Cold chain · Quality

Temperature excursion in transit: the evidence to expect

If a pharmaceutical shipment suffers a temperature excursion in transit, the European Commission's Good Distribution Practice guidelines say it should be reported to the distributor and recipient, and a procedure should exist to investigate it. WHO guidance adds that affected product is quarantined and not released until checks are completed satisfactorily.

This article is for manufacturers and exporters who ship temperature-sensitive products to a distributor abroad. It sets out what the two frameworks say and what evidence you can reasonably ask your distributor for. It does not describe any Yemen specific rule, and it says nothing about how long a given product tolerates an excursion. That depends on your own stability data.

What does Good Distribution Practice say about a temperature excursion?

It says the storage conditions must be kept during transport and that an excursion must be reported and investigated. The European Commission's Good Distribution Practice guidelines of 5 November 2013 (2013/C 343/01), section 9.2 on transportation, state that the required storage conditions should be maintained within the limits described by the manufacturer or on the outer packaging.¹

The same section covers what follows a deviation. If a temperature excursion or product damage has occurred during transportation, this should be reported to the distributor and to the recipient of the affected products. A procedure should also be in place for investigating and handling temperature excursions.¹

What happens to the product while the investigation runs?

It is held apart and not released. WHO Technical Report Series No. 961, Annex 9 (2011), the model guidance for time and temperature sensitive pharmaceutical products (TTSPPs), says to quarantine defective or potentially defective products, and products that experienced unacceptable temperature excursions during transport. It says not to release them until checks have been completed satisfactorily.²

The same guidance says all unacceptable temperature excursions should be evaluated to determine their effect on the product.² Note the wording: the evaluation is about the effect on the product. It is a quality question, and the answer sits with whoever holds the product's stability data.

Who decides whether the shipment can still be used?

The manufacturer or marketing authorisation holder decides, not the distributor. Neither document asks a distributor to judge product quality from a temperature reading alone. WHO Technical Report Series No. 961, Annex 9 points the same way for returned product: where appropriate, obtain written advice from the holder of the marketing authorization regarding handling and disposal.²

In practice this means you should agree, before the first order, who you want to be told and how quickly, and what you need from the distributor to make your decision. This is common industry practice rather than a requirement drawn from either document.

What evidence should you expect from your distributor?

You should expect records that show what the shipment experienced and that the devices producing them were reliable. WHO Technical Report Series No. 961, Annex 9 sets out the basis for this. For temperature-controlled road vehicles it calls for air temperature monitoring systems, sensors calibrated as described in its clause 6.7.2, and documentation which can be stored and accessed.²

Its calibration clauses ask that transport temperature control devices, temperature monitoring devices and humidity monitoring devices are each calibrated against a certified, traceable reference standard at least once a year, unless otherwise justified. Alarm equipment is also checked: temperature and humidity alarms are tested at the designated set points, and security alarm systems are tested, at least once a year unless otherwise justified, with records kept to demonstrate compliance.² The stated reason is that products can be transported safely within the profile defined for each product, and that compliance can be shown to the regulatory authorities and other interested parties.²

As common practice, and not as a citation, a manufacturer will usually want the following after an excursion:

• the temperature record for the whole journey, not only the period around the alarm;
• the calibration status of the device that produced the record;
• confirmation that the affected stock has been quarantined and where it is held;
• the written report of the investigation the distributor's procedure requires.

What should you agree with a distributor before shipping?

Agree the reporting route and the records in writing before the first shipment. Section 9.2 of the EU guidelines expects a procedure to exist for investigating and handling excursions,¹ so ask to see it, and check that it names who you are told and that quarantine is automatic rather than a judgement call at the loading dock.

If you are still choosing a partner, our guides on qualifying a distributor and on cold chain at the border cover the wider checks. Import documentation is covered in how medical products are cleared for import. Local specifics for Yemen are confirmed case by case, so ask us rather than rely on a generic checklist.

In summary

Keep the limits with the manufacturer, the reporting duty with the distributor, and the release decision with the marketing authorisation holder. Insist on monitoring records from calibrated devices, and on quarantine until checks are complete.