Cleaning Validation Memos from 2013

2013

A Way Forward for “Health-based” Limits

Last month I critiqued the EMA document on “dedicated” facilities, which takes an approach not unlike Risk- MaPP to set limits for all actives (drug substances or APIs) for cleaning validation purposes based on a comprehensive toxicological evaluation. As most of you know I am not a big fan of such an approach for all […]

Nov

2013

Comments on the EMA Guideline on Dedicated Facilities

I am writing this Cleaning Memo with some hesitation, because the EMA draft guideline is currently undergoing a review and probable revision. Just in case (my pessimism is coming through), but also because it has some very good aspects (as compared to ISPE’s Risk-MaPP), I am venturing with this critique. First, here are some of […]

Oct

2013

Revisiting Rinse Sampling Recovery Studies

The purpose of rinse sampling recovery studies is to address the “baby and bath water” question posed by the FDA. The question is this: “If you have bathed your baby, and you want to know if the baby is clean, what do you do, look at the baby or look at the bath water?” Well […]

Sep

2013

Revisiting Linearity of Recovery Studies

In the past I have questioned the value of doing sampling recovery studies at multiple levels, as well as doing so to demonstrate linearity (see the Cleaning Memos for July 2007, July 2009, and October 2010). My assumption when talking about linearity was my perception that people were expecting a significantly changed (decreasing or increasing) […]

Aug

2013

Conductivity vs. pH vs. TOC for Final Rinse Monitoring: Part 2

Last month we discussed final rinse monitoring, and considered general issues related to conductivity, pH, and TOC. This month we cover some additional issues in final rinse water monitoring. For clarification, my use of the term “monitoring” is to refer to the activities related to the collection of data I do on every cleaning event […]

Jul

2013

Conductivity vs. pH vs. TOC for Final Rinse Monitoring: Part 1

“Monitoring” is a term that is used in different ways by different companies. For some, monitoring is part of validation maintenance in which I repeat one or more validation protocol runs on a regular basis (such as yearly or every two years). For others, monitoring is the actual sampling and testing I do in my […]

Jun

2013

Are Health-Based Limits Enough?

Both the RiskMaPP ADE (Acceptable Daily Exposure) and the EMA’s PDE (Permitted Daily Exposure) are attempts to set cleaning validation limits based on a toxicological evaluation, primarily using either a NOAEL (for an ADE) or NOEL (for a PDE) value as the fundamental basis for a limit. That NOAEL or NOEL value is then adjusted […]

May

2013

More on Limits Based on Compendial Water Values

Last month we covered issues related to setting limits based on a 500 ppb TOC “requirement”. This month we will expand that to cover other compendial water quality values that are sometimes used for cleaning validation limits. They include conductivity, bioburden and endotoxin. The USP requirement for conductivity is a staged approach. Stage 1 is […]

Apr

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 […]

Memo Year: 2013

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

A Way Forward for “Health-based” Limits

Comments on the EMA Guideline on Dedicated Facilities

Revisiting Rinse Sampling Recovery Studies

Revisiting Linearity of Recovery Studies

Conductivity vs. pH vs. TOC for Final Rinse Monitoring: Part 2

Conductivity vs. pH vs. TOC for Final Rinse Monitoring: Part 1

Are Health-Based Limits Enough?

More on Limits Based on Compendial Water Values

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

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