Application of Visible-Residue Limit for Cleaning Validation Richard J. Forsyth and Vincent Van Nost

Richard J. Forsyth , Vincent Van Nostrand

Pharmaceutical Technology, Oct 2, 2005
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Pharmaceutical plants must have visually clean equipment to operate according to good manufacturing practices. Formulators must visually inspect manufacturing equipment for cleanliness before formulation work begins (1). Manufacturers establish and perform visible cleanliness and analytical methods to ensure regulatory compliance. An analyst conducts a visual inspection and confirms visible cleanliness before taking swab samples for chemical analysis (2). The formulator of the subsequent batch conducts a visual inspection before manufacturing work begins. A correlation between available analytical data and visible cleanliness of manufacturing equipment over an extended period of time can expand the practice of performing visual inspections in lieu of swab sampling.

Yet, the US Food and Drug Administration's Guide to Inspection of Validation of Cleaning Processes (3) and other literature (4) discount using a visible limit as the sole acceptance criterion for cleanliness. Conversely, Mendenhall concluded that visible cleanliness criteria were more rigid than quantitative calculations and are clearly adequate for determining cleanliness (5). Other recent articles describe the justification and application of a visible-residue limit (VRL) (6, 7).

Many research teams have established quantitative VRL levels. Fourman and Mullen determined a visible limit of ~100 μg per 2 X 2-in. swab area (8) or ~4 μg/cm2 . Jenkins and Vanderwielen observed residues as low as 1.0 μg/cm2 with a light source (9). Forsyth et al. determined <0.4->10-μg/cm2 VRLs for active pharmaceutical ingredients (APIs) and excipients (6).

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