New Year, Same Challenges: Pharma’s Ongoing Struggle with FDA 483s

All pharmaceutical or medical device companies with products destined for the United States market operate under strict manufacturing practices to ensure public safety, efficacy, and consistent product quality. FDA plays a pivotal role in this oversight through the employment of good manufacturing practices (GMPs). Despite intensive internal controls and monitoring systems, these industries frequently receive FDA Form 483s—inspectional observations—and in the most serious cases, a warning letter. This paper examines inspection findings most commonly related to documentation practices and procedures including standard operating procedures (SOPs), incomplete or inadequate deviations, and non-conformances and outlines strategies to address and prevent regulatory non-compliance.

Background

FDA conducts inspections of manufacturing facilities of drugs, biologics, and devices. These inspections can be due to the following:

• Surveillance inspections, which are conducted to monitor a manufacturing process or the quality of the product on the FDA market
• For-cause inspections, which are conducted when FDA has a reason to believe that the facility may have quality issues

• Application-based inspections, which are conducted on approximately 20% of the application reviews for new products
• Follow-up inspections, which are conducted to confirm that compliance, or corrective actions, are appropriately in place.

FDA inspections are regularly conducted overseas in regions such as Europe, the United Kingdom, China, India, Australia, and Singapore. This is because the pharmaceutical supply chain extends well beyond US borders. FDA has the authority to halt the importation of drug products, medical devices, and biologics into the US, making foreign inspections a common and necessary practice.

These inspections can lead to the following outcomes: No Action Indicated (NAI), Voluntary Action Indicated (VAI), or Official Action Indicated (OAI). An NAI classification is generally seen as a favorable result, usually without any issued FDA 483 forms. However, VAI or OAI may indicate the presence of FDA Form 483s. Additionally, warning letters may be issued alongside or instead of 483s due to federal quality violations, a series of repeat violations at time of inspection, or noncompliance. These actions can significantly damage a company’s reputation, particularly when there are potential concerns that the quality of the finished product may be compromised. Across industry, the issuance of an FDA Form 4 83 or a warning letter can significantly impact a company in the following ways:

• Reputation damage: Reports are public information, and clients, partners, shareholders, and industry colleagues may be especially sensitive to potential disruptive findings, leading to negative industry opinion.
• Impact on new drug approvals: FDA can place any New Drug Application (NDA) or any market application on hold if the manufacturing facility in question is affected, until the identified issues or complaints are fully addressed by the company.
• Impact on revenue, supply chain, and business: Depending on the severity of the warning letter, partners, clients, government agencies (both state and federal), and other business entities may cancel, postpone, or delay investments, contracts, and/or agreements with the company.
• Management attention: Upon receiving an FDA Form 483 or warning letter, companies must allocate management time and resources to address the immediate issue. Ideally, management will also invest in a deeper root cause analysis to address any systemic problems that may have contributed to the situation.

Issuance of an FDA Form 483 or a warning letter could be regarded in some way as a potential barometer of regulatory performance, but if a company acts responsibly and thoroughly, they can resolve the concerns quickly and professionally to minimize potential impacts and maintain and improve compliance over time.

Read the article in the Quality and Regulations 2025 eBook.

About the authors

Patrick Falvey is principal consultant 2 of Chemistry Manufacturing and Controls. Georgia Sloboda is managing director of Chemistry Manufacturing and Controls. Sarah DeDonder, PhD, is manager of Quality Assurance. Lauren Schoukroun-Barnes, PhD, is associate manager of Regulatory Affairs, all with Sia/LBG.

Article details

BioPharm International®/Pharmaceutical Technology®/Pharmaceutical Technology® Europe
Quality and Regulations 2025 eBook
August 2025
Pages: 10–15

Citation

When referring to this article, please cite it as Falvey, et al. New Year, Same Challenges: Pharma’s Ongoing Struggle with FDA 483s. BioPharm International®/Pharmaceutical Technology®/Pharmaceutical Technology® Europe Quality and Regulations 2025 eBookAugust 2025.