With the development of flexible manufacturing technology and the increasingly mature application of sterilization-free (abbreviated as RTU) packaging materials, the pharmaceutical market has an increasing demand for this. To this end, this passage specifically introduces a multi-functional (hereinafter referred to as Combo) system that can meet the requirements of pilot production, which can be applied to multiple varieties of drugs and various packaging materials, and can also be used for R&D/clinical trials/formal production.
The Combo pilot filling system is compatible with three packaging materials: pre-filled, vials, and cartridges. This series can provide low-risk, high-flexibility and advanced sub-packaging processes for RTU packaging materials. Combo system can be configured with isolator and O-RABS according to process requirements and background environment. Pilot Combo model + ISOLATOR is a customized system, this passage mainly introduces the Combo model + O-RABS solution.
1. Application fields and adaptable packaging materials of Combo system
1.1 Application fields
Application fields of of Combo system: R&D/clinical trials/official production of crude drugs, vaccines, oncology, insulin, cancer, hepatitis and other drugs, growth hormone, CDMO (Contract Research and Development Organization) and other fields.
1.2 Packaging material
The Combo system is compatible with packaging materials: three types of RTU packaging materials: pre-filled, vial, and cartridge.
1.3 Introduction to the scheme of the Combo system
“Three-in-one” prefilled syringe equipment.
(1) Suitable for small batch and pilot production (PFS＜2400pcs/hour, freeze-dried plate area＜2㎡);
(2) Can be used for R&D/clinical trials/pilot production;
(3) To achieve flexible production, suitable for multiple varieties of packaging materials;
(4) Use in combination with disposable technology;
(5) Compact design, the clean room occupies a small area;
(6) It can realize rapid change of production and speed up the time to market of drugs.
2. Technology and Characteristics of Combo System
2.1 Design Elements of Combo System
(1) The design follows corresponding regulations such as cGMP, FDA, EU-GMP;
(2) Modular design, compact design, easy to expand;
(3) The equipment has high safety, strong stability and reliable filling accuracy;
(4) Adopt RTU packaging material and Single-use technology;
(5) Adopt liquid surface filling technology to effectively prevent liquid splashing;
(6) A variety of filling doses and filling methods are available;
(7) Vacuum stopper technology, perfect solution for viscous liquid medicine and coating rubber stopper;
(8) Integrated control system: highly integrated production data, safety interlocking, and whole process recording. At the same time, the software design meets 21CFRPart 11 and GAMP5 requirements.
2.2 Single-use liquid medicine delivery
In the process, the liquid medicine transmission can take into account the Single-use (one-time use) technology. Figure 4 is a schematic diagram of the single-use liquid medicine transmission. It uses a disposable plastic bag for liquid dispensing, and the liquid medicine transmission pipeline can be made of disposable silica gel, which is matched with a peristaltic pump for metering and filling.
2.3 Combo system at environmental level in O-RABS
The background environment between the corresponding functions is as follows：
Grade B: Inner Unpacking, filling and plugging, slotting, feeding and discharging, and capping;
Grade C: outer Unpacking;
Grade D: clean area;
CNC: Freeze dryer workshop.
2.4 Combo system process
2.4.1Packaging material type and process equipment configuration (Figure 6)
2.4.2 Combo system in ORABS flexible filling production type
According to the form of RTU packaging materials, there are three main types of Combo system in oRABS flexible filling production: prefilled syringe filling and sealing and cartridge process (Figure 7), vial injection process (Figure 8), vial freeze-drying process (Figure 9) )
This passage starts with the application field of Combo system and adaptable packaging materials, and introduces the technology and characteristics of Combo system from three aspects: design elements of Combo system, single-use liquid transfer, and Combo system technology.
The Combo system can be summarized as follows: (1) Equipment functional requirements: outer unpacking machine, inner unpacking machine, all-in-one filling and plugging machine, freeze-drying machine, capping machine; (2) RTU packaging material type: prefilled syringe, vial bottles, cartridges; (3) Liquid delivery: Single-use technology; (4) Aseptic isolation system: oRABS, cRABS, ISOLATOR can be configured;