An Analysis Of FDA FY2018 Drug GMP Warning Letters

BioProcess Online has a nice summary of the drug GMP warning letters issued in FY2018, as well as a comparison of trends since fiscal year 2013.
— Read on www.bioprocessonline.com/doc/an-analysis-of-fda-fy-drug-gmp-warning-letters-0003

Data Integrity definitely continues to be a theme, and I agree that we are seeing a growing trend around process validation. I also think root cause investigations was a theme of 2018 that we are going to be seeing a lot more of.

FDA draft guidance – Continuous Manufacturing

The FDA published today a new draft guidance “Quality Considerations for Continuous Manufacturing Guidance for Industry.” Which, together with ICH plans continues to demonstrate the emphasis on continuous manufacturing.

More a set of questions than anything else, this is a good document for those who are grappling with the challenges of continuous manufacturing.

FDA launching pilot program on established conditions

The FDA has announced a pilot program to “propose explicit established conditions (ECs) as part of an original new drug application (NDA),
abbreviated new drug application (ANDA), biologics license application
(BLA), or as a prior approval supplement (PAS) to any of these.”

As the FDA mentioned, this is a followup of two draft guidances: The 2015 FDA ‘‘Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products’’and the draft Q12.

It is exciting to see Q12 move forward. We can argue about its imperfections, but at the end of the day this is a big step for the industry.

The role of a data steward

With data integrity on everyone’s mind the last few years, the role of a data steward is being more and more discussed. Putting aside my amusement on the proliferation of stewards and champions across our quality systems, the idea of data stewards is a good one.

Data steward is someone from the business who handle master data. It is not an IT role, as a good data steward will truly be invested in how the data is being used, managed and groomed. The data steward is responsible and accountable for how data enters the system and ensure it adds value to the process.

The job revolves around, but is not limited to, the following questions:

  • Why is this particular data important to the organization?
  • How long should the particular records (data) be stored or kept?
  • Measurements to improve the quality of that analysis

Data stewards do this by providing:

  • Operational Oversight by overseeing the life cycle through defining and implementing policies and procedures for the day-to-day operational and administrative management of systems and data — including the intake, storage, processing, and transmission of data to internal and external systems. They are accountable to define and document data and terminology in a relevant glossary. This includes ensuring that each critical data element has a clear definition and is still in use.
  • Data quality, including evaluation and root cause analysis
  • Risk management, including retention, archival, and disposal requirements and ensuring compliance with internal policy and regulations.

With systems being made up of people, process and technology, the line between data steward and system owner is pretty vague. When a technology is linked to a single system or process it makes sense for them to be the same person (or team), for example a document management system. However, most technology platforms are across multiple systems or processes (for example an ERP or Quality Management System) and it is critical to look at the technology holistically as the data steward. I think we are all familiar with the problems that can be created by the same piece of data being treated differently between workflows in a technology platform.

As organizations evolve their data governance I think we will see the role of the data steward become more and more part of the standard quality toolbox, as the competencies are pretty similar.

Bystander Effect, Open Communication a​nd Quality Culture

Our research suggests that the bystander effect can be real and strong in organizations, especially when problems linger out in the open to everyone’s knowledge. 

Insiya Hussain and Subra Tangirala (January 2019) “Why Open Secrets Exist in Organizations” Harvard Business Review

The bystander effect occurs when the presence of others discourages an individual from intervening in an emergency situation. When individuals relinquish responsibility for addressing a problem, the potential negative outcomes are wide-ranging. While a great deal of the research focuses on helping victims, the overcoming the bystander effect is very relevant to building a quality culture.

The literature on this often follows after social psychologists John M. Darley and Bibb Latané who identified the concept in the late ’60s. They defined five characteristics bystanders go through:

  1. Notice that something is going on
  2. Interpret the situation as being an emergency
  3. Degree of responsibility felt
  4. Form of assistance
  5. Implement the action choice

This is very similar to the 5 Cs of trouble-shooting: Concern (Notice), Cause (Interpret), Countermeasure (Form of Assistance and Implement), Check results.

What is critical here is that degree of responsibility felt. Without it we see people looking at a problem and shrugging, and then the problem goes on and on. It is also possible for people to just be so busy that the degree of responsibility is felt to the wrong aspect, such as “get the task done” or “do not slow down operations” and it leads to the wrong form of assistance – the wrong troubleshooting.

When building a quality culture, and making sure troubleshooting is an ingrained activity, it is important to work with employees so they understand that their voices are not redundant and that they need to share their opinions even if others have the same information. As the HBR article says: “If you see something, say something (even if others see the same thing).”

Building a quality culture is all about building norms which encourage detection of potential threats or problems and norms which encouraged improvements and innovation.