Tag Archives: stability testing

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Setting the Standard with Reference Standard Qualifications

The term Reference Standard Qualifications (RSQ) “is defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria,”1 and incorporate these quantitative reference standards to do so: purity, potency, identification, impurities content, and generally full characterization.  

Identity Testing

There are a range of tests to ensure the identity of the drug product or drug substance. These can be done by a variety of equipment, including LC-MS, 1H NMR, 13C NMR, FTIR (Fourier Transform Infrared Spectroscopy), TGA (Thermal Gravimetric Analysis)/DSC (Differential Scanning Calorimetry), and UV-Vis. Appearance testing can be achieved by chiral or ion chromatography, elemental analysis (identifying C, H, and N), TGA/DSC, and XRPD.  

Quantitative Testing
For quantitative reference standards, there is a standard formula that should utilized (HPLC Purity) x (100% − % Residual Solvents − % Inorganic Impurities) = The Determination and Confirmation of the Assay Value % (i.e., weight %).  These component values can be quantified by using HPLC for the purity analysis, residual solvents by LOD or KF Water Content and HSGC, and inorganic impurities by ROI (Residue on Ignition), ICP-MS/OES ((Inductively Coupled Plasma Mass Spectrometry or Inductively Coupled Plasma Optical Emission Spectroscopy). (For a limited number of sample quantities of both residual solvent or inorganic impurities, they can alternatively be tested by TGA.) Finally, to access the weight percentage confirmation, titration and qNMR are excellent techniques. 

 Concurrent with identity and quantitative testing, storage conditions and stability should be established.  This includes storage (container/closure), expiration dating, re-testing procedures, and usage and tracking.  

We Can Assist with your Reference Standard Qualifications Needs  

SK pharmteco has years of experience and numerous experts in Reference Standard Qualifications. Compendia methods (USP/EP/BP/JP) are utilized in tandem with analytical method development, validation, and transfer to ensure optimal success with your drug substances and drug products. Please contact us with any specific questions or to receive a quote for your RSQ needs.   

References  

  1. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-6-test-procedures-acceptance-criteria-new-drug-substances-new-drug-products-chemical_en.pdf 
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Shedding Light on Photo-Stability Forced Degradation

Triple Quad HPLC

blank pharmaceutical and drug packaging

Forced Degradation is the testing of a drug product or drug substance using situations more taxing than those if conditions were simply accelerated. This type of stability testing is designed to demonstrate various degradation pathways within the product or substance and assists with the development of the product itself, along with its packaging. Within forced degradation testing, there is a subset of studies known as photo-stability.  The guidelines are outlined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the FDA. As the ICH Topic Q1B document states, “The intrinsic photostability characteristics of new drug substances and products should be evaluated to demonstrate that, as appropriate, light exposure does not result in unacceptable change.”1  

They recommend a range of different studies that address potential areas of concern: 

A systematic approach to photostability testing is recommended covering, as appropriate, studies such as:  

(i) Tests on the drug substance;
(ii) Tests on the exposed drug product outside of the immediate pack; and, if necessary,  

(iii) Tests on the drug product in the immediate pack; and, if necessary,  

(iv) Tests on the drug product in the marketing pack.1 

The type of lights used in photo-stability are also described.  They offer options, including:   

    • …any light source that is designed to produce an output similar to the D65/ID65 emission standard…  
    • A cool white fluorescent lamp designed to produce an output similar to that specified in ISO 10977 (1993) … 
    • A near UV fluorescent lamp having a spectral distribution from 320 nm to 400 nm with a maximum energy emission between 350 nm and 370 nm…1    

Additionally, temperature control should be maintained to minimize changes and variations.  

Triple Quad HPLC

Finally, these guidelines also provide and elucidate the differences between procedures for drug products and drug substances. It is a crucial reference for administering or simply learning more about photo-stability forced degradation testing. 

AMPAC Analytical has the equipment and expertise to provide comprehensive photo-stability studies for your products. Additionally, we have high-resolution and triple-quadrupole mass spectrometers to aid in the identification of potential degradants. Contact us today to learn how AMPAC Analytical can support your photo-stability needs.

References  

  1. https://www.fda.gov/media/71713/download (PDF) 

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