Assessment of the Current State of Pharmacovigilance System in Pakistan Using Indicator-Based Assessment Tool

Objectives: Pakistan felt the need for an effective and robust pharmacovigilance (PV) system after one of the deadliest drug-related tragedies causing more than 300 deaths in 2012. The country set up its national PV center in 2015 and joined WHO’s Program for International Drug Monitoring (PIDM) in 2018 as a full member. The current study was aimed to evaluate the PV system’s functionality, identify the gaps, areas of improvement, and a strategy to lead a functional PV system in Pakistan.Methods: The descriptive cross-sectional study was conducted by providing an interviewer-administered questionnaire of the PV system across Pakistan by utilizing the Indicator based Pharmacovigilance assessment tool (IPAT). By a convenience sampling method 36 study participants were selected from the Drug Regulatory Authority of Pakistan (DRAP), drug administration of provincial health departments of 4 provinces and federally affiliated areas, 5 national public health programs, and 23 public and private hospitals. The assessment includes document review, interviews of the key informants by structured open-ended questions, and a review of websites of relevant organizations.Results: Drug Regulatory Authority of Pakistan (DRAP) with a national PV center received a 75% overall performance score on IPAT. To be regarded as “minimally functioning,” a country’s PV and drug safety system must meet all core indicators. DRAP scored 80.76% on the core indicators so cannot be deemed functional at this time. The only province with a regional PV center, Punjab, had scored 72.13% on relevant parameters. Despite receiving funding from the Global Fund, none of the National Public Health Programs (PHPs) have PV centers or associated activities. All hospitals except two private hospitals could not qualify the minimum requirements for functional PV. The absence of a legal framework for mandatory ADR reporting, lack of drug information center, budgetary constraints, no active surveillance activities, the nonexistence of pharmacovigilance risk assessment expert committee, and insufficient coordination among stakeholders were identified as major gaps.Conclusion: The results of the study reveal that Pakistan’s PV system is not fully functional at all levels. A two-phased strategy encompassing the non-financial and financial interventions is proposed to improve the PV systems at the national, provincial, PHPs, and hospitals levels.

The Counterproductive Effect of Pharmaceutical Marketing in Pakistan: A Qualitative Study

This study explores the effects of pharmaceutical marketing on patients and society in Pakistan. Pharmaceutical marketing is an integral part of the drug industry, which channels product-related information to healthcare professionals. Physicians are the target audience as they prescribe medicine to the users. The pharmaceutical industry mobilizes all resources to influence physicians’ prescriptions in favor of their brands. It is commendable from the organizational perspective, however; it leads to unintended negative consequences for society. The primary reason is the blind pursuit of commercial interest and near-total neglect of ethical behavior in marketing drugs. This study conducted open-ended 20 interviews from primary stakeholders of this issue that includes physicians, pharmaceutical managers, and officials of drug regulatory authority through purposive sampling. The findings show that misleading promotional strategies influencing physicians are responsible for the misuse and abuse of drugs and antibiotics. Pharmaceutical drug incentivization, the personal obligation for physicians, skewed data, and inappropriate promotions were the major categories developed during analysis. The study recommends various steps to minimize these ill effects.

A call for revamping the policy on import process of anticancer drugs in Pakistan

Madam, cancer therapy in Pakistan is a costly treatment financially exhausting patients and their caregivers. Due to the sky high costs of treatment, there is a lack of cancer care facilities in the country. The sale and regulation of anticancer drugs and biologics is controlled by the Drug Regulatory Authority Pakistan (DRAP). DRAP is responsible for granting No Objection Certificate (NOC) to import unregistered drugs either for the patient or the institutional use of a hospital, both subject to renewal. This process can take up from a minimum of 10 days to a maximum of 30 days, for an individual patient it may take up to 1 to 3 days. This was a task almost unachievable before the formation of DRAP. (1,2) In Pakistan, there have been challenges such as price hike in local medicines (3), anticancer drug shortages due to unavailability of active pharmaceutical ingredients (4) as well as COVID19 related raw material and drug availability (5). The average time for importing an unregistered drug from outside the country is about 4-6 weeks, which may be further delayed for months. Our discourse aims to bring attention to this issue, as delay in initiation or continuation of treatment significantly reduces the chances of the patient’s survival with time, which is something they do not have much of We propose the following steps as part of making this process easier for the stakeholders and patients alike: Reduce the time of import of unregistered drugs to 1 week (revamp import process/fast-track) Decentralize authority to provincial DRAP to reduce the burden Once an unregistered drug is imported, it should be registered in the list of special status drugs to fasten future process Facilitate the cancer centers on procurement of import medicines. Hospitals who face inventory challenges- should be able to easily borrow an imported medicine item from a nearby hospital where it is available. Exempt custom duties and taxes on import of such medicines Encourage local manufacturing of generic drugs Abolish regularity duties on import of raw material of said medicines for the manufacturer of such generic drugs Allow multiple sources of drug import Trainee program for DRAP officials dealing with biologics Derive an online process/portal to communicate and update patients and hospitals for delays and implement procedures to deal with such issues (6). Continuous...

