Carl Fiorini, Dec 31, 2024 12:00:00 AM
Pharmaceutical mixing and blending require advanced technology, precise timing, and meticulous control to ensure uniformity, which is critical for product efficacy and safety. Inconsistent mixing or failure to meet regulatory standards can result in compromised quality, regulatory penalties, or patient harm.
Unlike other industries, pharmaceutical mixing and blending necessitate specialized techniques to comply with stringent regulatory requirements. Choosing a skilled toll processing partner is critical to navigating these challenges.
This article dives into the expertise a toll processing partner brings to pharmaceutical mixing and blending, emphasizing the importance of mitigating risks and maintaining compliance. It also highlights three key fundamentals to consider when outsourcing:
Unique Challenges in Pharmaceutical Powder Blending
In some industries, using a blender for dry ingredients to combine multiple particulate materials is a straightforward process. Often, ingredients are pre-processed to refine particle size, improve flowability, or achieve a tighter particle size distribution, ensuring a smoother and more efficient blending process.
Dry blending in pharmaceuticals is more intricate, precise, and often involves greater complexity. In the pharmaceutical industry, a small quantity of active pharmaceutical ingredients (APIs) is typically blended with excipients, the non-active ingredients that serve as the drug's carrier. Some common pharmaceutical excipients include:
- Gelatin
- Lactose
- Starch
- Cellulose
- Titanium dioxide
- Lubricants
- Talc
Excipients serve various purposes, such as adding bulk, improving absorption, protecting APIs from degradation, and stabilizing formulas. When APIs and excipients have different characteristics, such as varying particle sizes or stickiness, blending becomes more complex, leading to potential segregation.
Pharmaceutical manufacturers must prioritize product quality while also seeking opportunities to optimize efficiencies, reduce time to market, and control costs. Outsourcing processes like pharmaceutical mixing, milling, and blending can provide these benefits. When evaluating cGMP toll processors for pharmaceutical projects, it’s essential to consider these three key factors.
1. Process Control Is as critical as the Blending Process
Toll blenders with experience in the pharmaceutical industry understand that the process of becoming supplier qualified is often more challenging and time-consuming than the 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 requires extensive documentation for traceability, due diligence, and audits. A customer audit includes reviewing the toll blender’s cleaning programs, practices, and blending processes, as well as examining upstream and downstream material flows. This means tracking the source of each ingredient and documenting how and where it’s transported after blending.
Qualification is a thorough and time-consuming process. Completing the full qualification, including all documentation and the customer audit, can take anywhere from three months to a year.
Along with time constraints, a crucial aspect of process control is conducting process validation and equipment qualification batches. Specialized protocols are developed to run test batches, ensuring consistent quality from the blender with each run.
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. Maintaining Cleanliness is Critical in cGMP Mixing and Blending
Toll processors emphasize cleanliness, particularly in the pharmaceutical industry, where quality is critical. In pharmaceutical mixing and blending, proper processes are essential to ensuring the final product’s quality. This sector is known for its strict cleanliness and testing standards.
A clean room with sanitized surfaces is the foundation of a well-prepared blending environment in pharmaceuticals. To prevent equipment contamination—whether microbiological or from residual materials—multi-level cleaning programs are implemented, tailored to industry standards and the specific materials being processed.
Blending typically involves various grade levels, such as food grade, technical grade, pharma grade, and allergen grade, among others. The FDA’s regulatory standard for pharmaceuticals is the Current Good Manufacturing Practice (cGMP) for human drugs. Throughout processing, samples from batches are tested for cleanliness and blend uniformity to meet specifications.
By adhering to cGMP regulations, processors maintain the quality, strength, and purity of pharmaceutical products. Process controls at every stage of manufacturing ensure that pharmaceutical manufacturers deliver safe and reliable products.
3. Selecting the Right Equipment and Expert Operators
Traditionally, dry blending has been a bottleneck in manufacturing operations due to the limitations of industrial blending equipment, which can only perform one task at a time. The equipment cannot be filled or emptied until the active mixing of a batch is complete, meaning that emptying, cleaning, and refilling all consume valuable time.
This highlights the importance of selecting an outsourcing partner with the right blending equipment, ready to combine ingredients with both precision and efficiency. The ideal equipment may include a ribbon blender, paddle blender, continuous blender, tumble blender, or vertical cone blender, depending on the specific needs of the process.
The choice of blender depends on particle sizes, shapes, and densities of excipients and APIs.
A double-ribbon blender’s low shear provides the homogenization and consistency needed for safe, pure, and effective pharmaceutical products. However, different blender styles are often used to process and prepare the finished product.
The blending process greatly impacts a drug's ability to deliver accurate dosages, maintain visual appeal, taste as intended, and remain stable over time. Pharmaceutical blending is inherently challenging—if ingredients aren't properly processed, it can affect the blend's uniformity. In turn, the product may not perform properly, and the brand can suffer.
tips for selecting the Right Toll Processing Partner for Your 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 evaluating equipment, consider these key questions:
- Do they have the necessary capacity to manage your projects? This can vary from just a few dozen liters to multiple metric tons. Seek out a blending company with equipment that covers the entire 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.?
Additional capabilities might include temperature control (such as heating) and process flexibility, like the ability to spray-treat particle surfaces during blending.
Seek a technical sales team of three to five professionals to collaborate with your quality department. The team usually consists of a technical sales engineer, food safety and pharma manager, quality control specialist, and production manager. Their expertise ensures a comprehensive understanding of the process, making supplier approval and audit procedures more efficient.
While most customers typically approach a contract blending company with a specific formula, a team with R&D formulation experience can provide valuable guidance and troubleshoot processes effectively.
Discover how to evaluate and select the right toll processor for outsourcing by downloading our free guide, Blending for Pharmaceuticals. Simply click the link below to get your copy.
