Annex 1 and fill-and-finish processes: impact on equipment setup and batch preparation

Optimization potential in various equipment areas

With the implementation of the EU GMP Annex 1 ("Manufacture of Sterile Medicinal Products"), pharmaceutical companies are facing new challenges, particularly in the fill-and-finish processes—the filling and final processing of medicinal products. Annex 1 introduces expanded requirements for both existing and new production lines. Our expert, Ralf Wagner, Sales Director for the DACH region, Portugal, and Spain at Optima Pharma, explains the impact on equipment setup and batch preparation and presents suitable solution approaches.

Handling of filling needles and product path setup

According to Annex 1, it is crucial to avoid direct contact of gloves with product-contact materials, especially when handling filling needles (§5.5, §4.11). To meet these requirements, Optima offers automated or semi-automated solutions within isolators, ensuring aseptic handling of filling path components in compliance with Annex 1. An alternative method involves the manual installation of filling needles using clip holders as handling devices. This allows operators to manually position the needles without direct contact.

Safe transfer with Rapid Transfer Ports (RTP)

Rotary lobe pumps that come into contact with the product must be autoclaved or undergo a ClP/SIP (Cleaning in Place /  Sterilization in Place) process according to Annex 1 requirements. To facilitate this, mounting aids have been developed that enable contact-free assembly. The pumps are first autoclaved and then mounted using these aids, ensuring that operators do not touch product-contact parts. RTP ports also play a crucial role in transferring equipment and materials into the sterile area. Optima offers two solutions here: a manual and a motorized, fully automatic variant for opening the ports from the outside. This avoids manual handling with gloves. Both variants have already been successfully installed in various systems.

Efficient introduction of sorting bowls

One of the biggest challenges is the sterile introduction of sorting bowls, which are used for feeding stoppers and closures into filling and sealing machines. Annex 1 requires sterilization of these components. Optima has developed a handling system for this purpose, which is especially used for high-speed systems with relatively large and heavy sorting pots. The handling system transports the sorting pot into the system ergonomically and with little contamination. This significantly reduces the risk of contamination and at the same time improves work ergonomics.

Automated calibration of weighing cells

Another critical aspect of batch preparation is the calibration of weighing cells. Previously, calibration weights had to be manually placed on the weighing cells via glove ports. A new automated solution now handles this task, reducing the number of necessary glove port interventions especially in high-speed systems. This solution was developed in alignment with the requirements of Annex 1, minimizing the risk of contamination during calibration.