Challenges of Pakistani Pharmaceutical Industry: Pakistan Case

The population of Pakistan is fast growing and the need for supply of medicine will continue to increase. The local pharmaceutical market is growing at a faster pace as compared with the international market. Until 1990, the reliance on the supply of medicine to cater to the national demand was on multinational companies holding major market share. Thereafter, the national pharmaceutical companies started investing to improve the quality of their product lines, employing qualif ied professionals, and ensuring compliance with the global standard of quality and good manufacturing practices. Consequently, national com- panies' market share drastically increased and the national demand for medicine is locally produced. The study results based on interviews of key stakeholders and available literature revealed that the local pharmaceutical sector is facing critical challenges of counterfeit medicine, pricing controversies, affordability of the medicine, lack of Research and Development (R&D) initiatives, and unethical marketing (bribing/cash incentives to the doctors). The Drug Regulatory Authority of Pakistan (DRAP) seems ineffective to overcome these challenges, eliminate counterfeit medicines, and take measures to curb the unethical marketing practices that are risking patient life, health, and treatment cost. The study further explored that unethical marketing practices, and prescribing expensive brands by doctors, creates a serious conflict of interests and fast a decline in patient trust and affordability of medicine cost. Thus strong regulatory controls,transparency, moral and ethical values are needed to enforce drug acts and make the stakeholder's groups accountable. There is a need to punish both the companies bribing the doctors on the pretext of product promotion and doctors accepting such benef its to protect the patient's interest and limit treatment cost. Strict regulations and incentive plans for the pharmaceutical sector are needed to promote Research and Development (R&D).

Analysis of adverse drug reactions reported to national pharmacovigilance center of Bhutan

Introduction: Medicines prescribed for diseases often causes adverse drug reactions in patients ranging from mere inconvenience to permanent disability and death. This is because, most of the adverse drug reactions especially the serious and latent ones may not have occurred during the clinical trials and vulnerable populations like children, pregnant women and the elderly are not all included in clinical trial studies considering the ethical and safety issues. Objectives: To study the demographic characteristics, types of adverse drug reactions and common drugs causing these reactions from the adverse drug reaction reports received by the national pharmacovigilance of Bhutan. Methods: A total of 222 adverse drug reactions were received at the national pharmacovigilance center from January 2016 to May 2018 were analyzed retrospectively. The Drug Regulatory Authority is the national pharmacovigilance center of Bhutan and is a member to the International Drug Monitoring Program since 2014. Results: 73% of adverse drug reactions occurred in adults while 13.5% occurred each in children and elderly. 48.7% of the total adverse drug reactions reports were caused by antibiotics out of which penicillin was the most common causal drug (32.4%). The most commonly reported adverse drug reactions was rashes (36.5%) followed by gastro-intestinal system disorder (14.9%). Conclusions: Antibiotics are common causal drugs for adverse drug reactions. All categories of health professional must be encouraged to report adverse drug reactions. Active surveillance for drug safety monitoring especially for those of patients who are on antibiotics is recommended.

Molecular Elucidation of Pancreatic Elastase Inhibition by Baicalein

ABSTRACTThe serine protease, elastase exists in various forms and plays diverse roles in the human body. Pharmacological inhibition of elastase has been investigated for its therapeutic role in managing conditions such as diabetes, pneumonia and arthritis. Sivelestat, a synthetic molecule, is the only elastase inhibitor to have been approved by any major drug regulatory authority (PMDA, in this case) – but still has failed to attain widespread clinical usage owing to its high price, cumbersome administration and obscure long-term safety profile. In order to find a relatively better-suited alternative, screening was conducted using plant flavonoids, which yielded Baicalein – a molecule that showed robust inhibition against Pancreatic Elastase inhibition (IC50: 3.53 μM). Other than having an IC50 almost 1/5th of that of sivelestat’s, baicalein is also cheaper, safer and easier to administer. While Microscale thermophoresis validated baicalein-elastase interaction, enzyme-kinetic studies, molecular docking and molecular dynamic simulation revealed the mode of inhibition to be non-competitive. Baicalein exhibited binding to a distinct allosteric site on the enzyme. The current study demonstrates the elastase inhibition properties of baicalein in an in-vitro and in-silico environment.

