(FDA Guidance for Industry) (Excerpts)
November 2020

I. INTRODUCTION
II. BACKGROUND
III. POLICY
A. Examples of Insanitary Conditions

2. Insanitary Conditions Applicable to the Production of Sterile Drugs Only

1. Gowning and Aseptic Practices (Covered in last week's newsletter.)
   
   
2. Equipment/Facilities
   • Microbial contamination in the ISO 5 area
      
   • Lack of adequate routine environmental monitoring
     • This includes nonviable airborne particulate sampling; viable airborne particulate sampling; and surface sampling, including but not limited to equipment, work surfaces, and room surfaces
   • Lack of adequate personnel sampling (including glove fingertip sampling)
      
   • Lack of routine and rigorous certification of the ISO 5 area, including smoke studies performed under dynamic conditions
      
   • A facility designed or operated in a way that permits the influx of lesser quality air into a higher quality air area. This includes, for example:
     • inadequate pressure differentials between areas of higher quality air and lower quality air
        
     • material flow directly between an unclassified area and a room in which sterile compounding is conducted (e.g., unclassified pass-through)
        
     • an ISO 5 area open to the surrounding area with minimal or no physical barriers separating it from non-aseptic activities (e.g., weighing of non-sterile materials, gowning, container labeling)
        
     • air returns located next to the high efficiency particulate arrestance (HEPA) filter rather than near the floor
        
     • an open door or series of open doors between an uncontrolled area and the room in which sterile compounding is conducted
   • Failure to detect and adequately address a change in air quality (e.g., through the environmental monitoring program) of any classified area before there is a loss of environmental control that may impact drug sterility
      
   • No or infrequent measurement of room pressure differentials during operations to demonstrate proper airflow (i.e., airflow from areas of higher quality air to adjacent areas with lower quality air)
      
   • A pattern of frequent or acute pressure reversals from areas of less clean air to areas of higher air cleanliness
      
   • A lack of HEPA-filtered air, or inadequate HEPA filter coverage or airflow, over the critical area
      
   • HEPA filters that are not sealed around the perimeter
      
   • Rooms not properly classified for the activities conducted within them
      
   • Unsealed or loose ceiling tiles in production areas
      
   • Production areas or equipment that are difficult to clean or contain porous, particle-generating, or visibly dirty (e.g., rusty) equipment or surfaces (e.g., shelving, floors, walls, doors, ceilings)
      
   • Buffer room or ISO 5 areas that contain overhangs or ledges capable of collecting dust (e.g., utility pipes and horizontal surfaces, such as windowsills)
      
   • The presence of sinks, drains, or water sources in the buffer room where the ISO 5 area is located; the presence of floor drains in the anteroom
      
   • The presence of equipment unnecessary for aseptic operations, particularly particle-generating equipment, in the ISO 5 area
      
   • Equipment within or in close enough proximity to the ISO 5 area that could compromise the air in the ISO 5 area
      
   • Exposing sterile products to non-sterile or non-depyrogenated supplies (e.g., transfer tubing, temporary bulk containers)
      
   • Using lyophilizers that are not sterilized by routine sterilization cycles and protected from contamination by sterilizing filters on vacuum break air lines/vents

[Continued next week.]

III. POLICY
A. Examples of Insanitary Conditions
1. Insanitary Conditions Applicable to the Production of Sterile and Non-Sterile Drugs
2. Insanitary Conditions Applicable to the Production of Sterile Drugs Only

• Gowning and Aseptic Practices
• Equipment/Facilities
• Sterilization
• Cleaning and Disinfecting
• Other Insanitary Conditions

B. Preventative and Corrective Actions for Insanitary Conditions
C. Regulatory Action

PLEASE NOTE THAT THESE ARE EXCERPTS ONLY AND THE ENTIRE DOCUMENT SHOULD BE OBTAINED AT THE LINK BELOW AND READ.

Insanitary Conditions at Compounding Facilities (fda.gov)

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
IJPC
Remington: The Science and Practice of Pharmacy Twenty-second edition

Announcement

REPORTING VACCINE REACTIONS

Free Patient Handout

Bob Listecki of Glen Ellyn Pharmacy in Glen Ellyn, IL is making available a Patient Handout on Reporting Vaccine Reactions prepared by Mursal Rashid Roslind a student at Franklin University. It can be downloaded free at:

Vaccine SE Reporting.pdf

Did You Know...

...that it's hard to play by the rules when the rules are always changing or you don't know what the rules are? This is especially true in pharmacy compounding.

Thought of the Week

Many of us have been in situations where what is expected is not clear or the expectations seem to be always changing. It is best to have clear rules and definitive guidelines/standards on what needs to be done. Laws are generally hard and fast. However, when we get to "guidelines," "standards," and sometimes "regulations," things are not firmed up or they frequently change or they are misinterpreted. It would be great if what is expected in compounding would be standardized and be consistent for years to come.