Finding the cause of unexpected drug degradation

European Pharma Co.

Challenge
Find the cause of an unusually rapid degradation of an oncology drug packaged as a gel in a pre-filled syringe, sealed within a triple-laminated sachet.

Approach
After full analysis of the drug, device and packaging, we undertook advanced modelling and experimental work to examine the relationships between device, drug and sachet.

Outcome
We showed that moisture could exist between the gel and the device, and found a solution that could be implemented at minimal cost with negligible disruption to production.

A longstanding client in the pharma sector asked Team to help resolve a serious problem affecting the shelf life of one of its high-value oncology drugs. The drug, carried in a gel, was pre-filled into a plastic syringe-type delivery device and sealed within a triple-laminated sachet.

The packaging was designed to ensure a two-year shelf life, but stability trials showed significant and unacceptable degradation after only six months, badly affecting the potency of this very expensive drug.

 
Our approach

After undertaking a full analysis of drug, device and packaging, Team identified the possible cause – that water within the gel could be migrating into the plastic of the device, thereby affecting the quality of the drug and reducing its shelf life.

To confirm this, Team undertook extensive, advanced modelling and experimental work in order to examine the relationships between device, drug and sachet, exploring the water content levels of the different materials under different environmental conditions.

As a result, Team’s work showed that a significant moisture gradient could exist between gel and device; the sachet, originally designed as a sterile moisture barrier, instead formed a micro-climate in which water was drawn out of the gel and into the drier plastic delivery device.

As gel, device and packaging design could not be changed, the challenge was to adjust conditions within the sealed sachet in order to maintain the gel’s ideal water balance for two years.

 
Outcome

After a detailed assessment of the whole manufacturing process, the solution was to implement new temperature and humidity controls to ensure all components contained enough inherent water before final assembly and sachet sealing, to eliminate the risk of a water gradient within the sachet.

This proved to be a straightforward and elegant solution; it could be implemented at minimal cost, with minimal disruption to production, and results were almost immediate – components showed ideal levels of moisture content within one week after manufacturing settings were introduced.

 
Reflection

This project was a real demonstration of Team’s ability to bring together a variety of interrelated skills – from troubleshooting to packaging technology, material science and math modelling, together with an understanding of the pharmacological issues involved – in order to understand a problem which the client’s in-house skill set proved unable to solve.

It also demonstrated the value of an external, informed, but neutral perspective, where distance provided the understanding that those close to project had lost.

Although this solution was developed in response to a specific problem relating to a gel drug, the lessons learnt have significant implications for other areas of pharmaceutical manufacture and packaging – especially for those companies currently investigating lyophilised drugs (freeze-dried drugs where all moisture is removed).

These drugs can be stored in dual chamber delivery devices containing both the drug and the diluent required for reconstitution; total and continuous separation of moisture and drug is therefore essential, but the risk that device and packaging materials could encourage moisture imbalance and enable drug degradation may not yet be fully appreciated.

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