Lauren Schoukroun-Barnes, PhD, is associate manager of Regulatory Affairs,  Sia/LBG.

Lauren Schoukroun-Barnes

Industry inspector team working, QC staff work checking machine operation for safety and hygiene | Image Credit: ©Quality Stock Arts – stock.adobe.com

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.

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.

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.

BioPharm International®/Pharmaceutical Technology®/Pharmaceutical Technology® Europe

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 

Articles

Pharmaceutical and medical device companies targeting the U.S. market must adhere to stringent manufacturing practices, with the FDA enforcing compliance through good manufacturing practices (GMPs). Despite robust internal controls, companies often receive FDA Form 483s or warning letters for documentation and procedural deficiencies. FDA inspections, both domestic and international, can result in No Action Indicated (NAI), Voluntary Action Indicated (VAI), or Official Action Indicated (OAI) outcomes. Non-compliance can damage reputations, delay drug approvals, and impact business operations, necessitating prompt and thorough corrective actions.

The authors examine common FDA 483 findings and outline strategies to address and prevent regulatory non-compliance.