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Is minus 20 °C an acceptable storage condition for lyophilised tirzepatide?

Asked 8 Oct 2024Modified 18 months agoViewed 52k times
36

Conditions: minus 20 °C · tirzepatide.

The claim is plausible, which is exactly why I want to check it.

I am able to read a paper if someone points me at one.

Can anyone point me at a primary source, or confirm that there is not one?

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BN
askedbirk_nordahl16k388 Oct 2024

5 Answers

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10

minus 20 °C is colder than anything a lyophilised cake needs. minus 20 °C is 25 kelvin below a refrigerator, and below the glass transition of a lyophilised cake the ten-degree rule of thumb stops applying at all — solid-state chemistry is not slow liquid chemistry, it is a different regime, and the failure modes that survive it are mechanical rather than chemical. A dry cake has no solvent to react in, so the marginal benefit below a domestic freezer is small and the marginal risk is not: freeze-thaw on the way in and out, and condensation on a cold stopper when you open it, are the failure modes that actually happen at minus 20 °C. Nothing here is medical advice, and research-use-only material is not approved for human use.

The relevant practical failure is not chemical at all: it is losing the link between a vial and its certificate when the box gets thrown away.

Keep the certificate with the vial, physically or as a photograph filed under the lot code. A vial without a traceable certificate is an anonymous vial regardless of where it came from.

Store with the desiccant sachet if one was supplied, inside the secondary container rather than loose in a drawer. Residual moisture is the dominant variable in solid-state stability.

Residual moisture is the dominant determinant of solid-state stability, which is why desiccants accompany lyophilised material.

Minus eighty buys very little over minus twenty for a dry solid.

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RI
answeredrukhsana_iqbal17k3715 Dec 2024
Two lots stored differently, reassayed at a year — the difference was smaller than I expected. – Dr_Bram_Verhoeven 5 months ago
2Confirming that opening a cold vial in a humid room is a genuinely bad idea. – nils_karlberg 6 months ago
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6

It helps to be literal here: this is the tag where the advice is cheapest to follow and most often ignored.

Keep vials in their original carton or in an opaque box. Light exposure matters for tryptophan-containing sequences and for anything with a chromophore, and a closed box is free.

Position matters less than people think: upright or on its side makes no difference to a lyophilised powder, and upright is marginally better for a reconstituted vial because it keeps the stopper dry.

Two-to-eight-degree refrigeration and minus-twenty freezing are the standard storage conditions for lyophilised peptides in supplier documentation across the market.

Label the vial at reconstitution with date, concentration and units per dose.

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GP
answeredg_paskevicius60k2726 Dec 2024
5Worth adding that residual moisture predicts this better than any printed date. – low_dead_space 35 days ago
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3

Desiccant matters more than the last few degrees of cold for a lyophilised powder.

Label the vial at reconstitution with the date, the concentration and the resulting units per dose. This is the single most useful thirty seconds in the whole process.

Lyophilised powder: refrigerated at two to eight degrees for months, frozen at minus twenty for longer. The gain from minus eighty over minus twenty is small for a dry solid and is not usually worth the arrangement.

Photodegradation of tryptophan-containing peptides is documented and is the basis for light-protected storage recommendations.

A printed expiry on research-grade material has no stability programme behind it.

Dry, cold, dark, still. Four words and you have the answer.

edited 24 Nov 2024 by grainne_ahearn — added the citation requested in comments

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GA
answeredgrainne_ahearn50k3822 Nov 2024
2

Keep the paperwork with the material, or the material becomes anonymous.

Reconstituted with a preservative-containing diluent: refrigerated, conventionally treated as usable for about 28 days from first entry. Without a preservative, single use and discard.

The 28-day in-use period for preservative-containing multi-dose preparations is printed on the diluent labelling and is a long-standing pharmacy convention.

Appearance does not indicate stability; a normal-looking cake can be substantially degraded.

Equilibrate before opening or you condense water into the cake.

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C8
answeredcoldpack_8850k374 Dec 2024
1

Start with the physical state, because lyophilised and reconstituted material have completely different storage answers.

Let a refrigerated or frozen vial equilibrate to room temperature before opening, so humid air does not condense water onto a cold cake.

Deamidation kinetics for asparagine in peptides are well characterised and strongly sequence-dependent: the residue following the asparagine dominates the rate, with glycine and serine at the n+1 position accelerating it by an order of magnitude relative to bulkier residues. That is why two peptides in the same buffer at the same temperature can have quite different shelf lives.

Keep the desiccant with the vial and the certificate with the lot code.

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BU
answeredbufferline4230k13828 Jan 2025

Your answer

Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.

Not medical advice. Research-use-only compounds are not approved for human use.