Maintaining Compliance in the Global Pharmacovigilance Landscape

Specialty Pharmacy TimesSept/Oct 2013
Volume 4
Issue 5

A satisfactory system for the collection and reporting of adverse events is increasingly important as manufacturers place additional requirements on their specialty pharmacy and health care provider partners, and these needs go beyond the United States.

A satisfactory system for the collection and reporting of adverse events is increasingly important as manufacturers place additional requirements on their specialty pharmacy and health care provider partners, and these needs go beyond the United States.

Pharmaceutical manufacturers are accustomed to establishing robust procedures and systems to support compliance with the pharmacovigilance regulations set forth by regulatory bodies around the globe. On the other hand, pharmacies have traditionally followed local state pharmacy law as it relates to reporting adverse events.1

Specialty pharmacies are playing an increasing role in patient support and disease management programs. This role requires compliance with the guidelines that exist in the global pharmacovigilance landscape. Here we will explore the intersection between the global regulations governing adverse event reporting and operational considerations for the specialty pharmacy.

Pharmacovigilance is the science of collecting, monitoring, researching, assessing, and evaluating information from health care providers and patients on the adverse effects of medications and biologics. The objective of a pharmacovigilance initiative in the post market setting is to implement a systematic approach for harvesting information that facilitates the ongoing development of a medicinal product’s safety profile and disseminate that information to regulators and health care providers with the ultimate goal of promoting patient safety. Because pharmaceutical products are developed and launched on a global scale, including through licensing partners, we will look at the regulatory landscape from both the United States and European Union perspectives.

To understand what is needed to support a compliant pharmacovigilance initiative, we must first understand what constitutes reportable information and the criteria for an individual case safety report (ICSR). ICSRs for a given product are compiled in a database and support the generation of aggregate data listings that inform the safety profile of the drug and allow for the detection of safety signals. A valid ICSR must constitute these 4 elements: 1) an identifiable reporting source; 2) an identifiable patient; 3) at least 1 adverse event1 (as broadly defined below); and 4) 1 suspect medicinal product.


An adverse drug experience is defined in the FDA 21 CFR Part 314.80 as “Any adverse event associated with the use of a drug in humans, whether or not considered drug related.…” Similarly, European Medicines Agency (EMA) Module VI defines an “adverse reaction” as a “response to a medicinal product which is noxious and unintended.” It is important to note that these definitions for reportable information purposefully do not establish criteria such as seriousness, severity, or previous knowledge about this event. A sufficient pharmacovigilance system therefore must ensure that reportable information meeting these broad definitions is collected in a comprehensive approach from all applicable sources.

EMA guidelines state that reportable information can come from various sources, including “clinical trials, non-interventional studies, registries, post-approval named patient use programs, patient support and disease management programs, surveys of patients or health care providers, compassionate use or name patient use, or information gathering on efficacy or patient compliance. Adverse reactions reports obtained from any of these data collection systems should not be considered spontaneous.”

FDA 21 CFR Part 314.80 requires manufacturers to promptly review all adverse drug experience information obtained or otherwise received by the applicant from any source, foreign or domestic. This includes information derived from commercial marketing experience, post-marketing clinical investigations, post-marketing epidemiological/surveillance studies, reports in the scientific literature, and unpublished scientific papers.

Interestingly, the regulations cited here are not exclusively targeted to specialty pharmacies. Given the global nature of product commercialization and punitive nature of penalties, many manufacturers contractually mandate compliance with global and national regulatory bodies for various outsourced functions, including PAP, expanded access programs, clinical call centers, and REMS services. As these health care service providers become more integrated, they frequently act as both a clinical call center and a dispensing pharmacy. Thus, the conservative interpretation of these regulations and the absolute mandate for compliance with the regulatory guidelines may be warranted.


