Determination of Principal Components in RLD

In general, the consistence evaluation of the generic drug products starts with the comprehensive characterization of RLDs. In terms of pharmaceutical equivalence, improving the prescription similarity between generic drugs and the Reference Listed Drugs (RLDs) will increase the chances of developing generic drugs with better stability and bioequivalence to reference preparations. Most of pharmaceutical products are multi-component dosage forms composed of various excipients and APIs, each of which has its own role. Therefore, characterization of the principal components of the RLDs is a systematic, scientific and cost-effective strategy to accelerate the generic drug development. Alfa Chemistry provides method development and validation for the analysis of principal components of the RLDs, and we are able to qualitatively analyze and confirm the structure of API, excipients and other components in the RLD formulations.

Figure 1. Generic vs. Brand drug. (Sean. 2018)

Quantitative Analysis of Prescription Composition

Literature Analysis

We obtain the formulation composition of the RLD from two pathways:

• A good source of information is the public section of the "Summary of Basis for Approval" submitted by the originator company, which can be found in the "Drug@FDA" section of the US FDA website
• Product information brochures and the Physician's Desk Reference

Qualitative Analysis of Prescription Composition

• Identification of API
  The quality of the active ingredients in the formulation is of great importance. If there is a problem with the quality of the API, it will have a great impact on the final drug product. APIs from different sources may have differences in impurity types, contents, and solvent residues due to factors such as their synthesis processes and control levels. Therefore, it is necessary to accurately determine the active ingredients in the RLD.
• Identification of Excipients
  Excipients are also one of the components of the RLD preparations, and will affect the quality of the RLDs. When the excipients used in the drug production process are different, it may affect the quality consistency of the drug.
1. We provide excipients identification services to determine the types of excipients in RLD
2. Our experts perform research on the key factors such as the manufacturer, and the type of the polymer material, so as to ensure the consistency with the RLDs preparation in terms of quality and efficacy
• