Memos - Page 14 of 16 - Cleaning Validation Simplified

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 different […]

Aug

2004

More on Specificity of Analytical Methods

Judging by the questions I get on the topic, the 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 […]

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 quantify 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 quantify the organic residues that may be on the equipment product contact surfaces after cleaning. The post-cleaning residues are one source of organic carbon on surfaces. Those organic residues may […]

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: As a general principle for finished drug manufacture, endotoxin should be included as part of the protocol testing for products that have endotoxin specifications. This generally means injectable products. One could argue that since the final product is tested for endotoxin, it is not […]

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, […]

Dec

2003

Revalidation

The 1993 FDA cleaning validation guidance document calls for validation procedures to address “when revalidation will be required”. What, then, are the appropriate conditions for revalidation of a previously validated cleaning process? As a general rule, the requirements for revalidation for cleaning processes should follow the same principles as revalidation for general process manufacture. After […]

Nov

2003

Correlation of TOC with a Specific Analytical Method?

Sometimes the question is asked, “Do I have to correlate my TOC method for my active with a specific method, such as HPLC, during the analytical method validation?” As with other questions of this nature, it depends on what you mean by “correlate”. If by “correlate” you mean run side by side full validation of […]

Oct

2003

PAT and Cleaning Validation

Surprise!! This month’s Cleaning Memo is not what was listed last month. That topic, “Correlation of TOC with a Specific Analytical Method?” will be covered in November. The reason for this change is the release of the draft guidance from the FDA entitled “PAT – A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance”. Since […]

Sep

2003

Correlation of Swab and Rinse Sample Results?

Sometimes the question is asked, “Should my swab and rinse sample results be correlated?” Like a lot of things, the answer to this depends on what you mean by “correlated”. If it just means that every time you’ve performed a cleaning study, you have obtained either (1) all good (passing) results on both swab and […]

Aug

2003

Why TOC is Acceptable?

A recent “publication” from the FDA hopefully put to rest the issue of using TOC for measuring residues for cleaning validation studies. The question was asked in the First Quarter 2002 Human Drug CGMP Notes, “Can Total Organic Carbon (TOC) be an acceptable method for detecting residues of contaminants in evaluating cleaning effectiveness?” The beginning […]

Jul

2003

Adequate “Documented Evidence” for Cleaning Validation

A short definition of cleaning validation is “documented evidence with a high degree of assurance that a cleaning process will consistently produce equipment and products meeting predetermined quality specifications.” In an internal audit or regulatory investigation, a key is reviewing that “documented evidence”. What could be included with that documented evidence? One usually first thinks […]

Jun

2003

Limits for Drugs with Multiple Actives

One thing that is almost always done for cleaning validation of finished drug products is to set residue limits for the active and then measure residues of that active in the validation protocol. This is a relatively straightforward process (at least conceptually) if there is only one active ingredient in the drug product. If there […]

May

2003

What’s Really Different About Biotech?

There certainly are several things about pharmaceuticals produced by biotechnology processes that require them to be handled differently from traditional pharmaceutical manufacturing. As for cleaning and cleaning validation, one of the main differences is the type of analytical test used to measure residues following cleaning. While TOC is certainly an option for measuring residues for […]

Apr

2003

Using Statistics in Sampling?

Questions sometimes asked about swab sampling are “How many swab sites must I sample?” and “Can I determine the number of swab sites statistically?” While statistics are critical for many sampling purposes, one must be careful about applying statistical principles to the sampling of different locations in a manufacturing vessel. The purpose of picking swab […]

Mar

2003

Is a Dirty Swab a “Visually Clean” Failure?

The purpose of visual examination as part of a cleaning validation protocol is to confirm that the equipment, when used for manufacture, is compliant with 21 CFR 211.67(b)(6). It is a reasonable expectation that if equipment should be visually clean at the beginning of manufacture, it should also be visually clean at the end of […]

Feb

2003

Using Sampling Recovery Percentages

Three recent Cleaning Memos (October, November, and December 2002) discussed sampling recovery studies. What is an acceptable recovery percentage for sampling a chemical residue is dependent on how that recovery percentage is used. There are basically two ways that companies can handle those specific recovery percentages in dealing with actual analytical values obtained from swab […]

Memos by Destin

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

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

Revalidation

Correlation of TOC with a Specific Analytical Method?

PAT and Cleaning Validation

Correlation of Swab and Rinse Sample Results?

Why TOC is Acceptable?

Adequate “Documented Evidence” for Cleaning Validation

Limits for Drugs with Multiple Actives

What’s Really Different About Biotech?

Using Statistics in Sampling?

Is a Dirty Swab a “Visually Clean” Failure?

Using Sampling Recovery Percentages

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