Pharmaceutical Cleaning Validation

Avoiding cross contamination and reducing risk to patients.

When creating pharmaceutical products, a machine might be used to create a number of products. Cross contamination must be avoided in the pharmaceutical industry at all costs and successful cleaning validation ensures that patients are not put at risk due to cross contamination. Cleaning validation is a requirement in industries that follow Good Manufacturing Practice (GMP). It is a guarantee that the cleaning can be performed consistently and repeatedly.

The process can be divided into a number of sections each of which must be fully understood and areas of concern addressed to ensure a successful outcome across the entire process. This is not just based on the cleaning of the equipment, but also on the training of the individual, and the analytics of the data collected. Within this application note we will focus on swabbing, a commonly used technique for cleaning validation.

 

Steps in today's traditional swab & test methods

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Walking the plant

One of the key aspects of cleaning validation is understanding your equipment, and how best to clean it, it is frequently called “walking the plant”. By walking the plant you can understand areas of concern and either engineer them out of your manufacturing process, or include them in your cleaning procedure. Areas of concern may include components such as small service lines, filter meshes, valves, pumps, and other difficult geometries.

It is also important that the individuals who carry out the cleaning do so in a controlled, documented, and repeatable way. In order to achieve reliable results, extremely detailed documents are produced that go over training requirements, procedures, and details on what to do if things don’t go as planned.

 

 

Swabbing and active pharmaceutical ingredients (APIs)

Once the machines are cleaned, they need to be tested to ensure that no residues of the active pharmaceutical ingredient (API) remain. The common method to do this is swabbing. Different swabs are used on different surfaces or structures to extract as much information on residual APIs and detergents as possible. These swabs then need to have their contents extracted and evaluated. The standard practice for this is through high-performance liquid chromatography (HPLC). This technique separates pressurised liquids (mixtures of solvents and sample) by passing through an absorptive material. Each component of the liquid is retarded at a different rate leading to a separation of the constituents making up the sample. The separated chemicals can then undergo a variety of qualitative and quantitative tests such as absorption or reflectance spectroscopy and compared with a reference sample.

Should any of the results come back with a positive indicator for residual APIs, then the whole process needs to be conducted again. This can result in days of downtime for a facility.

Once the machine has been deemed clean of all contaminants, only then can it be used again in production.

 

Steps for today's TraC sensor

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More recently, optical methods for cleaning validation have been introduced for testing. By using either Raman spectroscopy or deep UV excited autofluorescence, it is possible to determine the type of ingredient present in an area and also its abundance. With this technique a user can get information on the surface they are inspecting in a matter of seconds, in a repeatable way that is independent of the user. Whilst this technique may not completely replace swabbing, it can potentially significantly reduce  the down time needed for repeated swabbing tests, as measurements are done in-situ in real-time.


API Fluorescence Spectrum

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DUV excitation causes autofluorecence in residual APIs.
Each API has a unique Spectral ouput and can therefore be identified and quantified. 

 

 

 

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