Bring up the recently updated and finalized EU Annex 1 – Manufacture of Sterile Medicinal Drug Products (here) in polite pharmaceutical water cooler conversation and a frequent topic that comes up is the Contamination Control Strategy (CCS) language. Buzzwords abound for a “holistic”, “global”, or “wholesale” CCS to be incorporated into all elements of aseptic manufacture of sterile drugs products. A common response to the Annex 1 CCS presented is one of feeling overwhelmed with guesses as to what response is needed to meet the EU Annex 1 expectations. Is a total CCS overhaul called for? Or perhaps an adaptation to the existing CCS documentation? For most mature companies manufacturing sterile drug products, the answer is likely somewhere in the middle of these two options. However, this CCS conversation started in the updated EU Annex 1 presents an opportunity for all companies to perform a reassessment of their practices as a means of continuous improvement.
So, where to begin in this holistic CCS endeavor? It’s not glamorous and nobody generally lists this item on their “most fun to do” lists, but the foundational building block of any CCS defaults to a robust cleaning validation. A well-designed cleaning validation sets the tone for a CCS that can be the needed “plumb line” to all sections of EU Annex 1 and the quality by design (QbD) principles ubiquitously found in ICH and FDA guidance. More often than not, a cleaning validation is designed with the best intentions of CCS and QbD principles. However, the reality is that things change over time, despite those initial best intentions. Facilities get updated, methods are transferred, trained personnel depart, drug product types expand, manufacturing steps are revised, and more recently, the availability of cleaning agent(s) become inaccessible due to supply chain issues. Consequently, every facility will be its own “special snowflake” in how cleaning validation is designed and implemented.
The recommendation from this author is to make a commitment to the CCS continuous improvement message of EU Annex 1 by considering the cleaning validation as the baseline conversation starter. Ideas for improvement include initiating a diverse group representing all applicable departments as key contributors. There are good common ground resources to provide baseline framework some of which include but are not limited to; PDA Technical Report 29 (Points to Consider for a Cleaning Validation) and ISPE’s Guide: Cleaning Validation Lifecycle – Applications, Methods, & Control. The message here is to consider the cleaning validation as a great launching point to ultimately show diligence in meeting the continuous improvement sentiment in EU Annex 1 – Manufacture of Sterile Medicinal Drug Products.
If your firm needs advice regarding integrating the concepts of Annex 1 into a robust cleaning validation program, Lachman Consultants can help! Please reach out to LCS@LachmanConsultants.com for an evaluation of your practices and a discussion of how to update them in order to achieve compliance with these new requirements.