Memos - Page 3 of 15 - Cleaning Validation Simplified

2021

Action and Alert Levels

We will cover three issues in this Cleaning Memo. They are (a) how action and alert levels are defined, (b) how action and alert levels are used, and (c) how action and alert levels are established, all in the context of pharmaceutical process equipment cleaning validation. The first issue is one of clarifying terminology (as […]

Jul

2021

Recovery Studies for Microbial Sampling – Revisited

In the recent (2020) ISPE Guide: Cleaning Validation Lifecycle – Applications, Methods, and Controls there is one section and a related appendix on bioburden sampling recovery methods (including methods for swab, contact plate and rinse) that state the following: “The recovery study results should be assessed by the QC laboratory when reviewing cleaning validation and […]

Jun

2021

Risk Assessment for Indirect Product Contact Surfaces

Last month we focused on limits for indirect product contact surfaces (IPCSs). This month we will focus on studies that could be performed as part of a risk assessment related to cleaning validation for such surfaces. In particular, the examples I use will involve the interiors of isolators, although the principles of the studies should […]

May

2021

Residue Limits for Indirect Product Contact Surfaces

This Cleaning Memo is focused on limits for indirect product contact surfaces. It first covers my recommendations, and then specifically addresses the considerations in setting limits for isolators as recommended in a November 2017 PDA Letter (“Isolator Surfaces and Contamination Risks to Personnel”, by Richard Denk et al). I’ll start with a clarification of the […]

Apr

2021

Why a Default of 10 ppm “Solids” for Detergents?

I sometimes get the question as to why I recommend a “default” value for a detergent limit based on the solids content of the detergent. After all, shouldn’t the default value for a detergent be the same as the default value for an active (an API), which is 10 ppm. This Cleaning Memo will discuss […]

Mar

2021

An Unusual Situation for Shared Surface Area

In taking a look at the shared surface area (SSA) between two products, there are several options that are typically used for limits calculation purposes. As a reminder, the SSA is in the denominator of the typical carryover calculation; therefore, the larger the SSA between the two products, the lower the limit. There are several […]

Feb

2021

What’s a “Worst Case”?

I commonly hear companies say that they use a “worst case” approach for their cleaning validation program. My first question is usually “Which worst case aspect are you referring to?” The term “worst case” could cover a variety of different things for cleaning validation. For example, there are worst case aspects that may be used […]

Jan

2021

Statistics in Cleaning Validation?

There is an increasing call for the use of statistics for use in cleaning validation programs. Statistics can be appropriately used to evaluate data to determine variability. Statistics conceivably could be used in the following situations related to cleaning processes: Statistics for evaluating data in the design of a cleaning process.A. Statistics for evaluating data […]

Dec

2020

Visual Residue Limits – Part 2

In this second of a two-part series, we will look at using Visual Residue Limits (VRLs) as part of routine monitoring to establish that a quantitative residue limit is being met. If you haven’t read (and understood) last month’s Cleaning Memo, please do so before considering this one. Before I start, here is a little […]

Nov

2020

Visual Residue Limits – Part 1

For this two-part series, we will look at how to establish visual residue limits in this first part. In Part 2 we will look at the recent (2018) EMA Q&A that deals with using a visually clean criterion in routine monitoring to establish that a quantitative residue limit is being met. Before I start, here […]

Oct

2020

Two More Nails in the Coffin?

I have for years taught (or preached) that performing quantitative swab recovery studies at multiple spiked levels is a waste of effort and resources. Furthermore, I have also maintained that, other things being equal, the percentage recovery of spiked material will decrease as the spiked level increases. If this is true, then one spiked level […]

Sep

2020

Avoiding “Visually Dirty” Observations

A frequent question I get is “What is the most common FDA (or another regulatory body) finding in an inspection?” Well, I certainly haven’t seen them all, and don’t have any clear data. However, based on my experience one of the most frequent observations I see is that in an inspection some item of equipment […]

Aug

2020

Causing Cleaning Validation Problems by Analogy

Last month we discussed how analogies can be useful when we are faced with a new cleaning validation issue. This month we will look at how analogies can do just the opposite – lead us down a rabbit hole that just may seem to be a solution, but in reality just complicates life. A key […]

Jul

2020

Solving Cleaning Validation Problems by Analogy

I have been very interested in recent popular discussions of “models”. No, I don’t mean fashion models; I mean models in scientific thinking. We in the cleaning validation community have a certain model of what happens in a cleaning process that could lead to cross-contamination of the next manufactured product. That model usually envisions that […]

Jun

2020

Another “Worst Case” Product Grouping Idea

I frequently teach that the solubility of the active, when used alone, is not the most appropriate way to select the “hardest to clean” product in a product grouping approach. Note that I sometimes refer to the “hardest to clean” as the most “difficult to clean”; so for purposes of this Cleaning Memo consider them […]

May

2020

Words (Again??)

I wrote several Cleaning Memos last year about the importance of using terminology more carefully. While it may seem to be more of a problem now (perhaps because of the widespread dissemination of information on the internet), it is not something new in the arena of cleaning validation. In this Cleaning Memo I will focus […]

Apr

2020

Protocol Limits for Yeasts/Molds?

Meeting protocol requirements for bioburden is generally not a significant problem provided the final rinse is with hot Purified Water (PW) or hot Water for Injection (WFI). It is not likely that such a water final rinse would contribute to bioburden, and it is likely that the hot temperature would significantly reduce any vegetative microorganisms […]

Mar

2020

Routine Monitoring for Highly Hazardous Products

This is a continuation of a discussion of products with highly hazardous actives, and deals with the question of routine monitoring for highly hazardous products. Hopefully (if you follow my Cleaning Memos) you know that I generally define a “highly hazardous product” as a drug product with an active that has a significant toxicity concern […]

Feb

2020

Highly Hazardous Products in Shared Facilities

This is a continuation of a discussion on products with highly hazardous actives, and deals with the question of manufacturing highly hazardous products in the same equipment or in the same facility as products that are not highly hazardous. The obvious answer to that question is “Yes”, that certainly can be done from a regulatory […]

Jan

2020

EMA vs. ISPE on Cleaning Limits?

You might be mystified at this title. What is Mr. LeBlanc getting at? Well, what I will discuss this month is the difference (or conflict?) between the EMA and ISPE on setting limits for cleaning validation. For the EMA “position”, I will refer both to the 2014 “Guideline on setting health based exposure limits for […]

Memos by Destin

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

Action and Alert Levels

Recovery Studies for Microbial Sampling – Revisited

Risk Assessment for Indirect Product Contact Surfaces

Residue Limits for Indirect Product Contact Surfaces

Why a Default of 10 ppm “Solids” for Detergents?

An Unusual Situation for Shared Surface Area

What’s a “Worst Case”?

Statistics in Cleaning Validation?

Visual Residue Limits – Part 2

Visual Residue Limits – Part 1

Two More Nails in the Coffin?

Avoiding “Visually Dirty” Observations

Causing Cleaning Validation Problems by Analogy

Solving Cleaning Validation Problems by Analogy

Another “Worst Case” Product Grouping Idea

Words (Again??)

Protocol Limits for Yeasts/Molds?

Routine Monitoring for Highly Hazardous Products

Highly Hazardous Products in Shared Facilities

EMA vs. ISPE on Cleaning Limits?

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