Temperature limit for storage/transport

[Med_eng22]

HI All,

We have a product (sterile implantable) in development for which I would like to restrict the storage conditions to 10-30C for long term storage. Products will be stored in a controlled environment in which we can guarantee these temperatures will not be exceeded. Therefore, I put the symbol on the label (ISO15223-1, Symbol 5.3.7).

I am now preparing the transport and shelf life validation plan. The product will be shipped through standard couriers, without conditioning. I am planning to simulate transport conditions using three environmental conditions (ASTM D4332, subzero, tropical and desert). All these conditions exceed the temperature limits (for storage) on the labels.

My question is as follows: how can I put a temperature limit for long term storage on the product without forcing myself into implementing temperature conditioned transport? I am fine with short temperature excursions (up to 60C, desert conditions), but I would not like to allow long term storage at this temperature.

Thanks a lot for your help.

 

[Steve Prevette]

I'd make the suggestion that I don't see why you could not establish short term termperature limits (kind of like how long a person can stay in the heat at a certain temperature and humidity). And I'd back it up with shipment indicators such as Temp Stick (no I have no knowledge or recommendation for this specific product, just came up on a search for shipment indicators.

 

[planB]

You may want to have a look into ISO 11607-1:2019, section 8: what you want to validate in terms of this standard is "stability" (= storage over your labelled shelf life) and "performance" (= package integrity through the hazards of distribution"). Section 8.1, NOTE 2 provides you with guidance to make your life easier by splitting these tests into two independent activities:

NOTE 2 Stability testing and performance testing are separate entities. Performance testing evaluates the interaction between the packaging system and the products in response to the stresses imposed by the manufacturing and sterilization processes and the handling, storage and shipping environment.

Specifically for your (labelled) temperatures: it is indeed acceptable to define a (maximum) storage temperature that is different from the temperature range permissible during distribution.

HTH,

 

[Med_eng22]

Thanks a lot Steve and planB, those are both really useful comments.

As I see it now, I need the following validations:

- Primary packaging process validation

• IQ, OQ, PQ
• Peel strength, dye penetration, visual inspection

- Sterilization validation per ISO11135.

- Sterile Barrier Stability Testing per ISO 11607-1, ASTMF1980

• Real time (RT)+accelerated (RT+XX)
• Peel strength, dye penetration, visual inspection
• Empty pouches justifying that product does not influence aging
• Since sterility is concerned: high risk --> high sample size

- Transport Validation (ISO11607-1, ASTMD4332, ASTM D4169)

• Environmental pre-conditioning (exceeding the labeled temperatures)
• Transport simulation
• Peel strength, dye penetration, product appearance and performance
• Since sterility is concerned: high risk --> high sample size

- Shelf Life Validation (ASTM F1980)

• Focusing ONLY on the performance of the product itself
• Product appearance and performance
• Since product performance is concerned: low risk --> low sample size)

There is a potential to combine the tree last items in one validation effort, but that will require a high number of actual products. With the above approach I limit the the number of samples, while still covering every aspect. Is this approach valid?