Consequences of Failing FDA Data Integrity Standards and the 483

The United States Food and Drug Administration (FDA) is responsible for protecting public health by ensuring safety, efficacy and security of the food and drug supply. 

So, what really happens if, one day, an organization commits an error and the FDA takes notice?

A court visit? 

The shutdown of the business? 

Months of tedious follow-up paperwork? 

What really happens when there's a failure to meet FDA data integrity standards? 

In December  2022, that question was answered, at least for one firm under the watchful eye of federal regulators. 

Between November 22, 2022, and December 2, 2022, FDA inspectors visited a large pharmaceutical manufacturing facility in India nine times. The FDA also inspects locations overseas that import food and drugs into the United States.

The inspectors described the inspection of the facility as a “cascade of failure,” resulting in the dreaded 483 form.

The 483, in simple terms, is a warning letter. 

When an FDA inspector finds a violation serious enough to warrant one of these notices – which can be the result of a violation of data integrity protocols or insufficient monitoring or a host of other violates – it prompts action.

The FDA publishes most of the letters on its website, making the threat of public embarrassment real and lasting. 

The organization is given the chance to address the issue which, if left unchecked, could result in a U.S. sales ban for a foreign manufacturer like this firm. Regulators take seriously their charge to protect the public and it's not unreasonable for an organization to be shut down if the violations are egregious or persistent. 

Some of the violations can also be associated with allowing temperature and environmental conditions to fall out of specification, threatening food and drug safety and effectiveness. 

Many Sonicu customers turned to our trusted and affordable monitoring solutions following an adverse report like a 483 warning letter. Our reliable sensors and probes coupled with Sonicu's intuitive software, is a vital element to a robust regulatory compliance program. 

A remote, wireless temperature monitoring program can significantly improve virtually any organization's ability to be prepared for an FDA audit or inspection, and avoid the dreaded 483 warning letter. 

The coverup is often worse than the crime

In the aforementioned incident, the 483 form was issued following a single initial instance of alleged wrongdoing within the facility that was eventually found to have expanded into a much larger institutional problem. 

Further examination found that the facility’s employees were allegedly hiding data and paperwork from the inspectors. 

These findings, in turn, led the inspectors to do additional digging within the area in question.

The FDA’s action showed reasonable likelihood that the facility knew violations were being committed, and senior team members, rather than acknowledge the violations and take corrective action, chose a path of non-transparency coupled with non-compliance, putting the public at risk. 

This is exactly why FDA data integrity standards are enforced. 

Simple mistakes may go unnoticed until an inspection uncovers the issue and, ideally,  remediative action is taken. It’s the willful obstruction of investigators and coverup of known violations that caxn lead to serious punitive action once authorities uncover the violations. 

On Nov. 22, 2022, the day of the initial inspection, FDA investigators stumbled upon a revelation that would eventually uncover a breathtaking web of deceitful conduct. 

Investigators reportedly discovered a truck containing a clear, plastic bag with shredded documents that also held a black plastic bag found to contain additional documents that appeared to have been torn by human hands. 

To compound the discovery, additional plastic bags were concealed beneath a staircase, each cradling fragments of GMP (Good Manufacturing Practice) documents deliberately ripped into pieces. 

In order to help ensure the high efficacy and quality of products manufactured by the pharmaceutical industry, the FDA mandates that all data submitted to the agency for market approval must be both reliable and accurate. 

The FDA will automatically assume the authenticity of the data from the moment it is generated to the end of its lifecycle.

However,  in this scenario, the facility knew its data was inaccurate and failed to meet FDA data integrity standards, and that the FDA would not approve production until the issues were resolved.

Their suspicions piqued by the shredded documents, the FDA inspectors began to investigate further. 

Upon prying open the bag, they were met with an overpowering chemical aroma which revealed the torn and shredded documents were saturated with moisture.

The facility's quality control management attempted to play off the smell, explaining that an unrelated spill had been wiped up with tissues that had been discarded in the same bag as the documents.

Unconvinced, the investigators persisted with their inquiry and learned that, during the initial walkthrough, a quality control employee had deliberately torn up balance printouts and other key documents. 

