Chain Drug Review, March 16th, 2020

Pharmacovigilance Vital to Drug Regulation Focus GENERIC DRUGS Retail Pharmacy GENERIC DRUGS R CFRSearch cfm fr 31480 describes the adverse events reporting obligations for marketing authorization holders within a defined time frame i e within 15 calendar days for all serious and unlisted adverse events and as part of aggregate reporting for all other adverse events Development of a safety profile is an ongoing process for drugs and it can sometimes take years of patient exposure data to identify rare and potentially hazardous side effects The safety profile can also be updated as part of continuous monitoring Even for generic manufacturers the clinical trial and post marketing adverse events reporting requirements from regulatory agencies are applicable and mandated Pharmacovigilance is very satisfying in that it gives one an opportunity Generic Companies Ready for COVID 19 WASHINGTON As global experts Jeff Francer phen Hahn emphasized there are other alternatives to the drug in shortage that can be used by patients and that FDA was working with the manufacturer as well as other manufacturers to mitigate the shortage Under the Food and Drug Administration Safety and Innovation Act FDASIA generic manufacturers work with the FDA as it conducts active AAM is committed to communicating with all stakeholders from patients to policy makers supply chain surveillance alerting the agency to known drug shortages This reporting system has been in place for years because shortages based on a myriad of market based factors continue to vex the pharmaceutical system commented Francer He pointed to the comments before Homeland Security last month from former FDA commissioner Scott Gott lieb that there are many steps we can take to address these risks both in the setting of this current public health crisis as well as preparing for the next one There will always be a next one Threats to the drug supply are not new noted Francer whether from a virus or a hurricane and our manu Foram Vaishnav ly every drug has therapeutic benefits to cure certain diseases and inherently may cause side effects which occur during administration or use This benefit to risk ratio constitutes the safety profile The serious side effects reported during clinical trials of drugs helps establish a baseline safety profile that helps regulatory agencies to approve or deny marketing authorization However due to limited patient exposure in clinical trials not all rare or severe side effects may have been documented from clinical trials in the PI Exposure to a wider patient population may also demonstrate certain drug drug interactions severity of known side effects and dangers of drug misuse abuse These instances warrant ongoing monitoring of drug safety even after approval and an updated safety profile Pharmacovigilance for generic drugs broadly speaking is global in nature as the same drug may have authorization in multiple countries and the regulations for each country may differ For example Health Canada requires all domestic serious adverse events even if listed in PI to be submitted within 15 calendar days the FDA however requires serious and only unlisted adverse events to be submitted Thus understanding of the various regulatory requirements is extremely critical to maintain compliance The developed markets i e the U S Canada and the EU have extensively defined regulations China India and Russia have identified the need for stringent pharmacovigilance regulations in the last 20 plus years and have implemented their own requirements China officially joined the WHO International Drug Monitoring Program for detecting adverse drug reactions in 1998 Over the last 20 years China FDA has been in the process of streamlining the regulations around clinical trials risk management and assessing benefit risk profiles China joined the International Council for Harmonization ICH in 2017 and adopted its guidelines on electronic submissions E2 M1 and M4 This has led to some challenges for manufacturers to maintain compliance and a constantly evolving market Around the world the patient population size is not relevant Wherever a drug is sold the marketing authori By Dr Foram Vaishnav The World Health Organization WHO defines pharmacovigilance as the science and activities relating to the detection assessment understanding and prevention of adverse effects or any other drug related problem Pharmacovigilance or in lay terms drug safety involves monitoring approved drugs and investigational medicinal products under clinical trials to Identify previously unknown adverse effects Recognize changes in the frequency or severity of known adverse effects Assess a drugs risk benefit to determine if action is required to improve safety Ensure the accuracy of information communicated to health care professionals and patients and to ensure up to date information is captured and readily available via prescribing information PI Pharmacovigilance is vital to the whole regulatory process for drugs It starts with clinical trials to provide information on the safety and therapeutic benefits of a drug The aim of monitoring during the clinical trials An opportunity to make an impact on peoples lives is to demonstrate that the therapeutic benefits outweigh the risk severe side effects and if proven the respective data is submitted to a regulatory agency i e the Food and Drug Administration to gain approval to commercialize the drug It is primarily due to pharmacovigilance that the drugs we consume are documented to be mostly safe and those that are found harmful are