XYZ, Inc. is a global pharmaceutical manufacturer of ophthalmic and otic drugs and medical devices. In an effort to align with the FDA’s Guidance for Industry, Process Validation: General Principles and Practices, the firm wished to review several existing (not new) sterile products. The review was to focus on an internal deliverable of Continuous Process Verification (CPV) – an important component of the overall quality system of Product Process Validation.


CPV can be approached in several different ways; for XYZ, Inc. this meant the continuous monitoring of critical process inputs to insure the expected process output or in other words, drug and medical device product batches that meet predetermined specifications every time. The design of the review included establishing process flow diagrams; which would then feed into Failure Mode Effects Analysis (FMEA) of those processes. Finally, those two documents would be evaluated together to determine which process variables would be selected as most critical and then enrolled in a CPV effort that will include automation of data collection and statistical analysis via Cumulative Sum Control Charts (CUSUM).

Challenges

Not unlike many large, complex, sterile pharmaceutical-manufacturing facilities, XYZ Inc. had pertinent information that would inform the creation of the required documents for evaluation in many different places. There was no single repository of information from which to draw out the information. Not surprisingly there were also contradictions between documents that had to be reconciled with the site’s stakeholders before proposing a consensus set of documents. At the conclusion of the effort, this challenge became one of the projects major deliverables, that is, the firm required a unified collection of information related to process description and CPV that could be carried forward as the defining high-level document by multiple interrelated departments.

The timeline of the project was also a notable challenge. Ten (10) sterile drug and medical device products were to be analyzed, mapped, viewed through the process of FMEA and critical process parameters selected for automation of data collection and measurement with CUSUM in the span of approximately eight (8) weeks.

Project Plan

Given the complexity of this project with products ranging over the entire company portfolio, the validation and project management expertise required, and the short timeline for project completion, XYZ Inc. partnered with The Catalyst Group to meet project goals and deliverables.

Using an internal matrix to sort through the product portfolio, ten (10) sterile drug and medical device products were selected as in scope for this effort. The selection matrix included a variety of measures such as differences in formulation and equipment used that ultimately grouped products into a “family”. The final products selected were representatives of each of these families. Representative selection allowed analysis across a large cross section of technologies within a short time period and created templates; which could then be used in the future for other similar products within the related family.

The analysis of the products was approached by complexity from simplest to most complex. This allowed The Catalyst Group to present the simplest product process first and achieve consensus on a variety of issues before continuing on with the more sophisticated product processes. The basic scope and format of documents was the focus of the early work; which translated into flexibility to focus later work on complex problems rather than organizational decisions and improved overall project efficiency.

Results

By getting stakeholder alignment and management approval on the report scope, content, and design early in the project, The Catalyst Group was able to efficiently and effectively meet the project plan within the timeline and budget. In eight (8) weeks, The Catalyst Group was able to deliver analysis, process flow diagrams, FMEA and summary reports identifying critical process parameters for the selected ten (10) sterile drug and medical device products. At the conclusion of the project, XYZ Inc. received a comprehensive set of documents for organizational alignment that served to document the decision making process based upon risk, and established templates that the client can follow for other less critical processes to achieve their future CPV goals. Partnering with The Catalyst Group, allowed XYZ Inc. to continue their daily manufacturing operations without interruption or re-allocation of key resources while at the same time accomplishing goals and deliverables in a complex, fast-paced, compliance project. XYZ Inc. is now in a better, stronger position respective to the FDA guidance requirements and has a more solid, well organized collection of information related to their internal manufacturing processes and entire product portfolio.