|
(FDA Guidance for Industry) (Excerpts)
November 2020
I. INTRODUCTION
II. BACKGROUND
III. POLICY
A. Examples of Insanitary Conditions
B. Preventative and Corrective Actions for Insanitary Conditions
It is critical that all compounding facilities prevent the occurrence of any insanitary conditions within their facility (including those not included as examples in this guidance). Prevention of insanitary conditions begins with the identification of risks associated with a process, procedure, or facility. Risk management tools offer a way to evaluate risk and to develop controls designed to prevent the occurrence of insanitary conditions within a compounding facility. In the event that insanitary conditions occur, having adequate monitoring and other management controls should facilitate the identification of insanitary conditions before the conditions result in drug contamination and patient harm. FDA recommends that compounding facilities consider consulting a third party with relevant drug production expertise to conduct this risk assessment and to help develop appropriate controls.
Upon identifying insanitary conditions, a compounding facility should immediately assess the impact of the insanitary conditions on drug products produced. The compounding facility's assessment should include an evaluation of how widespread the insanitary conditions are and over what period of time the conditions have existed, as well as the lots of drug product that remain on the market that could be affected.
The compounding facility should also determine whether to cease production of drug products until the conditions have been corrected and whether to initiate a recall of all potentially affected lots on the market within expiry. Below is a list of insanitary conditions that FDA has observed and considers to be particularly serious. If any one of these conditions exists, FDA strongly recommends that a compounding facility immediately initiate a recall of purportedly sterile drugs and cease sterile operations until the condition has been corrected.
- Vermin (e.g., insects, rodents) or other animals (e.g., dogs) in ISO 5 areas or areas immediately accessible to production
- Visible microbial growth (e.g., bacteria, mold) in the ISO 5 area or in adjacent areas
- Sources of foreign matter in the ISO 5 area (e.g., rust, glass shavings, hairs, paint chips)
- Performing aseptic manipulations outside of a certified ISO 5 area or area of higher quality air
- Personnel aseptic practices that are a contamination hazard to an exposed sterile drug product or its constituent sterile components
- Exposing sterile drugs and materials to lower than ISO 5 quality air for any length of time. This would include, for example, exposing partially stoppered drug products or stock solutions in a container/closure system that is not fully closed (airtight), and open packages of sterile wipes.
- Cleanroom areas with unsealed or loose ceiling tiles
- Production of drugs while construction is underway in a nearby area without adequate controls to prevent contamination of the production area and product
- A pattern of frequent or acute pressure reversals from areas of less clean air to areas of higher air cleanliness
- Using a filter for the purposes of product sterilization that is not appropriately graded for sterilization, not appropriate for pharmaceutical use, or used in excess of its volume or pressure capacity
- Using parameters for sterilization (e.g., temperature, pressure, time) that are not lethal to resistant microorganisms
If a compounding facility decides to initiate a product recall, we recommend that it document the implementation of the recall in accordance with the facility's procedures and immediately notify its local FDA Drug Division recall coordinator. We also recommend that the compounding facility notify the applicable state regulatory body in the state(s) to which the facility ships drugs, consistent with state laws and guidance.
In addition to the immediate actions recommended above, if a compounding facility identifies insanitary conditions, it should comprehensively assess its operations, including facility design, procedures, personnel, processes, materials, and systems, as applicable to prevent the occurrence of insanitary conditions within its facility. FDA recommends that the facility consider consulting a third party with relevant drug production expertise to conduct this comprehensive evaluation and to help implement appropriate corrective actions.
Compounding facilities producing purportedly sterile drug products under insanitary conditions should not rely upon or cite a passing sterility test result as an indication of product sterility. Microbial contamination, when present, is not uniformly distributed within a batch; therefore, it may not be identified in a sterility test. Compounding facilities must correct all insanitary conditions at their facility regardless of whether the drugs pass a sterility test.
C. Regulatory Action
If a compounding facility produces drugs under insanitary conditions, the facility and responsible individuals may be subject to several regulatory actions, including, but not limited to, a warning letter, seizure of product, or injunction. FDA may also recommend that the facility initiate a recall of some or all of its drugs and cease operations until the insanitary conditions have been adequately addressed. The applicable state regulatory agency may also pursue regulatory action against the facility under applicable state authorities.
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
|
