3 Crucial Factors to Achieve Annex 1 Compliance

On August 25^th 2022, the FDA alongside EMA jointly released its new Annex 1 regulations for sterile drug manufacturing processes, monitoring, quality control, and more. The revision has been 14 years in the making, and largely overhauls the original 2008 good manufacturing practices with the aim of reflecting the changes of evolving manufacturing processes. The new regulations take effect on August 25th 2023, which means that time is of the essence when updating your cleanroom standard operating procedures to become Annex 1 compliant.

1.   Cleaning Protocols

One of the new required changes will be your cleaning processes. The definitions of “cleaning” and “disinfecting” are independently defined in Annex 1; the regulations affirm that for a production space to be considered aseptic, it must be first be cleaned — that is, non-viable contamination must be removed — then disinfected, to ensure microbial kill. Annex 1’s implication here is that “cleaning” and “disinfecting” have different goals — and, therefore, different processes — and should be approached as two distinct tasks that keep your surfaces aseptic. 

Current Annex 1 states:

4.24   The Cleaning process, prior to the Disinfection process, is Essential.
Any residues that remain may inhibit the effectiveness of the Decontamination process
4.36   For Disinfection to be effective, prior cleaning to remove surface contamination should be performed
5.4     The Cleaning process should be Validated to:
Remove any residue or debris that would detrimentally impact the effectiveness of the disinfecting agent used.
Minimize chemical, microbial, and particulate contamination of the product during the process and prior to disinfection.

The goal of this cleaning requirement is to remove the residue often left by most disinfectants. These residues run risk of compromising the efficacy of the disinfectant, and so should be captured and removed. This is a protocol you can commence immediately and be in compliance once the new regulations are enforced. The process can be easily updated by using tools with scientifically proven Ultra-Fiber technology that was designed with Annex 1 compliance in mind. 

2.   Residue Removal and Disinfectant Application

Benchmark’s Suite® products are intentionally designed and rigorously tested to ensure that residues, bioburden, endotoxins, and other contaminants are easily captured and removed. The new regulations within Annex 1 are approaching fast and provide a perfect opportunity to evaluate the effectiveness and ability of the products you’re using to clean and disinfect your surfaces. Suite^® uses proprietary Ultra-Fiber technology in its cleaning products including mops, sponges, wipers, and reaching tools. Ultra-Fiber material is densely packed with the maximum concentration possible of high-grade microscopic fibers. These fibers break surface tension to penetrate the submicron crevices of cleanroom surfaces down to an endotoxin level, while eliminating the possibility of cross-contamination from carryover.  

3.   Disinfecting Protocols 

Annex 1 also provides guidance on the qualification of disinfectants. All disinfectants, including, but not limited to, pre-saturated wipes, sprays, and solutions diluted from concentrate, must undergo efficacy testing to ensure that they perform properly for the duration of their shelf lives. The requirement specifies that tests are done on the surfaces of each specific facility to validate the application process is effective on the equipment surfaces for which their use is intended.

Continued in Annex 1’s disinfectant regulations are updates regarding rotation. More than one disinfectant is expected to be used, including the periodic use of a sporicide. Annex 1 does not provide strict directives on which compounds should be used, when, or in what rotation; rather it leaves these decisions up to the discretion of risk management teams and regular auditing of the products available.

Also included in the Suite^® family are product transfer tools and personal protection equipment like gloves, masks, hoods, and goggles that will protect your team from any aggressive broad-spectrum and sporicidal biocides used in your cleaning process.

Annex 1 is intended to recognize the advances in life science manufacturing technology and best practices. While additional regulations may develop in the future, it is certain that these requirements for cleaning and disinfecting will be enforced. Begin evaluating your tools, processes, and equipment now to ensure your production facilities and scope are meeting good manufacturing practices come August 2023. 

Browse our SUITE products to get ready for Annex 1 regulations to take effect, and contact your Benchmark Regional Manager today for additional help in getting your facilities and processes prepared.