The long-anticipated revision to Annex 1 (from EudraLex's good manufacturing practices requirement for sterile drug manufacturing) is now closed for public consultation. Post consultation, many debates will continue around the timing of its publication, implications, perceived meaning and the level of implementation expected from the final version.

Annex 1 is understood to significantly affect the use of disinfectants within sterile manufacturing. As a holistic, risk-based approach to contamination control is fundamental to Annex 1, this is a critical aspect for consideration when reviewing the proposed updates.

Similar but not the same

The first aspect for consideration is cleaning and disinfection. It has long been widely accepted that cleaning and disinfection are two distinct processes within the cleanroom environment, trying to achieve two different processes: the removal of gross contamination and to kill microorganisms, respectively. Annex 1 adds much greater clarity around the requirements for disinfection validation, and the burden of proof for processes and efficacy.

Ready-to-use products

With increasing stringency over filter use, water use, and general requirements for proof of sterility and performance in use, the burden of producing disinfectants from concentrates increases significantly. This may make readyto- use products a more attractive option, when total cost of ownership is considered.


With specific requirements now in place on the removal of residues, and potential risks to product and processes being attributed to residues, there is a strong need for a risk-based approach for the control of disinfectant residues.

Transfer disinfection

The proposed Annex 1 introduces the need to have a validated list of items transferred in with the process and chemistry used to disinfect these items. Anything not on the list requires monitoring, and a risk-based approach is to be taken in line with the bioburden risk, thus providing greater transparency on the effectiveness of the material transfer process.

The proposed Annex 1 lists a full set of requirements

that should be considered as part of any assessment when moving to single-use technology, which includes pinhole leak verification, leachable and extractable validation.

The potential revision of Annex 1 provides a comprehensive re-examination of the previous version, with a focus on the application of quality risk management and pharmaceutical quality system to sterile manufacture. Public consultation is now closed for comment, but as with all new publications – especially drafts – there are some points of contention. Public consultation may be able to address these. Regardless, it is expected to deliver changes that will affect cleaning and disinfection, and the requirements around it, for all involved in the pharmaceutical industry.