CMO | Oligonucleotide API Manufacturing

Looking for manufacturing of oligonucleotide & peptide APIs? Find CMOs & CDMOs offering contract manufacturing for oligonucleotides on PharmaCompass.

Q1: What are oligonucleotides and how are they used in therapeutic applications?

Oligonucleotides are small synthetic nucleic acid polymers, typically composed of short sequences of nucleotides (DNA or RNA) ranging from 13 to 25 bases in length, which can be single or double stranded. The manufacturing of oligonucleotide APIs involves creating sequences complementary to target mRNA or DNA strands. Its specific binding capability enables oligonucleotides to target any gene, making them more precise than small molecule drugs.

Oligonucleotide API clinical manufacturing and commercial oligonucleotide API manufacturing are gaining traction in the pharmaceutical industry, covering antisense oligonucleotides, small/short interfering RNA, and microRNA. Contract development and manufacturing organizations (CDMOs) and contract manufacturing organizations (CMOs) play a pivotal role in the production of oligonucleotide APIs, catering to the growing demand for these advanced therapeutic molecules.

An oligonucleotide API manufacturer faces many challenges in the clinical manufacturing of APIs, custom oligonucleotide synthesis and contract manufacturing of oligonucleotide and peptide APIs including stability, cellular uptake, and targeting. These CMOs for oligonucleotides provide end-to-end solutions to overcome these challenges including process development, scale-up, and commercial manufacturing, ensuring regulatory compliance.

Oligonucleotides can be administered through various routes, including intravenous, intravitreal, and intrathecal methods. Muscle-targeted oligonucleotides are injected intravenously to reach muscles affected by genetic diseases, while most antisense oligonucleotide drugs are administered parenterally. However, oligonucleotides are susceptible to nuclease degradation, limiting their half-life.

Oligonucleotides play a crucial role in gene silencing (e.g., antisense oligonucleotide drugs), RNA interference (RNAi), and aptamers used to inhibit protein function, modulating gene expression or protein production in conditions such as cancer, genetic disorders, and viral infections.

Additionally, it shows promise in targeting non-coding RNAs such as microRNAs and long non-coding RNAs, which are emerging as potential therapeutic targets. As this field advances, contract manufacturing of oligonucleotide and peptide APIs may help efficiently for developing innovative treatments across a variety of applications, including antisense oligonucleotide drugs.

Q2: What new technologies or methods are being explored to enhance oligonucleotide API manufacturing?

Oligonucleotides have wide applications in therapeutic, diagnostic, and research fields, driving a strong demand for specialized GMP oligos manufacturers and CMO for oligonucleotides with expertise in oligonucleotide synthesis. Some emerging technologies are revolutionizing oligonucleotide API manufacturing. Advances in solid-phase synthesis and automation are enabling high-throughput production and customized modifications.

Several new technologies and methods are being explored to enhance oligo manufacturing:

Continuous flow systems: Continuous flow systems are emerging as alternatives to traditional batch processes, offering reduced cycle times, improved scalability, minimized waste, and increased product consistency. Efficient linkers and improved resin materials are being explored to boost yield of oligonucleotides, reducing solvent use in oligo manufacturing.

Eco-friendly alternatives: Enzymatic methods in custom oligo synthesis services, such as template-independent polymerase approaches, are emerging as eco-friendly alternatives to chemical synthesis, in cGMP oligonucleotide manufacturing. Green chemistry is driving the development of less toxic solvents for manufacturing of oligonucleotide APIs to lower environmental impact.

Purification enhancement methods: Methods such as multimodal chromatographic resins, combining ion-exchange and size exclusion, enhance purification by minimizing impurities. Oligo API manufacturing increasingly adopts these advanced purification techniques.

Consistency and stability: Lyophilization technology for oligonucleotides is being optimized with improved drying cycle design and automation to enhance product consistency and stability, essential for manufacturing for oligonucleotides. The manufacture of oligonucleotide API in powder-form produced via lyophilization streamlines manufacturing processing by enabling direct sterilizing filtration for fill-finish.

Artificial Intelligence (AI) and Machine Learning (ML): The integration of AI and ML into process monitoring and control systems improves yield prediction, deviation detection, and real-time optimization in oligonucleotide API manufacturing, enabling better real-time decision-making. Novel delivery platforms, conjugation techniques, such as attaching oligonucleotides to peptides or lipids, and advances in nanoparticle-based delivery systems are being enhanced to improve therapeutic efficacy.

These advancements aim to improve the efficiency, scalability, and sustainability of oligonucleotide API manufacturing, addressing both current challenges and future demands in the pharmaceutical industry.

Q3: How do pharmaceutical companies synthesize and manufacture oligonucleotides?

Research scale manufacturing of oligonucleotide APIs by contract manufacturing organizations (CMOs) and contract development and manufacturing organizations (CDMOs) goes through a series of highly specialized steps.

