Global Regulatory Pulse

FDA Warning Letters for Non-US Manufacturers

In Consulting, European Market, Regulatory by Stephan Buttron

The US Food and Drug Administration (FDA) has recently released information on 14 warning letters to non-US device manufactures. These letters were delivered from the Center for Devices and Radiological Health’s (CDRH), Office of Compliance to 5 device manufacturers located in the UK, three 3 in China, 2 in Germany, and 1 each in Argentina, France, Italy and the Philippines.

Warning letters are publicly available information on FDA’s website on observed medical manufacturers Quality System deficiencies to meet US-FDA Regulatory Requirements for the design, manufacturing, storage, and distribution of medical devices throughout their life-cycle. The requirements of the Quality System Regulation (QSR) is set forth in the 21 Code of Federal Regulation in Part 820. Additional regulatory requirements apply for Medical Device Reporting (21CFR Part 803) and Corrections and Removals (21CFR Part 806).

A warning letter usually follows suit if a manufacturer failed to satisfactorily respond to inspectional observations—formally documented on a so called 483 Inspection Form within a 15 calendar day timeframe. While some information is public, others are not—confidential and proprietary information is usually redacted.

By far, the most common issues cited by FDA for these medical device companies were:

Number of Citations Issue
11 Failure to establish and maintain adequate procedures for implementing corrective and preventative action (CAPA), as required by 21 CFR 820.100(a)
8 Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a)
7 Failure to adequately establish and maintain procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a)
6 Failure to establish and maintain procedures to ensure that all purchased or otherwise received products and services conform to specified requirements, as required by CFR 820.50

Additionally, nearly all of the warning letters (11 out of 14) cited the recipient for violating a subsection of 21 CFR 820.30, which requires manufacturers to establish and maintain procedures related to device design.

Medical device reporting was also cited as an issue in 5 of the warning letters. These medical device manufacturers failed to develop, maintain, and implement medical device reporting requirements as set forth in 21 CFR 803.

In 4 of the 14 warning letters, FDA stated it did not review all or part of the companies’ responses to their respective inspection observations because they were made available after the 15-day window in which FDA requires a formal response.

Refusal of admission under section 801 (a) of the Act, 21 U.S. C. § 381 (a), simply means that inspected medical devices appear to be adulterated (i.e., out of specified design and manufacturing controls). As a result, FDA may take action to refuse entry of these devices into the US, known as “detention without physical examination”—until observed violations are corrected.

Are FDA Warning Letters Avoidable?

The answer is YES!  One of the biggest mistakes for medical device manufacturers, regardless of US and OUS origin, is not to be familiar with the US-FDA Quality System Regulation and other referenced regulatory requirements. The referenced 21CFR are not be mistaken as Quality Management System Standards. FDA Form 483 observations are not to be confused with Notified Body Audit non-conformances/audit deviations.

The 21 Code of Federal Regulations do represent legal and enforceable requirements. A non-conformity is considered a violation of legal requirements subject to enforcement.

Another mistake is incorrectly interpreting the regulatory language in these formal warning letters. The below lists some prominent, but common mistakes:

This letter is not intended to be an all-inclusive list of the violations at your firm’s facility means a device manufacturer is requested to further analyze if additional or other related violations exists. The cited observations may only be the tip of the iceberg.

We reviewed your firm’s response, dated YYYY-MM-DD, and conclude that it is not adequate means the formal response may not have included objective evidence to correct and mitigate the root causes of cited deficiencies. The formal and timely response to a 483 observation must be embedded into the framework of a corrective action plan with comprehensive timelines and milestone deliverables included. FDA considers objective evidences as available information based on facts that can be verified through analysis, measurements, observations, and other such means.

It is necessary for you to take action on this matter immediately means a medical device manufacturer should immediately initiate a comprehensive corrective actions plan within the framework of its CAPA procedures. This also requires a regulatory remediation plan to determine how to avoid further severe regulatory enforcement actions including, but not limited to, seizure, injunction, and/or civil penalties. In addition, it should be determined how to interact with FDA Office of Compliance, Enforcement Branch contact points as well as other concerned stakeholders to avoid miscommunication.

These recent warning letter demonstrate how FDA is serious about enforcing US Federal Medical Device Regulations inside and outside the US. The understanding and implementation of these regulations into a predominately small medical device operational environment maybe challenging, but necessary to protect the revenue stream. As with all challenges, there is professional help to get better, smarter, and likely faster results.


U.S. Food & Drug Administration. (n.d.). Warning Letters. Retrieved September 8, 2016, from


Stephan Buttron currently serves as NAMSA’s Senior Product Development Strategist. Mr. Buttron has over 20 years’ experience in achieving EU, U.S. FDA and other international regulatory medical device approvals and registrations. He has provided global consulting services on regulatory strategy development to medical device manufacturers regarding least burdensome pathways for 510(k)/PMA and MMD-CE mark applications. He has successfully managed FDA pre-submission meetings for Investigational Device Exemption (IDE) pathways with multiple FDA specialty branches. Stephan is considered a key industry thought leader on risk management, and has provided multiple training sessions to medical device manufacturers on structured risk management process per EN ISO 14971 & EU MDD 93/42 as amended with directive 2007/ 47. Mr. Buttron has also provided countless educational opportunities to international organizations regarding medical device design and development issues related to ISO 13485 & EU MDD 2007/47 compliance.