It’s a chicken and egg situation that has bedevilled pharmaceutical companies for generations: how to know what the shelf life of your drug is when it’s only in early development and so hasn’t yet had any life on a shelf.

The key, argues Henryk Junker, quality assurance manager for Allergan Clinical Supplies in the UK, is two words: stability data.

"The first priority, obviously, is to make sure you are protecting the patient. One of the biggest challenges with clinical trials is that with a drug in early development you will have limited shelf-life data, which is one of the reasons why stability data is so important," he explains.

"If you have proper stability data, then you can be more confident about setting an expiry date, which is of course one of the key regulatory requirements. You need to generate the data to come up with a justifiable shelf life and to ensure a patient is never, as a result, dosed with a drug that is outside its shelf life.

"If your predictions are incorrect, then you may end up with an out-of-trend stability result, which may result in shortening shelf life. The impact can be high – supplies at sites, depots, patients and so on, as well as the need to notify authorities of an amendment," he adds.

Stability data is also needed to set up temperature excursion plans in order to evaluate excursions during shipment and at site. The less data you have will mean, too, a greater requirement for tighter control and monitoring of your shipping/site storage conditions.

"Stability data is important because, with the development of any drug and start of any clinical trial, you need to set and meet important milestones and be able to tell this to the marketplace," Junker argues. "Ideally you need at least six months’ stability data, starting off from the compound, through into the formulation and right the way to ensuring the product can be delivered to the patient. So there are a lot of hoops to jump through.

"However, in an early-phase product, it is likely that you are only going to have a very limited amount of data, normally three months. What we tend to do is have three points: point zero (or the start of the process), then how it has reacted inside the stability chamber at one month and three months.

"What you are aiming for is a flat line, which will show your drug is stable. If the line is going downwards it shows the drug is degrading, and if it is going upwards it is also problematic as it shows that other things are happening that will need investigation," Junker adds.

Key tools to get this challenge right are: forecasting, being able to project plans for supply of the drug and understand your supply chain and, at a basic level, effective project management.

"You need to make sure you stick to International Conference for Harmonization global recommendations as otherwise, two or three years down the line, you might find an assessor saying they don’t like your data and, in the worst case scenario, find you are having your to-market timeframe pushed back," Junker explains.

"Stability data is important because, with the development of any drug and start of any clinical trial, you need to set and meet important milestones and be able to tell this to the marketplace."

"If you have a room-temperature product then you should be monitoring it between 25 and 40°C but you also need to stress test it with ‘freeze/thaw’ studies. These, as their name suggests, put the product through a cycle of down to -20°C up to +50°C over normally a ten-day period. So it really stresses the product.

"You have to be aware as you ship products that we do not live in a perfect world. So while it may be refrigerated and you may be monitoring it you have to know if the temperature has dropped or gone above a certain point and, if it has, you need to be able to make a decision about the product’s quality. That is when a freeze/thaw really comes into play because you should have that data.

"It all comes back to being in a position to pass the regulatory submissions, even just to carry out a clinical study. A factor here is, if you can, ‘future proof’ the product. What you are doing now may be acceptable but will it still be the case in five or ten years’ time? So it makes sense to play it safe to the extent of overkill to ensure you remain compliant," he adds.

Finally, communication – and lots of it – is essential. All those who manage supplies need to understand a stability protocol and when data will be generated. The supplies, clinical and regulatory teams also all need to know the plan for any changes to shelf life. Moreover, as the drug expires, there may be issues around resupply and whether you can resupply from existing batches that have been date extended or do it from new batches.

"You need to involve your clinical and regulatory teams, and you may need to involve manufacturers and vendors," concludes Junker.