GMP Case Studies Presented by FDA Investigator Ileana Barreto-Pettit: Part IV
Stainless steel perforated cleanroom tables are designed to allow vertical airflow through the table and prevent stagnant pockets of air. However, when using perforated tables or work surfaces, the room airflow pattern and cleanability are often facets that are not fully evaluated and may represent contamination potential, according to a prominent FDA investigator.
[Related: Download a FREE compilation of this article and the three preceding ones here.]
At the International GMP Conference held virtually in March 2022, co-sponsored by the University of Georgia at Athens and FDA, FDA Office of Regulatory Affairs National Drug Expert Captain Ileana Barreto-Pettit presented in-depth case studies from recent drug GMP inspections that illustrate agency findings and concerns.
Barreto-Pettit has been with FDA for 23 years. She has been a drug investigator since 1999 and a Drug National Expert Investigator since 2017 and is a Captain in the U.S. Public Health Service Commissioned Corps.
The GMP inspection case studies Barreto-Pettit provided include an in-depth analysis of the findings, lessons learned, and how companies can avoid similar shortcomings. Areas examined in the case studies are:
- Inadequate change management systems
- Cross-contamination in solid oral dosage facilities
- Inadequacies and potential contamination hazards in aseptic manufacturing
- Perforated tables and work surfaces in cleanrooms
Part I covering change management findings in warning letters is available here. Part II covering cross-contamination in pharma manufacturing facilities is here. Part III covering deficiencies in aseptic manufacturing can be found here. The final case study is covered in this part.
Perforated Tables in Manufacturing: The Good and the Bad
Barreto-Pettit shared photos of perforated tables and work surfaces in cleanrooms (Figure 1) and asked, “Are there any obvious hazards with these stainless steel tables?”
“The idea is that these perforated tables allow air to flow through the perforation to provide better contamination control,” she explained. However, some of the tables will have perforations that are quite small or have enough surface area between their holes so that the air, as represented by neutrally buoyant smoke particles during smoke studies, does not flow very well through the bench.
[Related: What can recent FDA inspections tell us about expectations for equipment? Contact us to find out and also see how Redica can be the main tool in your inspection preparation toolbox].
In addition, sometimes these holes may be difficult to clean. “There have been some reports of clumps of some cleaning residue in these holes,” she said. “This is something that you need to look at if you have this type of table.”
And “even more concerning,” the FDA investigator emphasized, is that airflow conditions in the room, or the area near the benches, can create, under certain conditions, an upwards movement of air from under the bench through the perforations into the critical area.
“What this means is that air may potentially move from the operators’ feet through the bench due to the bounce back created by the overhead HEPA filter, personnel, or equipment moving past the workstation.”
If you have this type of table in your ISO 5 area, she suggested paying “close attention” to the associated smoke studies to evaluate whether the airflow situation just described occurs in your facility. “There have been reports of microbial particulate and fungal contamination transport via these openings in the tables,” she said.
In addition, sometimes these holes may be difficult to clean
Barreto-Pettit also recommended demonstrating and documenting that the perforated tables can be adequately cleaned, and “that the air does not flow in reverse through the holes under any circumstances.”
She provided another picture (Figure 2) of an ISO 5 aseptic area that was discussed in her third case study. The photo shows a perforated table inside the ISO 5 area.
That table is “quite cluttered with trays,” in addition to a piece of equipment in the room. “I do not know exactly how the air flows through here because there were no smoke studies conducted for this operation,” the FDA National Expert explained.
She pointed out other deficiencies shown in the photo as well. For example, the second operator is moving from the ISO 7 area to the ISO 5. In doing so, “he grabbed the curtain, touched it with his hand, touched the other operator, and was observed to then continue touching components and things within the ISO 5 area without first sanitizing his hands with isopropyl alcohol (IPA).”
Case Study Lessons
Barreto-Pettit provided takeaways from the four case studies she presented.
“We continue to see similar GMP deficiencies across the pharmaceutical industry. Many firms still have very immature quality systems that are reactive instead of proactive. They react because they get a 483. They react because they have a failure. They react because they have a Warning Letter. They should be identifying these GMP deficiencies on a constant basis through their operations by their quality systems or monitoring systems, and not wait for an inspection to suddenly act.
“The continued monitoring of operations and improvement programs are essential to stay and to be in compliance.
“An ongoing commitment to quality assurance includes the use of capable modern technologies. Technology is advancing. Are you going to stay with processes and technology from 40 or 50 years ago, or are you going to try to keep improving to enable sustainable cGMP compliance to serve the patients through robust quality and availability of needed medicines?
“Less capable manufacturing operations like the aseptic filling lines in these case studies will continue to receive extra FDA scrutiny during inspections.”
[Related: Click here to download a FREE compilation containing this and the three preceding articles to have on hand as you prepare for your next FDA GMP inspection.]
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