Oligonucleotides are manufactured using solid-phase chemical synthesis which employs phosphoramidite chemistry on a solid support, typically a resin. The manufacture of oligonucleotide API requires sequential addition of nucleotides to a growing chain, starting from the 3' end to create the full-length oligos.

cGMP oligonucleotide manufacturing involves cycles of deprotection, coupling, and capping. The oligonucleotide is cleaved from its solid support, with protecting groups removed from nucleotide bases and the phosphate backbone via chemical treatments. The manufacture of oligonucleotide APIs also requires purification and isolation. Some of the impurities that may arise are depurination during detritylation, nucleoside base loss, strand breakage, or depyrimidination due to improper reagent use.

In cGMP oligonucleotide manufacturing, large-scale purification often employs tangential flow filtration. Single-stranded oligonucleotides are concentrated, desalted, and lyophilized into powder; duplex strands are similarly processed, annealed, then lyophilized.

Storage is another major step in synthesis and manufacturing of oligonucleotides. Companies ensure cold-chain logistics for temperature-sensitive oligonucleotides, which are typically stable in solution at 2°C–8°C with neutral pH.

Stability considerations throughout the oligo API manufacturing process, include room temperature exposure and time out of refrigeration. Oligonucleotide APIs are commonly supplied and stored as powders, with equipment selected according to batch size.

CDMOs offering oligonucleotide manufacturing services ensure scalability of oligonucleotide APIs while maintaining product quality through robust process development, advanced manufacturing technologies, and strict adherence to GMP. Oligo CDMO companies offering custom oligonucleotide synthesis optimize synthesis and purification processes, employ scalable solid-phase synthesis systems, and utilize high-throughput purification techniques like preparative HPLC to maintain yield and purity at larger volumes.

Q4: Which are the leading pharmaceutical CDMOs and CMOs offering oligonucleotides contract services?

There are various CMOs and CDMOs that may provide contract manufacturing for oligonucleotides, clinical manufacturing of APIs and custom oligonucleotide synthesis services for the pharma industry. Both oligo CDMOs and CMOs ensure regulatory compliance and high-quality standards, driving innovation in oligonucleotide API contract manufacturing.

Contract development and manufacturing organizations may also assist in scaling up the oligonucleotide manufacturing process from the lab to industrial scale, focusing on optimizing conditions and integrating it into existing oligonucleotide API clinical manufacturing workflows. GMP oligos manufacturers serve specialized contract services such as oligonucleotide contract manufacturing and custom nucleic acid production.

Some of the leading pharmaceutical CMOs offering oligonucleotide manufacturing services are: -

Anhui Ribobay Pharmaceutical: Oligonucleotide manufacturing services

Anhui Ribobay Pharmaceutical has expertise in oligonucleotides including siRNA, miRNAs, aptamers, oligonucleotides CXOs, and antisense oligonucleotide custom synthesis. Ribobay is a contract research, development, and manufacturing organization (CRDMO) offering oligonucleotide API clinical manufacturing, GMP-grade oligonucleotide API contract manufacturing and commercial oligonucleotide API manufacturing services across all stages of drug development, from drug screening to commercialization of oligonucleotide APIs.

EUROAPI: Oligonucleotide API contract manufacturing

EUROAPI provides CDMO services for active pharmaceutical ingredients. It provides contract manufacturing for oligonucleotides for different classes of Tides using solid-phase chemistry. It is a CDMO for oligonucleotide API contract manufacturing, clinical manufacturing of APIs and commercialization of oligonucleotide APIs offering a full array of development activities for Tides including oligonucleotides and peptides.

Bachem: CMO for oligonucleotides

Bachem specializes in the development and cGMP manufacturing of peptides and oligonucleotides. Bachem has extensive experience in the contract development and contract manufacturing of oligonucleotide and peptide APIs. It is a CMO for oligonucleotides that along with oligo API manufacturing also offers amino acids, complex organic molecules, and biologically active pharmaceutical ingredients.

Aurigene Pharmaceutical Services: Oligonucleotide API contract manufacturing

Aurigene is a CMO for oligonucleotides in accelerating drug innovation through discovery, development and oligonucleotide API clinical manufacturing. It provides custom oligo manufacturing, contract manufacturing for oligonucleotides and the manufacturing of all classes of carbohydrates such as monosaccharides, polysaccharides, pentasaccharides, and iminosugars. It offers cGMP manufacturing of complex multi-step carbohydrates for commercial scales, oligonucleotide API custom synthesis and commercialization of oligonucleotide APIs.

Porton Pharma Solutions: CDMO for oligonucleotides

Porton Pharma Solutions offers Tides CDMO services and is involved in the oligonucleotide contract manufacturing and custom oligo synthesis services. Its oligos include antisense oligonucleotide custom synthesis, siRNA, miRNA, aptamer, sgRNA, and oligo modifications. As a GMP oligos manufacturer, it offers oligonucleotide manufacturing, which includes a range of custom oligos and custom DNA oligos.

Nippon Shokubai: Oligonucleotide API custom synthesis

Nippon Shokubai is an oligo CDMO that offers a range of contract services including oligonucleotide contract manufacturing, oligonucleotide API clinical manufacturing and peptide API manufacturing. It provides RNA custom oligo synthesis services, custom DNA oligos, API oligos, DNA and RNA oligonucleotides, oligonucleotide cGMP manufacturing, and supply.

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