Cleaning Validation Memos from 2017

2017

What’s at Stake with HBELs

As you are hopefully aware, the EMA in December 2016 issued a draft “Q&A” clarifying some issues in its 2014 guidance on limits in shared facilities (see the July and August 2017 Cleaning Memos). I for one thought it was a “breath of fresh air”. In June 2017 the EMA had a stakeholders’ meeting where […]

Nov

2017

Toxicity as a Worst-Case Grouping Factor

In a grouping (matrixing) approach to cleaning validation, one product is selected as the “worst case”, and cleaning validation is done on that product. Successful validation of that product constitutes coverage of validation for all products in the group. My recommended approach is to select the “most difficult to clean” product in the group as […]

Oct

2017

Meaning of “Dedicated”?

I often get questions about how to handle cleaning validation for dedicated equipment. As I mentioned in a recent Cleaning Memo, words and wording are very important when we read regulatory documents or ask questions about what we should do. What “dedicated’ means is a good example of this. I generally see the word “dedicated” […]

Sep

2017

Another Issue for API Synthesis

Earlier this year I critiqued the APIC cleaning validation guide for small molecule API (drug substance) manufacture (Cleaning Memo of January 2017). That guide has many good points (and a few areas for improvement). One issue not addressed by that guide is dealing with processing of multiple lots of the same product (by “product” I […]

Aug

2017

EMA’s Q&A Clarification: Part 2

This is a continuation of last month’s Cleaning Memo dealing with the EMA’s recent Q&A on HBELs for cleaning validation. Please read that July document before jumping into this one. This month we will cover Questions #6 though #14. As mentioned last month, care must be used in trying to understand what the EMA means […]

Jul

2017

EMA’s Q&A Clarification: Part 1

The EMA issued its draft Q&A on health based exposure limits in December 2106. The official title is “Questions and answers on implementation of risk based prevention of cross contamination in production and ‘Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities’ […]

Jun

2017

Pass/Fail Analytical Test Methods

A pass/fail test method is an analytical test method that only tells me whether I am below a certain value. For example, I may have a HPLC method that strictly tells me that I am at or above a value of X ppm in my sample, or I am below a value of X ppm. […]

May

2017

Issues in Product Grouping

This is part of a clarification on a topic I have written about in the past (See the July 2001 Cleaning Memo) and where I have subsequently expanded on in my training seminars and webinars, but have not updated in Cleaning Memos on my website. So this is an opportunity to share that information with […]

Apr

2017

Dirty and Clean Hold Time Protocols

I sometimes get asked about doing a dirty hold time (DHT) protocol after the cleaning validation protocol is complete. Implicit in the question is the assumption that a protocol to determine the effectiveness of the cleaning process is different from a protocol to determine the dirty hold time. That is, I first complete my cleaning […]

Mar

2017

Establishing Clearance for Degraded Protein Actives

Last month we covered a possible approach for setting “health-based” limits for biotech manufacture based on the “fact” that the biotech active protein would be degraded and inactivated during cleaning. There is an important difference between “inactivation” (or deactivation) and “degradation”. Inactivation means that the protein loses specific biological activity based on a change in […]

Feb

2017

A Possible Approach for Biotech Limits

For years the biotech industry has argued that cleaning validation limits for biotech manufacture should not be based on the safety of the native protein, because those proteins are deactivated and degraded during a cleaning process with hot, alkaline aqueous cleaning solutions. The 2014 EMA guide on limits for “shared facilities” finally provides some regulatory […]

Jan

2017

A Critique of the APIC Guideline

The APIC “Guidance on Aspects of Cleaning Validation in Active Pharmaceutical Ingredient Plants” was revised in September 2016. This guide is one of the few that specifically addresses issues with cleaning validation in small molecule API facilities (those that manufacture API’s by chemical organic synthesis, usually in solvents). While some of the concepts may apply […]

Memo Year: 2017

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

What’s at Stake with HBELs

Toxicity as a Worst-Case Grouping Factor

Meaning of “Dedicated”?

Another Issue for API Synthesis

EMA’s Q&A Clarification: Part 2

EMA’s Q&A Clarification: Part 1

Pass/Fail Analytical Test Methods

Issues in Product Grouping

Dirty and Clean Hold Time Protocols

Establishing Clearance for Degraded Protein Actives

A Possible Approach for Biotech Limits

A Critique of the APIC Guideline

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