Calculating Cleaning Agent Safety Based Limits

Q. Does Alconox, Inc. provide information on calculating cleaning agent safety based limits?

A. Pharmaceutical product manufacturing requires identifying and setting acceptable residue limits for potential residues, including:
• Limits for the active drug
• Excipients
• Degradation products
• Cleaning agents
• Bioburden
• Endotoxins

Determining acceptable levels of each residue must take into account how the residue will affect the next product ingredient to contact that equipment or processing surface during production. Residue levels must maintain pharmacological safety and stability while avoiding toxicity or contamination of the product that follows. Typically, limits are set for visual, chemical, and microbiological residues. Cleaning agent limits are generally covered under chemical limits, which can be expressed in any of the following ways:
• Maximum concentration in the next product (µg/ml)
• Amount per surface area (µg/cm2)
• Amount in a swab sample (µg or µg/ml)
• Maximum carry-over in a train (mg or g),
• Concentration in equilibrated rinse water (µg/ml)

A calculated safety-based acceptance limit should be determined. A lower internal action level, plus a lower process control level based on actual manufacturing and measuring experience, may also be desirable.

Calculations for these limits can include the Allowable Daily Exposure (ADE)/Permitted Daily Exposure (PDE) approach, Allowable Daily Intake (ADI) and/or the 10 ppm carry over method.  Please refer to our Cleaning Validation References Whitepaper for further details in how this relates to pharmaceutical, biotech and medical device manufacturing.

Other useful whitepapers and reference documents:

To request an Alconox, Inc. detergent for free, please complete the questionnaire at Get Sample. For more information about any one of our Alconox, Inc. detergents, consult the technical bulletin for each product. Or click here to access each of our detergent’s  Safety Data Sheets.

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