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Compliance Case Study #4—Cleaning Validation Unknown HPLC Peaks
Author: Paul L. Pluta

“Compliance Case Studies” discusses compliance situations useful to practitioners in compliance and validation. Each case presented deals with a specific compliance problem, elements of which are described to demonstrate strategy to solve compliance problems. We intend this column to be a useful resource for daily work applications. The main objective of this column: Useful and practical information.

Reader comments, questions, and suggestions are needed to help us fulfill our objective for this column. Case studies illustrating compliance issues submitted by readers are most welcome. Please send your comments and suggestions to journal coordinating editor Susan Haigney at shaigney@advanstar.com.

KEY POINTS DISCUSSED
The following key points are discussed in this case study:
• A compliance case study involving cleaning validation and the observation of unknown peaks in high performance liquid chromatography (HPLC) chromatograms is discussed
• Unknown peaks were observed from testing of swab samples following cleaning of suspension products containing insoluble active drug, suspending agents, colors, and flavors
• Equipment was visually clean
• Following the original failures, a “shotgun” approach with a new cleaning procedure was attempted but was unsuccessful
• Technical personnel then conducted laboratory studies using multiple cleaning agents based on the chemical and physical properties of the product residues. A new cleaning procedure was developed.
• Cleaning process parameters (i.e., concentration, time, volume, etc.) were clearly specified in the new cleaning procedure
• Analytical scientists determined that the unknown peaks were associated with the hydrophobic flavoring ingredients in the formulation
• An improved visual inspection procedure was developed
• The new cleaning procedure was successfully validated
• Post-validation monitoring confirmed the success of the new procedure
• Additional improvements in between-lot cleaning and campaign cleaning were implemented based on knowledge gained in the investigation
• The most important benefit was the demonstration of a scientific and technical approach to problem solving, cleaning method development, understanding residue chemistry, specifying process parameters, etc.—a scientific and technical basis for validation.

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