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Is minus 80 °C an acceptable storage condition for lyophilised dulaglutide?

Asked 31 Mar 2024Modified 2.1 years agoViewed 22k times
This question was closed as needing detail or clarity.Closed 18 Apr 2024. Answers already posted are preserved; new answers are not accepted. Questions here need enough detail that they can be answered as written.
6

What I have: minus 80 °C · dulaglutide.

I am asking for verification rather than opinion, ideally with something I can read myself.

It is possible the evidence exists and I am searching for the wrong term.

Is this actually true, and what is the evidence?

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NK
askednadia_kowalczyk20k2831 Mar 2024

5 Answers

Accepted answer first, then by votes
41

Accepted answer

minus 80 °C is colder than anything a lyophilised cake needs. minus 80 °C is 85 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 80 °C. Nothing here is medical advice, and research-use-only material is not approved for human use.

The honest answer is that ordinary refrigeration handles almost every case people ask about.

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.

Degradation pathway by condition

PathwayDominant whenDetected by
DeamidationSolution, neutral to alkaline pHRP-HPLC, +1 Da on MS
OxidationLight, trace metals, peroxidesRP-HPLC, +16 Da on MS
HydrolysisSolution, extremes of pHRP-HPLC, fragment masses
AggregationAgitation, interfaces, high concentrationSEC, visual haze; often invisible on RP-HPLC
Freeze-concentration damageFreeze-thaw of buffered solutionSEC, loss of recovered content

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.

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

The caveat is that storage conditions preserve what you have and cannot improve it.

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

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answered · acceptedhalvard_ness69k478 Jun 2024
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41

This is the tag where the advice is cheapest to follow and most often ignored.

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.

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

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.

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

edited 23 May 2024 by forty_two_c — tightened the wording; no substantive change

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answeredforty_two_c66k5816 May 2024
3Is there a reason to prefer minus eighty here, or is minus twenty genuinely enough? – marta_okonkwo 6 months ago
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29

Answer first: dry, cold, dark and still, with the lot code where you can still read it in a year.

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.

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.

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

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

Equilibrate before opening or you condense water into the cake.

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EL
answeredesben_lykke84k1585 May 2024
Worth adding that residual moisture predicts this better than any printed date. – bac_or_bust 10 months ago
Same experience here, different supplier. – pascal_thibault 8 months ago
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19

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

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.

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

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

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LM
answeredlucia_marchetti19k2728 May 2024
6Aliquoting before the first freeze is the advice I wish I had read two years ago. – esther_vandeVelde 5 months ago
7Adding a vote because this deserves more of them. – ines_brandt 7 months ago
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17

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

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.

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.

Nothing here is medical advice, and research-use compounds are not approved for human use.

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

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MV
answeredmala_venkatesh22k372 Apr 2024
6Thank you — this is the answer I was looking for. – s_bhattacharya 6 months ago
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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.