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Oligonucleotide Stability Studies

Stability study design, analytical testing and reporting support for oligonucleotide development programs.

45+ Years of Expertise ISO 9001:2015 / ISO 13485:2016 Bench to Kilo Scale Confidential & IP-Protected U.S.A Facilities - Texas

Overview

ICH Q1A(R2)-aligned stability programs for DNA, RNA, ASO, siRNA and sgRNA can include accelerated, intermediate and long-term studies, stress testing, photostability, freeze-thaw and sodium content trending.

Bio-Synthesis designs and executes oligonucleotide stability studies for DNA/RNA, ASO, siRNA and sgRNA programs. Studies can include accelerated, intermediate and long-term storage, with photostability, freeze-thaw and stress conditions added when needed.

Pull schedules and testing attributes are tailored to formulation, storage conditions, intended use and target shelf life. Stability-indicating methods can track purity, impurities, identity, residuals, sodium content and general attributes across each pull.

Study design can be configured for RUO, GLP, diagnostic, ISO13485 or cGMP-oriented workflows depending on documentation requirements and program stage.

Stability Study Scope

Study Coverage

A compact view of the major stability study components Bio-Synthesis can configure for oligonucleotide lots.

Study Conditions

Accelerated, intermediate, long-term, photostability, freeze-thaw and stress studies.

Pull Management
Custom pull points, aliquoting strategy, chain-of-custody and environmental monitoring.
Stability-Indicating Methods

HPLC, CE, IEX, LC-MS identity, residuals, elemental impurities and general attributes.

Reporting

Protocols, chromatograms, spectra, trend tables, plots, interim summaries and final reports.

Stability Studies at a Glance

Quick View

A practical view of study timelines, methods and deliverables.

01
ICH Q1A(R2)-Aligned Programs Designed around accelerated, intermediate and long-term stability conditions.
02
Custom Pull Schedules Typical 0, 1, 3, 6, 12 and 24 month pulls, customizable per protocol.
03
Sodium Content Trending Optional IC or flame photometry trending across selected pulls.
04
Audit-Ready Reports Includes data summaries, trend tables, chromatograms, spectra and final stability report.

Study Types

Core Stability

Accelerated, Intermediate & Long-Term

Typical programs include 40 °C / 75% RH accelerated, 30 °C / 65% RH intermediate and 5-25 °C long-term storage conditions, adjusted to the formulation and intended use.

Handling Stress

Freeze-Thaw & Shipping Conditions

Freeze-thaw cycling, temperature excursions and shipping-condition studies help assess handling robustness for liquid, lyophilized or buffered oligo formats.

Forced Stress

Photostability, pH, Heat & Nuclease Stress

Stress studies can help identify degradation pathways and support stability-indicating method development for sensitive RNA, ASO, siRNA or conjugated oligos.

Example Conditions & Pull Schedule

Condition 0M 1M 3M 6M 12M 24M Sodium Trending
Accelerated (40 °C / 75% RH) Yes
Intermediate (30 °C / 65% RH) Optional
Long-Term (5-25 °C) Optional
Photostability Optional
Freeze-Thaw Optional

Note: ✓ = typical pull point. Additional pulls can be defined as needed. Sodium content can be trended by ion chromatography or flame photometry and reported at selected pulls.

Stability-Indicating Methods

Stability-indicating methods track degradation, impurity growth, identity, moisture, residuals and formulation-related attributes over time.

Testing Category Methods Purpose
Identity LC-MS (ESI), MALDI-TOF, optional enzymatic digest mapping Confirm intact mass and identify sequence or conjugate changes across pulls.
Purity / Impurities RP-HPLC, IP-RP-HPLC, CE, IEX for charge variants Track full-length product, shortmers, depurination, conjugate loss and impurity growth.
Residuals / Elements GC residual solvents, ICP-MS elemental impurities Assess residual solvents and elemental impurities when required by study scope.
Sodium Content Ion chromatography or flame photometry Trend sodium or salt content across pulls when counter-ion consistency is important.
General Attributes Karl Fischer water, pH, appearance, osmolality, endotoxin or bioburden as required Support formulation, storage and handling conclusions.

Sample Requirements & Study Setup

The study plan should define sample amount, storage format, pull points, testing attributes and chain-of-custody before study start.

Sample Requirements

Material & Format

  • Typical minimum per condition and pull: ≥200 µg, method dependent
  • Dry, lyophilized, buffered or formulation-specific formats
  • Include sequence length, chemistry, purification, concentration and storage conditions
  • Ambient shipping for DNA; cold chain recommended for RNA, ASO or sensitive constructs

Study Setup

Pulls, Storage & Monitoring

  • Custom pull points such as 0, 1, 2, 3, 6, 12 and 24 months
  • Aliquoting strategy to minimize freeze-thaw events
  • Chain-of-custody, storage labeling and environmental monitoring
  • Interim data summaries and final reporting plan

Data & Deliverables

Deliverables can be scaled from focused interim data tables to complete stability-summary packages for audit-ready workflows.

Study Protocol

  • Study design and storage conditions
  • Pull schedule and testing attributes
  • Sample handling and aliquoting plan
  • Acceptance criteria where applicable

Analytical Data Package

  • Chromatograms and spectra
  • Impurity profiles and identity data
  • Sodium, purity and general attribute trends
  • Interim data tables and plots

Final Stability Report

  • Study summary and conclusions
  • Trend interpretation
  • Deviation notes when applicable
  • Audit-ready documentation support
Custom attributes: Additional attributes such as buffer ions, counter-ions, conjugate ratio, excipient compatibility or delivery-format changes can be added to the study plan.

FAQ

What stability study types are available?
Accelerated, intermediate, long-term, photostability, freeze-thaw and stress studies can be configured for DNA, RNA, ASO, siRNA, sgRNA and modified oligonucleotides.
What pull schedule do you recommend?
Typical pulls include 0, 1, 3, 6, 12 and 24 months, but the final schedule depends on formulation, storage conditions, intended use and target shelf life.
Which stability-indicating methods are used?
Methods may include HPLC, CE, IEX, LC-MS, MALDI, GC, ICP-MS, Karl Fischer water, pH, appearance, osmolality, endotoxin or bioburden depending on scope.
Can sodium content be trended?
Yes. Sodium content can be trended using ion chromatography or flame photometry and reported alongside purity, impurity and general attribute trends.
How much sample is needed?
 A typical minimum is ≥200 µg per condition and pull, but more material may be needed for broad analytical panels, microbial testing or extended pull schedules.
What deliverables are provided?
 Deliverables may include the study protocol, finalized pull schedule, chromatograms, spectra, trend tables, plots, interim summaries and final stability report.

Need an Oligonucleotide Stability Study Plan?

Share your formulation, oligo modality, storage conditions, target shelf life, pull schedule expectations and required testing attributes. Our team can design a fit-for-purpose stability protocol with analytical and reporting deliverables.

Related Services

Connect stability studies with release QC, analytical method development, process development and oligo synthesis.

Fast Quote Checklist

Include modality, sequence or length, chemistry, formulation, storage condition, target shelf life, pull schedule and required test attributes.

Why Choose Bio-Synthesis

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