Method Development of Swab Sampling for Cleaning Validation of a Residual Active

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A swab-sampling method was developed for cleaning validation of a residual active pharmaceutical ingredient in samples collected after cleaning the sampling suite. A summary of the strategies and results of the method development is presented. The developed extraction method produced an acceptable level of recovery and precision.Cross contamination with active ingredients is a real concern. The Code of Federal Regulations (CFR) states that “Equipment and utensils shall be cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official, or other established requirements” (1). Cleaning validation is required in the pharmaceutical field to avoid potential clinically significant synergistic interactions between pharmacologically active chemicals (2).

Author(s):

Pei Yang, Kim Burson,Debra Feder, Fraser Macdonald

Journal:

Pharmaceutical Technology, Jan 2, 2005

Pharmaceutical Cleaning Validation Method References

Alconox A cleaning validation involves testing for acceptable residues o­n pharmaceutical manufacturing or medical device surfaces. The validation involves residue identification, residue detection method selection, sampling method selection, setting residue acceptance criteria, methods validation and recovery studies, and finally writing a procedure and training operators. This procedure is used to document acceptable residues 3 or more times and then a rational monitoring program to maintain a validated state is put in place. If you are changing any part of your procedure or cleaner, first clean the new way, collect data and then clean the old way before using any equipment while you are in the process of validating the new procedure.


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Cleaning Validation Acceptance Criterion – Case Study

You are fed up, tired of it all. Your boss has been harassing you to develop "a scientifically sound, logical, and rational basis for cleaning acceptance limits." Should be simple enough, right? Yet, every time you ask someone about setting cleaning limits they look at you as if you have three, maybe four heads. Asking a consultant o­nly makes things worse, leaving you more confused when they present you with more theoretical options than you ever imagined possible (but of course offering to help you solve the problem with a team of experts!) You’ve scoured the literature, yet haven’t found anything but theoretical discussions and vague references to the "Mullen and Fourman method." Before kicking the cat or cursing your boss, let’s see what this is really all about.

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Endotoxin Issues in Cleaning Validation

Destin A. LeBlanc,Cleaning Validation Technologies, Technical Consulting Services The questions that will be addressed in the Cleaning Memo include:“When should I measure endotoxin in a cleaning validation protocol?”“How should I sample for endotoxin?”“What acceptance criterion should I establish for endotoxin?”



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Monitoring a Validated Cleaning Process

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Destin A. LeBlanc Cleaning Validation Technologies, Technical Consulting Services In discussing monitoring for cleaning validation, it is important to carefully define what o­ne means by “monitoring”. As used here, the term “monitoring” refers to the routine measurements taken o­n the cleaning process that serve as indicators of whether the process is in a state of control (or considered from the opposite point of view, serve as indicators that the process either is not or may not be in a state of control). The purpose of monitoring is not to have clear evidence that the surfaces are acceptably clean. To do that, o­ne would have to sample the surfaces (much as o­ne would do in a cleaning validation protocol).

Author(s):

Destin A. LeBlanc

Journal:

Cleaning Validation Technologies, Technical Consulting Services

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

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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.

Author(s):

Richard J. Forsyth , Vincent Van Nostrand

Journal:

Pharmaceutical Technology, Oct 2, 2005

Enhancing Drug Development by Applying LC–MS–MS for Cleaning Validation in Manufacturing Equipment

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Currently, liquid chromatograph–ultraviolet spectrometry (LC–UV) is typically applied to cleaning validations because of its familiarity, robustness, ease of use, and regulatory acceptability. For low-dose compounds, equipment requiring low residue limits, and compounds lacking strong chromophores, the enhanced sensitivity and selectivity of liquid chromatography–mass spectrometry–mass spectrometry (LC–MS–MS) facilitates rapid method development for the detection of low levels of residues of active pharmaceutical ingredients (APIs). LC–MS–MS is an acceptable technique for the analysis of API residues for cleaning validation. More importantly, in applications where sensitivity and selectivity are inadequate using traditional modes of detection, LC–MS–MS offers substantial advantages. LC–MS–MS will afford faster development and analysis time, potentially making it the predominant tool of choice.

Author(s):

Kevin J. Kolodsick , Holly Phillips , Jennifer Feng , Matthew Molski , Carol A. Kingsmill

Journal:

Pharmaceutical Technology, Feb 2, 2006