Memos - Page 14 of 15 - Cleaning Validation Simplified

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 The reason for this change is the release of the draft guidance from the FDA entitled “PAT – A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance”.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

Dec

2002

Additional Considerations in Recovery Studies: Part 2

Last month’s Cleaning Memo covered several issues in designing sampling recovery studies. This month’s memo continues with three more considerations. Drying time: Since in most cases, swabbing of equipment surfaces will involve swabbing of dry equipment surfaces, it is a reasonable expectation that the spiked residue be allowed to dry on surfaces for a recovery […]

Nov

2002

Additional Considerations in Recovery Studies: Part 1

Last month’s Cleaning Memo suggested that swab recoveries were relatively straightforward. That is definitely true in comparison to recovery studies for rinse sampling- the swab procedure utilized in the lab recovery study is exactly the same as that used in the validation protocol, whereas the rinse sampling procedure has to be simulated in the lab. […]

Oct

2002

Recovery Studies for Rinse Sampling

A key feature of any cleaning validation protocol is having sampling methods and analytical methods that can accurately assess the levels of residues on the sampled surface. One regulatory expectation is that the sampling method be challenged in conjunction with the analytical method to determine the percentage recovery of the sampling method. Doing a sampling […]

Sep

2002

Sampling the Sampling Rinse

I have discussed in most of my cleaning validation training seminars that there are two types of rinse sampling. One type (the more conventional) involves taking a “grab” sample at the end of the process rinse. A second type is a “sampling rinse”, in which a separate, discrete rinse (following the final process rinse) is […]

Aug

2002

Selecting Swab Sampling Sites

If sampling is designed to identify potential residues on cleaned equipment surfaces that might be transferred to the next manufactured batch, then it is necessary to select swab sample sites that can appropriately provide that information. This Cleaning Memo will cover selection of sampling sites for swab sampling (next month’s will cover an equivalent subject […]

Jul

2002

Worst-case Process Conditions

Cleaning validation generally involves three PQ runs where one challenges the cleaning process under worstcase process conditions to demonstrate that within normal process variations, the cleaning process is effective. This generally involves stressing under worst-cases within normal process conditions. For example, if the cleaning process temperature were 70° ± 5°C, one would NOT conduct a […]

Jun

2002

Recovery Studies for Microbial Sampling?

Measurement of potential microbial contamination has become a more of an expectation in cleaning validation protocols for process manufacturing equipment. Sampling for bioburden on surfaces has usually involved contact plates, swabs and rinse water (with membrane filtration) analyses. A common question that arises for this microbial sampling is whether or not recovery studies (analogous to […]

May

2002

Cleaning Validation for Medical Devices

Apr

2002

Understanding and Applying “Visually Clean”

I have recently published a paper on the use of a “visually clean” standard as the sole acceptance criterion in cleaning validation protocols. That publication was based on a presentation at the December 2000 PDA meeting in Washington, D.C. and a similar presentation at the February 2001 Japan PDA meeting in Kyoto, Japan. Since that […]

Mar

2002

What’s a Contaminant?

At recent FDA Basic Drug School, I was asked the question whether allowing a specified level (such as 0.001 of a therapeutic dose of a previous active) of residue in a manufactured product was, in fact, allowing manufacturers to produce and release drug products which were “contaminated”. My answer at the time was related to […]

Memos by Destin

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

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

Additional Considerations in Recovery Studies: Part 2

Additional Considerations in Recovery Studies: Part 1

Recovery Studies for Rinse Sampling

Sampling the Sampling Rinse

Selecting Swab Sampling Sites

Worst-case Process Conditions

Recovery Studies for Microbial Sampling?

Cleaning Validation for Medical Devices

Understanding and Applying “Visually Clean”

What’s a Contaminant?

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