Processing nested RTU packaging containers

Filling nested RTU packaging containers

Steps for filling and closing a ready-to-use syringe, vial or cartridge.

Ready-to-use Vial, Cartridge and Syringe Filling Machines: From product development to commercial filling

For many years, the use of ready-to-use packaging containers (RTU) in the pharmaceutical industry has been steadily increasing. There are several reasons for this: increasingly smaller batch sizes, increased demands for flexibility in production and, above all, drop in prices for RTU packaging containers and, as a result, cost advantages for your investments.

Aseptic filling machines series from groninger process pre-sterilized glass and polymer objects from almost all suppliers. A format changeover is possible without the use of any tools and thus creates only minimal set-up work, this shortens the downtime and enables maximum flexibility in aseptic filling. The areas of application inside the pharmaceutical industry are diverse: from CDMOs and Biologics up to Cell and Gene Therapies.

The nested containers are brought to the filler in the clean room, single or double bags, and is unpacked there using a semi or fully automated procedure. There are two main approaches for transferring the nested material into the aseptic area. The first option is outside decontamination with E-Beam, or by using H2O2. The other option is the no-touch transfer (NTT). In recent years, however, the no-touch transfer has slowly gained market share with small batch up to high-speed applications.

Ready-to-use Vial Filling Machine
Ready-to-use solution for filling vials
Ready-to-use Syringe Filling Machine
Ready-to-use solution for filling syringes
Ready-to-use Cartridge Filling Machine
Ready-to-use solution for filling cartridges

Steps of our RTU vial, cartridge and syringe filling machines


Outside decontamination, irradiation or aseptic no-touch transfer (NTT)

The transfer of the containers to the aseptic area is a crucial in the pharma industry. Particularly, in the case of small and medium-sized production quantities, the so-called no-touch transfer (NTT) provides an option for aseptic transfer, which is becoming increasingly important alongside decontamination with E-Beam or H2O2.

As the leading supplier of filling and closing machines for nested syringes, vials and cartridges, groninger was one of the first pharmaceutical machine manufacturer whose liquid filling machines were commissioned in combination with an E-Beam or the no-touch transfer technology and approved by the regulatory authorities for GMP production.

In the area of ​​non-contact aseptic transfer, it is differentiated between different stages of development:

No-touch transfer (NTT) basic

With the compact NTT basic, the RTU objects are packed in two plastic bags and delivered to the line. The outer bag is manually cut open under a class A laminar air flow and then the tub in the inner bag is pushed over into the class B zone. There the bag is automatically clamped, cut and the tub is transferred semi-automatic to the aseptic filling area (isolator class A/ISO 5).

No-touch transfer (NTT) advanced

The nested objects are also delivered in two bags for the fully automated NTT. The outer bag is clamped manually or automatically at the machine, cut open, and the tub in the inner bag is moved over to Class B. This is followed by fully automated bag stretching, followed by fully automated clamping and cutting. The tub is then transported to the aseptic core area (clean room class A/ISO 5).


For decontamination with H2O2, a single-packaged bag is manually cut open under laminar class A air floor and transferred to the decontamination chamber. A 6-log outside decontamination of the RTU tub is then carried out using H2O2 and a manual or automatic transition to class A.


For the E-Beam outside decontamination, single bagged RTU containers are unpacked and fed into an e-beam chamber at up to seven units per minute. This allows for a safe procedure with a 6-log rate, which means that the packaging can be introduced sterile.


Opening tubs without risk of contamination

groninger uses the patented pull-off rollers to open tubs. In this step, the adhesive points of the packaging cover are first heated to loosen the adhesive bond. It also minimizes the generation of particles when the liner is pulled off. Vacuum rollers pull off the lid and liner at the same time at a uniform speed in an extremely process-reliable and reproducible manner.

This also guarantees ideal first-air contact, i.e. there is no movement above the opened containers, which prevents the primary packaging from becoming contaminated with particles.

Irrespective of the machine's output, this technology enables continuous processing independent of the actual batch size.

