Memos - Page 13 of 16 - Cleaning Validation Simplified

2006

FTIR with Fiberoptic Sampling

Last month, I mentioned two new analytical techniques that have been promoted for pharmaceutical cleaning validation in the last five years. “Ion mobility” was discussed in last month’s Cleaning Memo. The other “new” technology is FTIR with a fiberoptic probe. In one sense, this is just a novel combination of two technologies, “conventional” infrared analysis […]

Jun

2006

Ion Mobility Spectrometry

Two analytical techniques have been newly promoted for pharmaceutical cleaning validation over the last five or so years. They are (1) ion mobility spectrometry, and (2) FTIR with a fiberoptic probe. The latter is certainly more an example of the combination of infrared analysis with a fiberoptic probe for sampling. This Cleaning Memo, however, will […]

May

2006

Measuring Bioburden in Protocols

The question sometimes arises as to the value of establishing bioburden specifications and measuring bioburden following cleaning in validation protocols. Those involved in non-sterile manufacture sometimes object that bioburden is not significant. Those involved in aseptic processing sometimes object that bioburden is not relevant because the equipment undergoes a SIP (steam in place) cycle following […]

Apr

2006

More on Using Rinse Sampling Alone

Several months ago, I discussed the option of using rinsing sampling alone for cleaning validation protocols. The purpose of this Cleaning Memo is to possibly explain why this could be a valuable option to consider, as well as why there may be objections to that approach. I believe the main reason why there appears to […]

Mar

2006

Separating CEHT Protocols from Cleaning Protocols

Last month, I discussed setting bioburden limits in a CEHT (clean equipment hold time) protocol. This is ordinarily done by evaluating bioburden proliferation during storage. This involves comparison of the bioburden on equipment surfaces at the beginning of storage and the end of storage. Since the data at the beginning of storage is essentially the […]

Feb

2006

Bioburden Proliferation in CEHT Protocols

A primary concern in clean equipment hold time (CEHT) protocols is that there should be a lack of bioburden or microbial proliferation. This emphasis has a good scientific rationale. In addition, it is specifically mentioned in the FDA cleaning validation guidance (1993): “There should be some evidence that routine cleaning and storage of equipment does […]

Jan

2006

Acceptance Criteria for Dedicated Equipment

This Cleaning Memo addresses the question of what residue limits should be set for manufacture of one product in dedicated equipment. Before we get into those details, it is necessary to restate some important issues related to dedicated equipment so that it is clear that residue limit must be set for dedicated equipment, and that […]

Dec

2005

Selecting the Swab Sampling Area

This Cleaning Memo addresses the question of the specific surface area to swab in a cleaning validation protocol. For clarification, this will address the size of the swab area, not the location of the swab area. Most companies will swab areas of 25 cm2 (4 square inches) to 100 cm2 (16 square inches), although I […]

Nov

2005

Averaging Swab Sample Results?

In cleaning validation, limits are set for swab samples (usually based on a carryover calculation). The question is often asked, “Am I allowed to average different swab samples and compare that average to my calculated established acceptance limit?” This is usually asked in the context of having one (or more) swab samples exceed the established […]

Oct

2005

Limits for Rinse “Grab” Samples

Limits for rinse samples in finished drug manufacture have always been a problem area for pharmaceutical cleaning validation. How does one justify limits on a scientific basis, much like is ordinarily done for swab sampling? I have answered this in part in a May 1998 Pharmaceutical Technology magazine publication. However, I have gone one step […]

Sep

2005

More on Limits for Formulated Cleaning Agents

In last month’s Cleaning Memo, I discussed that for formulated cleaning agents (those cleaning agents containing surfactants and other functional aids), residue limits are generally set based on the toxicity of the cleaning agent. Rather than using something like 0.001 of a dose (as is used for actives), the limit of the formulated cleaning agent […]

