By Dan Schell, Editorial Director, Life Science Leader
Explain how pharma companies can reduce operating costs through CIP processes.
Malcolm McLaughlin, VP, product & business development, Alconox, Inc.:
Clean-in-place processes reduce time and labor required to disassemble and clean out of place. By allowing more latitude in the use of cleaning chemistry compared to manual cleaning, one is able to clean some products that otherwise may not be able to be effectively cleaned. For example, heavy creams and lotions containing metal oxide pigments, such as titanium dioxide and zinc oxide, and silicon oil excipients, such as simethicone, can be cleaned using appropriate concentrations and temperatures of low-foaming liquid detergents and low-foaming acid cleaners faster and more safely than using manual cleaning.
Chris Yessayan, CEO, MORK Process, Inc.:
Efficient CIP technology allows for customers to reduce water, chemicals, waste, and time to clean from traditional CIP, while maintaining their cleanliness standards. It is dependent on the type of facility and the quality of water being used, but if we use WFI (water for injection) in a sterile filling facility as an example, at a cost to produce of $5 to $6/gallon, the reduction in WFI usage alone achieved by changing from traditional CIP technology can result in millions of dollars of annual savings in a single filling suite, let alone across an entire facility or an organization. These savings don’t take into consideration the additional improvement in profit margins associated with reduced chemicals and waste disposal costs as well as increased manufacturing capacity through shortened cleaning cycles.
Another way to save money is to standardize on a common equipment platform, which allows manufacturers to reduce the amount of one-time engineering, validation (and the associated time and costs involved), equipment downtime, etc. that is required for custom CIP applications, that historically have been the norm.
Faster cleaning frees up capacity, and for a customer that is running 24 /7, the additional capacity can result in millions of dollars of additional revenue opportunity as well as savings through reduced labor and/or capital requirements.
Explain Some Of The Ways The CIP Process Has Gone “Green.”
McLaughlin: Clean-in-place processes can be optimized to:
- reduce cleaning chemical needs
- use cleaning chemicals with more desirable environmental characteristics
- use less heat or energy
- use less water.
By designing a CIP system to optimize the amount of mechanical and heat energy delivered to the surface being cleaned, less of a harsh chemical cleaner may be required, or a milder pH, less toxic cleaner may be successfully used.
Yessayan: Replacing the traditional “fill, boil, and dump” cleaning approach with truly automated CIP allows for the complete elimination of solvents in the cleaning of API reactors, which cuts down on hazardous waste disposal. Overall reduction in water and detergents in the cleaning cycle means less waste into the waste water treatment facility or down the sewer, while shorter cleaning cycles mean lower energy consumption.
What Are Some Common Misconceptions About CIP Systems?
McLaughlin: You need to choose the correct cleaning chemical to remove different residues. It is often difficult to use one cleaner that will remove all different residues when multiple kinds of products are manufactured in shared equipment. Also, often CIP cycles do not incorporate sufficient rinsing to remove residues. A significant amount of cleaning occurs during rinsing. Furthermore, during initial rinsing, the temperature should not drop precipitously. This drop runs the risk of breaking the emulsion and redepositing contaminants on the surface. For example, certain metal oxides, starch derivatives, amphoteric proteins, and amines are often better cleaned by acid cleaners, compared with the majority of other residues that are best cleaned by alkaline cleaners. In an effort to save energy, sometimes only ambient temperature rinse water is used; this can result in breaking the emulsions formed with hot cleaning solution — doing an initial rinse with hot rinse water will avoid redepositing residues by breaking emulsions.
Yessayan: We often encounter the philosophy of “clean until clean” because that has become an acceptable standard. As a result, it has enabled certain manual cleaning practices to remain relevant, as well as opened the door for disposable technologies to become a viable alternative in some biopharmaceutical applications. Making the cleaning process more repeatable and reproducible and demonstrating an ability to reduce time-to-clean, water, chemicals, and waste, while improving consistency in clean makes disposable technology less financially attractive than previous calculations indicated. The ROI on CIP improves dramatically when taking the new approach to cleaning in place.
Another notion we have to dispel is that a CIP system with a small buffer vessel (less than 100 gallons) is sufficient to clean a large (> 5,000 gallons) tank. Customers who are familiar with CIP are accustomed to the high water usage associated with centralized CIP systems using static spray balls. This approach, which is focused on chemical cleaning only, necessitates significantly larger buffer vessels and consumes inordinate amounts of water and chemicals. By taking the approach of wetting the vessel vs. soaking the vessel and using chemical cleaning as well as mechanical cleaning, customers can dramatically cut down on the water required in the cleaning cycle and, therefore, the size of the equipment used.
What Is A Common Mistake Made When Choosing A CIP System?
McLaughlin: You need to be very careful when specifying placement of spray balls in tank systems to make sure there are no shadowed areas that do not get contact with the cleaning and rinsing solutions (e.g. behind mixing blades or shafts and at the tops of tanks and tank openings). Perform a riboflavin test to determine surface area coverage. (A riboflavin test involves coating all surfaces to be cleaned with a riboflavin solution which you then use the CIP process to remove with water and use a black light to flouresce any residual riboflavin and easily detect any deficiencies in spray ball coverage or excess shadowing by mixing blades and shafts that may need to be addressed by changing spray ball configurations.) Also, make sure that the system has sufficient rinsing cycles to effectively rinse.
Yessayan: Not all CIP technology is created equal. Too often we see systems specified based on the size of the process equipment and piping to be cleaned. Little thought goes into the actual product residue being removed or whether the system being designed will remove the residue consistently in a timely fashion. If the system is proven to be capable, does it require the customer to invest in a new water treatment system in order to create additional volume of purified water or treat said water once it goes through the cleaning cycle due to the excessive water requirements introduced by the CIP system? There are inherent shortcomings associated with traditional CIP technology, particularly when it comes to cleaning challenging product residues (solid dosage, lotions, creams, and API manufacturing, to name a few), as well as the amount of water and chemical consumed.
6 Steps In The CIP (Clean-In-Place) Purchase Process
As described by Chris Yessayan, CEO, MORK Process, Inc.:
1. Define a cleaning strategy that is comprehensive across your operations, yet has the ability to be implemented at the plant or project level. How do you measure clean? What levels of clean are acceptable? Which products are the hardest to clean and why? These questions need to be answered to ensure that your goal of 100% automated cleaning is achieved — that is the only way to ensure repeatability and reproducibility.
2. Analyze whether your process equipment is actually capable of being cleaned in place or may require disassembly and some cleaning out of place. This step applies whether it is a new process train being developed or automating the cleaning process with an existing one. Do this analysis prior to finalizing your process design and equipment selection.
3. Write a user requirement specification (URS) that defines the level of clean your CIP system must deliver, the expected time to clean, and targets for water/chemicals consumed per cleaning cycle. This improves the likelihood of validating your process the first time while still being focused on bottom-line results for your operations (past the point of cleaning validation).
4. Try to avoid being too specific in defining system hardware components in your URS — it puts unnecessary risk into the equation. Your desired result is repeatable and reproducible cleaning — the benefit of delivering this should outweigh the benefit of standardizing on a valve. You can always use the compliance to your standardized hardware components as part of your evaluation criteria.
5. Utilize standard IQ (installation qualification)/OQ (operational qualification) packages that your CIP provider has developed. These packages are already proven to work. What benefit could you have from starting all over again?
6. Get references on your vendor and its solution. Ask for examples of situations where they have developed systems that have been validated with products and process equipment similar to what you have. Ask how long it took for the validation to occur.