On November 22, 2017, EMA launches a “new and improved” version of EudraVigilance (analogous to FDA Medwatch program). The result will be a total transition in the way that Individual case safety reports (ICSRs) are tracked and reported throughout Europe. ICSRs will be reported to the EudraVigilance database in the E2B(R3) format, replacing the E2B(R2) format.
Similar safety surveillance changes are on the way in the U.S.
As recently as April 2017, FDA noted that it intends to implement these safety-surveillance changes in the US at Q2 2019* and guidance was issued in February 2014.
*International Council for Harmonisation, US FDA, and Health Canada Regional Public Consultation April 24, 2017.
Impact on drug sponsors expected to be significant
The impact on drug sponsors’ adverse event reporting and data collection is expected to be significant. Overhaul of multiple ICSR processes and procedures will be required to implement the new standards in time for a rapidly approaching deadline. Transition planning should be undertaken immediately. According to Quintiles “The R2 format had 271 unique data elements with the average file using 120-150 of them. In R3, there are 333 unique data elements — 38 of which are new, and 33 of which have been altered.”
A logical and sound approach to compliance assistance
PDG® has significant experience in clinical trial design and safety reporting, post-marketing safety surveillance, and overall pharmacovigilance. This includes development and implementation of systems to include electronic data capture and reporting, SOPs, intake, standardized letters, periodic reporting, medical assessments and labeling changes. We start by asking our clients to complete a questionnaire in order to identify gaps. The balance of this paper describes our approach to implementing, auditing pharmacovigilance systems, or simply providing supplemental assistance.
Standard Operating Procedures (SOPs)
Drawing on our years of experience, PDG initially reviews and/or prepares SOPs incorporating organization, infrastructure, and pharmacovigilance related workflows. Included are processes for intake, handling, escalation and coding/reporting of adverse events, complaint handling, medical inquiries and labeling currency. Also addressed are commonly occurring issues and concerns such as medical emergencies, child safety, medication errors, overdose, lack of equivalence, recalls, safety related labeling changes and other consumer/prescriber communications. Integration with the overall quality system is critical. Always included is an SOP for maintaining currency with regulations, guidances, standards and other best practices e.g. preparation for conversion to E2B (3R).
PDG maintains a staff of regulatory affairs professionals on call 24/7/365 to accept both verbal and written adverse event reports. We also have affiliated call centers located at strategic points around the world. Our staff and affiliates are well versed in receipt, processing, narrative generation, MedDRA coding, medical review and submission to FAERS, including 15-day reporting. This includes literature reports which we routinely monitor for both 15-day reports and periodic safety reporting (PADERs and/or PSURs). Those reports requiring immediate attention are addressed accordingly, with all others processed the next business day. Staff are trained on client SOPs and always have immediate access to clinicians as needed.
As noted, PDG prepares PADERs and PSURs and will submit to the applicable regulatory agency, or provides to the client in a format suitable for electronic submission. In doing so, we monitor the literature for potential 15-day reports. Each report will include the standard regulatory requirements (e.g. narrative summary and analysis of the information in the report, analysis of the 15-day reports submitted during the reporting interval, history of actions taken since the last report because of adverse drug experiences).
Adverse Event Database
Your database is critical for a multitude of reasons e.g. data mining/signal detection, post-marketing safety studies (voluntary or required), electronic data transmission among others. In a recent guidance, FDA noted that “A robust safety database is critically important to accurately assess and adequately characterize the risks of a new drug. Sponsors collect extensive safety-related data throughout the course of drug development, and knowledge about a drug’s safety profile continually evolves as safety data accumulate.”
We help our clients by preparing for changes such as the impending conversion from E2B(R2) to E2B(R3). If you believe your database is inadequate or on the verge of being outdated, or you believe outsourcing certain of the efforts may be advantageous, let us know.
As with the SOPs, we draw upon our years of experience to develop templates to facilitate drafting responses to medical inquiries as they occur. Source materials include product labeling, review of the scientific literature, FAERS database and other relevant public sources (e.g. FDA, other regulatory authorities). Inquiries may be addressed by either of our medical teams as they occur. Examples of templates may include most frequently occurring events, information relating to vulnerable sub-populations such as pediatrics, geriatric or any others that might be expected to use the drug product.
The President of PDG is a longstanding member of the faculty at a well-known medical school. She has also designed and placed a multitude of clinical trials, including sourcing of primary investigators. As such, PDG has various clinicians with drug safety and adverse event assessment experience on the team. We dedicate a clinician to your project who will review all necessary ICSRs, and all medical templates developed by the PDG research team. A back-up clinician is also assigned and stays fully briefed, to help ensure program continuity and responsiveness should the primary clinician become unavailable. Both will be knowledgeable in the prescribing information and client SOPs and will know the others on the team.
Whether you need to implement your first pharmacovigilance system, upgrade your existing system or outsource some or all of it, feel free to contact PDG® for assistance. As noted above, we have significant experience in clinical trial safety reporting, post-marketing safety surveillance and overall pharmacovigilance.
About the Authors
Charles Jaap is Vice-President of Operations and Business Development for PDG®, a global pharmaceutical and medical device consultant with extensive experience in the strategic development of drug products and medical devices.
Darren Scheer, MPH, RAC is Director of Epidemiology and Safety Surveillance for PDG. He has over 10 years of regulatory and pharmaceutical/device safety experience as well as clinical trial protocol design, statistical endpoint development, and FAERS database analyses. Darren is also a Ph.D. candidate in epidemiology focusing on pharmaceutical and disease outcomes in a large healthcare claims database.
Mikel Alberdi, MPH, RAC is Director of Regulatory Affairs/New Product Development for PDG®. He has over 15 years of regulatory affairs experience, with expertise in facilitating FDA meetings and compiling NDA, 505(b)(2), and NDA submissions.
The opinions and statements in this paper are solely those of Charles Jaap, Darren Scheer, and Mikel Alberdi and do not necessarily reflect those of PDG®.