I am often asked “If I get a temperature excursion, can I justify it with the manufacturer’s stability testing data?” Well, as usual the answer is ‘it depends’! But you need to exercise a fair amount of caution here.

What is Stability testing?

First of all, let’s look at what stability testing is. Stability testing provides evidence on how the quality of a drug substance or product varies over a given period and under the influence of environmental factors including temperature, humidity, light and handling of such materials.

Studies are commonly the activity on the critical path to regulatory filing and approval. There are 2 typical types of stability testing in which either can be used, real time and accelerated. All studies should be controlled and clearly documented through record keeping and reporting which should be kept up to date and available.

Real-time – Products are stored at labelled storage conditions and monitored until it fails the specification.

Accelerated – Product is stored at elevated stress conditions; degradation can be predicted using known relationships between the acceleration factor and the degradation rate.

ICH Q1 guidelines set out requirements for stability studies and provides regulators from around the world a harmonised approach to the requirements.

Why is stability data relevant to a Wholesale Distribution Authorisation (WDA) Holder?

GDP says, “All actions taken should ensure that any wholesale activities are performed according to the information on the outer packaging ensuring particular attention is paid to products requiring specific storage conditions either at the premises or in transportation which is vital to ensuring GDP guidelines.” (GDP chapter 5 section 5.1) This means it is the obligation of the WDA holder to store under labelled conditions.

Upon any temperature excursions it is important to have a process detailing the steps to be taken and it is important to ensure all staff are trained and aware of these critical procedures.

I have often seen a poor approach to temperature excursions. A wholesaler makes a call to the manufacturer or marketing authorisation holder for information on stability data to help justify ‘no impact to product quality’ and release the medicinal products back into saleable stock, with no other considerations.

As a former MHRA GDP inspector the regulators view in GDP is that stability data alone cannot be used to justify ‘no impact to product quality’ when there are deviations outside of the labelled storage conditions, and this is for a number of reasons:

• The product marketing authorisation has been granted according to the labelled conditions and the safety data presented as part of the authorisation at those storage specifications.
• Wholesale supply chains can be complex therefore the cumulative use of the stability data and time is not visible and therefore impossible to calculate without the full visibility of the whole supply chain.
• Stability data providing extended storage allowances is for the benefit of the patient. For when the patient collects their medicine and delays transferring it to their fridge, or leaves it on a windowsill in direct sunlight, or on a warm day forgets the product in the car and so on and so on.
• Wholesale supply chain should ensure maintenance of product quality as though the product had been supplied directly from the manufacturer. This is the obligation of the licence holder.

How to use Stability Data

Stability data is useful and can aid your assessment on impact to product quality, but you should consider all mitigating factors before making this high-risk decision. Such as:

• Packaging and it’s insulating effect.
• Volume or size of dosage forms (smaller volumes are affected by temperature excursions more quickly than larger volumes)
• Length of the deviation.
• The severity of the deviation itself.
• Any other mitigating factors such as proximity of temperature monitoring devices.

It is important that the person documenting and investigating the deviation is well trained and understands how to determine the most probable root cause and any impact on product quality is fully justified and evidenced.

So, in summary – ‘it depends’. There is no right or wrong answer, but hopefully now you will see why MHRA inspectors have a dim view of wholesalers who refer to stability data and then release all medicines affected by a temperature excursion back into saleable stock.

At SeerPharma we have assisted a number of companies by providing training and mentoring on effective Deviation, CAPA and Root Cause Analysis (RCA), the correct approach to be used for a temperature excursion. We have regular scheduled courses, the next being in September 2021.

The training is provided by former MHRA GDP inspectors which is interactive and engaging and gives you the opportunity to ask questions and get an insight of what regulatory inspectors require.