Every so often, I take the time to catch up on the FDA’s findings that result from the latest audits of drug, device, biologics and combination product manufacturers. It always astonishes me as to how these nonconformities occur, namely because the findings seem like simple issues that can be easily avoided. Throughout my career, I have seen various incidents like these occur, such as while walking through the manufacturing areas on the way to my workstation, conducting internal audits, performing supplier audits, or being audited by the FDA.

It occurred to me while I was reviewing these findings that if I think these issues are a simple fix, my guess is others will too, and by bringing awareness to these issues maybe it can prevent some headaches for the next company to be audited. If you’re looking for some insight into what the FDA is still finding, these are just a few of the findings that I came across.

1. An FDA Inspector issued a Form 483 (warning letter) to a drug manufacturer that failed to follow proper procedures for sterile handling of products:
   • The FDA said the company neglected to check on the condition of a drum used in processing liquid glucose for producing ferrous sulfate, and failed to notice what appeared to be streaks of rust on the container.
   • The company also did not ensure its products were sterile, and did not follow proper procedures to prevent microbial contamination.
   • The agency found the facility used tools that were not properly sanitized.
   • The company also fell short in monitoring environmental conditions in sterile processing areas, and did not independently verify the sterility of containers received from suppliers.

2. An FDA inspector issued a Form 483 to a medical device manufacturer for its supplier controls and quality documentation:
   • The inspector found that supplier controls failed to define levels of control or quality requirements for affiliates, with the documentation stating the only affiliate requirement was to be listed on the approved supplier list.
   • The supplier files were also insufficient, lacking required documentation such as completed supplier agreements, and procedures did not define how a supplier is moved from “approved” to “conditionally approved” or “restricted” status.
   • Investigators also found the company’s motor supplier was listed on “restricted” approval status since 2012 and was using a protocol that expired in 2013.

3. An FDA inspector issued a Form 483 to a contract manufacturer for problems with their device master records, document control procedures, and equipment maintenance :
   • The inspector found the company did not have established DMRs for its device, it had no established procedure for changes to quality documents, such as procedures and forms, and updates to such documents included no description of the changes.
   • The documentation also did not follow the company’s own quality records procedure, with multiple corrections made using white-out.
   • The company did not establish a maintenance schedule for one of its devices. The facility’s director of operations told investigators that blades in the machine were switched out weekly, but that process was not defined or documented.

So why do these nonconformities continue to occur year after year? Throughout my career, I’ve heard three common responses to this question: inadequate processes, faulty systems, and unviable programs. When we speak about processes, systems, and programs, this applies to whether we refer to a manufacturing or a CAPA process. Why is this necessary? It is the breakdown in these processes, systems, or ultimately, the programs where we see these nonconformities emerge.

The Process

A process is a series of actions taken in an order to achieve a certain end. The process has inputs and outputs and is supported by a process flow and each action might be a procedure. Once the process is linked to other processes and each output from each process is fed back into the process, the process can be controlled. This is then called a system that is in control because variation has been minimized or kept within specified control limits. Programs utilize systems and processes to achieve outcomes, which change the state of the organization.
Where does the breakdown happen? It can be one or more of the following:

• Inadequate Processes – Processes can be inadequate for many reasons. The obvious is that the inputs and outputs are not clearly defined and supported by a process plan. There were many times back in my auditing days, when I would ask a machine operator to show me how a certain product was actually manufactured, step by step and many times this did not match the manufacturing process that was documented. This is still a common problem today – the written process does not match the actual process. This could result in a minor or major nonconformity.Another example relates to training. Throughout my career associates would often tell me that training was insufficient or not comprehensive enough for them to understand how to do their jobs. For example in cases of “Read and Signs” (where you would read a procedure and sign that you read and understood what you read as a form of training). I would expect the extent of training to be based upon the criticality or risk of the product being manufactured or there was no time for training, so there is no documented training for the associate at all. I do not think that most of us could swallow that pill, especially if the user is a family member. Lastly, associates would complain that there was no On-the-Job Training. This is where you would have the opportunity of shadowing a trainer to see how the work is done and then performing the work yourself and being assessed.
• Faulty Systems – Systems can easily become faulty if the processes are not being measured. The purpose of the feedback loop that I spoke about earlier was to monitor and measure the output to verify that it is in control and within specified process limits. For instance, a common situation is for CAPA’s to be open longer that the required closeout dates. There is a breakdown in the feedback loop as it is not triggering an action to stop this from happening.
• Unviable Programs – Programs may not be viable if they use the systems and processes to achieve outcomes, but are not given the resources or capabilities. Programs also do not work if they cannot validate outcomes. Associates often complain that programs do not work because upper management does not push its support of these programs down from the top. The programs are not based in electronic and automated systems that make being involved in the program as user-friendly as possible. It is very difficult to drive paper systems and not find compliance issues with them.

Although I am sure that you have probably heard similar reasons from your associates as to why these nonconformities continue to occur, these reasons are not really the root cause. We have seen a lot of improvements over the years in the tools, techniques, and methodologies to help us become more efficient at our work. Things like, Total Quality Management, Six Sigma, Lean Management, Project Management, etc.  Yet we still seem to find nonconformities in our quality systems. What is really driving these nonconformities? I believe that the reasons why these nonconformities continue to occur are due to the following:

1. Limited Resources – For all of the companies that I have worked or consulted for, associates tell me that there are not enough resources to complete the required tasks to remain compliant. Downsizing has been to blame for this decrease in resources, with little or no planning for who will pick up the existing tasks or how. Other reasons include reduction in workforce, employee turnover and employee absenteeism.
2. Competing Priorities – Keeping the focus on projects and standard work tasks can be difficult with the bevy of hot industry topics that surface to compete with current work (Serialization, Data Integrity, Genome Technology, Biosimilars, ISO 13485: 2016 Transition and Medical Device Single Audit Program (MDSAP) etc.). Other reasons include new projects, increased regulatory requirements and unplanned company objectives, with extra help and budget always being a factor.
3. Increasing Volumes – It can be difficult keeping up with increase in demand of the product, required validation runs, and increase in distribution channels.

With all the progress and improvements that have been made in our industry, the FDA findings of nonconformities in manufacturing should be decreasing significantly – but this doesn’t seem to be the case. However, the issues as to why these nonconformities are happening are very correctable and can be easily avoided. In order for employees to stay focused on what they need to do in an environment where new projects and changing requirements are happening on a regular basis, there needs to be adequate resources and support. It starts with enough of a workforce that can handle the projects at hand and budgets that can support the objectives of those projects. Even in a world where downsizing is a factor, basic planning and employee participation and support has to be at the start of any new project. It is when all of these things can come together, that programs to processes and systems will run efficiently and the likelihood of the FDA finding nonconformities will be greatly reduced.