Chemistry - The importance of the cold chain in the food and the pharmaceutical industry

Solution 1:

Avoiding cooling again after keeping it ( for non critical products ) at room temperature is mainly to prevent forgetting it was not cold all the time and that it may not last as long as expected.

Taking food from the fridge, you may not remember after a week or two that it was outside longer than it should have been. It can violate the safety by growth of microbes, which does not fully stop when it gets cold again.

For drugs or similar critical products, it violates stability and guarantee of usability, as thoroughly described by @Julian answer. I did related analysis within drug stability studies in past as well.

Food freezing is another case. Industrial freezing of food is done by shock freezing using liquid nitrogen. This leads to quick forming of small ice crystals that do not puncture the cell walls, so after melting food before usage, it is OK.

But when refrozen back e.g in a freezer, freezing is slow, leading to growth of large ice crystals puncturing the plant/animal cells. After another melting, cell liquids leak out, cells lose their tonus and the food gets unpleasant mechanical and sensory state, affecting the final taste. Additionally, what was told above about the fridge applies here as well.

Presence of free ice along with frozen vegetables is a sign the content was refrozen.

Slow melting of previously shock-frozen stuff leads to growth of bigger crystals, similar to recrystallization, as bigger crystals are thermodynamically preferred due to lower surface energy. So some cell wall tearing and subsequent deterioration of the content happens even during melting and continues until content is frozen again. Also, shock freezing still induces some stress on the product, even if lower than slow freezing.

So the final effect of

• fast freezing -> slow melting -> slow freezing -> melting

can be much worse than just

• slow freezing -> melting

as the former has more time and opportunity to cause damage.

Solution 2:

Answer here from a quality manager in the pharmaceutical field in Europe.

Pharmaceutical companies are obliged to perform stability tests for their products according to the relevant pharmaceutical (GMP) agency in your market (FDA/EMA/etc) and the international agreed guidelines like ICH Q1A-F and the WHO).

These tests are carried out in stability chambers with specific temperature and humidity according to your market. A product intended to be stored at room temperature in Europe and the US will need a study for minimum 12 month up to 5 years at 25 °C and 60% relative humidity (RH) as well as an intermediate study at 30 °C and 65% RH for 6 month to 5 years and a an accelerated test at 40 °C and 75% RH for at least 6 month. Cool stored products will have the long time storage at 5 °C and the accelerated test at 25 °C and 60% RH and there is a whole lot of other stability studies you can (or can be forced to) test. Based on a risk assessment and your stability protocol you will analyze your drug after defined times (like 1, 3, 6, 9, 12, 18, 24, … month).

For each pharmaceutical product there must be a defined specification. This might includes the assay, impurities like degradation products, metal residues, solvent residues, color, taste, microbiological contamination etc.

Now, after each time point you test your defined specification if everything is still within the specification. The scope is based again (as nowadays everything in the pharmaceutical environment) by a risk assessment.

Using this information you can define your storage conditions and shelf life of your drug. If you find out you fulfill the specification at 25 °C for the whole duration but not at 30 °C, you will define the storage condition to be below 25 °C to be on the safe/legal side. Same with the storage at 5 °C. If the tests at 25 °C fail after 2 month, you can e.g. define a storage of max 2 weeks at room temperature to be on the safe side.