Medical devices

Spike know-how by Jürgen Barth

Spike know-how by Jürgen Barth

Spikes without a particle filter?

Particle filter - yes or no? That is the question.
The anwer is: Better not.

An opinion

Minispikes are available with or without integrated hydrophilic particle filters (pore diameter = 5 µm) in the liquid channel. When selecting a spike, it should be known if the filter material is able to adsorb substances. This is especially important for low-dose cytostatics (e.g. in pediatrics).

Furthermore, attention needs to be paid to material incompatibilities. For example, Etoposide is incompatible with Acrylnitrile-Butadiene-Styrene (= ABS)-plastics. For this reason minispikes made from MABS (Methyl Methacrylate Acrylonitrile Butadiene Styrene) should be used. Incompatibility is generally a problem for cytostatics in organic solutions (apart from Etoposide presently taxanes and epothilones). Dactinomycin interacts with, for example, filters made from celluloseacetate, -nitrate and polytetrafluoroethylene (adsorption). For a spike manufacturer it is a virtually impossible problem to solve, i.e. to test the spike components for "all imaginable incompatibilities", as there is no way of knowing which substances the customer will want to use the spikes for.

This the reason why over the last few years the opinion has formed that a spike containing a filter in the liquid channel plus an aerosol-tight ventilation filter is defined as a chemospike. However, this is not so. A chemospike has to have a hydrophobic, aerosol-tight ventilation filter. Usually with a pore diameter of 0.2 µm.

A chemospike is a spike with a hydrophobic, aerosol-tight ventilation filter, pore diameter = 0.2 µm or smaller. 

In the meantime there also chemospikes available with a filter pore diameter of 0.1 µm. There are further problems with spikes containing filters in the liquid channel. Cytostatics with particulate properties (liposomal formulations, nanoparticles or albumin-bound substances) and suspensions (Azacitidin), but also mono-clonal antibodies should not be drawn up using these types of spikes. A suspension remains in the vial. A solution which does not contain any active ingredient is drawn up.

The same applies to liposomal preparations or, alternatively, the liposomes are destroyed.

Also, there is a possibility that the antibodies may be physically altered, damaged or - depending on the filter material - absorbed due to (strong) shearing forces.

This cannot be compared to the type of filters which need to be used for certain antibodies interconnected between infusion set and patient, even if these antibodies have a pore diameter of  < 0.5 µm. These filters must have a low protein binding capacity.  They serve as a collection device for the infusion solution formed (potentially immunogenic) protein agglomerates.

The following oncological antibodies require a downstream filtraton step:

Necessary downstream filtration step for antibodies:

Antikörper (INN) Porendurchmesser des Filters:
Atezolizumab 0,2 bis 0,22 µm
Blinatumumab 0,22 µm
Daratumumab 0,22 oder 0,2 µm
Elotuzumab 0,2 bis 1,2 µm
Ipilimumab 0,2 bis 1,2 µm
Nivolumab 0,2 bis 1,2 µm
Ofatumumab 0,2 µm
Panitumumab 0,2 oder 0,22 µm
Pembrolizumab 0,2 bis 5 µm
Ramucirumab 0,22 µm
Trastuzumab Emtansin 0.22 microns when 0.9% NaCl solution for infusion is used. 0.45% NaCl solution for infusion may be used without an 0.22 µm in-line filter made from polyether sulfone.
Stand: Juni 2016

To ensure the the highest level of safety when compounding drugs there should be no mixing of different types of spikes (spikes with and without filters in the liquid channel). Generally, it is better to keep the medical implement diversity as low as possible.

Thus there is no sense in keeping non-chemospikes (vented filter pore diameter 0.45 µm or similar) for the drawing up of solvents and chemospikes for the drawing up of cytostatics. If during a hectic working day an error occurs and the wrong spike is chosen to draw up one of the sensitive product named in the list above, this could have severe consequences for the patient (e.g. a solution without the active ingredient in the case of Azacitidine).

The recommendation is therefore for cytostatic production to be of "one type" only, i.e. to only use chemospikes in accordance with the definition above.

Jürgen Barth
Apotheker für Klinische und Onkologische Pharmazie
Justus-Liebig-Universität, Gießen

Expert opinion by (German): Barth - Zytostatikaherstellung in der Apotheke, 4. Aufl., Kap. II-5. ISBN 978-3-7692-5418-1

For many years Jürgen Barth has been working as an examiner of certificated seminars and further training courses in oncology pharmacy for different Chambers of Commerce and the DGOP.