Small interfering RNA (siRNA) drugs, as a hotspot in the development of small nucleic acid-based drugs, have been widely used for their high gene silencing efficiency, controllable adverse effects, and easy synthesis. Recently, HJB has also embraced the first siRNA formulation filling project, which was commissioned by SynerK, a leading company in siRNA technology, for the development of siRNA formulation prescriptions and filling work. During the project, the two parties cooperated and gave full play to SynerK's experience in the development and production of siRNA formulations and to HJB's experience in the development and filling of injectable liquid formulations. The technical team of HJB overcame many technical difficulties and challenges of siRNA formulation and completed the first batch of filling in one go, with a filling yield as high as 95%.

Difficulties and challenges

1. siRNA API powder is very fluffy and has a small weight per unit volume, making formulation more difficult.

2. Some physical properties of siRNA solutions are difficult to control.

3. The price of siRNA API is relatively expensive, and the production of finished products requires maximum control of losses.

4. The high concentration of the siRNA formulation posed a challenge to filling accuracy.

The HJB team rises to challenges.

Multiple strategies to solve project challenges.

Based on the above difficulties and challenges, the HJB team carried out the formulation prescription development, dilution test and filling accuracy test, and other preliminary work. Meanwhile, the self-developed liquid filtration system and specialized filling system greatly reduced the dead volume of the filtration process (controlled at ~110 mL), and efficiently completed the key parameters of the central control testing and formulation filling work, with a filling yield as high as 95%, and the filling output in line with the expectations.

HJB owns a Bosch fully automated aseptic GMP filling line with isolators, which is suitable for GMP aseptic filling and encapsulation of 2 mL/6 mL/10 mL/20 mL/25 mL/30 mL standard vials. The filling volume can be selected from 0.4 mL-35 mL according to the demand, and the maximum mass production can be up to 100,000 pcs/batch. The environmental level of the filling line is Class A with isolators in a Class C background. All parts in direct contact with the product use closed disposable systems to maximize product safety and prevent cross-contamination. With the state-of-the-art production line and the experienced formulation production team, the HJB team has completed about 30 batches of GMP aseptic injection filling production since the start-up of the filling production line.

This batch is the first siRNA drug filling project for HJB and we appreciate customers for their support and trust.