Analytical Testing & Development

Avista Pharma Solutions is a leading provider of comprehensive analytical testing and method development services.  We offer best-in-class services for structural characterization, impurity isolation and identification, material characterization, raw material testing, stability testing and full method development.

Structural Determination/Impurity Identification

Structurally characterizing small amounts of material is a key step in solving many challenging hurdles encountered during pharmaceutical development in the laboratory and manufacturing.

 

Materials of interest include:

 

  • reaction side products produced during process development and scale up
  • impurities formed during stability studies via API degradation or reaction with excipients
  • metabolites of APIs observed during clinical testing

 

The team at Avista Pharma Solutions has experience tackling all of these issues and a proven track record of identifying, isolating and characterizing these materials. Areas of expertise and capabilities  include preparative and semi-preparative chromatography, mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy.  The most difficult structure elucidation challenges require an integrated approach that utilizes these advanced analytical testing techniques in concert. Avista Pharma’s integrated team excels at tackling such problems efficiently and providing concise professional reports suitable for inclusion in regulatory filings.

Material Characterization

Identification of materials often extends beyond chromatographic or Fourier transform infrared spectroscopy (FTIR) analysis.  Knowledgeable staff at Avista Pharma have the capabilities to execute material and polymorphic form identification utilizing Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and X-Ray Powder Diffraction (XRPD).  The capability to perform TGA-Gas Chromatography-Mass Spectrometry (TGA-GC-MS) is also available.

 

Particle Size Determination

Particle size is critical to ensuring materials maintain expected processing and performance characteristics.  Avista Pharma is equipped with laser particle size (LPS) instrumentation to ensure materials are consistent from batch to batch.  If further investigation is necessary, the capability to provide large population particle imaging with particle gallery and various size and shape results is available.

 

Elemental Impurities

Implementation of ICH Q3D (see ICH Quality Guidelines) and USP <232>/<233> Elemental Impurity guidelines is set for the first stage of implementation.  Avista Pharma staff have extensive knowledge and experience providing consultation and analytical support to navigate and achieve compliance with the elemental impurity guidances.  We can assist in developing a risk assessment strategy via documentation, analytical screening and method development/validation to achieve compliance.  Analytical testing is performed using Microwave Plasma – Atomic Emission Spectrometry (MP-AES) and redundant Inductively Coupled Plasma – Mass Spectrometer (ICP-MS) instruments with microwave digestion available.

 

In addition to specific method development and phase-appropriate validation methods, a list of the most common USP tests that we perform includes (note: EP tests available also):

 

USP <941> Characterization of Crystalline and Partially Crystalline Solids by X-Ray Powder Diffraction

USP <891> Thermal Analysis

USP <661> Containers – Plastics

USP <429> Light Diffraction Measurement of Particle Size

USP <232> Elemental Impurities – Limits

USP <233> Elemental Impurities – Procedure

ICH-Q3D – Guideline for Elemental Impurities

Potential Genotoxic Impurities

Regulatory agencies now require that drug manufacturers evaluate potential genotoxic impurities (PGI’s) present in the production of drug substances/drug product manufacturing and place very strict controls on the levels of these species. Often, PGI’s must be reduced to single-digit parts per million (PPM) levels.

 

At Avista Pharma, an integrated team of experienced process and analytical chemists will:

 

  • Review your process to identify PGI’s, including the use of both structure-activity and literature-based software tools to screen structures
  • Comprehensively evaluate the clinical phase of your program (including anticipated dose levels) to establish the appropriate levels of PGI control
  • Utilize state-of-the-art synthetic processes to eliminate PGI’s whenever possible
  • Minimize PGI levels when they cannot be eliminated
  • Develop and validate the sensitive analytical methods required to quantify the levels of PGI’s present

 

The Avista Pharma team has sophistical analytical instrumentation – including Gas Chromatography/Mass Spectrometry (GC/MS), Liquid Chromatgraphy (LC)/High Resolution MS (Time-of-Flight – TOF), and LC/MS/MS – and extensive experience developing trace-level analytical methods for PGI measurements.

