Cell & Gene and High-value, Small Batch Processing Line

TILE-X can fill and close vials, syringes and pre-capped cartridges supplied in RTU packages.

TILE-X can handle:
– Vials in nest 2R – 50R.
– Syringes 0.5 ml – 20 ml. 50 ml to be evaluated case by case.
– Pre-capped cartridges 1 ml – 50 ml.

TILE-X is designed to be loaded with containers supplied mainly in tubs with single or double bag packages.

The layout of TILE-X modules can be configurated to produce up to 40 2R vials/min.

This type of layout configuration is under design.

The TILE-X module can automatically orient and place:
– Vial stoppers
– Syringe plungers & pre-capped cartridges
– Alu/Flip-off Caps
– Snap-on combo vial caps

Two possible configurations:
1. syringe & pre-capped cartridges renested outside the isolator on a dedicated TILE-X module

2. Vials:
– Renested outside the isolator on a dedicated TILE-X module
– Collected on a conveyor belt outside the isolator

TILE-X can be installed in two configurations:
– Background area Class “C” as an open gloveless isolator in operation.
– Background area Class “D” as a closed gloveless isolator in operation with dedicated loading and unloading procedures.

TILE-X has been designed especially for products that use single-use SUS filling circuits. The main reason is to allow the automatic assembly of the filling needles without the use of gloves, therefore the peristaltic or time-pressure dosing systems are outside the isolator on a dedicated module. This solution also allows correct management of the cooling and shaking of the main product bag if required by the biological product.
Different requirements will be evaluated together with the customer.

As per peristaltic pump standards. For any specific requirements, product tests will be carried out at IMA Life R&D development lab.

Currently our standard for normal machines is ±7mg. For any specific requirements, product tests will be carried out at IMA Life R&D development lab.

The pressure cascade of the current TILE-X in production is isobaric, except for the final capping section, where a protective pressure drop is present towards the filling and stoppering area. The TILE-X module operates independently for pressure control, and different pressure cascade schemes can be evaluated, taking into account the air consumption required to stabilise the pressure in relation with adjacent environments.

TILE-X uses an integrated and modular ventilation system to minimise space requirements, enabling installation in a cleanroom (height <3m) without the need for an HVAC system. For toxic products requiring high-containment configurations, a custom solution can be evaluated. Meanwhile, biohazard solutions up to BSL-2 can be accommodated with the integrated ventilation system, as post-batch deactivation strategies with VHP are feasible.

TILE-X is provided with disaster recovery strategies and can activate dedicated filling recipes to avoid using the filling nozzle with the damaged weight cell.

Automatically. A dedicated shuttle bringing the sample weight will reach the cell and perform the control operations. This process will be done at the beginning of the batch and at any time the operator will require it.

As standard, we use RTP XS190 manually operated from outside the isolator. Other RTP port sizes can be evaluated.

Yes, the closure feeding system is Annex 1-compliant, both during installation and during operation. Thanks to the automatic transfer of all closure feeding system components into their final working position, the installation is operated after VPHP with the isolator door closed.  

Capping is performed in a Grade A environment.

Capping unit, adjustable in height, equipped with 2 operating heads; sealing is carried out by means of vial rotation from the supporting plate and from the head that are mechanically synchronized, sealing through idle roller that guarantees low particle generation. Loading cells are present to control the applied closure force.

The decontamination principle of TILE-X follows a classic approach with vaporised dry H₂O₂, a well-established method used in IMA isolators. The chamber size and the absence of high-absorption parts such as gloves limit the cycle time.

The presence of air-heated phase in the aeration strategies to accelerate internal chamber desorption could allow 0.1 ppm to be reached in a relatively short time, to be evaluated during cycle development. The decontamination time to reach 0.1 ppm will therefore be assessed during the cycle development phases, using highly sensitive instruments, as standard electrochemical sensors (e.g. Drager) cannot achieve this level of sensitivity. The materials used in the chamber are suitable in terms of chemical resistance and desorption risk.

This solution is available upon request.

The isolator’s tightness is qualified at 2% and follows ISO 10648 method. This limit falls within Class 4 of the ISO standard. It is possible to request a tighter limit of 1%, which would place the isolator in Class 3, but this is typically recommended only for products with a high toxicological or biological risk.

The integrated air system ensures thermal stability (±3°C) by managing inlet air temperature, with options for full temperature and humidity control via HVAC or a dehumidifier if requested.

The foreseen groups to be placed in the tech zone are:
– EMS System
– VPHP generator
– Nebula VHP skid (if present)
– Chiller for TILE-X cooling
– Vacuum pump
– Electrical control cabinet

Standard TILE-X will fit into a 3-metre-high environment.

TILE-X has undergone several iterative cycles of design, CFD simulation, and optimisation. Ventilation aspects and pressure losses have been analysed through CFD, and using simulation systems. The internal unidirectionality within the chamber and critical process points have also been examined.

Localised CFD studies can be requested to evaluate specific machine zones.

Yes, the shuttles are running. We have done tests to demonstrate that also the bottom part of each shuttle is decontaminated by VPHP during the cycle.

Yes

The position of EMS points was defined following a detailed risks analysis performed using the Biophorum suggested template which is available for the customer upon signature of an NDA.

Viable monitoring can be passive, active and real-time.

The design of the TILE-X module (space under working plane) allows for easy integration of a real-time viable monitoring system. The connection between probe and system is performed using a straight pipe; no bend is necessary.

TILE-X:
– 100% weight control with feedback adjustment and reject reduction procedure at start and end of batch. Refilling capability.
– Check for stopper presence with re-stoppering for missed stoppers
– Check for cap presence with re-capping for missed caps
– Check of capping force
– Plunger position check

Detailed risk analysis has been performed to identify the riskiest operations (related to product losses) and the machine has been designed to address most of them:

– Ability to repeat the operations multiple times (i.e. filling, stopper & cap feeding, stoppering, capping, etc.).
– Redundancy (i.e. 2 needles, 2 stoppering stations, 2 capping stations), in case one station should stop working it is possible to complete the batch with the other station.
– As an extreme solution: emergency gloves.

The shuttles line up on the working plane and if not manually moved, when the power is back on, they maintain their position. However, considering that in the case of black-out the line will lose its sterility, we suggest to putting the entire line under UPS.

We confirm that the gripper can be sterilised.
As standard, it is assembled before the VPHP cycle.

The isolator is equipped with a fully automatic RTP port Type DPTE®-EXO ALPHA 190.
We have developed a system that, after the connection of the Beta-Bag containing the SUS nozzle, will allow the nozzles to move into the filling position.

Yes

Yes. We suggest the following process:

– Change parts for stoppers are sterilised and automatically assembled after the VPHP cycle via MTI and shuttle.
– Capper change parts are manually assembled before the VPHP cycle.

The vertical position of the container inside the shuttles has been decided after investigation of the residual value of the statically and dynamically induced electromagnetic field in order to eliminate risk. Detailed data are available for consultancy after signing an NDA.

TILE-X is targeting all those market segments where minimising product losses (in terms of process step failures and contamination) is a must.
TILE-X is specifically designed for small batches of small molecules and large molecules, especially on ATMPs and Cell & Gene biological products.