Memos - Cleaning Validation Simplified

2024

What Does Consistency Mean

The idea of consistency is fundamental to understanding the expectations (both of industry firms and regulatory agencies) for a cleaning validation program. If we look to dictionary definitions, we can find one definition that consistency is “agreement or harmony between parts of something complex”. While we want our cleaning validation programs to be internally consistent, […]

Nov

2024

Documentation for Selecting Swabbing Locations

This Cleaning Memo is a follow-up to last month’s where we covered criteria for selecting swab sampling locations. This month we will cover how to appropriately document that selection criteria and process. I am not advocating a “best practice”; there are many ways to appropriately document the selection process, so we will cover some of […]

Oct

2024

Selecting Swab Sampling Locations

This Cleaning Memo focuses on the rationales for selecting appropriate swab sampling locations. It is generally accepted that the major concern is dealing with “worst-case” locations, realizing that locations may be considered a “worst case” for a variety of reasons. Furthermore, sometimes we select locations that are not “worst-cases”, but are merely representative of certain […]

Sep

2024

More on Health Canada’s Guideline

This Cleaning Memo expands a discussion of Health Canada’s Cleaning Validation guidance (GUI-0028 June 29, 2021) to cover topics other than worst-case products in a grouping approach (which was covered last month). Specifically addressed are many topics that may help you design, audit, and/or improve your cleaning validation program and associated documents. Realize that many […]

Aug

2024

Health Canada’s Discussion of HBEL

There has been some misunderstanding of a statement in the Health Canada guideline GUI-0028 (dated June 29, 2021) about the use of HBEL values (such as PDE or ADE) in setting limits. The sentences of concern in Section 6.1.a are: “It should be noted that there may be multiple worst case products. For example, an […]

Jul

2024

More on Route Specific Health-based Limit Values

In August 2015 I wrote about “route specific” PDE values as a possible basis for cleaning validation limits. By “route specific” I am referring to situations where the cleaned product is administered by one route (such as parenteral) and the next manufactured product is by a different route (such as oral). While the basic principles […]

Jun

2024

More on Duration Specific Health-based Limit Values

In September 2015 I wrote about “duration specific” PDE values as a possible basis for cleaning validation limits. While the basic principles and/or consequences of that Cleaning Memo have not changed, I have significantly revised how that approach should be presented. First, I will just review the basic principle, which is if the product containing […]

May

2024

Dealing with Recovery for Sampling SOP Changes

Any change in the cleaning validation program requires an assessment as part of a company’s change control program. For this month we will consider a relatively simple way to deal with changes we might want (or might be forced to make) in your swab sampling or rinse sampling SOP. In most cases (but not all) […]

Apr

2024

Dealing with Low Rinse Limits

While this Cleaning Memo deals with rinsing, and utilizes studies similar to those described in the March Cleaning Memo, the focus is significantly different. What is covered here is the situation where the number of rinses has already been established, but where the analytical method has an LOQ or LOD such that we cannot establish […]

Mar

2024

Determining Rinse Times for CIP Processes

While a reasonable approximation of conditions (cleaning agent type, cleaning concentration, temperature, and time) can be obtained from relatively simple laboratory studies for the “washing” step of a CIP cleaning procedure, simple lab studies are less useful for the rinsing conditions, and specifically for the rinsing time and/or rinsing volume. Why is this the case? […]

Feb

2024

Defining the Beginning and End of the CHT

A common practice for the Clean Hold Time (CHT) is to consider it as the time from the end of the cleaning process to the beginning of the subsequent use of a specified vessel. This month’s Cleaning Memo is on how to define (or establish) those two “boundaries” for the CHT just like last month’s […]

Jan

2024

Defining the Beginning and End of the DHT

A common practice for the Dirty Hold Time (DHT) is to consider it as the time from the end of manufacture to the beginning of cleaning in a specified vessel. This month’s Cleaning Memo will cover how we define (or how we establish) those two “boundaries” for the DHT. Just like boundaries for land or […]

Dec

2023

Worst-Case Product Selection Criteria – Part 4

This is the fourth of several Cleaning Memos dealing with the selection of a worst-case product in a grouping approach for cleaning validation. In August we considered use of the pharmacopeia solubility categories, and also presented what may be a more useful system based on how “solubility bands” are defined. In September we considered issues […]

Nov

2023

Worst-Case Product Selection Criteria – Part 3

This is the third of several Cleaning Memos dealing with selection of a worst-case product in a grouping approach for cleaning validation. In August we considered use of the pharmacopeia solubility categories, and also presented what may be a more useful system based on how “solubility bands” are defined. In September we considered issues in […]

Oct

2023

Worst-Case Product Selection Criteria – Part 2

This is the second of several Cleaning Memos dealing with selection of a worst-case product in a grouping approach for cleaning validation. Last month we considered use of the pharmacopeia solubility categories, and also presented what may be a more useful system based on how “solubility bands” are defined. Many companies may use evaluation systems […]

Sep

2023

Worst-Case Product Selection Criteria – Part 1

This is the first of several Cleaning Memos dealing with selection of a worst-case product in a grouping approach for cleaning validation. I have taught for many years that solubility of the active (API or drug substance) alone is not the best parameter for determining the worst-case product in drug product cleaning validation. So over […]

Aug

2023

Considerations for CAPA Investigations

Last month we considered the elements of CAPA. This month we will be more “philosophical” and consider two things relevant to a CAPA investigation. Each item discussed is part of making sure we have identified the correct root cause. One is related to the investigation and corrective action proposed, and the second is related to […]

Jul

2023

Using CAPA for Cleaning Processes

CAPA (Corrective and Preventive Actions) is usually divided into three elements. If we have identified a problem with a cleaning process (which could be a process deviation or an analytical non-conformance), the parts of CAPA are: We will explore these different (but related) elements using examples to illustrate how they differ and how they can […]

Jun

2023

Recovery Studies for Sieve/Screen Sampling

Last month we covered some possible sampling methods that could be used for sieves/screens. This month is a follow-on Cleaning Memo that discusses sampling recovery studies for sieves/screens. Of course, if my suggestion made last month that sieves/screens be dedicated to one product (or at least to one active) were followed, then it would not […]

May

2023

Sampling Sieves/Screens

The issue of sampling sieves/screens (also called metal meshes) for cleaning validation protocols is a challenging one. For example, those sieves/screens may be used to sift dry powder for particle size control. Small particles may get trapped in the interstices of the crossing wires, and maybe difficult to clean. Those locations may also be difficult […]

Memos by Destin

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

What Does Consistency Mean

Documentation for Selecting Swabbing Locations

Selecting Swab Sampling Locations

More on Health Canada’s Guideline

Health Canada’s Discussion of HBEL

More on Route Specific Health-based Limit Values

More on Duration Specific Health-based Limit Values

Dealing with Recovery for Sampling SOP Changes

Dealing with Low Rinse Limits

Determining Rinse Times for CIP Processes

Defining the Beginning and End of the CHT

Defining the Beginning and End of the DHT

Worst-Case Product Selection Criteria – Part 4

Worst-Case Product Selection Criteria – Part 3

Worst-Case Product Selection Criteria – Part 2

Worst-Case Product Selection Criteria – Part 1

Considerations for CAPA Investigations

Using CAPA for Cleaning Processes

Recovery Studies for Sieve/Screen Sampling

Sampling Sieves/Screens

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