Pfizer's TMF solution overview
Pfizer's first step was to assign a dedicated process owner to manage the TMF process redesign, implementation, and ultimately,
serve as the single point of accountability for the TMF. A cross-functional team was also convened to support the redesign
and implementation of the new TMF solution.
The heart of the redesign is a standardized process enabled by a custom technology solution. The solution allows users to
easily access documents through a single interface across all business units, functions, and countries. It also provides the
organization the ability to monitor TMF quality for all studies, including those that are outsourced to clinical research
organizations. For long-term sustainability, Pfizer created a support infrastructure staffed by resources who guide study
teams in the management of the TMF. Additionally, a dedicated group of offshore resources was established to conduct quality
control of documents submitted to the TMF. This integrated solution provided the necessary process controls and measures to
help Pfizer move towards achieving "zero defects" in its TMF.
The Pareto Chart was used to identify critical areas for RCA.
Redesigning Pfizer's global TMF process
By leveraging the QbD methodology and tools, Pfizer was able to develop a deep understanding of customer requirements (both
internal and external stakeholders, including regulators and inspectors) and design a process that met those requirements.
The overall TMF process redesign effort included four key steps as described below.
Fishbone diagrams were developed to identify root causes for prioritized TMF Issues.
The development of a new TMF process began with defining the desired end state of the TMF and its associated quality characteristics.
To that end, Pfizer employed a number of QbD tools, including a voice of business analysis to better understand and elicit
the needs of its internal business stakeholders (TMF contributors and users) as well as a voice of customer analysis to determine
the requirements of its external customers, namely regulators and inspectors. Additionally, a root cause analysis (RCA) was
performed to systematically understand the issues and determine the underlying factors and causes that contributed to any
existing quality concerns (e.g., inconsistent filing locations for TMF documents). The RCA was used as a key input to the
design efforts as solutions were incorporated in the new process to correct or eliminate the causes, and prevent similar quality
issues from recurring. Several process improvement tools were used in the RCA including the fish-bone diagram which helped
the team systematically analyze cause and effect relationships and the Pareto chart which provided insights into the vital
factors causing the most issues within the TMF. By concentrating the efforts on the most critical issues, the team was able
to focus resources on the areas that have the greatest impact on quality. The results of the assessment phase provided key
information to inform the design of the TMF process and technology solution.
The output from Pfizer's assessment of the TMF, coupled with regulatory requirements and industry standards, served as input
to defining the critical to quality (CTQ) attributes. CTQs were used to establish the connection between key customer requirements
and quality criteria for the new TMF process. Pfizer took the extra step to map the CTQs against major regulatory requirements
(Table 1). For example, the ability to identify missing documents was determined to be a critical requirement. As a result,
Pfizer designed into its process, continual identification of document placeholders with associated due dates driven by milestone
or events to help detect missing documents. Establishment of CTQs enabled the team to design a process that met both regulatory
and business critical requirements, leading to consistent delivery of a quality product—the TMF.
Table 1: Categorized critical-to-quality (CTQ) elements mapped to the requirements of regulatory health authorities.
Before finalizing the new TMF process, the design team conducted a failure modes and effects analysis (FMEA) to understand
potential failure points in the process and incorporate necessary measures to prevent such failures from occurring. The FMEA
not only exposed potential failures but also the root causes and consequences of those failures. Examples of potential failure
points included poor document quality and delays in error correction which have downstream impact on timely submission of
documents and the completeness of the TMF. This analysis allowed the team to determine necessary refinements to the design
of the process to avoid potential issues and assure the highest possible quality and reliability in the new process.