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Global Postmarket Pharmacovigilance: A Generic Drug Perspective

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Abstract

Despite the recognized need for generic drug pharmacovigilance harmonization efforts, only a few studies compared generic drug postmarket safety and surveillance methods adopted by regulatory agencies in different countries. The purpose of this research is to collect available information from a sample of international regulators with the overall goal of providing a general overview of each agency’s decision-making processes for postmarket generic drug safety and surveillance. A structured four-part questionnaire of open-ended and multiple-choice questions along with a semi-structured interview were designed to elicit detailed information. Swissmedic, Medicines and Healthcare products Regulatory Agency (MHRA), Health Canada, and the U.S. Food and Drug Administration (FDA) provided information. Detailed information from participating regulatory agencies demonstrated some similarities and differences in their postmarket generic drug pharmacovigilance approaches. This study examines each agency’s scientific perspective to address generic drug safety issues, as well as to identify common barriers within decision-making processes, such as legislative restrictions and limited resources. Most agencies do not have specific processes that are unique to generic drug products. This exploratory study, through documenting common and unique approaches intends to create a greater awareness and to promote cross-collaboration between global regulatory agencies.

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Notes

  1. For this project, the participating agencies were provided with the following definition for a generic drug: a medication created to be the same as an already marketed reference listed drug (RLD) in dosage form, safety, strength, route of administration, quality, performance characteristics, and intended use.

  2. The participating agencies terminology for generic drugs and the RLD differs. For this paper, the RLD is defined as an approved drug product to which new generic versions are compared to show that they are bioequivalent.

  3. For signal definition refer to the World Health Organization (WHO). Safety of medicines: a guide to detecting and reporting adverse drug reactions. 2002.

  4. For spontaneous adverse event report definition refer to the International Conference on Harmonization of Technical Requirements (ICH). Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting E2D. 2003.

  5. VigiBase is the WHO’s global database of reported potential side effects of medicinal products that is available to all members of the WHO Program for International Drug Monitoring (WHO PIDM).

  6. This is referred to as the Weber effect, where the drug is subjected to a higher number of adverse event reports in the first two years, then the number of reports decreases (Alomar et al., 2020).

  7. For TE definition refer to CFR—Code of Federal Regulations Title 21 -FDA 314.3 Definitions.

  8. For the purpose of this paper, complex generics refers to products that have complex active ingredients, formulations, dosage forms, or routes of administration, or are complex drug-device combination products.

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Funding

This paper was coordinated by the U.S. FDA with contributions from Health Canada, MHRA, and Swissmedic. This project was supported in part by an appointment to the Research Participation Program at the U.S. Food and Drug Administration administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. This paper reflects the views of the authors and should not be construed to represent the FDA’s views or policies.

Author information

Authors and Affiliations

  1. U.S. Food and Drug Administration, Office of Generic Drugs, 10903 New Hampshire Avenue, Building 75, Room 3662, Silver Spring, MD, 20996, USA

    Taylor Dalsey, Edward Kim, Howard Chazin & Sarah Ibrahim

Authors
  1. Taylor Dalsey
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  2. Edward Kim
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  3. Howard Chazin
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  4. Sarah Ibrahim
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Contributions

EK, HC, and SI developed the project concept. TD designed the questionnaire and developed the interview questions, which were approved by EK, HC, and SI, who also served as experts during the interviews. TD and EK collected, reviewed, and analyzed the responses from the questionnaire and interviews. TD wrote the manuscript. EK, HC, and SI critically reviewed and revised the manuscript. HC responded to all requests from the journal editors and comments from the peer reviewers. All authors agree to be accountable for all aspects of the work ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Howard Chazin.

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The authors have no conflicts of interest to disclose.

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Appendix

Appendix

Sample questions from questionnaire

Signal detection process

Quality issues

• What data sources do your agency use to identify safety signals for generic drug products?

• What criteria do your agency use to determine a newly identified safety signal for a specific generic drug?

• What is your agency’s signal evaluation procedure for determining which data are significant and require further investigation?

• What methods have your agency employed for early identification and prevention of these types of quality issues in future?

Decision-making process for a potential safety concern

Generic drug recall process

• Does your agency follow any key process differences for postmarket safety surveillance of generic drugs compared to reference listed drug products?

• What is the decision-making process for a potential generic drug safety concern?

• What surveillance methods do your agency utilize to mitigate potential generic drug safety concerns?

• What is your agency’s process for recalling a generic drug from the market due to an identified safety concern?

• How is the root cause of the safety issue analyzed to potentially return the drug to the market?

• Does your regulatory agency have the authority to recall a drug from the market?

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Dalsey, T., Kim, E., Chazin, H. et al. Global Postmarket Pharmacovigilance: A Generic Drug Perspective. Ther Innov Regul Sci 57, 1180–1189 (2023). https://doi.org/10.1007/s43441-023-00558-6

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