The FDA is reinventing its approach to quality and compliance and is driving the industry in the direction of a more concrete and cohesive argument for process understanding. The real impact of the FDA’s guidance document, Pharmaceutical cGMPs for the 21st Century — A Risk-Based Approach, issued in 2003, has just begun to be felt. Subsequent agency guidance documents for aseptic process and quality system establishment have reinforced the position that building quality into a process at the design phase, while utilizing a risk-based approach to establish control and understanding, will be the expectation moving forward. This new mindset will impact the approach used to design and establish all facilities within the regulated life sciences. This article offers some considerations for developing one of the most rigorous types of controlled environments, an aseptic operation, in order to meet the new expectations ofthe agency.

REGULATORY GUIDANCE DOCUMENTS
Although the basic attributes of an aseptic facility are well understood, there are several key guidance documents to consider during the design process to later demonstrate that the facility meets the needs of the process and the product. The first two documents are not from the FDA but were issuedby the International Conference on Harmonization (ICH). ICH Q8 defines the basic elements for pharmaceutical product development. The document advocates a methodology that moves process understanding from the knowledge space, which encompasses all possible variables that can influence process predictability, to the control space, which defines the optimum operating space for those key parameters that control process predictability. This process is depictedin Figure 1.