The torn remnants were then doused with an acid solution in an attempt to destroy evidence and conceal the fact that the employee was tampering with key documents. 

FDA investigators reconstructed several documents, discovering that the destroyed records contained essential information for products sold within the facility. Subsequent investigations revealed widespread inconsistencies in the facility’s data management and recording.

The Associated Executive Vice President of Corporate Quality and Compliance noted, “The weighing activities documented in the “Instrument Usage Log” do not accurately represent the weight of samples with start and end times for each weighing activity related to a specific product lot. 

Additionally, a lack of uniformity among Quality Control employees for recording information in the LIMS logbook regarding the total number of tests was also identified.

Automating manual processes like logbooks can help any organization subject to an FDA audit. Sonicu makes it simple with our automated compliance reports to have the data ready at a moment's notice relative to temperature and environmental conditions.  

Some Quality Control employees may enter this information, while others may not, resulting in the lack of traceability for the exact number of lost tested and the start and end times of the analysis. Traceablity, or the ability to track down information over time with certainty, is a major function an FDA audit.

Sonicu has engineered its software with unique features - including a unique Persona Identification Number associated with each employee - for a digital signature that can serve as an important peg in the traceability log. 

This pharmaceutical company was allegedly committing numerous violations that were left unchecked and unsupervised. According to GxP Lifeline, pharmaceutical manufacturing plants have a multitude of moving parts and numerous personnel handling a considerable amount of data throughout a complex supply chain. 

And the FDA even has the power to pursue criminal charges if the issues found warrant. 

In business environments, employees are often expected to multitask and produce high levels of output.

That can sometimes result in mismanaged or unchecked data from human error, if not outright deception. In addition to the issues of consistency, inaccuracies were identified in the counting of environmental monitoring samples, stemming from either underreporting or incorrect calculation. 

U.S-based firms committed to complying with environmental monitoring regulations turn to Sonicu for a simple, affordable and trusted solutions that can collect, store and organize the data for a regulator. 

Furthermore, the Quality Control department invalidated failed results without providing data demonstrating sufficient control of the manufacturing process to ensure batch-to-batch consistency. In short, the failures were many and diverse. 

Why Data Integrity Matters  

Data integrity is a critical component of FDA standards for several reasons.

The scenario above illustrates why data integrity standards were put in place and why it is also important that the FDA expects all data to be accurate. 

Not only can bad data directly impact the reliability, accuracy and trustworthiness of information submitted by companies in the regulated industries– it can ultimately compromise the safety of products used by consumers. Organizations from the healthcare, manufacturing and researching industries in search of a wireless monitoring system that monitors clean rooms and other sensitive environments trust Sonicu to manage the data simply and accurately. 

Failing to meet FDA data integrity standards can have significant consequences for manufacturers.

While Form 483 citations encompass various compliance issues, data integrity is a common pitfall and can often be attributed to the complexity of regulatory requirements and the temptation to manipulate information during inspections to keep operations in motion.

Additionally, the 21 CFR Part 11 provides guidance to manufacturers on handling data submitted to the FDA. 

The key component emphasized in these guidelines is ALCOA+, an acronym signifying crucial principles for accurate tracking and storage of information which stands for: 

• Attributable: clear attribution, including the author’s signature data.
• Legible: Ensuring data is easily understandable, including explanations for symbols. 
• Contemporaneous: Prompt recording of data immediately after generation. 
• Original: Utilizing the original data or certified copy. 
• Accurate: Ensuring data reflects an accurate interpretation of the situation. 
• Complete: Inclusion of all relevant information, encompassing testing and retesting.
• Consistent: Uniform data entry, sequential time stamps, and consistent data generation. 
• Enduring: Recording data using valuated electronic systems or, if unavailable, controlled worksheets in laboratory notebooks. 
• Available: Ensuring data accessibility for review and audits throughout its lifetime 

While ALCOA+ provides a foundation for data integrity, effective maintenance requires equipment designed for compliance. 

Employing tools that automate data tracking and recording, and which prompt essential inputs is crucial to minimizing human error and upholding the integrity of data throughout its lifecycle. 

If attaining the ALCOA+ standard is important to your organization to meet regulatory standards, Sonicu has temperature and environmental monitoring solutions that can make it simple.