Plant and Equipment
Method Development
Analytical Method Qualification / Validation
Process Validation
Cleaning Validation
Continuous Verification
Method development and qualification are vital to the oligo API manufacturing process. Robust, qualified methods developed at the beginning of your program can save you time and money in the long-run. The experts at Agilent can transfer, develop, qualify and validate analytical methods from IND to NDA. We specialize in stability indicating methods for aptamers, conjugates and other complex nucleic acids.
Extensive experience in oligonucleotide separations using all HPLC, IC and GC techniques- World class spectroscopy including LC-MS / MS-MS and ICP-MS provide product understanding and process troubleshooting
We pride ourselves on finding solutions to difficult analytical problems such as positive identification of impurities and quantitative mass spectrometry for critical impurities. Customers are encouraged to be involved to whatever extent they want in the development and qualification/validation process.
We have a system of continuing improvement by looking at new technologies and new techniques in order improve the analytical methods and the quality of data generated.
Method Development
Method development is performed under Standard Operating Procedures (SOP) with emphasis on complete documentation of the development process. Agilent’s extensive array of analytical capabilities along with best in industry personnel allows for development of the simple to extremely difficult or complex methodology.
Complete method development services are offered for materials used at all stages in a manufacturing or development process, from raw materials to finished API and drug product formulations. Agilent’s in house small scale capability is utilized to produce reference materials necessary for complete method development.
Analytical Method Qualification / Validation
Compound specific methods are extensively developed to meet the criteria of a “scientifically sound” method for use in early stage research activities. Method qualification is offered to support intermediate stage clinical programs. For later stage clinical programs, generally Phase IIb and beyond, full method validation performed according to ICH Q2 guidance is offered. Qualification and/or validation activities can be custom designed to meet specific client or country requirements.
At Agilent, analytical methods are developed, qualified and validated for the following:
o Raw Materials
o In-process Testing
o Release Testing
o Stability Testing
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HPLC Chromatographic Techniques |
Standard Reverse Phase HPLC
Ion-Pair Reverse Phase HPLC
Ion Exchange HPLC
Normal Phase HPLC
Ion Chromatography (IC)
Size Exclusion (SEC) / Gel Permeation (GPC) HPLC
High Speed/High Pressure Reverse Phase and Ion-Pair HPLC (UHPLC) |
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Standard HPLC Detection Capabilities
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Single and Multi Wavelength UV
Photo Diode Array (DAD/PDA)
Evaporative Light Scattering (ELSD)
Fluorescence
Refractive Index (RI)
Multi Angle Light Scattering (MALS) |
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HPLC Mass Spectrometry
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Ion Trap
Single Quadrupole
Quadrupole Time of Flight –Standard Resolution
Quadrupole Time of Flight –High Resolution
Time of Flight |
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Gas Chromatography (GC) |
Capillary GC
Direct Injection
Static Headspace Injection |
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Transition Melt Analysis (TM) |
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Volumetric Karl Fischer Water Determination |
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Coulometric Water Determination |
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Osmolality |
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Endotoxin Analysis |
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Total Organic Carbon Analysis (TOC) |
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Fourier Transfer Infrared Spectroscopy (FTIR) |
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Nuclear Magnetic Resonance (NMR) |
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Ultra Violet Spectroscopy (UV) |
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Metals Analysis |
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Viscosity Determination |
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Auto Titration |
Plant and Equipment
Our facility and equipment have been validated to comply with current Good Manufacturing Practices (GMP) per Q7 International Conference on Harmonization (ICH) qualification guidelines.
Process Validation
Our manufacturing processes are validated using a life cycle approach to validation. During development and process design, the critical quality and processing parameters are established and the process control strategy is determined. These strategies and parameters are used to scale the process at which the process validation will be performed. After validation, the critical quality and process parameters are continually monitored for trends or variability. Any changes to validated processes are managed through change control.
Continuous Verification (CV)
CV is a systematic, science and risk-based approach to verify and demonstrate that a process operates in a way, such that it consistently produces material that meets the predetermined specifications, both at the time of commercial release and throughout the lifetime of the commercial production process. 1 Agilent utilizes CV in our commercial scale manufacturing (Phase III Clinical Trial and Commercial Material). Utilizing this system provides our clients with the peace of mind that comes from knowing that the manufacturing process is constantly monitored and remains in control. The system also facilitates continual improvement.
1 Kettlewell, et al, Pharmaceutical Engineering, January/February 2011 (18-26)
Cleaning Validation
Each oligonucleotide manufactured is unique; therefore, cleaning verification is performed on each piece of equipment until the cleaning process has been validated for each Oligonucleotide manufactured. The cleaned equipment is sampled for oligonucleotide residues, bioburden and endotoxin.