Bring your oligonucleotide-based therapeutics to the clinic
Oligonucleotides are single- or double-stranded DNA or RNA molecules classified according to their mode of action, including antisense oligonucleotides, RNA interference, aptamers, mRNA and pDNA. The oligonucleotide-based therapeutic industry continues to grow due to increasing regulatory approvals of this novel and emerging class of compounds. Improvements in medicinal chemistry have led to the development of effective, targeted, next-generation drugs and vaccines modulating the expression or function of proteins associated with rare, chronic and emerging diseases, such as COVID-19.
These highly chemically modified oligonucleotides, improving both efficacy and resistance to nucleases, come with additional analytical challenges. Eurofins CDMO has a proven track record of formulation and analytical services, drug product manufacturing, release testing and stability studies of this type of therapeutics in the clinical stage. We offer support to have a complete understanding of product quality and stability during your drug development process.
Formulating your oligonucleotide-based therapeutic
Parenteral administration is often the route of choice for delivering oligonucleotide-based therapeutics. The oligonucleotide-based drug is first screened for its stability and compatibility in liquid form using dedicated chromatographic methods. For an increase in stability or prolongation of shelf-life, Eurofins CDMO also offers the development into freeze-dried drug products. Here, the focus is divided between finding an optimal formulation to reach a stable lyophilized cake and optimizing the lyophilization cycle to an economically favorable process.
Deliver with Lipid nanoparticles
Lipid nanoparticles showed one of the steepest interest increases in the last decades. Eurofins CDMO can be your partner to optimize your lipid nanoparticle formulation of mRNA, siRNA or pDNA. Do not only get to know the stability of your incorporated oligonucleotide but monitor the lipid LNP composition in your formulation with our state-of-the-art analytics including High Resolution Mass Spectrometry.
Accelerate your drug program with state-of-the-art analytics
The diverse nature of oligonucleotide therapeutics, modified with new chemical moieties, increases the complexity of impurity profiling which presents new analytical challenges.
Developing and manufacturing oligonucleotide-based therapeutics requires identification and quantification of both process related impurities, such as n-1 shortmers, and product related impurities, e.g., oxidation, deamination and depurination. To monitor these different critical quality attributes multiple separation methods or detection systems are required. Our chromatography and mass spectrometry capabilities enable to characterize and quantify components of your drug product accelerating your drug program in accordance with regulatory guidelines and expectations.
Eurofins CDMO offers characterization techniques based on:
- Ion-pairing reversed-phase (IP-RP) to confirm identity and measure purity
- Anion exchange (AEX) for charge-based separation and new selectivity, including pDNA isoform separation
- Hydrophilic interaction chromatography (HILIC) as emerging alternative
- Size exclusion chromatography (SEC) for characterization of oligonucleotide duplexes in their native state
- Two-dimensional liquid chromatography (2D-LC) to enhance separation capabilities and improve peak capacity
- High-resolution mass spectrometry (HRMS) coupled to LC for supporting advanced purity/impurity and identity determination
- Coulometric Karl Fisher (cKF) titration for water content determination in lyophilized oligonucleotide-based therapeutics
Our integrated analytical support
Our analytical services include method development, subsequent method qualification and validation according to ICH guidelines, drug product release testing, and stability studies:
- Forced degradation studies (e.g., humidity, temperature, pH, oxidation)
- Photostability studies
- In-use stability studies
- Accelerated Stability Assessment Program (ASAP) studies for drug product prototype ranking and shelf-life predictions
- ICH stability studies and testing
Your oligonucleotide-based drug in GMP
Clinical manufacturing of your developed formulation is the next step in which Eurofins CDMO can support you. Our expertise in upscaling and transfer to a GMP environment is a plus for your project. Eurofins CDMO is capable of producing both sterile and non-sterile drug products with all required analytics in-house. Learn more about our sterile fill-and-finish facility.