A Look-back on Data Integrity in 2020 – Part 2

This is part 2 of a 2-part article series on Data Integrity trends in 2020. Find the link to part-1 here.

In this article, we will delve into some of the interesting trends in FDA inspections as well as warning letters, which sets-apart 2020 from the years before it.

Impact of the pandemic on FDA inspections in 2020

Often, challenging scenarios bring out the innovative side in humans, and the pandemic of 2020 was a prime example of that. During such times, the health and safety of the general public takes even more precedence, thereby enforcing the manufacturers, importers, distributors, and QC laboratories to comply with GMP (Good Manufacturing Practices) and GDP (Good Documentation Practices). To continue implementing effective inspection processes during this time when travel and on-site inspections are curtailed, the European Medicine Association (EMA) released a guidance on how to implement “distance assessments” of GDP/GMP in manufacturing facilities.

This guidance enlists the different steps of planning, assessing, and conducting distance assessments, which require the inspectors to be familiarized with the site to be inspected. The guidance explores the different practical setbacks of a distance assessment such as lack of complete access to documents via videoconference and unavailability of platforms that will enable the sharing of large chunks of electronic data. It also acknowledges the importance of technology, for example, the varying capabilities of sites to be able to provide live camera footage as a solution for remote reviewing of the manufacturing sites. The guidance dictates that the GMP/GDP certificates awarded at the end of an inspection must state the exact type of inspection that was carried out (distant or on-site), to provide clarity for future reference. In addition, existing regulatory risk management principles may be used as a reference to determine the duration of validity of these distant assessment certificates.

The COVID-19 pandemic imposed an undue amount of pressure on pharmaceutical companies as they competed against each other to be the first to produce the drug which effectively alleviates the various symptoms of this viral infection. This sudden increase in drug manufacturing in turn led to the increased responsibility of the FDA. Along with compliance responsibilities, the agency was facing additional political coercion to release an EUA (Emergency Use Authorization) for a particular drug against COVID-19 generated using the antibody therapy method, produced by one of the leading Pharmaceutical companies in the world.

However, according to an article published in Reuters, the granting of EUA for this drug could be complicated based on the company’s history with the FDA. In this report, it is mentioned that in an inspection carried out by the agency in November 2019 at one of the company’s many facilities, it was discovered that data related to manufacturing had been deleted. The associated audit trails of this data were also deleted and not reviewed by the Quality department, thereby prompting the FDA to issue an OAI (Official Action Indicated) notice to the company. Unfortunately, a follow-up inspection in August 2020 brought forth more issues, resulting in the issuance of a second 483 letter to the company. With this information in mind, the FDA would presumably proceed with caution in relation to the drug produced by this company, although there is an undeniable need for the drug in the market. The current update is that the clinical trials of this drug on hospitalized patients have been put on hold “out of an abundance of caution” over a potential safety concern. More developments regarding the release of this drug, and the fate of this facility, will depend on the decision of the FDA and will most likely unfold in 2021. This case stands as an example, that data integrity is still one of the key compliance topics.

FDA Warning letters in 2020

Based on the insights from an article by Barbara Unger for Pharmaceutical Online, it is interesting to note that the number of form 483s issued by the FDA in 2020 is less than half of that issued in 2019, owing to the unforeseen halt in travel and inspection procedures elicited by the COVID-19 pandemic. It is expected that the trend of reduced 483 forms issuance and FDA inspections will continue well into 2021. Incidentally, the most cited regulation of 2020 was 21 CFR Part 211.192, which deals with “Investigations of discrepancies”. This indicates that the industry is grappling with a lack of understanding on how to conduct effective investigations for unexpected as well as out of specification results. The FDA has paid special attention to OTC (over the counter) manufacturers, as there has been a pattern of non-compliance and lack of knowledge of basic cGMP and FDA guidelines.

The concept of data governance was explicitly mentioned and addressed for the first time in a warning letter issued by the FDA to a contract manufacturing company. This warning letter provides a holistic view on the different aspects of data integrity remediation and delves into the importance of segregating management responsibilities. The letter also touches upon some of the potential duties of a firm’s management team, such as quality management and resource allocation to preemptively combat quality issues. The warning letter goes as far as to require the management to come up with a strategy that details the CAPA procedures to ensure completeness and reliability of the data that is submitted to the FDA, including analytical data and manufacturing records. This warning letter offers a refreshing spin on how informative and instructive the FDA warning letters can be when approached from a DI governance point of view, and therefore it demonstrates what the “c” is in cGMP.

The Future of Data Integrity

As the world gravitates more and more towards scientific and technological advancements, the importance of data integrity will remain on the rise. As we understand more about the different features of data, we realize that some of the methods we may have implemented in the past to verify data integrity might be outdated. In today’s scenario, one needs to view data with utmost critical thinking skills, which requires the ability to drill down into the superficial data in a more granular manner, rather than simply observing and reporting trends which may or may not provide the full picture.

Global compliance specialist Paul Smith in his webinar about DI trends indicates that there are two ways by which we can choose to approach DI. One is the short-term approach, which is effective but myopic. This approach only focuses on a specific deviation after it arises during an audit trail, and is more in search of the regulatory answers, thereby making it a reactive method. The proactive strategy, on the other hand, is interested more in data as a whole to predict future trends in terms of risk management and is long-term. Although the former approach costs less, the latter is cost-effective in the long run, as we will never know the true cost of non-compliance. Therefore, it is safe to assume that data governance and quality culture at every level of the hierarchy will be the strategy that would help preserve holistic Data Integrity in the coming years.