Cleaning Validation Memos from 2004

2004

Establishing Adequate Solubility for TOC Analysis

A common objection to the use of TOC (Total Organic Carbon) analysis for analysis of trace residues in cleaning validation protocols is “My active is not water soluble.” This may or may not be an appropriate objection. The key to the use of TOC for trace analysis in cleaning validation protocols is whether the target […]

Nov

2004

Is Rinse Sampling Alone Acceptable?

In answer to a question during a recent conference, I presented a minority opinion on rinse sampling, namely that under certain circumstances rinse sampling alone can be an acceptable sampling technique for cleaning validation protocols. Objections were made that regulatory authorities do not find this acceptable. The next evening I arrived home to find a […]

Oct

2004

Selecting Worst-Case Products for Grouping

This Cleaning Memo supplements my July 2001 Cleaning Memo on the same topic. This current Cleaning Memo does not add anything radically different to that earlier one. The purpose for this Cleaning Memo is to discuss an alternative means for selecting the worst-case product in a product grouping. One alternative for selecting worst-case products has […]

Sep

2004

Issues in the Visual Examination of Equipment Surfaces

The issues that will be discussed include the extent of the visual examination, the training/qualification for those people doing the visual examination, the need for second person verification, and the need for a written SOP. What is required for each issue will depend on the nature of the visual examination. There are at least four […]

Aug

2004

More on Specificity of Analytical Methods

Judging by the questions I get on the topic, specificity of analytical methods seems to still be a difficult topic for many in dealing with selecting an appropriate analytical method for measuring residues in a cleaning validation protocol. This concern with the acceptability of non-specific methods seems to continue despite the fact that the FDA […]

Jul

2004

Cleaning After a Media Fill

For any equipment for which cleaning validation is complete, any intervention in the standard manufacturing process should require a consideration of the effect of that intervention on the cleaning validation for that equipment. This applies to dealing with cleaning and releasing equipment following a media fill for an aseptic processing line. Following the media fill, […]

Jun

2004

TOC Issues: Part 3 – Blanks for Recovery Studies

This Cleaning Memo will address issues in the proper selection of blanks for TOC in recovery studies. In this situation, the purpose of sampling is to quantitate the organic residues that may be on the coupon (the model surface used for the study), and then compare that value to the amount of organic residues spiked […]

May

2004

TOC Issues: Part 2 – Appropriate Blanks

This Cleaning Memo will address issues in the proper selection of blanks for TOC validation samples. In this situation, the purpose of sampling is to quantitate the organic residues that may be on the equipment productcontact surfaces after cleaning. The post-cleaning residues are one source of organic carbon on surfaces. Those organic residues may include […]

Apr

2004

TOC Issues: Part 1 – Sampling Materials

This Cleaning Memo will address the proper selection of sampling materials used if Total Organic Carbon (TOC) is the sampling method of choice. Particularly since TOC is subject to a multitude of interferences, it is necessary to make sure that the sampling materials provide a consistent TOC value due to those “interfering” materials. Those materials […]

Mar

2004

Defining Three “Consecutive” Runs

Another question I commonly get is “What constitutes three consecutive runs for cleaning validation protocol purposes?” The basic approach to answering this question is to use the same principles one uses for process validation. If I am validating a blending process in a certain manufacturing vessel, do the three validation runs have to be one […]

Feb

2004

Endotoxin Issues in Cleaning Validation

The questions that will be addressed in the Cleaning Memo include: “When should I measure endotoxin in a cleaning validation protocol?” “How should I sample for endotoxin?” “What acceptance criterion should I establish for endotoxin?” As a general principle for finished drug manufacture, endotoxin should be included as part of the protocol testing for products […]

Jan

2004

Monitoring a Validated Cleaning Process

In discussing monitoring for cleaning validation, it is important to carefully define what one means by “monitoring”. As used here, the term “monitoring” refers to the routine measurements taken on the cleaning process that serve as indicators of whether the process is in a state of control (or considered from the opposite point of view, […]

Memo Year: 2004

Destin LeBlanc has been publishing memos on Cleaning Validation since 2001.

Establishing Adequate Solubility for TOC Analysis

Is Rinse Sampling Alone Acceptable?

Selecting Worst-Case Products for Grouping

Issues in the Visual Examination of Equipment Surfaces

More on Specificity of Analytical Methods

Cleaning After a Media Fill

TOC Issues: Part 3 – Blanks for Recovery Studies

TOC Issues: Part 2 – Appropriate Blanks

TOC Issues: Part 1 – Sampling Materials

Defining Three “Consecutive” Runs

Endotoxin Issues in Cleaning Validation

Monitoring a Validated Cleaning Process

Take me to the memos

Subscribe to Destin LeBlanc's cleaning validation memos.