This is the third in PSC’s series on Quality Risk Management (QRM) in Commissioning and Qualification (C&Q) following on the concepts introduced in the first two installments: QRM in C&Q Planning, and Risk Assessments – One Size Does Not Fit All. This week’s discussion is about the identification and verification of “Critical Aspects” (as referred to by ASTM E2500) of pharmaceutical and biopharmaceutical manufacturing systems and facilities.

What are Critical Aspects?

ASTM E2500“Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment”, defines the Critical Aspects of manufacturing systems as follows: “…functions, features, abilities, and performance or characteristics necessary for the manufacturing process and systems to ensure consistent product quality and patient safety.”

Put another way, Critical Aspects are the features, functions and characteristics systems must possess to adequately control manufacturing process risks and protect the patient, and therefore to be fit for their intended use. In that context, identifying Critical Aspects also identifies (and provides rationale for) Qualification testing requirements for the overall system.

How are the Critical Aspects of Manufacturing Systems Identified?

The process of Critical Aspect identification is one of risk assessment and evaluation of controls. The general process flow is depicted below:

Failure modes that potentially impact Process User Requirements (see previous PSC Risk Management blogs for definition and discussion of PURs)

Critical Design Elements

Following the identification of the necessary Critical Aspects of a given system or facility, the next step is to assure that these aspects are included in the design for same. A Critical Design Element (CDE) is defined by ISPE as a: “…function or feature of an engineered system that is necessary to consistently manufacture products with the desired quality attributes” (emphasis by author).

The review of system designs against the identified CDEs is the basis for Design Qualification (DQ). While development and design of equipment and facilities is generally an Engineering Unit responsibility, designated process SMEs, including representation from the Quality Unit, should review and approve the DQ for all new or significantly modified Direct Impact systems and facilities.

Keep in mind that multiple CDEs may be required to adequately ensure achievement of a single Process User Requirement. As an example, a critical alarm along with multiple system interlocks and data capture requirements may all be CDEs of a steam sterilizer control system.

See an upcoming PSC blog for detailed information on Best Design Review/Qualification Practices.

Verification / Qualification Planning for Critical Aspects

The subject of C&Q planning based on Quality Risk Management has been addressed in a previous PSC blog, here we will only refer again to the ICH Q9 principle that the level of effort, formality and documentation should be commensurate with the risk. The linkage of Critical Aspects to the Process User Requirements for a given system and/or process provides a roadmap to the Commissioning and Qualification (also known in combination as “verification”) of Direct Impact manufacturing systems and facilities.

PSC Biotech® is one of the largest providers for Commissioning, Qualification, and Validation services for the life science industry. Our team consists of seasoned experts in the validation of equipment, facilities, utilities, computer systems, processes, and cleaning validation. We provide end to end solutions with expertise in Validation Master Plans, Requirement Specifications (URS/FRS/DS), Risk Assessments, Traceability Matrices, IQ/OQ/PQ Protocols, Summary Reports, and Turnover Packages. Contact us to find out more!

Authored by David Dolgin

Editor: Crystal McClain, PhD

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