ICH stability studies, photostability, forced degradation and beyond-use date studies for drug products, APIs, peptides and compounded preparations
A stability program shows how the strength, purity and quality of a drug product or API change over time under temperature, humidity and light, and gives you the data to set an expiration date, a retest date or a beyond-use date. We store samples at ICH conditions, pull them on a schedule, and test them with stability-indicating methods. When a new peak shows up, we can identify it by high-resolution LC-MS here in the same lab instead of sending it out.
Studies are quoted to your protocol.
Long-term, intermediate and accelerated storage with testing at each pull. Storage only is also available.
Exposure to the ICH Q1B dose of at least 1.2 million lux hours of visible light and 200 watt hours per square meter of near-UV, with dark controls.
Acid, base, oxidation, heat, humidity and light stress to find out how your molecule breaks down and to prove a method can see it.
HPLC methods developed or adapted for your product, with forced degradation to show specificity, and validation or verification to ICH Q2.
Unknown peaks identified by Orbitrap high-resolution LC-MS and confirmed by LC-MS/MS.
Stability studies for compounding pharmacies and outsourcing facilities that want to extend BUDs under USP 795 and 797.
| Study | Condition | Usual length | Usual pulls |
|---|---|---|---|
| Long-term | 25 C / 60% RH (or 30 C / 65% RH) | 12 months or more | 0, 3, 6, 9, 12, 18, 24, 36 months |
| Intermediate | 30 C / 65% RH | 12 months | 0, 6, 9, 12 months |
| Accelerated | 40 C / 75% RH | 6 months | 0, 3, 6 months |
| Refrigerated product | 5 C long-term, 25 C / 60% RH accelerated | 12 months / 6 months | as above |
| Frozen product | -20 C | case by case | case by case |
Intermediate storage is usually only needed when the accelerated samples show a significant change, such as a 5% loss of assay or a degradant over its limit. Custom conditions, freeze-thaw cycling and in-use studies for multi-dose or reconstituted products can be set up on request.
Every program is built around your specification, but most pulls include:
A stability study is only as good as the method behind it. If a degradant co-elutes with the main peak, the assay looks fine while the product is breaking down. Forced degradation stresses the drug substance and product with acid, base, peroxide, heat, humidity and light until roughly 5 to 20 percent has broken down, then checks that the method separates every product of that breakdown from the active and from each other. We use diode-array peak purity on the HPLC and mass spectrometry to confirm that nothing is hiding under the main peak.
Monograph methods often aren’t stability-indicating for a specific formulation. We can develop a new method, adapt a compendial one, or verify a method you already have, and validate it for specificity, accuracy, precision, linearity, range and robustness.
Peptides break down in ways small molecules don’t: oxidation, deamidation, aggregation, truncation and loss on container surfaces. Semaglutide, tirzepatide and similar peptides also have degradants that sit very close to the main peak and are hard to separate. We test peptide purity and identity every day, and we can follow lyophilized and reconstituted peptides over time and identify what forms with intact mass and peptide mapping on the Orbitrap. See peptide testing.
USP 795 and 797 give default beyond-use dates that are often shorter than a preparation really lasts. A stability study on your formulation, in your container, with a stability-indicating method, is how you support a longer date. A typical design tests potency and degradants at day 0, 30, 60, 90 and 180, with container closure integrity, particulates for sterile products, sterility and endotoxin at selected points, and preservative efficacy for multi-dose containers. We’ll help you set the design before you send samples.
You get a report at each pull with results against your specification and any trends, and a final report with all of the data and the shelf life or beyond-use date it supports, from the laboratory director. If a result is out of specification or out of trend, we tell you right away and investigate before reporting.
Tell us the product, the dosage form, the container, the markets and the date you need to support.
We write or review the protocol: conditions, pulls, tests, methods and acceptance criteria.
If you don’t have a stability-indicating method, we develop or verify one with forced degradation.
You send the lots, we test the starting values and place them in storage.
Samples are pulled and tested on schedule, with a report each time.
All the data and the date it supports.
It depends on where the product will be sold and how it’s stored. Most US products use 25 C / 60% RH long-term and 40 C / 75% RH accelerated. Refrigerated products use 5 C long-term and 25 C / 60% RH accelerated.
ICH calls for three batches for a registration program. For development work, a compounded preparation or an early product, one or two lots is common. We’ll help you decide.
It can support a provisional date, but long-term data at the labeled storage condition is what confirms it.
Yes. Without one, a breakdown product can hide under the main peak and the assay looks fine. Forced degradation is how a method is shown to be stability-indicating.
Verifying an existing method usually takes a few weeks. Developing and fully validating a new method takes longer and depends on the molecule. We give you a timeline with the quote.
Usually assay, related substances, appearance and water, plus the tests your dosage form needs. Not every test has to be done at every pull, and we can help you set a reduced schedule.
Enough for every test at every pull, plus extras for repeats. We calculate the exact number from the protocol.
Yes. We identify unknown peaks by high-resolution LC-MS and confirm them by LC-MS/MS.
Yes. A study on your formulation and container, with a stability-indicating method, is the way to support a BUD longer than the USP default.
Yes. We can store samples at the conditions in your protocol and ship pulls back to you.
Usually about 10 business days after the pull.
Yes, to the ICH Q1B dose, on the drug substance, the exposed product and the product in its package, with dark controls.
Tell us about your product and we’ll send back a quote. You can also email [email protected].
