Beyond the Clean Room: Pharmaceutical Industry Concerns

The pharmaceutical and biotech industries have unique concerns when manufacturing their products. Clean rooms are used both to make these products and also to sterilize material and equipment. However, the standards for purity depend on more than just the clean room. If the equipment is not chosen properly, even sterile materials can become contaminated. Additionally, products must be both sterile and clean. Manufacturers need be proactive to ensure their final product is safe for the public.

Equipment

Pharmaceutical Processing published an article titled, “How to Specify Equipment for High-purity Processes” that examines the many considerations in the design of fluid motion and control systems. Contamination via equipment, according to the article, is a possibility when there are “dead cavities, corners, seams or obstructions that exist in processing equipment.” These concerns can arise anywhere from the valve to the surface finish.

One of the first considerations one should have when choosing high-purity equipment is how it stands up to harsh cleaning processes. Cleaning agents like steam, caustic sodas, and light acids must be able to flow uninhibited to reach all parts of a system. Additionally, material needs to consistently withstand high temperatures.

Wetted surfaces must be built from material that will not rust or corrode. This is yet another factor when choosing pumps and equipment whose material will not generate particle contamination. The article discusses the popularity of polymers for their resistance to corrosion and inherent purity.

The specific material comprising the equipment is one piece of the puzzle. The equipment itself is diverse, and each application has its own unique requirements.

Valves

There are generally two kinds of valves to choose from: diaphragm and ball valves. While the diaphragm valves are more commonly used, ball valves are preferred in some applications like freeze-drying and fermentation. No matter the type of valve, “metallurgy and surface finish preparation are arguably the most important factors to ensure valve integrity.” Within the valves, attention must be paid to the sulfur content of the end connections and precisely matching the dimensions of the connecting tubing. Failing to choose correctly here can create contaminates. Additionally, valves should be assembled in a clean room to ensure purity.

Seals

Seals are another crucial element in keeping a system contaminate-free. Companies have had instances where inner seals allowed vapors to pass through, thereby compromising the integrity of the entire system. When seals have gland rings that don’t need to be threaded or ported, there are fewer places for bacteria to hide. Both threads and sharp corners can create spaces that are difficult to clean. Pretesting seals is an effective way to ensure their integrity. Some seals even come with cartridges that allow for pretesting.

Personnel

Maintaining a high-purity system means keeping it in check. This takes expertise. As the article states, “High-purity processes are very specialized, and different applications include varying pressure and temperature requirements, materials, standards and levels of sterility.” It is essential for any plant to have personnel who are highly trained for the specific standards and equipment utilized at the facility. Furthermore, it is wise to hire outside experts to consult on equipment, processes, and validation. As standards and technology continue to evolve, so should the expertise of the personnel working with them. Contractors will be more currently trained on these specific items.

Clean vs. Sterile

As Pharmaceutical Processing’s article, “Clean Versus Sterile” states, “It is recognized that any medical device that punctures the skin or any medication that enters the bloodstream must be sterile, and sterilization procedures are reasonably well-established in the pharmaceutical and medical device industries. What may not be as well understood is that devices and medications should also be essentially free of particles (i.e. clean).”

Sterilizing products does not ensure that they are free of particles. Even sterilizing vials and other equipment in cleanrooms does not guarantee that they won’t introduce particles. Additionally, other necessary processes can create an unclean product – which is unacceptable in the pharmaceutical industry. We will look at a couple of the common sources for particulates that the article discusses.

Silicone

Silicone oil has a number of uses in this industry. It aids in processing and packaging, and it’s used as a lubricant for stoppers and plungers. In most cases, the silicone is safe and doesn’t create any problems. However, just a little too much of it can result in high particle counts. When this happens, residue needs to be isolated and removed. Here again, this is a job that need be performed by a highly qualified individual.

Glass

Glass is a common material to use in this industry because it’s highly stable for sterile packaging. However, on rare occasions, it can leave lamellae – glass delamination flakes – which can be tough to spot. Delamination may occur if active ingredients attack the glass during processing or if there are irregularities in the glass container.

In both of these cases, products, vials, and packaging needs to be thoroughly inspected with the proper methods to detect particulates and then remove them. Depending on the situation, removing them may be quite a challenge. Identifying the source of the issue is also vital to prevent the problem from happening again.

In this field, it is crucial that both equipment and product be tested regularly for quality.  As such, it couldn’t be more important to invest in training and consulting personnel.

For high-purity processes, it is also critical to have the highest quality clean room. Gerbig Engineering Company not only builds clean rooms, but also provides validation of facility and equipment qualification. For more information, call 888-628-0056, email info@gerbig.com, or fill out the information form on this website under the “Contact Us” tab.

 

 

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