Pharmaceutical manufacturers have an obligation to ensure that their manufacturing equipment is properly designed, installed,
tested, operated, and maintained throughout their service lifetimes. During these service lifetimes, manufacturing equipment
will likely require both preventive and corrective maintenance activities that may involve the replacement of parts within
the systems. Parts replacements must be performed under the appropriate change controls to ensure that manufacturing equipment
remains in a validated state with respect to installation, operation, and performance. Change-control considerations are greatly
facilitated when replacement parts are exactly identical to the original parts. However, it is not uncommon for pharmaceutical
manufacturers to resort to procuring and installing replacement parts that are not identical to the original parts due to
changes affected by parts suppliers (e.g., product redesigns, discontinuations). In these instances, a risk-management approach
may be used to systematically assess whether replacement parts are functionally equivalent (i.e., like-for-like) with original
parts to ensure proper change control while also preventing unnecessary revalidation activities.
This case study on functional equivalence for equipment replacements is the second of eight in a series put together by the
Product Quality Research Institute Manufacturing Technical Committee (PQRI–MTC) risk-management working group. The series
is meant to advance the understanding and application of the International Conference on Harmonization (ICH) Q9 Quality Risk Management guideline by providing actual examples of risk-management assessments used by the bio/pharmceutical industry. The introductory
article explaining the history and structure of the series, as well as the first case study, on defining design space, appeared
in the July 2011 issue of Pharmaceutical Technology (1).
In this case study, a risk-management approach was taken by the firm to identify the following:
- Risks associated with equipment-parts changes that might adversely impact the validated state of manufacturing equipment
- Risks associated with the process of determining whether original and replacement parts are functionally equivalent
- Proper roles and responsibilities of the functional areas involved in the process of determining whether original and replacement
parts are functionally equivalent.
The outputs of the risk-management approach used by the firm included a generic, robust, and repeatable process for performing
functional-equivalence assessments as well as defining organizational roles and responsibilities supporting the process.
Risk question and risk-assessment method
The risk question developed for the subject case study was: What process and associated functional area roles and responsibilities are required in order to assess whether replacement
parts are functionally equivalent with original parts in order to ensure proper manufacturing-equipment change control while
also preventing unnecessary revalidation activities?
The firm elected to craft one risk assessment for the overall (generic) functional-equivalence assessment process to achieve
- Identify potential gaps, inconsistencies, and redundancies within the process that had historically been used for replacement-parts
functional equivalence determinations
- Identify new or improved activities that would lead to robust, efficient, and consistent functional-equivalence assessments
To support selection of a risk-assessment method, the team examined the above risk question and identified the core activities
supporting the historical functional-equivalence assessment process. Core activities examined included the equipment change-control
process and the maintenance-systems inventory process-control flow. The team noted the following observations:
- The functional-equivalence assessment process was historically dependent upon human judgment, expertise, and experience
- Process risks (e.g., potential breakdowns of the process) were qualitative in nature and difficult to quantify with specificity.
Given these observations, the risk-assessment team selected Fault Tree Analysis (FTA) as its risk-assessment method because
it is well suited for analysis of qualitative fault conditions that may be related to human performance factors.