Authors: George Kwiecinski, Kevin Yuan

DOI: 10.1007/s12247-026-10406-3

With the globalization of the pharmaceutical industry, the majority of active pharmaceutical ingredients and finished drug products entering the U.S. market originate from overseas manufacturing sites. From 2014 to 2024, FDA-conducted foreign Good Manufacturing Practice (GMP) inspections have fallen sharply. This study examines how trends in FDA inspection quality relate to increasing import volumes of drugs into the United States by analyzing FDA-issued observations since 2014. Increasing import volumes corresponded with declining inspection frequencies from 2014 to 2019. For every additional billion dollars of drug imports to the United States, there were 23 fewer inspections conducted during 2014–2019. The documented decline in inspection intensity, stable inspection outcome rates despite varying inspection volumes, and persistent disparities between MRA and non-MRA countries provide empirical support for the FDA's May 6, 2025, shift toward unannounced foreign inspections.

Authors: George Kwiecinski

DOI: 10.1007/s12247-024-09879-x

This study investigates trends in the issuance of FDA warning letters from 2019 to 2023. The paper aims to assess past and present FDA statements of inspection efficiency from a quantitative and qualitative perspective. An analytical approach combining regex filtering and web scraping was developed to log citations of law within FDA warning letters. The process included identifying recurring keywords for categorization by keyword, department, and legal reference. From 2019 to 2023, the FDA went from issuing a warning letter 2.98 times per 100 inspections to 4.27 times per 100 inspections, a 43% increase in warning letters issued per 100 inspections.

Authors: Yiyi Bao, Nicholas Buhay, Qiang Zheng

DOI: 10.1007/s12247-024-09825-x

This research proposes a dynamic model designed to investigate the underlying principles of regulatory science and assess the effectiveness of pharmaceutical GMP regulation. A dynamic model for the state of compliance of a pharmaceutical manufacturing firm is constructed by using a generalized Ornstein-Uhlenbeck equation. The model is based on quantitative characterization of principles of proportionality, transparency and consistency, and regulatory effectiveness as measured by efficiency, cost and quality. The dynamic model is capable of characterizing a wide range of compliance behaviors and regulatory actions.

Authors: Yiyi Bao, Qiang Zheng

DOI: 10.1007/s12247-024-09844-8

This study examines the structure and content trend over time of FDA GMP Warning Letters for their roles in effective communication. The structure and content trend over time of Warning Letters are studied using a combination of parsing text based on function, manual coloring and Python automation. The observed trends using these methods indicate that the content of suggestions on how to respond to a Warning Letter, for third party participation and further reading consistently increases over time. Warning Letters have become increasingly informative, showing FDA's good practice of transparency as a way to improve regulatory effectiveness.

Authors: Manish Singh, Roland Rocafort, Cathy Cai, Kien Wei Siah, Andrew W. Lo

DOI: 10.1371/journal.pone.0272851

We perform an event study analysis that quantifies the market reaction to clinical trial result announcements for 13,807 trials from 2000 to 2020, one of the largest event studies of clinical trials to date. We first determine the specific dates in the clinical trial process on which the greatest impact on the stock prices of their sponsor companies occur. We then analyze the relationship between the abnormal returns observed on these dates due to the clinical trial outcome and the properties of the trial, such as its phase, target accrual, design category, and disease and sponsor company type (biotechnology or pharmaceutical). We find that the classification of a company as 'early biotechnology' or 'big pharmaceutical' had the most impact on abnormal returns, followed by properties such as disease, outcome, the phase of the clinical trial, and target accrual.

Authors: Matthew J. Higgins, Xin Yan, Chirantan Chatterjee

DOI: 10.1016/j.respol.2020.104132

This study examines the impact of adverse regulatory events on pharmaceutical companies through the lens of drug relabeling. Using comprehensive data on FDA-mandated label changes, we analyze how these regulatory interventions affect firm value, innovation trajectories, and competitive dynamics in the pharmaceutical industry. Our findings reveal significant heterogeneity in firm responses based on company size, pipeline diversity, and the severity of the relabeling event. The research provides crucial insights into how regulatory actions shape pharmaceutical innovation and market structure, with implications for both policy makers and industry stakeholders.

