Cleaning Validation Memos from 2016

2016

Limits for Batch Splitting – Part 2

This is a continuation of last month’s Cleaning Memo dealing with batch splitting (if you haven’t read last month’s Cleaning Memo, please do so before proceeding with this one). In this Cleaning Memo we will consider another case of batch splitting, in which the final processing step involves a split batch. The idea is that […]

Nov

2016

Limits for Batch Splitting – Part 1

What do I mean by “batch splitting”? The idea is that you start off processing a given product in a relatively large batch size on initial equipment, then the batch is split in two or more small batches for processing separately on two or more subsequent “equivalent” equipment items, and then those smaller “partial” batches […]

Oct

2016

Limits for Products with Multiple Actives

If I have a drug product with multiple (two or more) actives, do I have to set limits for and measure all actives in my cleaning validation protocols? Or, is there a rationale for perhaps focusing only on one active as a representative active? That is, just like grouping of different products together and selecting […]

Sep

2016

What is Placebo Cleaning?

Placebo sampling was discussed in the August 2016 Cleaning Memo. Sometimes “placebo sampling” is confused with “placebo cleaning”. This Cleaning Memo will address what placebo cleaning is, and its relationship to placebo sampling. Just to refresh our memories, placebo sampling is done after a cleaning process; it involves manufacturing a placebo product on the cleaned […]

Aug

2016

What is Placebo Sampling?

Placebo sampling (also called a “placebo run”) is a procedure in which I process a placebo product (with no active) in my manufacturing equipment. After processing that placebo product, I measure a residue of a prior active (the residue of the prior active left after the cleaning of that prior product) in the placebo product. […]

Jul

2016

Should 10 PPM be Used for Limits?

A recent publication (“Cleaning Limits – Why the 10-ppm Criterion Should be Abandoned”, by Michel Crevoisier et al, PharmTech, Volume 40, Issue 1, pp 52-56) advocated abandoning the 10-ppm criterion for pharmaceutical cleaning validation limits. The authors point to the EMA document on health-based exposure limits, as well as the lack of any regulatory guidance […]

Jun

2016

Limits for Small Molecule API Synthesis – Part 3

This is a continuation of the April and May 2016 Cleaning Memos. If you haven’t read those (Part 1 and Part 2), please do so. In those previous Cleaning Memos we considered limits for intermediates, and discussed how to determine clearance of residues by subsequent processing steps. Now we’ll consider limits for cleaning of the […]

May

2016

Limits for Small Molecule API Synthesis – Part 2

This is a continuation of the March 2016 Cleaning Memo. If you haven’t read that one (Part1), it would be prudent to do so. In that previous Cleaning Memo we discussed a situation where there were two API synthesis routes for two final APIs, and these were made on the same equipment train comprised of […]

Apr

2016

Limits for Small Molecule API Synthesis – Part 1

There have been past publications on setting limits for cleaning validation for manufacture of small molecule API’s by an organic synthesis route (including the 2014 APIC guidance and some of my older publications). In my mind, none of them fully address all the complex issues involved in setting limits for these situations, which involve setting […]

Mar

2016

Meeting EMA Requirements for Existing Products

An industry working group has published a paper (A. Teasdale et al, “EMA Guideline on Setting Health-based Exposure Limits”, BioPharm International, 29:1, January 2016; also published in Pharmaceutical Technology, 40:1, December 2015) proposing a streamlined way to prioritize meeting the EMA requirement for limits in shared facilities for existing products. The EMA date for compliance […]

Feb

2016

Understanding Sources of Variation in Validation Protocols

This is a follow-up to the January Cleaning Memo where we discussed variations in cleaning processes. This month we’ll cover variations in the cleaning validation protocol itself (variation in the protocol as well as in the execution of the protocol). Reducing variability involves first understanding the sources of variation in a protocol, and then designing […]

Jan

2016

Understanding Sources of Variation in Cleaning Processes

More and more as I present training classes I am emphasizing the issue of understanding sources of variation in a cleaning process. For me, the 2011 FDA process validation guidance has been one source of this emphasis. However, it should have been more obvious to me earlier. In its discussion of 2004 pharmaceutical manufacturing in […]

Memo Year: 2016

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

Limits for Batch Splitting – Part 2

Limits for Batch Splitting – Part 1

Limits for Products with Multiple Actives

What is Placebo Cleaning?

What is Placebo Sampling?

Should 10 PPM be Used for Limits?

Limits for Small Molecule API Synthesis – Part 3

Limits for Small Molecule API Synthesis – Part 2

Limits for Small Molecule API Synthesis – Part 1

Meeting EMA Requirements for Existing Products

Understanding Sources of Variation in Validation Protocols

Understanding Sources of Variation in Cleaning Processes

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