FDA has posted 18 Form 483s, to 503B facilities, thus far in the third quarter of 2018. FDA has identified 69 observations of potentially objectionable issues within these 18 facilities. A summary of the 2018 Q3 FDA Observations follows:
Table 1 – 69 observations categorized by topic
|Category of Observation||Frequency of occurance|
|Poor Facility Design||7|
|Critical Air Flow||3|
|Finished product testing||2|
|Adverse Event Reporting||1|
As we can see from the above table, the two largest groupings of observations fall into the disinfection and aseptic techique. The specific observations from the FDA 483 attributed to disinfection include:
Table 2 – FDA observations concerning disinfection practices by the inspected 503Bs.
|Non-sterile disinfecting agents are used in the aseptic processing (ISO 5) area.|
|Materials or supplies were not disinfected prior to entering the aseptic processing areas.|
|Disinfecting agents used in the ISO 5 aseptic processing areas are not sterile.|
|The use of sporicidal agents in the cleanrooms and ISO 5 aseptic areas is inadequate.|
|Equipment was not disinfected prior to entering the aseptic processing areas.|
|Materials or supplies were not disinfected prior to entering the aseptic· processing areas.|
|Disinfectant contact lime (also known as “dwell time”) and coverage of the item being disinfected were insufficient to achieve adequate levels of disinfection.|
|Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions.|
|Disinfectant contact time|
|Equipment, materials, and/or supplies are not disinfected prior to entering the aseptic processing areas.|
|The use of sporicidal agents in the ISO 5 classified aseptic processing area was inadequate.|
|Disinfecting agents and cleaning pads used in the ISO 5 classified aseptic processing areas were not sterile.|
|Disinfecting agents, cleaning pads, and cleaning wipes used in the ISO 5 classified aseptic processing area were not sterile|
|Materials or supplies were not disinfected prior to entering the aseptic processing area|
With regards to aseptic technique, FDA identified the following observations:
Table 3 – FDA observations regarding aseptic techinque.
|Personnel engaged in aseptic processing failed to prevent cross-contamination on the working surface of the ISO 5 laminar flow hood work bench.|
|Personnel conducted aseptic manipulations and placed equipment/supplies in an area that blocked the movement of first pass air around an open unit, either before or after it was fi!le.d with sterile product.|
|Personnel engaged in aseptic processing were observed with exposed hair.|
|Personnel did not disinfect to prevent contamination.|
|Personnel engaged in aseptic processing were observed with exposed skin around the face and with their face and exposed skin inside of the ISO 5 hood. Personnel did not disinfect gloves to prevent contamination.|
|Personnel were observed conducting aseptic manipulations that blocked the movement of first pass air around an open unit, whether before or after it is filled with sterile product.|
|An operator was observed placing her gloved hands outside the ISO 5 area and not re-sanitizing prior to placing her gloved hands under the ISO 5 hood. The same operator was observed wearing a face mask and hairnet which left the skin of her forehead partially exposed. The operator was observed to introduce the exposed skin of her forehead inside the ISO 5 hood.|
|Personnel engaged in aseptic processing were obse1ved with exposed hands, exposed wrists and exposed hair.|
|Personnel touched equipment or other surfaces located outside of the ISO 5 classified aseptic processing area with gloved hands and then engaged in aseptic processing without changing or sanitizing gloves.|
|Personnel engaged in aseptic processing failed to follow proper aseptic techniques.|
|Personnel engaged in aseptic processing were observed with exposed skin.|
|Personnel engaged in aseptic processing wear non-sterile gloves|
Historically, FDA has posted the results of 503B inspections as a matter of public interest on the FDA website at the following Link. The data for the above post was retreived from the FDA website, and qualitatively analyzed to fit the FDA observations into predefined categories. Within each Form 483, each observation has examples from which the observation was drawn from. for example, Observation 4 from Form 483
Materials or supplies were not disinfected prior to entering the aseptic processing areas.
Specifically, employees were observed taking vials of ingredients from the storage area under the ISO 5 hood and putting them directly into the ISO 5 laminar flow hood without any decontamination step on multiple occasions.
If you would like a listing of the specific observations for the above table – please contact Dr. Van Doel, of Performance Valiation.