Memos - Page 10 of 15 - Cleaning Validation Simplified

2009

The Rationale for Rinse Sampling for Cleaning Agents

For CIP cleaning processes some companies that sample for active by both rinse sampling and swab sampling will only use rinse sampling for measuring residues of the cleaning agent. Why is this done, and is there a rationale for it? I assume part of the reason it is done is because those companies believe that […]

Nov

2009

“Continued” vs. “Continuous” Process Verification

Continued process verification” is a term used in the November 2008 FDA Process Validation Guidance. “Continuous process verification” is a term used in ICH Q8 (R2) Pharmaceutical Development. They sound similar, but are they really referring to the same thing? I believe it is clear they are two different concepts; however, because they sound similar, […]

Oct

2009

Use of Multiple Swabs for Sampling

Who says you can’t teach an old dog new tricks? Well, this old dog has learned a new trick, or at least now has a different view. If you had asked me about swab sampling five years ago, I would have generally said that the preference is to use only one swab for a given […]

Sep

2009

“Design Space” for Cleaning Processes

“Quality by Design” (QbD) and “Design Space” are currently two hot topics in pharmaceutical manufacturing. If you justify a project with these concepts, you are more likely to get it funded. Certainly design of manufacturing processes, including cleaning processes for process equipment, is a very desirable thing. In the past, I have heard some cleaning […]

Aug

2009

The Changing Paradigm for Cleaning Validation

One definition of paradigm is “A set of assumptions, concepts, values, and practices that constitutes a way of viewing reality for the community that shares them, especially in an intellectual discipline”. Applied to cleaning validation, a paradigm is those “assumptions, concepts, values, and practices” that define the way we do cleaning validation. We are currently […]

Jul

2009

Revisiting Linearity of Swab Recovery Results

Those of you familiar with my writings and seminars know that I am not of fan of doing sampling recovery studies (either swab sampling or rinse sampling) using multiple spiked levels to establish linearity of results. In part my view is based on the high variability of any individual recovery experiment. In other words, if […]

Jun

2009

Use of Alkali/Acid Cleaning Agents in Biotech

The most common equipment cleaning process in biotechnology manufacture involves cleaning first with an alkaline cleaning solution, followed by use of an acidic cleaning solution. Of course, the cleaning process usually involves a pre-rinse with ambient temperature water, a rinse after the alkaline solution and a more stringent rinse following the acidic solution. However, the […]

May

2009

The Science Behind Limits

There has been a lot of discussion (at least in the USA) in the past months about returning science to its rightful place. What does this mean for cleaning validation limits? What is the role of science in setting limits? While we might all like to say that our limits are scientifically set, there is […]

Apr

2009

What’s Happening to Worst-case Process Conditions?

Past practice for cleaning validation has been to perform cleaning validation protocols under “worst-case” process conditions. The idea of worst-case conditions comes from the 1987 FDA process validation guidance, which states “Parts of the process which may vary so as to affect important product quality should be challenged. In challenging a process to assess its […]

Mar

2009

Differing Ways to Express Limits

In this Cleaning Memo, I will discuss the conventional way limits are set for finished drug manufacture. This discussion will not cover fundamentally different basic calculations; it’s just how those basic principles are expressed that is different. I will illustrate the different ways (again, with the same scientific basis) using limits for the active ingredient. […]

Feb

2009

Another Alternative for Rinse Sampling Limits?

Last month we discussed setting limits for rinse samples, focusing on limits for grab samples of the final process rinse (FPR) for CIP rinses. This month I’ll cover (and critique) a different way for setting limits in that same situation. This approach is essentially based on estimating the amount of rinse water left behind in […]

Jan

2009

Limits for Rinse “Grab” Samples, Revisited

There are generally two types of rinse samples taken for cleaning validation protocols. One is a separate sampling rinse (SSR) performed after the final process rinse (FPR). This SSR is only done in a protocol where one is attempting to measure residues to compare the results against acceptance limits. A second type of rinse sample […]

Dec

2008

Solvent Reflux Sampling Recovery

A general principle for cleaning validation protocols is that if you utilize a certain sampling technique to measure residues that are then compared to acceptance criteria (limits), then it is necessary to perform a sampling recovery study to confirm that the sampling method appropriately measures residues if they were present. This is covered by the […]

Nov

2008

Limits for Topicals

This Cleaning Memo addresses cleaning validation limits for topical dermatological finished drug products. Since the typical dose-based (or carryover) calculation involves the dose of the cleaning product active as well as the dose of the next manufactured product, the key question is how those doses are defined, specifically if the two drug products can be […]

Oct

2008

Are We Setting Limits Correctly?

This Cleaning Memo is a shortened version of my recent (August) webinar of the same title. The way limits are currently set for cleaning validation protocols has been critiqued by Andy Walsh (of Clean6Sigma) as not risk-based, as not science-based and as arbitrary. This critique was given in presentations at an ISPE conference this summer, […]

Sep

2008

Sampling Recovery for Biotech

The focus of this Cleaning Memo is the issue of what residue to spike onto coupons for sampling recovery studies (whether they be swab sampling recoveries or rinse sampling recoveries) for biotechnology manufacture. The ideal is to spike the residue that will be sampled in the cleaning validation protocol. With small molecule drugs, for example, […]

Aug

2008

Do Three Verifications Make a Validation?

The traditional approach to validation, including cleaning validation, is to perform a minimum of three validation runs. Of course, there is no statistical justification for three runs being acceptable. It is just something that pharmaceutical manufacturers and regulatory authorities have agreed on. In some regulatory documents (for example, the European PIC/S PI 006-03) it is […]

Jul

2008

What’s Happening to Revalidation?

At the recent PDA annual meeting a representative of the FDA mentioned that in the upcoming FDA revised process validation guidance the term “revalidation” will no longer be used. What’s behind this move? And will it apply to cleaning validation? The latter question is probably easier to consider. Cleaning is a just another manufacturing process, […]

Jun

2008

Still More on Floors and Walls

Last month’s Cleaning Memo elicited more responses than usual. Therefore, I am taking the liberty to wait until July to talk about “revalidation”, and will continue to discuss the issue of setting limits for and measuring residues on floors and walls. Two basic assumptions in last month’s Cleaning Memo were (a) that floors and walls […]

May

2008

More on Floors and Walls

I am hearing more and more about regulators asking questions about measuring residues for non-product surfaces such as floors and walls. Is that an appropriate question to ask for a cleaning validation program? My answer is “No”. Is that an appropriate question to ask a pharmaceutical manufacturer? My answer is “Yes, under certain circumstances”. Why […]

Memos by Destin

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

The Rationale for Rinse Sampling for Cleaning Agents

“Continued” vs. “Continuous” Process Verification

Use of Multiple Swabs for Sampling

“Design Space” for Cleaning Processes

The Changing Paradigm for Cleaning Validation

Revisiting Linearity of Swab Recovery Results

Use of Alkali/Acid Cleaning Agents in Biotech

The Science Behind Limits

What’s Happening to Worst-case Process Conditions?

Differing Ways to Express Limits

Another Alternative for Rinse Sampling Limits?

Limits for Rinse “Grab” Samples, Revisited

Solvent Reflux Sampling Recovery

Limits for Topicals

Are We Setting Limits Correctly?

Sampling Recovery for Biotech

Do Three Verifications Make a Validation?

What’s Happening to Revalidation?

Still More on Floors and Walls

More on Floors and Walls

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