Dr. Foram Vaishnav

Dr. Foram Vaishnav heads up North America Pharmacovigilance and Risk Management for Dr. Reddy’s Laboratories

 

A. How would you describe your position at Dr. Reddy’s Laboratories?

  • Currently I am heading North America Pharmacovigilance and Risk Management team at Dr. Reddy’s where I’m responsible for oversight of collection, monitoring, assessment and reporting of Adverse events as well as Risk Evaluation and Mitigation Strategy (REMS) programs for North America generics business.

 

B. One of your responsibilities is to monitor the side effects of the drugs that Dr. Reddy’s sells. How long after the drugs go to market do you follow and monitor their side effects.

  • The interesting and challenging aspect of Pharmacovigilance is that per some regulatory agencies, i.e. FDA, the monitoring of side effects begins at the time of approval of the product and is mandatory to continue irrespective of marketing status.

 

C. Can you explain the term “safety profile” and how do you go about this process?

  • The term “safety profile” and its continuous monitoring is the core purpose of pharmacovigilance. Essentially every drug has therapeutic benefits to cure certain diseases and inherently may cause side effects, which occur during administration or use of the drug. This benefit to risk ratio of a drug constitutes the safety profile. The serious side effects reported during clinical trials of drugs helps establish a baseline safety profile which 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 prescribing information (PI). Exposure to 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 drug approval and updating the safety profile.

 

D. Can you explain the term “Pharmacovigilance” and what it entails?

  • As per WHO, the term ‘Pharmacovigilance’ is defined 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’ activities involve 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 drug’s risk/benefit to determine if action is required to improve safety
  • Ensure the accuracy of information communicated to healthcare professionals and patients, and to ensure up to date information is captured and readily available via Prescribing Information (PIs)

 

E. Why is Pharmacovigilance so important to the whole drug regulatory process?

  • Pharmacovigilance (PV) activities start with clinical trials to provide information on the safety and therapeutic benefits of a drug. The aim of PV monitoring during the clinical trials 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. FDA) to gain approval to commercialize the drug. It is primarily due to the work of Pharmacovigilance activities that the drugs in the market that we consume are documented to be mostly safe and those that are found harmful are recalled from the market.

 

F. In terms of Pharmacovigilance how is that managed when you’re marketing a particular drug in different countries? Does it make it more complex?

  • 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 in terms of reporting obligations. For example, Health Canada requires all domestic serious adverse events (even if listed in PI) submitted within 15 calendar days for products marketed in that market however, FDA requires serious and only unlisted adverse events submitted for the same products approved in the USA. Thus, understanding of the various regulatory requirements is extremely critical to maintain compliance.

 

G. With the countries that are more regulated do you have to work harder to satisfy their requirements?

  • The developed markets (i.e. US, Canada, EU) have extensively defined regulations and the manufacturers are obligated to comply with them but additional countries (i.e. China, India, Russia) have also identified the need for stringent pharmacovigilance regulations in the last 20+ years and have implemented their own requirements which manufacturers are mandated to adopt in order to market their products in those territories.
  • Article attached on how 5 Major Upcoming Asian Countries are adopting PV regulations (file:///H:/Media%20Q&A/Asian%20Countries%20PV%20regulations.pdf )
  • Link on new PV regulation Order established in Russia since 2017 (http://www.lidings.com/eng/legalupdates2?id=330 )

 

H. How has China changed over the past several years in terms of regulations for pharmaceutical companies?

  • China officially joined the WHO International Drug Monitoring Program (Program for monitoring Adverse Drug Reactions) in 1998. Here is an interesting article on the development of China’s ADR reporting and management of the program (file:///H:/Media%20Q&A/ADR%20Reporting%20changes%20in%20China.pdf )
  • 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 profile of drugs to be marketed in China.
  • China joined the International Council for Harmonization (ICH) in 2017 and adopted their guidelines on Electronic submissions (E2, M1 and M4). This has also led to some challenges for manufacturers to maintain compliance and currently is a constantly evolving market.

 

I. Are there other countries that are becoming more highly regulated as well?

  • Article attached on how 5 Major Upcoming Asian Countries are adopting PV regulations (file:///H:/Media%20Q&A/Asian%20Countries%20PV%20regulations.pdf )

 

J. Does it matter whether a drug is marketed to a small or large population as far as keeping track of the side effects?

  • The patient population size is not relevant, as long as the drug is marketed in that country, the marketing authorization holder has to have systems in place to collect, monitor and report adverse reactions.

 

K. What is your relationship to the FDA in tracking side effects? Does the FDA track them as well and do you compare data?

  • It is every marketing authorization holder’s 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 does track its own safety database (FAERS – FDA Adverse Event Reporting System) as well and manufacturers are guided to compare the FDA database with their own safety database to confirm if the potential signal is justified.
  • Here is a presentation from FDA describing how they analyze the adverse events to identify any potential safety signals (https://www.fda.gov/files/about%20fda/published/Drug-Safety-Surveillance-and-the-FDA-Adverse-Event-Reporting-System-%28PDF—1.31MB%29.pdf )

 

L. Is the data on side effects something you submit to the FDA as a requirement?

 

M. The FDA is very focused on analyzing data from clinical trials to determine whether a drug will be approved. How is this different then when Dr. Reddy’s develops a generic version of a particular drug?

 

  • Generic manufacturers like Dr. Reddy’s are required to conduct clinical trials to demonstrate bioequivalence to brand products. The attached presentation (https://www.fda.gov/media/79217/download ) from the FDA best describes the requirements generic drug manufacturers need to meet to be able to demonstrate safety and efficacy equivalent to branded products to receive approval.
  • Per the FDA requirements, In order to receive FDA approval, generic drugs

must:

  • contain the same active ingredient
  • be the same strength
  • be the same dosage form (tablet, capsule, etc.),

and

  • have the same route of administration (oral,

topical, injectable, etc.) as the brand name

drug.  

 

N. How long does it usually take to develop a safety profile on a drug?

  • The development of a safety profile is an ongoing safety surveillance 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.

 

O. In your job do you collect safety information on a drug both before and after it’s approved by the FDA?

  • Yes, even as generic manufacturers, the clinical trial and post-marketing adverse events reporting requirements from regulatory agencies are applicable and mandated.

 

P. What would you say is the most satisfying part of your job?

  • Pharmacovigilance is very satisfying in that it gives you an opportunity to make an impact on people’s 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!