Revised GMP Annex 1

Loading/Unloading of Lyophilizers

The latest update of the EU Annex 1 "Manufacture of Sterile Medicinal Products" was officially released on 25 August 2022, with an implementation deadline set for 25 August 2023. The requirement for compliance with Section 8.123 concerning freeze-drying and product transfer will be enforced from 25 August 2024.

Lyophilization (Freeze-Drying) is a crucial step in the production process. Associated activities such as transfers of partially and fully stoppered units and loading/unloading operations that could compromise the sterility of the product must now be considered extensions of the aseptic processing of the sterilized material. It is imperative that the lyophilization equipment and affiliated processes are meticulously designed to prevent contamination throughout the entire lyophilization process, from filling to completion. All control measures should be determined by the manufacturer’s Contamination Control Strategy (CCS) to ensure the maintenance of product sterility.

Contamination Control Strategy (CCS)

CCS is a systematic approach to detecting and preventing potential sources of contamination during the manufacturing process and involves implementing measures and protocols to ensure the product’s purity, efficacy, and safety. It may include aspects such as maintaining clean and sterile environments, using appropriate equipment, and implementing rigorous quality controls.  

What is the main impact of Annex 1 on lyophilization loading/unloading?

Generally, the goal is to ensure that the loading and unloading process for lyophilization is conducted in a controlled and sterile manner to minimize the risk of contamination and ensure the quality of the final product. Lyophilizers and associated product transfer and loading/unloading areas should be optimized for efficient automated operation to reduce the need for manual intervention by operators.

As per “Section 8.123,” from revised Annex 1, manually loaded and unloaded lyophilization processes without barrier technology require sterilization of the lyophilizer chamber before each load. 

What steps should drug manufacturers follow to ensure an aseptic environment when loading and unloading lyophilizers?

• Identify potential sources of contamination both internal sources, such as equipment and processes, and external such as raw materials

• Assess risks: Evaluate the likelihood and potential impact of contamination from each source identified

• Develop a control strategy: Based on the risks identified, develop a comprehensive plan that outlines specific measures to prevent contamination such as implementing physical barriers, establishing cleaning and sanitization procedures, and conducting regular monitoring and testing

• Train personnel

Without separation between the operator and the products, manual loading and unloading generates high risks of contamination. In order to minimize the risk of cross-contamination or loss of sterility, it is essential to to implement the right barrier system that complements the lyophilizer.

Working with a partner who has expertise in integrated systems and able to tailor the design to accommodate your loading and offloading procedures is essential for success.

Have you implemented a contamination control plan and are your procedures in compliance with current regulations?

Dec offers comprehensive solutions including aseptic filling lines for powders and liquids, aseptic powder transfer solutions, and a range of semi-/ automated solutions for loading and unloading lyophilizers, all designed for efficient product transport and to minimize contamination risks.

Lyophilization Loading/Unloading