Aug

2005

Issues in Limits for Formulated Cleaning Agents

For formulated cleaning agents (those cleaning agents containing surfactants and other functional aids, perhaps in addition to an alkali or acid), residue limits are generally set based on the toxicity of the cleaning agent. Rather than using something like 0.001 of a dose (as is used for actives), the limit of the formulated cleaning agent […]

Jul

2005

Revisiting Cleaning Validation for Medical Devices

I recently presented at an ASTM conference on the cleanliness of medical device implants. An expanded paper based on that presentation will hopefully be published shortly in ASTM’s online Journal of Testing and Evaluation. The industry seems to be heading in the direction of the ASTM testing procedure being adopted. My position is slightly different. […]

Jun

2005

Setting Limits Based on Process Capability?

As some of you might know, I am not generally a fan of setting residue limits based on process capability. Where this sometimes comes up is when a manufacturer sets limits based on standard dosing calculations (also called maximum allowable carryover calculations), but then the actual residue data measured is much below that calculated limit. […]

May

2005

Objectionable Microorganism Concept in Cleaning Validation

A special Cleaning Memo authored by Dr. Tony Cundell A common question asked of pharmaceutical microbiologists by their counterparts in validation is what microorganisms should be absent from the surface of pharmaceutical manufacturing equipment when monitored for microorganisms during cleaning validation? For equipment used for the manufacture of non-sterile pharmaceutical and over-the-counter drug products, we […]

Apr

2005

Cleaning Validation for Packaging Equipment: Part 2

This is a continuation of last month’s Cleaning Memo. In that Cleaning Memo, I discussed the criticality of cleaning for primary packaging equipment. That this is important is evident from the fact that the principle involved (non-uniform contamination of the next batch) is mentioned in the FDA cleaning validation guidance. This month, I will focus […]

Mar

2005

Cleaning Validation for Packaging Equipment: Part 1

Sometimes I am asked about cleaning validation for packaging equipment, and the thought behind the question appears to be that this is not a critical cleaning process and therefore doesn’t require cleaning validation. While it is true that effective cleaning of some packaging equipment may be much easier to achieve, it is not necessarily true […]

Feb

2005

Dealing with Unknown Peaks

A common question in training seminars is “How do I deal with unknown peaks in HPLC analysis?” My first answer is a facetious one: “Try TOC; there are no unknown peaks in TOC!” However, TOC is not without its problems. To directly answer the question about unknown peaks in HPLC analysis, the first attempt should […]

Jan

2005

Understanding the Cleaning Process

A key issue in the FDA’s recent report on a risk-based approach to pharmaceutical CGMPs was that manufacturers should move to a better understanding of their manufacturing processes. A clear statement of this is on page 5 of that report: “Quality and productivity improvement share a common element – reduction in variability through process understanding….” […]

Dec

2004

Establishing Adequate Solubility for TOC Analysis

A common objection to the use of TOC (Total Organic Carbon) analysis for analysis of trace residues in cleaning validation protocols is “My active is not water soluble.” This may or may not be an appropriate objection. The key to the use of TOC for trace analysis in cleaning validation protocols is whether the target […]

Memos by Destin

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

FTIR with Fiberoptic Sampling

Ion Mobility Spectrometry

Measuring Bioburden in Protocols

More on Using Rinse Sampling Alone

Separating CEHT Protocols from Cleaning Protocols

Bioburden Proliferation in CEHT Protocols

Acceptance Criteria for Dedicated Equipment

Selecting the Swab Sampling Area

Averaging Swab Sample Results?

Limits for Rinse “Grab” Samples

More on Limits for Formulated Cleaning Agents

Issues in Limits for Formulated Cleaning Agents

Revisiting Cleaning Validation for Medical Devices

Setting Limits Based on Process Capability?

Objectionable Microorganism Concept in Cleaning Validation

Cleaning Validation for Packaging Equipment: Part 2

Cleaning Validation for Packaging Equipment: Part 1

Dealing with Unknown Peaks

Understanding the Cleaning Process

Establishing Adequate Solubility for TOC Analysis

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