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Filtration for pharmaceutical processing
 
Q: What filtration do we require in solid dosage processing, and where should we locate those filtration steps?
 
 
It's essential to preserve the quality of gas, compressed air, steam, and liquids in solid dosage processing. Compressed air dries sterilized equipment, is sometimes used to move ingredients through lines, and for semi-liquid (gel) formulations, protects liquids in storage tanks. Organisms that make their way into these areas can quickly multiply downstream, compromising the safety of your product.
 
A well-designed filtration system prevents contamination from moisture, oil, or debris. Filtration is particularly important in some locations, including 1) the utility and bulk storage room(s), 2) the formulation area, and 3) the intermediate holding and encapsulation areas.
 
Utilities and bulk storage
Address your utility and bulk storage room(s) first because they are where your facility brings in municipal water, generates steam, and gathers and stores compressed air and/or nitrogen. When you purchase tanks of nitrogen, the supplier delivers it in liquid form, and it reverts to gas at your plant, providing opportunity for contamination. If you generate nitrogen on site, the air feeding your compressor can lead to corrosion, oil leaks, and flaking metal. Stainless steel components and careful maintenance can minimize these problems but aren't always foolproof.
 
For better protection, start filtration in the utility and storage areas themselves. Put a pre-filter on the pipes supplying water, gas, compressed air, and steam as they enter your facility. Place the filter at a location before the system branches into separate lines for cleaning and process use. Pre-filtration improves the efficiency and longevity of your finer filters downstream. At the pre-filtration point, a 5-micron liquid element will remove forms of contamination from your supply sources that are larger than 5 microns in diameter, providing an acceptable level of clean supply water for your steam-in-place (SIP) or clean-in-place (CIP) processes.
 
Then, on your process line, use fine, point-of-use sterile filters for additional filtration of any steam, liquids, or compressed air that contact your ingredients or the surfaces those ingredients touch. For water and liquid-chemical applications, they can be 1 to 0.2 microns, while sterile air might require a filter of up to 0.03 micron. Staged filtering achieves two things: 1) Pre-filtering saves money by preventing overloads on and frequent replacements of more expensive elements that are downstream; and 2) finer filters near your point of use provide extra assurance of an aseptic process. Properly staged filtration minimizes risk by producing fluids of the highest purity at a lower cost.
 
Formulation
If you formulate liquid or semi-solid (gel) capsules, another area of concern is the sterile formulating area with steel tanks, where you mix and/or store active pharmaceutical ingredients (APIs). These tanks are subject to spoilage and can be a breeding ground for bacteria that personnel and ambient air can introduce.
 
After you sterilize the steel tanks, inject clean dry air (CDA) or nitrogen into the empty tanks before you add the APIs. This air blanket provides a barrier against the ingress of microorganisms and serves to counterbalance pressure as the vessel empties, protecting it from collapse. As an alternative to CDA, pharmaceutical companies commonly use nitrogen, an inert gas, because it's non-reactive and has the additional benefit of drying out the tank faster between uses.
 
Both blanketing methods require a high level of purity, so you need to remove moisture and potential bacteria. Although nitrogen can't harbor organisms, it can transport microscopic particles that it picks up in your system. Best practices recommend adding a filter of 0.2 micron on your tank's nitrogen- or air-injection equipment. This procedure adds a layer of protection against any contamination that might remain after pre-filtering.
 
Intermediate holding and encapsulation
From the primary area where you formulate APIs, your product moves into intermediate processing, where you may add other ingredients. In the solid dosage world, they often are coatings or binding agents. For liquid gels, you may have another set of storage tanks just before encapsulation, which requires a new round of nitrogen or CDA buffers and point-of-use filters.
 
It's important to realize that wherever you introduce a substance or utility source into your process, new opportunities for contamination occur. Filter each new gas, air, or liquid stream with a fine-micron membrane filter before it touches your product.
 
The reason for later filtration is that a contamination risk can stem from your system itself, even if you keep it up to date. Instances have occurred in pharmaceutical processing where a company's personnel have installed a new valve or hose with the wrong gasket or O-ring tying it into the system. This small component can gradually degrade over time and introduce contamination. The costs can be astronomical if such circumstances trigger a product recall.
 
Conclusions
The goal of the filtration steps described above is to build in redundancy to minimize risk. When a product involves costly ingredients and offers little risk tolerance as it does in pharmaceuticals, filtering early and often is a good policy.
 
As a final word of caution, be sure to collaborate with a trustworthy filtration partner. Every processing facility is different and poses unique questions: What's the right micron size and filter efficiency at a certain location? How many CIP and SIP sterilization cycles can an element tolerate? Are the chemical properties of the housing and all components non-reactive to my chemicals? If they're stainless steel, do they have the right polish and weld technique to avoid points that can harbor bacteria?
 
Obtain knowledgeable recommendations from a reputable filtration company with experience in pharmaceutical processing. It can help you formulate a sound strategy customized for your particular needs and operation.

Chris Lehmann, is the North American product manager of the process filtration division at Donaldson Company.

Do you have a question for our experts? Send your questions to pwright@cscpub.com and we'll have an expert answer it.
November 27, 2017
 
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T&C Solid Dosage Sourcebook
 
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Peggy Wright
T&C Solid Dose Digest
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T&C Solid Dose Digest
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T&C Solid Dose Digest
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