In 2012, a major pharmaceutical manufacturer was cited by the Medicines and Healthcare Products Regulatory Agency (MHRA), which is responsible for regulating all medicines and medical devi-ces in the United Kingdom, for failing to report adverse events that had been reported during the conduct of a patient reimbursement program being carried out in the United States. This inspection resulted in findings of deficiency and a requirement for the manufacturer to implement a corrective action plan. The potential penalties for findings of this nature also include fines and loss of marketing authorization.

In order to ensure compliance and limit exposure to penalties, manufacturers are placing additional requirements on their specialty pharmacy partners and other health care service providers regarding staff training and implementation of processes for adverse event capture and reporting. These processes require careful consideration as manufacturers plan their resourcing and budget forecasts for patient support, reimbursement programs, and pharmacist interactions. Important factors in the resourcing and budgeting of these processes include:

  • Development and implementation of complex standard operating procedures
  • Incremental staff training on product-specific adverse-event criteria and reporting procedures
  • Extended call interaction time and post interaction follow-up activities
  • Documentation of training and procedures
  • Audit and inspection preparation and support
  • Enhancements to pharmacy database systems


The financial impact of compliance with adverse event mandates can be significant. Increasingly, pharmacies and health care service providers require compensation for these incremental tasks, which should be based on fair market value (FMV). Entities typically determine FMV by utilizing 1 of 2 methods—cost plus or market value. Regardless of the method, FMV is crucial in determining the appropriate compensation for services rendered. As noted in the Federal Register, Vol. 71, No. 231, the appropriate method for determining FMV “may depend upon the specifics of the contracting terms, such as the activities the entity will perform and the agreed-upon mechanism for establishing the payment.”

As specialty pharmacies and health care service providers adapt to an increasingly complex regulatory environment, open dialogue with pharmaceutical and biotech manufacturers will facilitate these interactions. Efficiency, experience, and a thorough understanding of national and global regulations are critical factors to consider when integrating processes for capturing and reporting events. With a sound knowledge of the regulatory requirements, “right size” processes can be designed that will ensure compliance while limiting cost escalation associated with non—value added activities. SPT

1. For the purposes of abbreviation, the term “adverse events” will be used as an umbrella term throughout this paper to include reports of adverse drug reactions, adverse experiences, product quality complaints, medication errors, overdose, misuse and abuse, medication errors, and lack of drug effect.

About the Authors

Kevin G. Cast is vice president, global pharmaceutical business development, at United BioSource Corporation (UBC). He joined the Express Scripts management team in February 2003, and in his role oversees contracting for specialty pharmaceuticals and the sale of ancillary services that support pharmaceutical manufacturer products. Kevin leads the business development team, which is focused on the UBC offerings of Express Scripts, including pharmacovigilance, risk mitigation, specialty pharmacy, specialty distribution, third party logistics, risk evaluation and mitigating strategies (REMS), reimbursement, patient assistant programs, custom adherence programs, data and sales reporting, consulting, and nursing networks. His team is exceptionally qualified to leverage UBC’s unique strength: providing integrated business solutions that support the lifecycle of a drug. With more than 25 years of experience in the pharmaceutical and biotech industries, Kevin plays an integral role in developing, managing, and implementing fully integrated business solutions and comprehensive specialty product services. He holds a bachelor’s degree in biology from Illinois Wesleyan University and a master’s degree in botany from Oklahoma State University. He remains dedicated to enhancing the relationship between manufacturers and specialty pharmacies to ensure the success of critical therapies and the health of patients.Aaron Berger, PMP, is director, biometrics and pharmacovigilance at UBC and joined the UBC team in 2003. He has served in many roles, leveraging the company’s global capabilities to support the execution of peri- and post approval product development programs, REMS implementation, and pharmacovigilance service delivery. In his current role, Aaron leads a global project management team and oversees the operational delivery of UBC’s full-service pharmacovigilance offering. He plays an integral role in the development and implementation of the company’s integrated solution, which is designed to enhance patient safety through data analysis while maintaining compliance in the global regulatory landscape.

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