|
|
|
Pharmadite® for Pharmaceutical Applications |
 |
Proligo® Reagents |
|
|
| |
|
| Product Breadth of Proligo Reagents |
|
|
|
|
| Product Breadth of Proligo Reagents |
|
The Pharmadite product line represents a new class of standard protected DNA and RNA phosphoramidites designed with highly controlled impurity profiles and exceptional overall purity.
Pharmadite products fulfill all the requirements of starting materials for the manufacture of active pharmaceutical ingredients as defined in the EMEA 'Note for guidance on chemistry of the new active substance'*, making them suitable building blocks for oligonucleotide drugs. |
|
|
Pharmadite amidites are manufactured in
scales of up to multi-hundred kilos, under certified ISO 9001 quality systems at SAFC Supply Solutions manufacturing facility in Hamburg, Germany.
We start with traceable, non-animal and very pure raw materials, use highly controlled synthesis and purification processes, validated analytical methods and cleaning processes, all governed with strict change control and documentation to yield unprecedented high quality products with purity ratings at 99.5% or higher for DNA and 99.0% or higher for RNA.
All remaining impurities, if present, are identified and characterized at a level of 0.1%.
The high level of control and documentation imposed at every step of the production process support regulatory requirements to make Pharmadite amidites ideal for pharmaceutical applications.
|
| Key Features of Pharmadite |
Benefits |
| |
Consistent quality |
|
Reproducible oligonucleotide synthesis |
| |
Suitability as starting material for API manufacture |
|
Accordance with regulatory guidelines |
|
- Raw material control and traceability |
|
|
|
- Process control |
|
|
|
- Validated analytical methods |
|
|
|
- Tight specifications |
|
|
|
- Known impurity profiles |
|
|
| |
Very high purity |
|
High production efficiency |
| |
Non-animal origin of starting materials |
|
TSE safety |
| |
Available in large scale |
|
Secure supply |
| |
Supply through our worldwide supply chain |
|
Long-term reliability |
Manufacturing
Pharmadite amidites are prepared from DMT-protected nucleosides and the phosphitylating agent "bis-amidite." To ensure the highest quality our production process begins with starting materials that possess stringent specifications and defined impurity profiles. The crude phosphoramidites are then purified by preparative HPLC, dried and packaged. Our HPLC production line is cleaned using validated cleaning methods and cleaning verification is performed prior to each batch. Reactions are conducted at a minimum synthesis scale of 50 kg per batch. Each processing step is monitored using analytical in-process controls, including HPLC.
Specifications
Pharmadite amidites are characterized by their exceptional purity and well-defined impurity profile. In particular, they are essentially free from contaminants which interfere in coupling reactions, such as other nucleosidic or non-nucleosidic phosphoramidites (P(III)-contaminants).
| DNA Pharmadites Characteristics |
Acceptance Limit |
| Appearance |
white to off white powder or granules |
| Appearance of Solution |
≤ 10 Hazen (c = 0.2M in ACN) |
| Solubility |
clear solution (c = 0.2M in ACN) |
| HPLC Identification |
conforms |
| HPLC Purity |
≥ 99.5 % area |
| Single Specified Impurity |
(see impurities table for referece below) |
| Single Unspecified Impurity |
≤ 0.1 % area |
| 31P NMR Purity |
≥ 99.5 % area |
| 31P NMR P(III) Impurities (@ 100 to 169 ppm) |
≤ 0.1 % area |
| 31P NMR P(V) Impurities (@ -25 to 99 ppm) |
≤ 0.5 % area |
| 31P NMR ≥170 ppm Impurities (@ 170 to 225 ppm) |
not detected: S/N < 2.5 |
| Residual Solvent Content |
≤ 3.0 % wt |
| Water Content |
≤ 0.40 % wt |
| Origin of Nucleoside |
non animal origin |
| RNA Pharmadites Characteristics |
Acceptance Limit |
| Appearance |
white to off white powder or granules |
| Appearance of Solution |
≤ 10 Hazen (c = 0.2M in ACN) |
| Solubility |
clear solution (c = 0.2M in ACN) |
| HPLC Identification |
conforms |
| HPLC Purity |
≥ 99.0 % area |
| Single Specified Impurity |
(see impurities table for referece below) |
| Single Unspecified Impurity |
≤ 0.1 % area |
| 31P NMR Purity |
≥ 99.0 % area |
| 31P NMR P(III) Impurities (@ 100 to 169 ppm) |
≤ 0.3 % area |
| 31P NMR P(V) Impurities (@ -25 to 99 ppm) |
≤ 1.0 % area |
| 31P NMR ≥170 ppm Impurities (@ 170 to 225 ppm) |
not detected |
| Residual Solvent Content |
≤ 3.0 (w/w) |
| Water Content |
≤ 0.40 (w/w) |
| Origin of Nucleoside |
non-animal origin |
All remaining impurities in Pharmadite amidites, if present, are identified, characterized and quantified. The impact of any such defined impurities on the synthesis of oligonucleotides is well understood and has been shown to be insignificant.
| Specified Impurities of DNA Pharmadites |
A |
C |
G |
T |
| DMT-dNucleoside-cyanoethyl-H-phosphonate |
≤ 0.3% |
≤ 0.3% |
≤ 0.3% |
≤ 0.3% |
| DMT-dNucleoside phosphoramidate |
≤ 0.3% |
≤ 0.3% |
≤ 0.3% |
≤ 0.3% |
| DMT-dNucleoside-diisopropylamino-H-phosphonate |
not
specified |
not specified |
≤ 0.3% |
not
specified |
| 03'-Benzoyl-O5'-DMT-dC(bz) |
not applicable |
≤ 0.3% |
not applicable |
not applicable |
| Specified Impurities of RNA Pharmadites |
A |
C |
G |
T |
| 2'O-Amidite-3'O-TBDMS-5'O-DMT-rNucleoside |
≤ 0.3% |
≤ 0.3% |
≤ 0.3% |
≤ 0.3% |
| DMT-rNucleoside TBDMS |
≤ 1.0% |
≤ 1.0% |
≤ 1.0% |
≤ 1.0% |
| DMT-rNucleoside TBDMS-cyanoethyl-H-phosphonate |
≤ 1.0% |
≤ 1.0% |
≤ 1.0% |
≤ 1.0% |
| DMT-rNucleoside TBDMS-phosphoramidate |
≤ 1.0% |
≤ 1.0% |
≤ 1.0% |
≤ 1.0% |
Quality system and production process designed to meet pharmaceutical standards.
Control of starting materials and production process is a key factor in the synthesis procedure of RNA Pharmadite. The phosphitylating reagent is controlled at a level of 0.1% P(III)- impurities. RNA Pharmadite amidites are purified by preparative HPLC in a highly automated purification plant.
Having been ISO 9001 certified since 1993, Proligo Reagents' production facility in Hamburg, Germany (GE) guarantees a reproducible quality, a predictable and controlled production:
- Robust process parameters
- In-process controls with specifications
- Batch integrity
- Change control
- Batch record review
- Process database and trend analysis
- Validated cleaning procedures
|
*EMEA: European Medicines Agency, www.emea.eu.int |
SAFC and SAFC Proligo Reagents are trademarks of Sigma-Aldrich Biotechnology, LP.
©2007 Sigma-Aldrich Biotechnology LP. All rights reserved. Reproduction forbidden without permission.
Other trademarks are the property of their respective owners.
To order or speak with a Customer Service Representative, contact your local SAFC office. |
|
|
|
|
|
){kind=link}
){kind=link}
){kind=link}
){kind=link}
