Analytical Method Development and Validation for Pharmaceutical

Process Analytical Science

Our process analytical sciences group supports research, development, and commercial production.

At Medicilon, the importance of analytical support in pharmaceutical development and manufacturing is well understood.  We provide our clients with analytical method development and all other services required to support their regulatory needs.

Services Offered

• • Analytical Method Development, Qualification and Validation For

  • • Assay

  • • Related Compounds

  • • Water Content

  • • Chiral Analysis

  • • Residual Solvents

  • • Trace Metals Analysis

• • IPC and Release Testing

• • Impurity Isolation and Structure Elucidation

• • Reference Standard Qualification

• • Stability Studies

• • PGI Method Development, Validation and Testing

• • Specification and Other Regulatory Filing Documentation Preparation

We have the following key instrumentation to support our analytical activities

• • Chromatography: UPLC, HPLC, LC-MS, GC, GC-HS

• • Solid State Characterization: DSC, TGA, XRPD, PSD, Polarized Light Microscopy

• • Elemental Analysis: ICP-OES

• • Identification: NMR, FT-IR

• • General Testing: KF, UV-Vis, Polarimeter

Analytic method development, validation and transfer are key elements of any pharmaceutical development program. This technical brief will focus on development and validation activities applied to drug products.  Often considered routine, too little attention is paid to their potential to contribute to overall developmental time and cost efficiency.

Methods are developed and validated to analyze in-process, finished products, stability samples, and swabs to verify the cleanliness of manufacturing equipment.

Typically, methods for in-process, uniformity of dosage units, and dissolution sample analysis are developed and validated using UV, HPLC, UPLC, or GC procedures.

Methods used to perform the chemical assay, identification, related substances/impurities, or chiral purity testing on API and finished drug product are typically developed and validated using HPLC, UPLC, or GC.

Methods developed for stability sample analysis are validated to ensure they are stability-indicating.

All validations follow FDA-ICH guidelines, client-approved protocols, and standard operating procedures.

Method Validation

By working with Medicilon, you gain an experienced partner with a good working knowledge of method validation requirements suitable for different phases of development. To ensure methods meet regulatory requirements, we follow relevant ICH guidelines such as ICH Q2(R1) or compendia guidance in combination with client-specific protocols.

Analytical Techniques and Capabilities Include:

• • UV/VIS Spectroscopy

• • Fluorescence Spectroscopy

• • ELISA

• • SDS-PAGE

• • Iso-electric Focusing

• • Capillary Gel Electrophoresis

• • UPLC

• • HPLC

• • Atomic Adsorption

• • FTIR

• • Peptide Mapping

• • Carbohydrate Analysis

• • Cell-Based Assays

HPLC Methods: HPLC methods with various high-resolution analytical columns represent the most effective and efficient means of monitoring various degradation of protein therapeutics.

• • Size-Exclusion Chromatography

• • Ion-Exchange Chromatography

• • Reversed Phase Chromatography

• • Hydrophobic Interaction Chromatography

• • Various Detectors: UV, Fluorescence, Reflective Index, Evaporative Light Scattering, Mass Spectrometry

The wide variety of equipment, columns, eluent, and operational parameters involved the high-performance liquid chromatography (HPLC) method, which makes the development seem complex. Following steps:
Step 1 – Selection of the HPLC Method and Initial System
Step 2 – Selection of Initial Conditions
step 3 – Selectivity Optimization
step 4 – System Optimization
step 5 – Method Validation

Structural Analyses: Measure the secondary, tertiary, and quaternary structure of biologically active proteins

• • Circular Dichroism

• • Fourier Transformed Infrared Spectroscopy

• • Fluorescence Spectroscopy

• • Differential Scanning Calorimetry

Electrophoresis: Separation of impurities based on both charge and mass makes electrophoresis an excellent orthogonal method

• • Capillary Electrophoresis (CE)

• • Sodium Dodecyl Sulfate Electrophoresis (SDS-PAGE)

• • Protein Analyzer