FDA 483 Observations in 503A Facilities

In this issue, we will look at FDA 483 observations in 503A facilities.

As previously mentioned, 503A compounding pharmacies are to be inspected by state boards of pharmacy in each state, but the FDA has the authority to and has become more proactive in conducting its own inspections and taking enforcement actions to protect public health when necessary.

A review of 185 Form 483s issued to 503A compounding pharmacies in 2016 and 2017 and presented at the 2018 National Home Infusion Association Annual Meeting reported 1,032 observations in three main categories:

• Issues related to the compounding process or compounder (46%)
• Issues related to the compounding area or equipment (44%)
• Administrative issues (10%)

Specific issues included lack of sterility, mislabeling, and procedural problems. The majority of the observations were related to the following:

• Potential contamination from improper garbing
• Potential contamination from the use of nonsterile garbing
• Improper aseptic technique
• Visible contaminations in the compound area, and
• Failure to monitor the environment to ensure the compounding area is maintained at proper pressure, temperature and airflow.

2018 to 2020 Specific Issue Categories
In this issue and the next two issues of this newsletter, we will break down a number of 483s and list specific items as related to the following categories in more detail:

1. Personnel
2. Facility
3. Equipment
4. Environmental Monitoring
5. Cleaning, Disinfecting, and Deactivating
6. Compounded Product Quality
7. Unapproved Components
8. Insanitary Conditions
9. Complaint Follow-up
10. Administrative and Regulatory

This week, we will look at the first two categories:

1. Specific Issues - Operators - Personnel

• Operator blocking first pass HEPA filtered air
• Operator did not move slow and deliberate in the ISO 5 environment
• Operator did not wear a beard cover
• Operators demonstrated poor aseptic practices such as failing to disinfect their gloved hands after touching nonsterile components prior to performing aseptic operations
• Equipment and supplies were not disinfected prior to entering the ISO 5 aseptic processing area
• Operator failed to wipe down the tubing package before placing it with the ISO 5 work area
• Operators donned gowning apparel improperly such that it may become contaminated
• Operators were observed touching their sterile sleeves against both the door handle leading to the cleanroom and a hood located within the ante-room
• Operator failed to use sterile gloves when preparing sterile drug products.

2. Specific Issues - Facility

• HEPA filters do not cover the entire room
• No full assessment of the room's pressure differentials
• Smoke studies not performed throughout the entire room
• Non-classified air coming from the ISO 8 Prep room to the ISO 5 room
• Partially stoppered "drug x" partially located under a light fixture the does not have a HEPA filter
• Your firm failed to demonstrate through smoke studies that there is not an influx of poor quality air entering the classified ISO 5 area
• Your firm has not performed smoke studies under dynamic conditions
• Your firm failed to monitor the differential pressure between areas with different air classifications
• There is a refrigerator adjacent to the LAFH
• A tabletop fan was observed on the counter between two hoods
• Air conditioning vents were observed in close proximity to two hoods and all hoods were cluttered containing supplies and equipment
• Your facility design allows influx of lower quality air into an area of higher quality air
• The ISO 5 workstation is located in a non-classified room that contains a sink and a dishwasher; both are potential sources of microbial contamination
• Your firm failed to confirm the water quality is suitable for the production of nonsterile drug products

As is evident in some pharmacies, there have been issues with the personnel and the facility. The positive aspect is that as these issues are addressed, quality increases. More information next week.