RTU tub opening
Patented groninger solution with pull-off rollers for safe opening of the tubs

Filling & closing

Filling and closing of RTU containers

How to fill a prefilled syringe, vial or cartridge? There are two basic technological approaches for filling a liquid pharma product into a RTU container: It is differentiated between a automatic filling machine with a Statistical In-Process-Control (IPC) and fillers with a 100% In-Process-Control (IPC). The decisive difference between the two methods is whether and when the objects are lifted out of the tub or nest and weighed.

Other steps like filling or stopper placement with vacuum, gassing of oxygen sensitive products as well as the use of various filling systems (i.e. rotary piston pumps, peristaltic pumps or time-pressure system) can be realized with both types of machines.

Systems with Statistical In-Process-Control (IPC)

For fillers with Statistical IPC, the objects can remain in the nest during filling and stoppering. The number of weighing processes can be set via the user interface, the objects are lifted out with robotic arms and weighed before and after filling.

With these syringe filling machine or cartridge filling machine the objects remain in the nest after they have been closed and can be inspected after they have been removed from the aseptic area.

The procedure may be different for a vial. If they are closed with integrated stopper caps, the process is similar to that for a syringe and cartridge. However, if they are to be sealed in the traditional way with stoppers and aluminum caps, the vials are lifted out of the nests by a robotic arm and individually fed to the crimping machine.

Aseptic filling equipment with 100% In-Process-Control (IPC)

Vial, cartridge and syringe filling machines with 100% IPC are characterized by the fact that all containers to be filled are brought individually into a transport system after the lid and liner have been removed from the tub.

Since the separation is done with a robot arm, this only has a minimal impact on the laminar flow around the objects. Manipulated they can also be weighed individually. With these systems, it is possible to define the filling range even more precisely, since direct adjustment is just as possible as redosing or replacing missing stoppers.

The smartfill feature established by groninger also minimizes product loss in these systems when starting up or running empty.

Filling and closing RTU cartridges
Filling and closing cartridges

Freeze drying

Integration of freeze drying processes

Freeze drying has been used successfully for years to increase the shelf life of liquid pharmaceuticals. For this, various suppliers provide suitable and proven technologies, which can be integrated into groninger filling equipment.

From manual FD loading up to automatic systems with up to 600 objects per minute, we have already gained experience with almost all lines worldwide. This enables us to easily implement the line integration of freeze dryers and loading solutions according to your specific requirements. You select the best technology, we will integrate it into our line concept.

Freeze drying integration
Solution for freeze dryer integration


The sealing is performed at the end of every vial processing with classic aluminum caps. groninger relies on the patented and proven single-disk flanging principle. All vials are closed with a single, adjustable flanged disc. With the appropriate setting, the objects can be sealed reliably in various performance classes from 10 to 600 objects per minute.

The advantages compared to solutions with several flanged discs are clear:

  • The line can be converted much more quickly,
  • the process risk is reduced, and
  • errors in the process can be detected and eliminated without delay.
Secure closure Vials with aluminum caps
Closing with aluminum caps

External cleaning

External cleaning of filled products

In the processing of toxic products, operator protection is certainly a priority alongside product protection. Therefore, requirements for the external cleaning of the filled vials are increasing for these products.

Whether in liquid form or as a powder after a freeze-drying, toxic components are not uncommon in personalized medicines. groninger has focused its work on their processing and offers an extensive portfolio of solutions that ensure external cleaning.

External washing of filled vials
Solution for external washing of filled vials

Downstream processing

When the containers has been pharmaceutically closed, the downstream processing of the packaging begins. These steps can usually be carried out outside of traditional clean rooms.

Possible work steps in this phase include:

  • Inspection,
  • labeling,
  • installing a finger flange or a safety device and/or
  • screwing in the piston rods.

It is only after these work steps that the goods are packed in the final packaging.

groninger always aims for an intergral solution. As a result, we aren't only contributing our own expertise in assembly and labeling, but also cooperate very closely with well-known line manufacturers in the area of inspection and final packaging.

Downstream processing of syringes - labeling, plunger rod, finger flange and safety device assembly
Downstream processing of syringes - labeling, plunger rod, finger flange and safety device assembly