We can help you with stability testing programs for drug substances and drug products that meet the requirements of the ICH Guidelines Q1A-F and Q5C.

We compile stability protocols containing the stability specifications and the chosen methods, justified as stability indicating. Each stability study is specifically designed to your project needs with analyses of those attributes that are susceptible to change during storage. Prior to stability testing it might be necessary to establish the stability indicating capacity of some methods. We can support your project with a range of stability indicating methods that enables us to perform complete studies under long-term, intermediate and accelerated conditions.

Our stability testing services include:

• Initial testing of stability indicating methods
• Long-term, intermediate and accelerated stability studies
• Forced degradation studies
• Freeze-thaw stability studies
• Photostability testing
• Shipment simulation studies

PROCESS INTERMEDIATES

Intermediate substances, created during the manufacturing of drug substances, may not be immediately processed. In these cases stability testing may be required. For example, the stability of inclusion bodies has to be demonstrated from isolation to downstream processing.

STORAGE

We can offer you a wide range of storage conditions according to ICH Guideline Q1A or any custom requirement:

25 °C at 60% RH
30 °C at 65% RH
40 °C at 75% RH
2-8 °C
-20 °C
-80 °C

The cooling devices and climatic exposure cabinets are equipped with data loggers permanently recording temperature and humidity. Additionally, all devices are connected to a 24/7 alarm system.

REFERENCE AGENTS AND KEY STANDARDS

Regardless of the analytical method, an adequately characterized reference material must be available for the vast majority of analytical assays. For some tests key reagents like antibodies are required. These need to be maintained in a qualified state.

We offer:

• Stability and retest programs

SYMBIOSIS offers the development of new and optimization of existing methods such as HPLC, SDS-PAGE and ELISA for (bio-) pharmaceuticals. We realise to come up with your specific requirements trying to find individual solutions for any analytical challenge.

Method validation according to ICH guideline Q2 is being performed upon successful establishment by request. For follow up analyses we can be the contract lab of your choice for planned stability or release studies including controlled storage of your stability study test items. Alternatively method transfer is being provided for implementation in your lab.

We have a proven track record for method establishment and validation throughout many years. Profit from our reliable expertise in that very important field of quality control of (bio) pharmaceuticals.

We are specialized to:

• Antibodies
• Recombinant proteins
• Peptides
• New chemical entities

SYMBIOSIS offers services ranging from method development and validation to taking on the complete responsibility for release, stability and comparability testing.

Release testing (drug substances and drug products)

All drug products entering the local or worldwide pharmaceutical markets require GMP compliant release testing to meet drug product specifications. SYMBIOSIS performs most required testing in-house. This creates an advantage for our customers by achieving a quick release of their final product.

For a more detailed overview of our expertise please visit our method section. All release-testing packages are customized to your demands.

Characterisation

Certain substances such as antibodies require a comprehensive characterization. In addition to common characterization methods such as chromatography and electrophoresis, we employ advanced analytical techniques like MALDI TOF mass spectrometry and N-terminal sequencing by Edman degradation also in combination with peptide mapping or amino acid analysis.

Comparability

After changes in the production process of biotechnological products, the comparability according to quality, safety and efficacy of the products before and after the change has to be shown. This is according to ICH Guidance for Industry Q5E.

Every product is analyzed for release with an appropriate set of methods to characterize the physicochemical properties and the biological activity. However, the complexity of proteins, polypeptides and their derivatives requires extended analytical characterization. For example, in the identification of oxidation, deamidation, carbohydrate linkages or the localization of disulfide bonding. We offer these methods and can support your comparability program.

Impurities and contaminants

Prior to testing for product and process-related impurities and contaminants (according to ICH Guidelines Q3A and Q3B) it is necessary to establish and validate suitable methods. We can provide our established methods or develop new methods for you. Exemplary methods for such analyses are enzyme-linked immunosorbent assays (ELISA) or RP-HPLC.

Cleaning validation

Cleaning validation is an important part of process validation. It involves checking the removal of an API by cleaning the manufacturing equipment according to a pre-defined cleaning protocol justifying the chosen content method as sufficient in respect to LOD/LOQ. Prior to cleaning validation, it might be necessary to optimize the LOD/LOQ capacity of the established method for content determination under the cleaning aspects.

We analyse your rinse and swab samples using chromatographic, spectroscopic or titrimetric techniques.

Since 2001 SYMBIOSIS provides you with a variety of Automated Edman sequencing services in a GMP/GLP regulated environment:

• Determination of the N-terminal amino acid sequence of peptides and proteins/antibodies according to ICH guideline Q6B
• Feasibility studies and method validation of Edman sequencing assays according to ICH guideline Q2
• Follow-up techniques such as MALDI-TOF MS and peptide mapping to generate supporting protein data on the complete sequence and the secondary structure (disulfide bridges)
• Determination of the C-terminal amino acid sequence of proteins or antibodies by complete N-terminal sequencing of the C-terminal peptide generated by peptide mapping
• N-terminal sequence analysis of Erythropoietin according to Ph. Eur.

Automated Edm an sequencing is a key technique for characterisation and quality control of peptides and proteins:

• As a direct sequencing technology the sequencing of not more than 10 to 15 N-terminal amino acids is usually sufficient for the positive identification of a protein, regardless of its size or structure
• Included in the Ph. Eur. monograph of the glycoprotein Erythropoietin
• Essential part of characterisation and comparability programs of antibodies

Automated Edman sequencing offers several advantages over competing mass spectrometry based sequencing technologies:

• It clearly distinguishes between equal-mass amino acids (I/L and K/Q)
• Provides a straightforward result traceability on the basis of HPLC chromatograms compared to the rather elaborate evaluation of complex fragmentation data

As one of the key sequencing technologies Automated Edman sequencing is a focus area within the service portfolio of SYMBIOSIS. Our expertise and techniques combined with the equipment available at SYMBIOSIS ensure highest quality in the performance and documentation of N-Terminal sequencing to meet your specific requirements. Now and in the future.

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