We introduced the sterility assurance of single-use systems in the past post (see Advantages of Single-Use Systems in Blood Product Manufacturing (Part 1)). We will continue to explain the technology of controlling foreign matter and reducing liquid residue in single-use systems:

Foreign Matter Control of Single-Use System (From Raw Materials to the Whole Production Process)

Production Control of Film Materials

The production methods of co-extrusion film include cast film method and blow molding method. The following table compares the two methods:

In general, cast film has a fast production speed, easy to control the uniformity of film thickness distribution, and excellent optical properties (such as transparency and gloss), which is suitable for large-scale use in the packaging industry; blown film has good mechanical strength, but the production speed is slow, which is suitable for applications that require higher strength.

Cobetter's single-use bioprocessing film is made by blow molding, with a high-cleanliness inner surface, good resistance to environmental stress, tear resistance, rubbing resistance, tensile resistance and chemical stability, and can be used in the entire process of blood product processing.

Production Process Control

• Production environment control: According to different application points, production is reasonably arranged in workshops of different cleanliness levels. Including ISO Class 7 grade accessories and tubing production injection molding workshop, ISO Class 7 grade bag and assembly production environment, preparation filling and other applicable full-grade A (ISO Class 4.8 grade) production workshop;

• Accessory pre-rinsing: Build a water flushing production line that meets the WFI standard, use flushing and drying equipment for pipelines, and use ultrasonic cleaning and Class 100 ovens for joint accessories to ensure the cleanliness of components;

• Personnel, material, and equipment control: Add spraying, double-layer changing, equipment dust removal, static electricity removal (reduce the impact of static adsorption of particles), etc.

Table 8. Production process control regular inspection items

Advantages of Single-Use Systems in Terms of Residual Liquid

Single-Use Redundant Sterilization Filtration System

Application Case:

5-inch stainless steel redundant filtration system VS 5-inch single-use redundant filtration system

Table 9. Comparison of Liquid Residue

In summary, only by switching the redundant filtration system from stainless steel to single-use, a single batch can produce 883.8 mL more product, which reduces the cost for high value-added blood products.

*Note: The residual calculation here is only the residual between the two-stage filter (the tubing before and after the filter are calculated as completely empty), and the actual residual needs to be evaluated according to the specific situation of the production line.

Single-use Filling System

Application Case:

5L stainless steel buffer tank VS 5L single-use filling bag

Dead volume of stainless steel buffer tank:

• The volume of product diluted by the residual condensed water after SIP V1 (the specific value is determined by the pipeline design, ranging from hundreds of milliliters to several liters);

• The volume of product wasted V2 caused by the residual at the end of filling (the specific value is determined by the tank body and public engineering system design, ranging from hundreds of milliliters to several liters).

Dead volume of single-use filling bags:

• Sterilization residue - pre-sterilization (irradiation sterilization without condensed water) V1;

• Bag body residue - large rounded corners on both sides of the bag body, bag body dead volume V2;

• Interface and tubing residue - drainage uses a single row of narrow boat port, which can be well connected with the bag body, and the liquid flows to the lowest point of the drainage hole by its own weight, and the dead volume of the interface and filling tubing is V3.

Drainage test:

Cobetter Lifecube AF 5L single-use filling bag, after integrity check, is sterilized by gamma irradiation of not less than 50kGy. Fill the bag with 15-25°C water to the marked volume. Hang the bag, confirm that there is no blockage or flow restriction in the drainage tubing, open the hose clamp on the liquid outlet tubing, let the liquid drain under gravity, record the drainage time and residual liquid volume, and calculate the drainage rate.

Table 10. Actual Measurement Data of Residual Volume of Liquid in Single-use Filling Bag

Conclusion

The drainage test results of Cobetter Lifecube AF 5L single-use filling bags made of Lifemeta KA film and Renolit 9101 film under laboratory conditions are for reference only. Since the use process also needs to take into account the different inner diameters of drainage tubings, different supporting containers, manual operation errors, etc., it is recommended to conduct tests under actual process conditions.

Although stainless steel equipment is still widely used in traditional blood product production lines, with the rise and development of single-use technology, some process steps are gradually shifting to single-use systems. In particular, in processes with higher sterility assurance, more flexible production, and lower drug liquid residue requirements, the introduction of single-use technology can make the production process of blood products more efficient, safe and reliable, and reduce the need for cleaning, sterilization and validation, which to a certain extent improves the sterility assurance and operational convenience of blood product production.