recalled from the market Generic manufacturers like Dr Reddys are required to conduct clinical trials to demonstrate bioequivalence to brand products To receive regulatory approval generic drugs must contain the same active ingredient be the same strength and dosage form tablet capsule etc and have the same route of administration oral topical injectable etc as the brand name drug One of my responsibilities is to monitor the side effects of the drugs that Dr Reddys sells The interesting and challenging aspect of pharmacovigilance is that per some regulatory agencies e g the FDA the monitoring of side effects begins at the time of approval of the product and must be continued irrespective of marketing status The term safety profile and its continuous monitoring is the core purpose of pharmacovigilance Essentialzation holder has to have systems in place to collect monitor and report adverse reactions It is every marketing authorization holders responsibility to monitor the trends in side effects that are reported for their drugs and identify any potential safety signal arising from that tracking This potential or identified signal may then lead to further monitoring or updating the prescribing information with the new information The FDA tracks its own safety database FAERS FDA Adverse Event Reporting System and manufacturers are guided to compare it with their own safety database to confirm if the potential signal is justified Data on side effects is required to be submitted to the FDA The 21CFR31480 www accessdata fda gov scripts cdrh cfdocs cfcfr to make an impact on peoples lives by ensuring only safe and effective medicines reach patients It is also challenging in that the regulations across the globe are ever expanding and being revised which makes my job critical to ensure compliance to these changing requirements I believe 10 or 20 years down the line the regulatory landscape may have changed but the pharmacovigilance side to ensure patients receive safe drugs is still going to be much needed Dr Foram Vaishnav heads the North America pharmacovigilance and risk management team at Dr Reddys She is responsible for oversight of collection monitoring assessment and reporting of adverse events as well as Risk Evaluation and Mitigation Strategy REMS programs for generics work to map the spread and impact of the novel coronavirus the Association for Accessible Medicines will work closely with stakeholders including the U S government to help ensure that patients may continue to access FDA approved generic and biosimilar medicines With regard to COVID 19 AAM and its members are first and foremost committed to the health of the American people by minimizing any possible disruption to access to life saving and healthmaintaining generic and biosimilar medicines blogged Jeff Francer the associations general counsel and interim chief executive officer As we consider the challenges this pandemic presents to the drug supply it is critical to understand where our medicines come from said Francer noting that 80 of brand and generic active pharmaceutical ingredient API manufacturing facilities are located outside of the U S with 13 in China Food and Drug Administration data show 1079 API facilities worldwide that make the 370 drugs on the World Health Organization Essential Medicines List that are marketed in the U S Of these factories 15 are in China In testimony before Congress in October FDA director of the Center for Drug Evaluation and Research CDER Janet Woodcock pointed out that none of the facilities producing API for influenza treatments are located in China Francer cited a late February new report noting that the FDA had contacted producers of about 20 drugs that either source main ingredients from China or are finished there and none of the drug makers expected a problem On February 27 the FDA did reveal that either a brand or generic manufacturer alerted the agency about a shortage related to a site affected by coronavirus FDA commissioner Stefacturers practice careful planning and have systems in place to mitigate them Pharmaceutical companies whether brand name or generic spend considerable time and resources proactively planning for contingencies and then adjust their ordering and scheduling needs appropriately Diversifying the supply chain and ensuring there is no single point of failure is key to these efforts While no one could have predicted that an outbreak would seemingly close all of China an event such as the coronavirus outbreak is handled by our member companies in the same manner as other emergency situations with an immediate review of their individual supply chains Our members may then make the adjustments necessary to minimize disturbances to supply manufacturing and distribution Notwithstanding all the planning and anticipation as COVID 19 evolves so will the operational realities facing all manufacturers he added Generic drug makers remain vigilant and are closely monitoring this significant public health crisis AAM stands ready to work with leaders in government and medicine to help ensure continued patient access As we learn of updates related to the generic and biosimilar industry AAM is committed to communicating with all stakeholders from patients to policy makers throughout the duration of this current crisis through this blog Twitter and formal statements As to treatment of COVID 19 no antiviral medication is currently recommended Treatment is aimed at relieving symptoms and may include pain relievers and cough syrup or medication as well as rest and fluid intake 68 Chain Drug Review March 16 2020