Selecting The Best Pharmaceutical Mixing Equipment For Your Operations

By Ken Langhorn

Efficient, consistent, and repeatable mixing are virtues of successful pharmaceutical operations. But finding the right mixing equipment and vendor to achieve those qualities isn’t as simple as selecting an item from a menu. This article will guide you through what to consider when choosing the pharmaceutical mixing equipment and vendor for your facility.

Repeatability of batches and cleanability of equipment are top priorities. Batches, especially of products that have been submitted for approval or are FDA approved, must be made by mixing equipment that is proven to create consistent, error-free products. Pharmaceutical manufacturers should engage in extensive product sampling, analysis of chemical composition, and QA/QC processes to ensure mixing equipment creates consistent, repeatable batches.

Cleaning processes of mixing equipment are unique from company to company — each company establishes best practices for their applications, products, and equipment. However, all mixing equipment benefits from having certain qualities, including:

• no bearings or agitator seals submerged in product to reduce contamination risks
• blades and agitators raised/lowered by a hydraulic lift from mixing vessels
• interchangeable mixing vessels that can be dedicated to a formulation
• 300 series stainless-steel construction to prevent corrosion
• seamless welding to prevent ingredient pooling and potential product contamination

Mixing equipment that is not easily cleaned can lead to inconsistent, contaminated batches. Products not meeting exact specifications create major impediments to operational efficiencies, threaten the manufacturer’s bottom line, and possibly even lead to regulatory intervention from the FDA should an out-of-spec batch be submitted for approval or need to be recalled.

How Today’s Mixing Equipment Has Evolved

There haven't been many big advancements in the physical components of pharmaceutical mixers recently. Mixing vessels, blades, and agitators have been designed to be more efficient, but these components have remained relatively unchanged. However, adjustments and upgrades to the mixer and the surrounding auxiliary features can be made on an as-needed basis. For instance, if a company is developing a new product with qualities and characteristics they have not worked with before, a pharmaceutical mixer vendor will have the capability to visit the facility, assess the current mixing equipment along with the qualities of the new product, and provide recommendations for new equipment or upgrades when needed. But again, these changes are often very small and take place over long periods over time.  

While advancements in blades, agitators, and mixing vessels may be small, major advancements have been made in the last 10 years in the controls, electronics, and user interfaces of pharmaceutical mixing equipment. Specifically, software, control systems, and user interfaces have evolved far enough for pharmaceutical makers to use recipe- and product-specific software in the manufacturing process. These features prompt operators on when to add each ingredient into the mixture (whether by hand for small batches or through automatic feeding for large ones) and when to add or scale back specific ingredients. Data management tools such as chart recorders help end users meet the 21 CFR Part 11 compliance spec established by the FDA. They automatically generate internal QA/QC reports and unalterable batch records. In an era when documentation is essential, these features have become important to many pharmaceutical manufacturers.

Pharmaceutical Mixing Equipment And Product Compatibility

Different physical characteristics of ingredients and the final product require different mixing equipment and processing strategies. So, it’s imperative to be cognizant of the physical characteristics — viscosity, density, liquid state, solid state, etc. — of the ingredients being mixed and the final product they will produce.

After evaluating physical qualities of ingredients and the final product, it’s important to assess what kind of energy, and how much of it, is needed to make the highest-quality product. Some products require very little energy to be made, while high-energy mixing is essential to create others. Further, some products can be damaged or made ineffective if the energy used in their creation is too high or too low.

It’s also important to understand that production rates will determine the size of the mixing equipment required. Generally, batch sizes are estimated by energy requirements, the time it takes to add ingredients, and how long it takes to empty the mixing vessel. However, batch size can be limited by chemical reactions of ingredients and the dwell time of the product in the vessel. For instance, let’s say an ingredient begins to cure over time in the vessel. That product may need to be discharged from the vessel and packaged within a certain time frame to keep it viable. In this instance, a large batch could be completely wasted and smaller batches and smaller-sized mixing equipment should be considered.

From there, auxiliary components of mixers can begin to be evaluated. Does the product need to be heated while in the mixing vessel? Does it need to be cooled? Does it need to be produced in a vacuum? Are there other environmental factors and circumstances that need to be addressed to create a high-quality product? Understanding the entire process of creating the product will narrow the final candidates for mixers, their auxiliary components, and additional features.

What To Expect From The Right Pharmaceutical Mixing Equipment Partner

Pharmaceutical manufacturers are always under the microscope and have razor-thin margins for error. That said, it’s not only essential to find the right equipment; finding the right vendor of that equipment to support your manufacturing processes is equally important.

First, it’s important to establish a good personal relationship with a mixing equipment vendor. This relationship can set the foundation for a long-term, mutually beneficial partnership. Mixing equipment providers should be willing to make site visits to develop equipment quotes, address end user questions and concerns, and assist with planning, and implementation of equipment. Vendors often have testing and development centers where end users can view and evaluate mixing equipment on a small scale. During those visits, technical personnel from R&D and production are able to learn characteristics of the mixer and how it is operated. This ensures a baseline of efficient operation of the equipment. Additionally, end users should be provided with installation and maintenance instructions. These documents will help keep mixing equipment running seamlessly for years.

Despite superior construction and maintenance of equipment, breakdowns do occur, and a bank of spare parts is purchased from the vendor by the end user for in-house repairs. The manual for each piece of mixing equipment contains a recommendation for spare parts to have on hand. However, the type and quantity of parts kept is a decision for the end user, normally based on how much downtime can be reasonably handled. If a day or more of downtime is out of the question, end users should keep at least one set of critical components on hand. Those parts should be made by the original equipment manufacturer (OEM) to ensure the right part is inventoried and will fit the machine properly.

In rare occasions, in-house crews won’t be able to replace/repair a broken or malfunctioning piece of mixing equipment. In these cases, vendor support is only a phone call away. The vendor should have reasonable hours for over-the-phone end user support; knowledgeable staff for problem solving; accurate, precise, and detailed corrective actions; and the ability to schedule on-site emergency repairs from a trained technician if necessary.

How Charles Ross And Son Company Can Help

Charles Ross and Son Company is the worldwide leader in mixing and blending equipment. Our pharmaceutical mixing equipment is available in either standard or custom designs to meet your specific processing needs. We have a reputation for innovative engineering, superb construction, and fast delivery. Ross equipment is designed and built in the U.S., China, and India. In the U.S, we operate five plants and a vigorous R&D program. Our plants are all fully equipped with advanced engineering and manufacturing tools for the pharmaceutical industry. We are uniquely equipped to meet the special needs of every customer, anywhere in the world.

Pharmaceuticals are highly process-dependent. Next to the chemistry of the formulation itself, the mixing operation has a decided influence on whether a drug will deliver the accurate dosage, have an acceptable appearance and texture, and be stable for the appropriate length of time. We engineer and manufacture mixing equipment for nearly all pharmaceutical applications including powder blends, hydrogels, liquid supplements, tablet granulations, tablet coatings, collagen solutions, vitamins and minerals, medical adhesives, blood reagents, transdermal patches, oral care products, eye drops, medicated creams and lotions, ointments, drug vehicles, electrolyte solutions, fish oils, bone repair putties, filled silicones, and injectable products.