Memos - Page 4 of 15 - Cleaning Validation Simplified

2019

Issues in Rinsing – Part 2

This Cleaning Memo is a follow-up to the November 2019 Cleaning Memo, and focuses on the impact of an understanding of rinse sampling and its effect on rinse sampling recovery studies. Please read this only after reviewing Part 1. In that first part we discussed that the objective of the washing step in an ideal […]

Nov

2019

Issues in Rinsing – Part 1

In this Cleaning Memo and in next month’s, we’ll cover issues in the rinse process itself, in rinse sampling, in limits for rinse sampling, and finally in rinse recovery studies. However, before we get to those issues, we’ll first need to cover what actually (or hopefully) happens in the washing step of a cleaning process […]

Oct

2019

Limits for “Product A to Product A”

Typically the greatest concern in limits for drug actives is when moving from one drug product to a different drug product. This is sometimes expressed as limit “ProdA to ProdB”. For this Cleaning Memo we will cover the situation where the same product follows the cleaned product; that is, it will be a “ProdA to […]

Sep

2019

Cleaning Validation for Homeopathic Drug Products

In order to discuss a possible approach to cleaning validation for homeopathic drugs, I first need to clarify what constitutes a homeopathic drug. “Homeopathy” is a practice in which a substance which causes disease symptoms at high levels is thought to have curative effects of those same symptoms at very low levels. A homeopathic drug […]

Aug

2019

What’s a Visual Limit?

“Visual Limit” (VL) is a term dealing with amounts of residue which could be on a surface that are detectable (or not detectable) by visual examination. We all know that the visual detectability of a residue on a surface will depend on such factors as the viewing distance, the lighting, the angle of viewing, the […]

Jul

2019

Use of the Terms Grouping and Matrixing

The terms “grouping” and “matrixing” are currently used to refer to the same concept of using a “worst-case” product in a cleaning validation protocol to represent a selection of other products where no or limited protocol runs may be performed for those other products. Successful validation of the cleaning process for that worst-case product constitutes […]

Jun

2019

Deviations and Non-conformances

Following up the last month’s Cleaning Memo, this month we will cover another example where clarity in use of language might help. It deals with the similarities and differences between a “deviation” and a “nonconformance”. How these are defined and how they are handled for cleaning validation purposes might vary among different companies, and those […]

May

2019

Use of the Term “Product”

I have become more concerned in the last few years about the correct and consistent use of words, in particular in cleaning validation documents. The December 2018 Cleaning Memo dealt with “blanks/controls” and the October 2017 Cleaning Memo dealt with definitions of “dedicated”. This month’s Cleaning Memo will consider an additional example, that of the […]

Apr

2019

Surfaces Areas in Carryover Calculations

The shared surface area between two products is one of the key factors used in a typical carryover calculation to determine limits for cleaning validation. The value for the shared surface area (typically in square centimeters or square inches) is in the denominator of a carryover calculation; therefore the larger the shared surface area, the […]

Mar

2019

Contaminants in API Manufacture

For the past six months the FDA (as well as many other regulatory agencies) has been dealing with recalls of drug products and drug substances contaminated with nitrosamines. Nitrosamines are probable human carcinogens. The products are associated with API manufacture of angiotensin II receptor blockers (ARBs), mainly with valsartan but also including other ARBs. The […]

Feb

2019

Significant Figures: Back to Basics

Those of you that have taken any of my training courses or webinars know that I have certain “pet peeves”. One of them is significant figures, particularly in expressing sampling recovery factors. For example, it is common that I see in company reports and in published papers where recovery percentages are given to three or […]

Jan

2019

The Value of a Protocol Worksheet for Manual Cleaning

In a protocol for pharmaceutical cleaning validation, there are generally many worksheets associated with that protocol. For example there might be a worksheet for entering sampling locations and ID numbers, with the time and date of sampling, along with the initials of the sampler. There might be a similar worksheet for analytical results, including analytical […]

Dec

2018

Clarifying Terms: Blanks vs. Controls

This month we’ll cover the use of terms as used in the cleaning validation. It should be recognized that as long as a company clearly defines its terms in an appropriate document, and uses them consistently, then different uses may be acceptable. As used for analytical measurements for cleaning validation studies, the two terms “blanks” […]

Nov

2018

More Swab Sampling Issues

Last month’s Cleaning Memo addressed the issue of “timing” in performing swab sampling in a protocol. This month we will consider four miscellaneous topics in swab sampling. Controlling the swabbed area in protocols There are basically two techniques used to control the swabbed area in protocols. One is what I call the “eyeball” method. That […]

Oct

2018

Timing for Swab Sampling in a Protocol?

In performing swabbing for chemical residues after completion of a cleaning process in a cleaning validation protocol, is the timing for taking the swab sample critical? In the tradition of being a consultant paid by the hour, the correct answer is “It depends.” When I do swab sampling at the end of a cleaning process, […]

Sep

2018

What If the Next Product is the Same Product?

In performing carryover calculations, we usually talk about limits for the active of Product A if Product B is the next product. Can carryover calculations be done if Product A is cleaned and then Product A is the next product? For clarification, this generally comes up in the context of there being two or more […]

Aug

2018

Other Issues in EMA’s Q&A

This is the third Cleaning Memo discussing issues in EMA’s Q&A on limits in shared facilities (April 19, 2018). It is also the least important of the three, so if you have more important things to do, you may be tempted to skip reading this one (of course, how will you know whether something else […]

Jul

2018

The EMA Q&A on Routine Analytical Testing

As discussed last month, the EMA issued it clarifying Q&A on limits in shared facilities on April 19, 2018. Last month we focused on HBELs and “historically used” limits. This month we’ll focus on Questions 7 and 8 dealing with routine analytical testing. The question in Q7 is as follows: “Is analytical testing required at […]

Jun

2018

The EMA Q&A “Clarification” on Limits

The EMA issued it clarifying Q&A on limits in shared facilities on April 19, 2018. This was a “final” document with changes from the draft version issued in January 2017. I say it was a clarifying document. However, in my view it just muddied the waters further as compared to the clear statements made in […]

May

2018

“Concurrent Release” for Cleaning Validation

I am generally an advocate of applying the principles of life cycle validation given in the FDA’s 2011 process validation (PV) guidance to a life cycle approach for cleaning validation (CV). As I have written before, there are many similarities between CV and PV, as well as some significant differences (see the Cleaning Memo of […]

Memos by Destin

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

Issues in Rinsing – Part 2

Issues in Rinsing – Part 1

Limits for “Product A to Product A”

Cleaning Validation for Homeopathic Drug Products

What’s a Visual Limit?

Use of the Terms Grouping and Matrixing

Deviations and Non-conformances

Use of the Term “Product”

Surfaces Areas in Carryover Calculations

Contaminants in API Manufacture

Significant Figures: Back to Basics

The Value of a Protocol Worksheet for Manual Cleaning

Clarifying Terms: Blanks vs. Controls

More Swab Sampling Issues

Timing for Swab Sampling in a Protocol?

What If the Next Product is the Same Product?

Other Issues in EMA’s Q&A

The EMA Q&A on Routine Analytical Testing

The EMA Q&A “Clarification” on Limits

“Concurrent Release” for Cleaning Validation

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