Top 7 Customer Questions About Wet Milling for Pharmaceuticals

The ability to produce extremely fine particles is essential for pharmaceutical manufacturers.

But achieving these fine particle sizes, whether in a micronization or nanonization size range, requires more than just the right types of milling equipment. It also takes expertise.

In a wet media milling process, the raw feed material particles, typically 200 microns or smaller, are suspended in a liquid slurry and forced through a milling chamber that has been charged with milling media by a high-speed agitator shaft. 

The suspended particles are recirculated until the target particle size has been met, which can require adjustments to the media size or material, agitator speed, product flow rate, slurry liquid-to-solid ratio, and time on the mill.

But a process that may seem simple can be surprisingly complex, especially when it comes to products meant for human consumption and the particle precision needed for pharmaceuticals.

That’s why manufacturers often have questions for their contract processors — and why the answers are so important.

Why Do Pharma Manufacturers Require Wet Milling Services?

Particles in the sub-micron ranges can have distinctly different material characteristics from larger particles of the same material. The differences can deliver numerous benefits to a manufacturer, including:

• Controlling costs by using less of expensive active pharmaceutical ingredients

• Reducing unwanted side effects

• Offering more varied alternatives for administering medication, including oral, transdermal, inhalation, parenteral, injectable, etc.

These are just a few reasons pharmaceutical manufacturers need to know they can trust their wet milling services providers to perform processing techniques exactly as they say they do.

Another important benefit of wet milling is safety. Dry milling methods such as jet milling can often achieve the desired particle size, but some materials can pose a risk to personnel — even with proper handling and personal protective equipment (PPE). In wet grinding, the raw feed material is suspended in a liquid slurry and recirculated in a closed-loop system, eliminating the production of dust.

Notably, that closed-loop also means lower yield loss on wet milling compared against dry methods like jet milling. And, the liquid slurry used in wet media milling can also act as a heat sink, protecting the material from fast-rising temperatures in processing. With all these benefits, it’s no surprise that wet milling is in high demand.

What Do Pharma Companies Need to Know About Wet Milling?

When pharmaceutical manufacturers come to CPS with milling projects, there are certain assurances they look for — and with good reason. Any company outsourcing critical processes to a third party should be able to trust that they’ll achieve the same level of quality or better from their contract manufacturing partner.

Here are some of the most important considerations that we most often discuss with customers in pharmaceuticals—and these questions often also apply to customers in food and beverage, nutraceuticals, and many other industry verticals:

1. HACCP Plans

A Hazard Analysis and Critical Control Point (HACCP) plan is essential for identifying, monitoring, and addressing hazards to the product throughout processing. Pharma customers should expect their processing experts to be well-versed in HACCP principles, and able to produce a HACCP plan for any process to mitigate risks of contamination or product degradation.

2. Validation of Cleaning Procedures

Cleaning validations establish documented procedures with evidence that the cleaning methods effectively remove contaminants to prevent cross contamination. This is especially important when working with a toll processor to protect product purity, as well as to ensure batch-to-batch segregation and control. 

A toll processor should be able to develop, test, and validate repeatable cleaning protocols for customers. In fact, disciplined, controlled cleaning procedures are as important as documented processing protocols for ensuring product quality, purity, and safety.

3. Temperature Control Capabilities on Wet Milling Equipment

The very nature of the process of attrition — the grinding down of particles that takes place inside the wet mill — can cause friction, which in turn can increase the material’s temperature.

Depending on the product, heat can cause concern for safety, quality, or product degradation. That’s why it’s important to inquire about a milling service provider’s ability to chill the slurry during mill operation.

4. Health & Safety Assurances

Pharmaceutical companies are in the business of health. Safety and health of the personnel needed to make their products is absolutely essential. Workers’ eyes, skin, lungs, and hands must be kept safe throughout every phase of work. 

Detailed safety protocols should be part of every processing step, and should include PPE specifics like respirators, safety eyewear, apparel, gloves, and other items. Customers should be able to verify correct use of all PPE as described in process steps.

But long before the question of process steps and PPE arises, customers should expect to provide Safety Data Sheets (SDS) for the raw material and final product, for review by the toll processing team’s Environmental Health & Safety manager.

5. Quality Systems & Certifications

Questions about quality systems, accreditations, and certifications are often an early step in establishing a vendor relationship with a trusted tolling partner. Pharma customers should expect their contract processor to be able to demonstrate Food Safety System Certification (FSSC 22000) accreditation, Current Good Manufacturing Practices (CGMP) certification, and the ability to provide kosher, organic, and halal certifications for products processed in their facilities.

In addition to these certifications, many pharmaceutical manufacturers perform their own audits and inspections for their vendor qualification programs. Your milling services provider should welcome the opportunity.

6. Shipping & Receiving Details

Materials destined for wet milling are often shipped in a dry, pre-milled state, often in bulk formats like super sacks or drums. But in other cases, customers provide the raw feed already added to an appropriate suspension liquid. Either way, it’s critical to know that a processor is equipped and ready to handle the product in your preferred format, and that as a customer, you understand the details of shipping and receiving.

7. Other Critical Services for Pharma Customers

Pharmaceutical customers might be surprised to find the range of services available at a single toll processing facility. While you might initially be looking for wet media milling services, future needs could call for jet milling, blending, liquid bottle filling, or a straightforward repackaging project to keep things moving smoothly through your own production facilities. 

As a customer, you should never hesitate to ask questions. Your toll processing team’s technical sales engineer is there to answer them and provide all the assurances you need to have total confidence in the quality of your product.

Learn more about working with a specialized, CGMP-certified toll processor for particle size reduction when you download our guide, Milling Methods for Food and Pharma. Click below to claim your copy now.