Impurity Isolation

Isolation of impurities may be required for a variety of reasons, including as part of a structural elucidation project, generation of materials for use as reference standards and separation of racemic mixtures into enantiomers.  Avista Pharma has preparative equipment with multiple modes of separation, including normal and reverse phase High Performance Liquid Chromatography (HPLC) and Supercritical Fluid Chromatography (SFC), to enable isolation of materials, as necessary.  The best-in-class Avista Pharma team has many years of experience with these techniques to enable rapid isolation in the most efficient possible manner.

Materials Testing

Avista is equipped to analyze raw materials to USP, EP, ACS or client-defined specifications. Testing can include identification only or an entire certificate of analysis (COA) verification. In many cases, we provide identity testing of all containers used for a manufacturing batch to meet European Union (EU) GMP Guidelines or to verify a COA as part of vendor qualification (as the cost to put procedures in place to test many samples on a non-routine basis can quickly accelerate). Fourier Transform Infrared Spectroscopy (FTIR) is used to identify many Raw Materials. Avista Pharma has built a raw material library from USP- and EP-certified standards analyzed on our FTIR equipped with an Attenuated Total Reflectance (ATR) accessory, allowing us to quickly meet these standards. Many raw materials have specific wet chemistry tests to confirm their identity. Avista Pharma routinely performs these methods that are detailed in USP <191> or the individual USP, EP or ACS monographs. Avista Pharma has the equipment and trained scientists available to meet your raw material testing needs.

 

In addition to specific titration and chromatography assays, a list of the most common USP tests (EP available also) we perform includes:

 

  • USP <191> Identification Tests – General
  • USP <197> Spectrophotometric Identification Tests
  • USP <201> Thin-Layer Chromatographic Identification Test
  • USP <231> Heavy Metals
  • USP <241> Iron
  • USP <281> Residue on Ignition
  • USP <345> Assay for Citric Acid and Phosphate
  • USP <401> Fats and Fixed Oils
  • USP <467> Residual Solvents
  • USP <611> Alcohol Determination
  • USP <731> Loss on Drying
  • USP <741> Melting Point
  • USP <791> pH
  • USP <841> Specific Gravity
  • USP <921> Water Determination

Method Development

The analytical testing methods used to monitor the synthesis and release of drug substances and drug products are your only window into the quality of your materials. Avista Pharma focuses on efficiently developing phase-appropriate, high-quality analytical methods that guarantee the quality of your products.

 

We have extensive experience developing and validating:

 

  • HPLC/UPLC methods for assay and related substances
  • Chiral HPLC methods for enantiomer resolution
  • GC-FID methods for residual solvents
  • GC MS methods for potential genotoxic impurities (PGI’s)
  • HPLC/UPLC methods utilizing a wide range of detection modes, including UV, charged aerosol detection (CAD), refractive index (RI), evaporative light scattering (ELSD) and others

 

We routinely develop methods to support:

 

  • cGMP Raw Material testing
  • API Release testing
  • Reference Standard Qualification
  • Final Product Release testing
  • ICH Stability Programs

Non-GMP DMPK

For Drug Metabolism and Pharmacokinetic (DMPK) studies, Avista Pharma has extensive experience in bioanalytical analyses to support discovery and pre-clinical drug metabolism studies utilizing state-of-the-art LC/MS/MS instruments. In addition, the Avista Pharma team has experience with metabolite identity (ID) from such studies (described above in Impurity Identification).

Stability Studies

Avista Pharma has over 3,000 square feet Stability areas that include over 25 environmental chambers for pharmaceutical Stability Studies across three (3) locations.  We can accommodate studies of various container and lot sizes, temperatures, humidities, lights and lengths of study. With fully-compliant GMP analytical chemistry and microbiological labs, Avista Pharma is your one-stop Stability Testing Partner with redundant storage locations for business continuity.

 

For more information, please see our Stability Studies section under Drug Product R&D.