Oligo API GMP Manufacturing from Grams to KiloGrams 

Team Experience
Supply Chain
Freedom to Operate

Agilent has a state-of-the-art facility built specifically to serve the oligo API needs of our customers.  We aren’t distracted by small molecule or biologics development programs; each and every one of our employees are dedicated and focused on being the nucleic acid expert you need for your oligo API program.   

Our 41,000 square foot facility offers total capacity in the hundreds of kilograms per annum with multiple GMP suites providing flexibility and scale from grams to kilograms. Our global customer base spans the Pharmaceutical and Biotechnology sectors.  We have manufactured over 400 batches at production scale with experience in all types of oligonucleotide classes including siRNA, miRNA, aptamers, antisense & immunostimulatory.

Manufacturing capabilities include eleven independent suites that create four separate synthesis/purification trains and two lyophilization units:

• Enables separate simultaneous production of multiple compounds
• Class 100,000/ISO 8 synthesis and purification areas
• Class 10,000/ISO 7 lyophilization and packaging areas

Agilent’s core strengths to support your project include:

• High yielding oligonucleotide process
• Experience in manufacturing of all types of oligo API molecules
• Analytical know-how, innovative analysis  techniques, and leading edge instrumentation
• Process innovations
• Product-focused process optimization
• Design of Experiments (DOE) and Proven Acceptable Ranges (PAR) expertise
• Robust GMP quality systems
• In-house stability for API and drug product
• Global raw material supply chain networks

Early Stage Development - Small to Intermediate Scale Manufacturing

The small to mid-scale manufacturing area is designed to produce multiple APIs simultaneously under GMP.  The facility is comprised of three manufacturing suites, covering the complete manufacturing process from synthesis to purification.  This design helps prevent the chance of cross-contamination.   

• Three GE AKTA OligoPilot 400s Three preparative HPLC purification skids with feedback controlled buffer delivery 

Late Stage Development - Commercial Kilogram Manufacturing

The large or commercial scale manufacturing area is the result of an expansion project undertaken in 2008 to meet the needs of our current and future partners. This enables Agilent to provide 100’s of kilograms of oligo API annually for late stage clinical trials and commercial launch. This increase in scale will drive efficiency and cost savings into the future.  

•  GE OligoProcess synthesizer capable of batch sizes up to 1 mol
•  30 liters per minute high capacity HPLC
•  UF with greater than 160 square feet of membrane capacity
•  Lyophilization capacity of up to 10 kilos of oligo API / drying lot
•  Integrated solvent and reagent delivery system

Experienced team
The Agilent team has decades of combined experience in nucleic acid therapeutic manufacturing, employing process technologies that enable efficient manufacture of a broad range of nucleic acids.  This experience allows Agilent to generate novel approaches to developing, processing and analyzing complex compounds, including:

• Long-mers
• Hairpin RNAs
• Ratioed duplexes
• Complex conjugates
• Oligos comprised of specialty monomers

The team has expertise in all classes of therapeutics including siRNA, miRNA, aptamers, antisense and immunostimulatory.

Supply Chain
Agilent has been involved in nucleic acids chemistry since 2000 and has been manufacturing oligonucleotide APIs at the Boulder location since 2003.  Agilent has developed a strong understanding of oligonucleotide supply side market dynamics and the sourcing risks associated with the critical raw materials.

With this knowledge, a reliable supplier network for amidites and other key raw ingredients has been established.  These suppliers are capable of satisfying Agilent’s demand for raw materials to support multiple kilogram scale manufacturing of oligonucleotide based APIs.

Long term, Agilent has a sourcing strategy based on supplier diversity designed to mitigate supply chain risk, improve quality and consistency, encourage competition and reduce raw material costs. This strategy incorporates three main elements: amidite or amidite intermediate sourcing from low cost manufacturing countries, implementation of long term manufacturing and supply agreements, and partnership for certain critical raw materials.

Supply chain security is a business critical item. Agilent has a full time supply chain manger overseeing strategic supply, materials management and procurement. By policy, Agilent has multiple vendors for each critical raw material used in its processes.  Agilent presently has multiple audited and approved phosphoramidite & ACN suppliers. 

For critical raw materials, we operate under supply agreements with a change control policy that assures notification is made to Agilent of site, process or critical raw material changes. Other ancillary reagents, processing aids and consumables, wherever possible, are secured from multiple suppliers as per Agilent procurement policies.

Freedom to Operate (FTO)
Agilent warrants that it directly owns or has access through license to all the IP needed to develop and manufacture its client’s oligonucleotide APIs and that it has all the necessary licenses, permits, and regulatory/governmental approvals to manufacture clinical and commercial APIs

 Agilent policy states that it will not knowingly infringe third party IP.  Agilent determines which IP to use and communicates its FTO position to clients.  Cost to procure and maintain any licenses is born by Agilent.  Finally, Agilent indemnifies clients in respect to any claim, loss, damage, or other liabilities.  Provisions in our Supply and Service Agreements (SSA) extensively detail Agilent’s FTO.