Memos - Page 8 of 15 - Cleaning Validation Simplified

2013

The 500 ppb TOC Myth A question

I get a lot relates to the acceptability of setting limits, and particularly rinse limits, based on the pharmacopoeial “specification” of 500 ppb TOC. Let me clarify that I am aware that the actual pharmacopoeial specification is not 500 ppb, but rather that the test sample have a response in the TOC instrument no greater […]

Mar

2013

Using Safety Factors Less Stringent than 0.001 of a Dose

The traditional approach for limits for actives that are not highly hazardous (that is, do not possess properties such as mutagenicity and teratogenicty) is to set limits based on 0.001 of a minimum daily dose in the maximum daily dose of the next drug product. Are there situations where factors less stringent than 0.001 could […]

Feb

2013

Does Risk-MaPP Offer More Patient Protection?

A key concern for cleaning validation is patient protection – to prevent consumers of drug products from getting unacceptable amounts of actives or other residues that may transfer to a product from cleaned equipment. We’ll cover the question of patient protection from the use of Risk-MaPP ADE values in two situations: for the manufacture of […]

Jan

2013

Recovery Studies for Different Surfaces for Rinse Sampling

Last month we covered recovery studies for different surfaces for swab sampling. This month’s topic is recovery studies for different surfaces for rinse sampling. Shouldn’t exactly the same practices applied to swab sampling apply to rinse sampling? Well, the same principles apply, but how it is fleshed out in practice is slightly different. What makes […]

Dec

2012

Grouping for Surfaces for Swab Recovery Studies?

Occasionally I forget what I have written in the past, or in this case, what I have not written in the past. While my seminars and webinars for the past several years have dealt with approaches to simplify sampling recovery studies, I recently realized I didn’t have a Cleaning Memo on the subject. So here […]

Nov

2012

Selecting the Number of Validation Runs for Equipment Grouping

I must be getting crabby now that I’m on Medicare. This month’s Cleaning Memo is on another subject where I see some bad ideas that won’t go away. This concerns the number of validation runs (PPQ runs if you like the new FDA process validation terminology) required for equipment grouping where the equipment in the […]

Oct

2012

Another Critique of Risk-MaPP

As many of you know, I like Risk-MaPP when it discusses using a toxicological evaluation to deal with highly hazardous actives (those with properties such as reproductive hazards, genotoxicity, etc.). It is a sound approach to use as an alternative to dedicating equipment, or to performing cleaning validation with limits of non-detectability, for such actives. […]

Oct

2012

Revisiting Limits Based on Process Capability

Some bad ideas won’t go away. In the Cleaning Memo of June 2005 I questioned the appropriateness of setting limits based on a “true” process capability study. I think the issue is being resurrected around the original context in which it had arisen, and that is setting limits in cleaning validation for bulk actives in […]

Sep

2012

My Revised Shorthand for Expressing Limits

Over the last decade I have used a shorthand method for expressing limits for cleaning process validation protocols. It originally started out with three categories (L1, L2, L3), and was revised several years ago to four categories (L1, L2, L3 and L4, with three subcategories for L4). Last year I made a further change because […]

Aug

2012

Differences between Cleaning and Process Validation

As those of you that follow my writings, webinars and seminars know, I am an advocate of applying the life cycle approach of the 2011 FDA Process Validation (PV) Guidance to cleaning validation (CV), where it is applicable and particularly where it offers advantages to make cleaning validation programs more efficient. Let me emphasize that […]

Jul

2012

Significance of Water Activity for Cleaning Validation

Sometimes I hear the opinion that bioburden doesn’t need to be addressed in cleaning validation because of low water activity of the manufactured product (for example, for oral solid dosages). There is an element of truth in that opinion; however, it is necessary to see exactly what is meant. In this Cleaning Memo we will […]

Jun

2012

Regulatory Guidances I’d Like to See Changed – Part 2

This Cleaning Memo is a continuation of last month’s Cleaning Memo dealing with statements and issues in guidance documents that I think only serve to confuse what is appropriate for cleaning validation. Here is my second set of statements and recommended changes. The following statement is in the PIC/S Recommendation PI 006-03: “For certain allergenic […]

