Cleaning Validation Memos from 2007

2007

More on Limits for API Manufacture

A group of European pharmaceutical scientists representing small molecule API manufacturers has published recommendations on setting limits for API’s in cleaning validation. They advocate some good things, but there are also things that should cause concern. Here is the web link to the document, which is entitled “Justification of Limits for Cleaning Validation in the […]

Nov

2007

Measuring Residues of Volatile Solvents?

A common question for residues for pharmaceutical manufacturers is whether it is necessary to measure for residues of volatile organic solvents in cleaning validation protocols. While this question primarily arises with API manufacturers who perform solvent cleaning for manufacturing involving organic synthesis of actives, it also comes up in finished drug manufacture where a volatile […]

Oct

2007

Downsides to TOC?

After HPLC, TOC (Total Organic Carbon) is one of the most widely used analytical methods for measuring residues in cleaning validation protocols. TOC is used because of its simplicity of method development, and because it measures degraded as well as undegraded organic chemical species. As with other analytical methods, TOC does have it downsides. Both […]

Sep

2007

TOC Analytical Method Validation

As given in the FDA’s “Q&A on CGMP”, one of the “requirements” for using TOC for cleaning validation purposes is to establish that “a substantial amount of the contaminating material(s) is organic and contains carbon that can be oxidized under TOC test conditions.” While it is somewhat easy to determine if the residue is organic […]

Aug

2007

Master Plans vs. Policies

While not a regulatory requirement, it is prudent (and practical) to have a high level document that describes how cleaning validation is performed in your facility. The rationale for this is the FDA’s “new” investigation program, which that states that the first thing to be evaluated is high level documents to see if a facility’s […]

Jul

2007

Spiking Amounts for Sampling Recovery Studies

If a sampling method is utilized in a cleaning validation protocol, it is important that a sampling recovery study be performed. This need is covered in the FDA’s cleaning validation guidance. One issue to consider is the amount of residue to be spiked onto the coupons (coupons of the same materials of construction as the […]

Jun

2007

Issues in Campaigns

There are at least three different kinds of campaigns, and accordingly three different considerations in cleaning validation for those three situations. Those three situations are as follows. Case I: A campaign in which there is fully validated cleaning between each batch in the campaign. Case II: A campaign in which there is some kind of […]

May

2007

Revisiting Medically Safe Limits

The FDA states in a Human Drug CGMP Note (Second Quarter 2001) that residue limits should be established that are practically achievable, are medically safe for the next manufactured product, and don’t affect the quality of the next manufactured product. For limits for drug actives in finished drug manufacture, the medically safe criteria is usually […]

Apr

2007

Limits for Bulk Biotech Manufacture – Part 2

Last month we discussed the basic way limits are set for bulk biotech manufacture, and the rationale for an approach based on “industry standard practice”. This month we will cover additional things to consider in justifying these limits. One item is that a carryover calculation for finished drug manufacture typically involves a carryover from the […]

Mar

2007

Limits for Bulk Biotech Manufacture – Part 1

A common issue in the manufacture of the bulk active in biotech manufacturing is setting of appropriate limits for the active (which for purposes of this Cleaning Memo we will call the “protein”). Can limits be set based on the standard maximum allowable carryover (MAC or MACO) calculation? After all, all you need to calculate […]

Feb

2007

Microbiological Test Method Validation?

It is a given in pharmaceutical cleaning validation that analytical methods for chemical residues, such as residues of the drug active or of the cleaning agent, will be validated for those specific residues. The principles of ICH Q2 are usually a starting point for such analytical method validation. For chemical residues, the analytical methods are […]

Jan

2007

Dealing with Deviations in the Clean Equipment Hold Time (CEHT)

This month’s topic is how to handle situations in which the clean equipment hold time (CEHT) is exceeded in ordinary cleaning processes (after a specific CEHT is validated in a cleaning validation protocol). Two types of CEHT will be covered. One type is the CEHT from the end of cleaning until subsequent use or sterilization. […]

Memo Year: 2007

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

More on Limits for API Manufacture

Measuring Residues of Volatile Solvents?

Downsides to TOC?

TOC Analytical Method Validation

Master Plans vs. Policies

Spiking Amounts for Sampling Recovery Studies

Issues in Campaigns

Revisiting Medically Safe Limits

Limits for Bulk Biotech Manufacture – Part 2

Limits for Bulk Biotech Manufacture – Part 1

Microbiological Test Method Validation?

Dealing with Deviations in the Clean Equipment Hold Time (CEHT)

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