Efficient Virus Removal. Reliable Protection.

Cobetter Viruclear™ RC H in Plasma-Derived Product Manufacturing: Application Case Studies

Plasma-derived therapies, from immunoglobulins to coagulation factors, are essential and often life-saving treatments for patients worldwide. As every products begins with human plasma, viral safety is not simply a quality attribute; it is a fundamental requirement.

In this article, we explain why viral clearance is mandatory in plasma product manufacturing, how it is applied across the major product classes, and how Cobetter Viruclear™ RC H virus removal filters have performed in immunoglobulin, coagulation factor and other plasma protein applications.

01  Why Is Viral Clearance Essential in Plasma Product Manufacturing?

Plasma-derived products are manufactured from healthy human plasma. Although every donor undergoes health screening and blood testing, a residual risk of viral transmission remains because of infection window periods and the inherent limits of detection methods.

Therefore, regulators require dedicated virus inactivation and/or removal steps in every plasma product manufacturing process. For this reason, regulatory authorities and Good Manufacturing Practice (GMP) requirements for plasma-derived products mandate dedicated virus inactivation and/or removal steps in every manufacturing process. This principal methods in use today are summarized in Table 1.

TABLE 1. PRINCIPAL VIRUS INACTIVATION AND REMOVAL METHODS FOR PLASMA-DERIVED PRODUCTS

02  How Is Viral Clearance Achieved Across Plasma Products?

According to the industry guidelines, albumin is typically treated by pasteurization. Immunoglobulins and coagulation factors, by contrast, generally rely on two orthogonal viral clearance steps with different mechanisms of action, so that both enveloped and non-enveloped viruses are addressed.

For immunoglobulins, low-pH incubation combined with nanofiltration is the most common approach. Coagulation factors are unstable at low pH, so S/D treatment is usually paired with either dry heat or nanofiltration.

Dry heat remains the most widely used option for coagulation factors. However, it imposes stringent process requirements, and balancing viral inactivation against product activity has long been a technical challenge. Reconstitution stability after dry heat can also be difficult to guarantee: flocculent precipitates or particles may form, creating potential safety risks such as thrombosis and febrile reactions.

Nanofiltration is therefore a key area of development for coagulation factors. Its wider adoption is constrained by the very large molecular size of these proteins and the resulting pressure on cost and throughput. Even so, it offers a route to robust viral clearance without compromising product quality.

Advancing viral clearance while preserving product quality remains a key challenge, and an important opportunity for innovation.

03  Cobetter Viruclear™ RC H: Application Case Studies

Cobetter Viruclear™ RC H virus removal filters feature a 20 nm pore size for effective viral retention and are designed specifically for high-concentration plasma products. The regenerated cellulose membrane is inherently hydrophilic with low protein adsorption, sustaining high process flux even with high-concentration protein solutions.

Figure 1. Cobetter Viruclear™ RC H virus removal filter

3.1  Immunoglobulins

Viruclear™ RC H filters have been evaluated in intravenous, hyperimmune (specific), subcutaneous and intramuscular immunoglobulin products. In each case, membrane capacity, flux and viral clearance met customer requirements. Applications now span lab-scale, pilot-scale and scale-up production, and several customers have completed multiple virus removal process validation batches.

Case A  |  Third-generation IVIG, protein concentration 55 g/L

Figure 2. Flux and volumetric throughput over time, lab vs. pilot scale (third-generation IVIG).

TABLE 2. FILTRATION PERFORMANCE, CASE A

*Data from laboratory testing.

Both lab- and pilot-scale runs met filtration performance requirements. Over the same 960-minute filtration time, pilot-scale throughput (215.82 L/m²) was in line with lab scale (201.92 L/m²), confirming good linear scalability. 

Case B  |  Fourth-generation IVIG, protein concentration 55 g/L

TABLE 3. LAB-SCALE FILTRATION DATA, CASE B

TABLE 4. PILOT-SCALE FILTRATION DATA, CASE B

*Data from laboratory testing.

Throughput met customer requirements at both scales. At equivalent filtration times, pilot-scale throughput reached 85%, 85% and 95% of the corresponding lab-scale values, demonstrating good linear scalability. 

3.2  Coagulation Factors

Viruclear™ RC H filters have been evaluated for filterability with human coagulation factor IX (FIX), human prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC) and thrombin, and several applications have already progressed to pilot scale.

Case A  |  Human coagulation factor IX (FIX), protein concentration 0.15 g/L

Figure 3. Flux versus volumetric throughput across three membrane lots (FIX).

TABLE 5. FILTRATION PERFORMANCE ACROSS MEMBRANE LOTS, CASE A

*Data from laboratory testing.

Viruclear™ RC H showed consistent membrane lot-to-lot performance, with throughput and flux meeting customer requirements.

Case B  |  Human prothrombin complex concentrate (PCC), protein concentration 6 g/L

Figure 4. Flux and volumetric throughput over time for two prefilter combinations (PCC).

TABLE 6. FILTRATION PERFORMANCE BY PREFILTER COMBINATION, CASE B

*Data from laboratory testing. SMD = Corevital™ SMD 0.2/0.1 µm prefilter; PNY = Viruclear™ PNY 0.1 µm prefilter; RC H = Viruclear™ RC H virus removal filter.

Virus filtration performance and product yield met customer requirements with both prefilter combinations.

Case C  |  Thrombin, protein concentration 6 g/L

Figure 5. Flux and volumetric throughput over time for two prefilter combinations (thrombin).

TABLE 7. FILTRATION PERFORMANCE BY PREFILTER COMBINATION, CASE C

Data from laboratory testing. Columns reordered (SMD first) for consistency with Cases B and AT III.

Both prefilter combinations achieved approximately 100% potency recovery across the virus filtration step, with throughput and flux meeting requirements.

3.3  Other Plasma Proteins

Case A  |  Antithrombin III (AT III), protein concentration 8 g/L

Figure 6. Flux and volumetric throughput over time for two prefilter combinations (AT III).

TABLE 8. FILTRATION PERFORMANCE BY PREFILTER COMBINATION, AT III

*Data from laboratory testing.

Protein recovery and potency recovery were both approximately 100%, with throughput and flux meeting requirements.

Partnering for Plasma Product Safety

Across immunoglobulins, coagulation factors and high-value plasma proteins such as antithrombin III, Viruclear™ RC H filters have demonstrated efficient viral retention, stable flux and throughput, and highly scalable process performance. Cobetter delivers tailored, compliant and efficient virus removal solutions that support a seamless transition from lab-scale development to commercial manufacturing.