Authors: Aakriti Rudra, Maninder Kaur

DOI: 10.1007/s12247-022-09678-2

The present study examines the causes of warning letters issued by the Center for Drug Evaluation and Research (CDER), FDA to pharmaceutical companies after post-approval inspections. Warning letters issued from 2010 to 2020 were obtained from the FDA website, and information about date of issuance, company, and type of violations was extracted. Poor compliance to CGMP and misbranding were the most common reasons for the warning letters. Detailed analysis of CGMP warning letters elucidated three major types of violations: deficiencies in process validation, documentation practices (data integrity), and quality control, corresponding to 26%, 21%, and 15% of warning letters, respectively. The findings demonstrate that the FDA's major concern is CGMP compliance, and that pharmaceutical manufacturers need effective quality management systems governing the entire manufacturing process, quality control, employee training, and documentation practice.

Authors: Suvrat Dhanorkar, Enno Siemsen, Kevin W. Linderman

DOI: 10.1287/mnsc.2017.2748

Regulatory agencies, auditing firms, and supply chain partners externally promote change in firms, commonly employing two contradictory intervention approaches: punitive tactics to coerce firms to change and supportive tactics to encourage change. Using the context of government agencies promoting environmental improvements, we examine whether such punitive (e.g., regulatory inspections with possible sanctions) and supportive (e.g., environmental assistance, improvement recommendations) tactics can be administered in a complementary manner. Using a longitudinal data set from two state-level environmental agencies in Minnesota, we analyze over 1,000 supportive environmental improvement projects in combination with intermittent punitive tactics. The timing, severity, and relatedness of punitive tactics is critical for directing managerial attention and improving the efficacy of supportive tactics: contingent on timing, inspections can increase implementation rates by up to 60% but can also reduce them by up to 50%.

Authors: John V. Gray, Enno Siemsen, Gurneeta Vasudeva

DOI: 10.1287/mnsc.2014.2104

This study investigates the conformance quality benefits of colocating manufacturing with research and development (R&D) activities. Findings from a panel data set of U.S.-based pharmaceutical plants over a 13-year period reveal that colocation of manufacturing and R&D relates to better conformance quality, on average, across the entire sample. These benefits of colocation persist throughout the 1994–2007 period, which is surprising given the rapid development of information and communication technologies during that time. The benefits are particularly enhanced for manufacturing plants operating with processes involving a high level of tacit process knowledge and that belong to large firms. The findings highlight the importance of matching organizational design with process and firm characteristics in settings involving knowledge interdependence, and the continued value of physical proximity between manufacturing and R&D activities to achieve desired quality outcomes.

Authors: John V. Gray, Gopesh Anand, Aleda V. Roth

DOI: 10.1111/poms.12252

This article examines the influence of ISO 9000 certification on plant-level process compliance, arguably its first-order, targeted performance dimension. The empirical setting is the medical device manufacturing industry, with process compliance measured through FDA inspections of manufacturing plants. We control for several observable factors by matching certified plants with non-certified plants. Using longitudinal data, we find plants that obtained certification in the earlier diffusion period tend to have significantly better process compliance than a matched, non-certified control group, and the compliance difference is greater for early-certified plants than for late-certified plants. We also find deterioration in process compliance over time after certification. The study provides a useful baseline for assessing causality in ISO 9000–performance linkages and highlights the need for continued vigilance post certification.

Authors: Gopesh Anand, John V. Gray, Enno Siemsen

DOI: 10.1287/orsc.1110.0709

In this study, we examine decay in adherence to operational routines over time. Our empirical setting is the worldwide pharmaceutical industry, and we focus on operational routines used to maintain product quality. Based on an analysis of longitudinal data from U.S. Food and Drug Administration (FDA) inspections, we find that the tendency of operational routines to decay is widespread. Our results also illustrate that FDA inspections act as external renewals that halt decay in adherence to routines. In addition, manufacturing plants are found to vary significantly in their level of decay. Using data on mergers and acquisitions affecting these plants, we find that mergers appear to cause decay in adherence to routines, while acquisitions appear to serve as renewals and halt such decay.