Top 3 Factors to Consider When Outsourcing Pharmaceutical Blending

Carl Fiorini, Mar 17, 2022 10:48:00 AM

Various pills from the pharmaceutical blending process

The technology, time, and energy inputs that go into blending processes for pharmaceutical products are all for the sake of a single goal: uniformity. That’s right: a perfectly homogenized product is the objective of every blend.

Mixing and blending ingredients is a critical step in manufacturing across multiple industries. For some products, blending is relatively easy and processes are simple. But the pharmaceutical blending process can be much more demanding — and regulatory demands further increase projects’ complexity.

In this article, we take a closer look at the capabilities and expertise a toll processing partner brings to the processes of pharmaceutical blending, and why it’s so important to be able to trust your toll processor. And we’ll cover the three fundamentals to consider when outsourcing pharmaceutical manufacturing to a toll processor:

 

Industry-Specific Challenges in Powder Blending for Pharmaceuticals

In some industries, when multiple particulate ingredients need to be dry blended, the process is relatively simple. In many cases, ingredients can be processed as needed before blending to make various constituents finer, help them flow more freely, and/or tighten particle size distribution to optimize the blending process.

Dry blending for pharmaceuticals is more delicate, more demanding, and often more complex. Typically in the pharmaceutical industry, a small quantity of active pharmaceutical ingredients (API) are blended with excipients, the non-active ingredients that serve as the carrier of the drug. Some common pharmaceutical excipients include:

  • Cellulose
  • Lactose
  • Starch
  • Lubricants
  • Gelatin
  • Talc
  • Titanium dioxide

Excipients can serve many purposes. They can add bulk, improve absorption, protect the API against degradation, and stabilize a formula. When the API and excipients have different characteristics, that complicates the blending process. Excipients may be sticky or have significantly different particle sizes, and that can cause ingredients to segregate.

Pharmaceutical manufacturers need to protect product quality — and yet, outsourcing manufacturing processes like milling and blending creates opportunities to optimize efficiencies, reduce time to market, and control costs. That’s why it’s essential to consider the following three factors when evaluating GMP toll processors for pharmaceutical blending projects.

1. Process Control is as Essential as the Blending Process

Toll blenders experienced in pharmaceutical blending know that becoming supplier qualified is more difficult and time-consuming than the actual blending projects themselves. That’s because in most cases, a contract blending company is required to become an approved supplier for every customer.

In pharmaceuticals, the supplier approval process involves a great deal of required paperwork for traceability, due diligence, and audits. A customer audit not only includes documenting the toll blender’s cleaning programs, practices, and blending processes; it explores and documents upstream and downstream material flows. That is, every ingredient’s source is mapped out, as well as where and how it’s transported after blending.

Qualification is a comprehensive, time-consuming process. Full qualification, including all documentation and the customer audit, can take from three months to a year.

In addition to time constraints, a vital part of process control is running process validation and equipment qualification batches. Unique protocols are written to run test batches, ensuring that the same processes result in the same quality coming out of the blender every time.

Just as in any industry, experience has its advantages for toll blenders. A team of experts with years of blending a wide range of raw materials, tackling different challenges, and completing many qualifications can make your next qualification quicker and less stressful.

2. There’s No Substitute for Cleanliness in cGMP Blending

Toll processors are, by nature, focused on cleanliness. This is elevated to obsessiveness for the pharmaceutical industry where quality is obviously paramount. Simply put, proper toll blending assures final product quality. No other industry is as strict with cleanliness and testing as the pharmaceutical industry.

A clean room with all surfaces sanitized is the core of a well-prepared blending environment in pharma. Equipment contamination, whether microbiological or cross contamination from previous materials, is avoided by employing multi-level cleaning programs based on industry requirements for the material being processed.

In general within blending, grade levels include food grade, technical grade, pharma grade, allergen grade, and others. The FDA’s regulatory standard for pharma is the Current Good Manufacturing Practice (cGMP) regulation for human pharmaceuticals.Throughout processing, samples are extracted from batches and checked against specifications, both for cleanliness and blend uniformity.

When processors adhere to cGMP regulations, their work maintains the quality, strength, and purity of drug products. Process controls at every step of manufacturing operations ensures that the pharmaceutical manufacturers deliver safe and trusted products.

3. Look for the Right Blending Equipment and Expert Operators

Historically, the dry blending process has been the bottleneck of manufacturing operations. That’s because industrial blending equipment can only do one thing at a time. It can’t be filled or emptied until the active mixing of the batch has been completed — emptying, cleaning, and filling take time.

This makes it all the more important that an outsourcing partner has the correct blending equipment available and ready to combine ingredients with precision…and in a timely manner.

Which equipment is right? It could be a ribbon blender, paddle blender, continuous blender, tumble blender, or vertical cone blender. The choice of blender depends on particle sizes, shapes, and densities of excipients and APIs. 

HOW DOES MICRONIZATION AFFECT A PHARMACEUTICAL PRODUCT?

For most pharma products, a double-ribbon blender’s low shear provides homogenization, consistency, and accuracy that ensures a safe, pure, and effective end product. Yet it’s not uncommon to use a number of different blender styles to process and prepare a finished pharmaceutical product.

The blending process has a huge influence on a drug’s ability to deliver an accurate dosage, look appealing, taste the way it should, and remain stable for a reliable period. Pharma blending has always been challenging. If the ingredients aren’t adequately processed, that affects the uniformity of the blend. In turn, the product may not perform properly, and the brand can suffer.

How to Choose the Right Toll Processing Partner for Your Pharma Blending Projects

These three critical factors are the most important considerations, and a good place to start. But if you’re looking to partner with a trusted toll processor you should dig a little deeper.

When it comes to equipment, be sure to ask the obvious questions:

  • Do they have the right capacity to handle your projects? This can range from as little as a few dozen liters up to multiple metric tons. Look for a blending company that has equipment spanning the full range. 
  • Are they capable of handling cellulose-based material (specifically organic pulp fiber), with ease?
  • Are they capable of handling many different bulk packaging formats, such as super sacks, drums, bags, pails, etc.?

Other capabilities may include temperature adjustment (such as adding heat) and process flexibility (the ability to spray-treat particle surfaces in the blending process, for example).

Look for a complete technical sales team of three to five professionals to work with your quality department. That crew usually consists of a technical sales engineer, food safety and pharma manager, quality control pro, and production manager. That team helps ensure a comprehensive look at the process, and their expertise makes navigating supplier approval and audit processes easier. 

And even though most customers usually come to a contract blending company with a formula in mind, a team with R&D formulation experience and insight can offer guidance and help troubleshoot processes.

Learn more about evaluating and selecting a toll processor for outsourcing when you download our free guide, Blending for Pharmaceuticals. Just click the link below to download your copy.

Evaluating toll processors for pharma blending. A cGMP manufacturers guide.

Posted in:BlendingPharmaceutical