Professional Services for Filtration Process Validation—Guidance of Adsorption Validation

Adsorption validation is one of the basis for the selection of process research prescriptions. It is a means to ensure reliable and controllable product quality. It is also the content of the first stage of process research. Adsorption studies are necessary if the filtered process fluid contains active ingredients or other functional ingredients, especially low-concentration multi-component process fluids.

In response to changes in regulatory requirements for adsorption validation, Cobetter Validation Center provides you with comprehensive guidance on adsorption validation test methods from R&D to mass production for your reference.

Adsorption testing is used to evaluate the likelihood that one or more components in a process fluid will adhere to the filter, causing the product concentration or quality to fail to meet established acceptance criteria for a drug product.

Adsorption tests can be conducted on a small scale in the laboratory or during actual large-scale production. During the test, you can use a reduced-size filter or membrane filter to simulate the necessary process parameters, sample the filtrate according to the preset sampling points, compare the concentration of the process fluid components before and after filtration, and analyze the difference with the drug acceptance standards. The difference between them is to evaluate the adsorption effect of the filter on the active ingredients or other functional ingredients.

The test results can be applied to the actual production scale process after being enlarged according to the filtration area, but they need to be confirmed again in large-scale actual production. If possible, it is recommended to conduct the adsorption test on the actual production line under the actual process conditions. if the single batch process cannot fully represent the worst process parameters, multiple batch test is recommended.

Product Development Stage (cartridge filter/ membrane material selection)

Users can choose a filter with a smaller filtration area or membrane filter according to the membrane material to be used, such as a syringe filter or a φ47mm membrane filter (filters of other sizes can also be used), and select the filter membrane material for the applicable product. Commonly used filter membrane materials are PES, PVDF, PTFE (hydrophilic/ hydrophobic), nylon, PP (cannot be used for sterilizing filtration), etc. Take the syringe filter/filter membrane as an example to illustrate:

• Use the same syringe filter or the same filter membrane to continuously filter the medicinal liquid, and conduct multi-point sampling of the unfiltered medicinal liquid, initial filtrate, and filtrate of different filtration volumes;
• For all sampling points, use the filtrate to detect the content/ concentration of the medicinal liquid ingredients of concern, and draw the filtration volume-content/ concentration curve if necessary;
• Select syringe filters/filter membranes of different materials and repeat the above steps;
• Comparing the adsorption of syringe filters/ filter membranes of different materials, select a material that has less adsorption to the medicinal solution, and then select the best filter material based on the chemical compatibility, the extractables, the filterability of the medicinal solution & the filter/ filter membrane material, etc.

Small Test, Pilot Test and Large-Scale Production Stages (filter model has been determined)

Filter membranes can be selected for evaluation, but if possible, it is recommended to use filters used in actual production on the actual production line for evaluation.

Evaluation by Using Filter Membrane

Basically, users can follow the steps under "Product Development Stage - filter element (filter membrane) material selection", However, the filtration capacity of the filter membrane of the size used in the experiment needs to be calculated based on the actual production filter area and the corresponding filtration capacity. When filtering, the actual production filtration pressure difference, filtration temperature, filtration flow rate and other process parameters need to be considered at the same time.

Evaluation by Using Filters(used in actual production line)

Since the filter configuration, filtration system configuration, direct filling etc of the actual production line are different, two typical situations are selected for description below for reference.

Direct Filling Method (no buffer tank after terminal filtration, filling while filtering)

There are 3 sampling situations to be chose from, namely sampling based on filtration time, filtration volume or filling bottles. Carry out multi-point sampling of unfiltered medicinal liquid, initial filtrate, and filtrate from different bottles with different filtration times/different filtration volumes/filling, and then detect the content/concentration of the medicinal liquid ingredients of concern on the filtrate at all sampling points, if necessary the filtration time, filtration volume, or different number of filling bottles and content/ concentration curves can be drawn, and finally the adsorption situation is evaluated based on the adsorption curve.

Indirect Filling Method (there is a buffer tank after terminal filtration)

That is, after terminal filtration, the medicinal liquid is first filtered into a buffer tank, and then filled after filtering to a certain volume. Evaluation method: Directly take the unfiltered medicinal solution and the medicinal solution in the buffer tank, respectively detect the content/concentration of the medicinal solution components of concern, and compare the changes of the unfiltered medicinal solution and the filtered medicinal solution.

Evaluation Criteria

There is no specific criterion for adsorption. Acceptable standards for adsorption can be formulated based on the internal control standards for the content/ concentration of the medicinal liquid ingredients of concern.

Adsorption Solutions

If the filter's adsorption of drug liquid does not meet the acceptance criteria, the following methods can be used to reduce the impact of adsorption on drug quality:

• Pretreat the filter to reduce adsorption, such as soaking or rinsing it with medicinal liquid in advance;
• On the premise of meeting process requirements, reduce the filtration area/ volume ratio;
• Discard the initial filtrate whose content or concentration does not meet the requirements;
• Replace the filter material.

Cobetter Validation Center has a comprehensive quality management system and more than 10 years of experience in filtration process validation, and can provide you with professional validation services that comply with international regulatory requirements. At present, the Validation Center has provided nearly 25,000 process validation reports to more than 1,200 pharmaceutical customers globally. If you have any validation needs or questions, please feel free to contact us!