussussception due to rotavirus vaccine were reported to PvPI. Of which 3 ICSRs were found to be causal relationship with rotavirus vaccine, as evidenced by the adequate information provided in ICSRs. CONCLUSIONS: Since intussusception, the emerging safety as one of the important safety concern, healthcare professionals are advised to monitor and report to the concerned authority for appropriate action.

Pharmacovigilance in radiopharmaceuticals.

Indian Pharmacopoeia Commission is Committed for maintaining the standards of drugs including Radiopharmaceuticals (RPs) by publishing Indian Pharmacopoeia. These RPs are being used in India for diagnostic or therapeutic purpose. RPs though contain relatively small quantities of active ingredient and administered in small volumes could cause some adverse reactions to the patients. The objective of presenting this article is to introduce the system of adverse drug reaction reporting to the nuclear medicine fraternity who are dealing with RPs.

Pharmacovigilance Programme of India: Recent developments and future perspectives.

Promoting safe use of medicines is a priority of Indian Pharmacopoeia Commission that functions as the National Coordination Center (NCC) for Pharmacovigilance Programme of India (PvPI). One hundred and seventy-nine adverse drug reactions (ADRs) monitoring centers currently report ADRs to NCC. Current India contribution to global safety database reaches 3% and the completeness score is 0.93 out of 1. NCC is taking several measures to enhance patient safety including capacity building for monitoring, surveillance, collaboration with national health programs and other organizations to increase ADR reporting and to ensure that PvPI is a vital knowledge database for Indian regulators. The Central Drugs Standard Control Organization has notified important safety label changes on drugs such as carbamazepine and piperacillin + tazobactam in the year 2015, other drugs are under monitoring for regulatory interventions.

Veterinary herbal medicines in India.

India has a rich and diversified flora. It is seen that synthetic drugs could pose serious problems, are toxic and costly. In contrast to this, herbal medicines are relatively nontoxic, cheaper and are eco-friendly. Moreover, the people have used them for generations. They have also been used in day-to-day problems of healthcare in animals. 25% of the drugs prescribed worldwide come from plants. Almost 75% of the medicinal plants grow naturally in different states of India. These plants are known to cure many ailments in animals like poisoning, cough, constipation, foot and mouth disease, dermatitis, cataract, burning, pneumonia, bone fractures, snake bites, abdominal pains, skin diseases etc. There is scarce review of such information (veterinary herbals) in the literature. The electronic and manual search was made using various key words such as veterinary herbal, ethno-veterinary medicines etc. and the content systematically arranged. This article deals with the comprehensive review of 45 medicinal plant species that are official in Indian Pharmacopoeia (IP) 2014. The botanical names, family, habitat, plant part used and pharmacological actions, status in British Pharmacopoeia 2014, USP 36 are mentioned. Also, a relationship between animal and human dose, standardization and regulatory aspects of these selected veterinary herbals are provided.

Quantitative Methods for the Identification of Signals for Individual Case Safety Reports in India.

BACKGROUND: The Pharmacovigilance Programme of India (PvPI) is responsible for collecting reports of adverse drug reactions (ADRs) to assess the association between particular drugs and ADRs. The aim of the present study was to apply statistical tools to determine associations between drugs and ADRs for signal detection in the PvPI. METHODS: Four methods were proposed for quantitative signal detection: one was based on Bayesian inference and others on classical inference procedures. The effectiveness of the proposed methods was assessed by applying them to 4 drug-ADR combinations. RESULTS: The proposed methods were easy to apply and relevant to the Indian context. In selected methods, the information component value was more specific, whereas the proportional relative risk was more sensitive. CONCLUSIONS: The proposed methods may help in the identification of new signals in Indian individual case safety reports.

Adverse reactions to contrast media: an analysis of spontaneous reports in the database of the pharmacovigilance programme of India.

BACKGROUND: Contrast media are used widely to improve medical imaging. Like all other pharmaceuticals, these agents are not completely devoid of risk, and continuous monitoring of adverse reactions with these agents is important. Spontaneous reporting is the simplest method for understanding the safety profile of pharmaceutical products after their approval. OBJECTIVE: Our objective was to identify the pattern and characteristics of adverse reactions attributed to contrast media in the Indian population reported to the National Coordination Centre for the Pharmacovigilance Programme of India (NCC-PvPI). METHODS: Individual case safety reports (ICSRs) attributed to contrast media submitted spontaneously to the NCC-PvPI were extracted from the database for July 2010 to September 2013. We analysed these reports for information related to reporter's professional category, patient's age and sex, reporter's diagnosis of the reaction, seriousness of the reaction, type of contrast media exposure, system organ class (SOC) affected (as described in World Health Organization Adverse Reaction Terminology [WHO-ART]) and outcome. RESULTS: Of the total 59,915 ICSRs in the database, 415 (0.7%) were suspected adverse reactions to contrast media; 44 reports were serious, including three fatal cases. The most affected SOCs were skin and appendage disorders, body as a whole-general disorders, gastrointestinal system disorders and respiratory system disorders. Hypersensitivity reactions were reported in the majority of ICSRs. The contrast media with the highest number of reports were iohexol (40.7%), iomeprol (17.8%), iopamidol (12%) and diatrizoate (12%). CONCLUSIONS: Most of the reactions to contrast media were allergic-like, and no previously unrecognised adverse reactions were observed in the Indian population. Further data and increased awareness among healthcare professionals is required to signal and prevent the consequences of adverse reactions attributed to contrast media.

Quality Standards and Current Status of Ophthalmic Formulations in Indian Pharmacopoeia and National Formulary of India.

The global ophthalmic formulations (OFs) market is expanding dramatically with the approval of new drug formulations for a variety of ophthalmic indications by competent authorities in various countries. In India, the Central Drug Standards Control Organization (CDSCO) and Indian Pharmacopoeia Commission (IPC) are making efforts for approval and setting the standards for OFs, respectively. In fulfillment of the requirements of the Drugs and Cosmetics Act of 1940, the IPC is publishing an official book of standards for drugs known as the Indian Pharmacopoeia (IP). There are 44 ophthalmic active pharmaceutical ingredients (APIs) and combinations approved by CDSCO as of 2011; the IP 6th edition (2010) prescribes the quality standards monographs for 41 ophthalmic APIs and formulations. The IP monograph of OFs also includes description, identification, impurities, assay, and specific tests. In addition, the IPC is publishing the National Formulary of India (NFI), which covers 23 OFs for the diagnosis and treatment of various eye diseases. Both the IP and NFI play a significant role in monitoring and improving the safety and efficacy of medicines, with specific emphasis on OFs.