Acceptability and barriers to implementation of N-of-1 tests in Ethiopia - a qualitative study

Background Locally produced generic drugs offer a cost–effective alternative to imported drugs to treat patients in Ethiopia. However, due to a lack of bioequivalence testing, additional assurance tests are needed to build trust in cheaper, locally made drugs. By testing bioequivalence of local drugs to gold standard, N-of-1 tests have the potential to promote patient centred quality use of medicines. Method We sought to assess the acceptability of, and explore barriers to, conducting N-of-1 tests to evaluate local medicines in a resource limited clinical setting. We conducted a descriptive qualitative study, analysing four focus group discussions and five key informant interviews. Participants were senior drug regulatory authority members, institutional review board members, physicians and patients. All interviews were audio taped and transcribed verbatim. Patient interviews were conducted in Amharic and translated to English prior to analysis. Data analysis used an inductive, thematic process. Results Five major themes were identified; (1) Appropriateness of N-of-1 tests to determine the therapeutic equivalence of local drugs, (2) N-of-1 therapeutic equivalence tests: clinical care or research? (3) Ethical and regulatory requirements (IRB), (4) Potential barriers to implementing N-of-1 tests and (5) Possible solutions to identified challenges. The study demonstrated considerable support for using N-of-1 tests for clinical equivalence studies between local and imported medicines, but important impediments were very likely to impact the feasibility of conducting N-of-1 tests in Ethiopia. Key informants from the regulatory authority did not support additional tests of local drugs. There were also mixed opinions regarding ethical requirements for conducting N-of-1 tests. The Institutional Review Board (IRB) members believed that IRB approval was sufficient to conduct N-of-1 tests, however, the regulatory authority members considered that N-of-1 tests constituted a clinical trial, and required approval at the regulatory level. Conclusion This study showed that there were key uncertainties that could impact the feasiblity of using N-of-1 testing local drugs in Ethiopia. Therefore, a number of protocol amendments to address contextual threats and regulatory challenges, would be needed before progressing to conducting these tests.

Regulation of Medicines in Bhutan: Current Status, Challenges and Opportunities

Medicines Regulatory Agencies (MRAs) are responsible for evaluation of quality, safety and efficacy of medicinal products before it is approved for consumption. The regulatory procedures, however, differs from one country to another. Medical products including vaccines, blood and blood products, diagnostics and medical devices are essential for healthcare delivery across the world. The Drug Regulatory Authority (DRA) is an independent national agency for regulation of medicinal products in Bhutan and reports to Bhutan Medicines Board (BMB), the highest policy making body for regulation of medicinal products in the country. Medicines Act of the Kingdom of Bhutan is the legal tool for regulation of medicines in Bhutan. Medicinal products are regulated through premarketing and post-marketing control systems. All medicinal products available in the Bhutanese market are registered. DRA regulates all the medicinal products including vaccines, blood products and traditional medicines used for human and veterinary. DRA is fully financed by the Government of Bhutan. Bhutan’s medicines regulatory system has evolved over the last one decade. However, as the regulatory mandate continues to increase, DRA is faced with several challenges in terms of human resource, infrastructure and testing laboratory among others. There are also opportunities for the DRA to improve its regulatory capacities to ensure availability of quality and safe medicines for the public. Understanding the current practice of medicines regulation in Bhutan can help identify gaps and existing opportunities for improving the regulatory capacity. This article documents the existing practices, challenges and opportunities for regulation of medicinal products in Bhutan.

AN OVERVIEW OF CHINESE DRUG REGULATORY SYSTEM: A REVIEW

The Drug regulatory authority of China was renewed from state pharmaceutical administration of China (SPAC) to state food and Drug administration (SFDA) with the announcement and declaration of Chinese ministry of health, the established regulatory standards of SFDA were keen to keep with international standards of EU, Japan and USA, the Drug registrations and Drug approvals are carried with established affiliated units for fast track evaluation within prescribed period ordered by SFDA, the state food and Drug administration is developed stringently and modified its standards according to the US healthcare regulatory system, in this review the permanently keeping standards of regulatory functions were detailed, and the untiring responsibilities of affiliated units of SFDA were to be recognized where their performance was a key aspect.