May

2012

Regulatory Guidances I’d Like to See Changed – Part 1

A common question I get at my training classes is “When is fill in the blank with a regulatory agency going to update their guidance on cleaning validation?” The reason for the question is that most guidance documents were written in the 1990’s, and we have learned a lot about cleaning validation over the past […]

Apr

2012

How to Completely Avoid Doing Cleaning Validation

Some of you might have thought the title of this Cleaning Memo was some kind of April Fools joke. Others might have thought it was dealing with single-use (a.k.a. disposable) equipment. Well it’s actually about doing “cleaning verification” in place of “cleaning validation”. Cleaning verification (a “one-time” determination of cleaning effectiveness) is commonly used for […]

Mar

2012

How Are ADE’s Determined for Non-Highly Hazardous Actives?

As you should be aware, the ISPE Risk-MaPP dismisses conventional ways of setting limits based on calculations such as 0.001 of a daily dose. It advocates setting limits for both highly hazardous actives (HHAs) and non-highly hazardous actives (NHHAs) using an ADE (Acceptable Daily Exposure). Certainly the principles of the ADE approach are appropriate for […]

Feb

2012

Hold Time Issues

There are several types of “hold times” that may need to be addressed for cleaning validation. They include: Dirty Hold time (DHT) – the time from the end of manufacture until the beginning of the cleaning process (also called things like “soiled hold time”) Clean Hold Time (CHT) – the time from the end of […]

Jan

2012

Issues in Cleaning Validation for Parts Washers

There are certainly lots of possible issues to talk about for parts washers. However, I am going to limit this Cleaning Memo to a discussion of issues related to cleaning different products in the same parts washer, either in sequential loads or in the same load. For clarification, a parts washer is usually considered as […]

Dec

2011

The Good, the Bad and the Inexplicable of Risk-MaPP

Your mom told you the same thing my mom told me, “Always say something positive about something before you say something negative”. Well, I’ve said enough negative things about Risk-MaPP, so it’s time I said something positive (don’t worry, I will also fulfill the second half of her admonition later in this Cleaning Memo). The […]

Nov

2011

Limits Below the LOD in Rinse Solutions – Part 3

This Cleaning Memo continues the thought processes in Part I and Part II, but goes beyond just the consideration of dealing with issues relating to the LOD/LOQ of the analytical method being too high. What I’m doing in Part III is discussing something related, but somewhat different. In the previous Cleaning Memos I discussed cases […]

Oct

2011

Limits Below the LOD in Rinse Solutions – Part 2

This Cleaning Memo continues the thought processes in Part I (the September 2011 Cleaning Memo) by discussing applications to CIP rinsing. If you remember, the situation is this. I have established limits in my rinse sample based on carryover calculations, and the limit is X ppm. However, my analytical method can only detect down to […]

Memos by Destin

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

The 500 ppb TOC Myth A question

Using Safety Factors Less Stringent than 0.001 of a Dose

Does Risk-MaPP Offer More Patient Protection?

Recovery Studies for Different Surfaces for Rinse Sampling

Grouping for Surfaces for Swab Recovery Studies?

Selecting the Number of Validation Runs for Equipment Grouping

Another Critique of Risk-MaPP

Revisiting Limits Based on Process Capability

My Revised Shorthand for Expressing Limits

Differences between Cleaning and Process Validation

Significance of Water Activity for Cleaning Validation

Regulatory Guidances I’d Like to See Changed – Part 2

Regulatory Guidances I’d Like to See Changed – Part 1

How to Completely Avoid Doing Cleaning Validation

How Are ADE’s Determined for Non-Highly Hazardous Actives?

Hold Time Issues

Issues in Cleaning Validation for Parts Washers

The Good, the Bad and the Inexplicable of Risk-MaPP

Limits Below the LOD in Rinse Solutions – Part 3

Limits Below the LOD in Rinse Solutions – Part 2

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