Cleaning Validation Memos from 2003

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 The reason for this change is the release of the draft guidance from the FDA entitled “PAT – A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance”.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 to 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 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 is 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 […]

Jan

2003

More on Dirty Equipment Hold Time (DEHT) Issues

In October 2001, I wrote a Cleaning Memo on setting a Dirty Equipment Hold Time (DEHT). This month’s memo provides additional reflections on the significance of challenging the cleaning process with the maximum DEHT. In addressing the maximum, one might ask, “Why challenge with the maximum time?” The answer is typically that the maximum time […]

Memo Year: 2003

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

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

More on Dirty Equipment Hold Time (DEHT) Issues

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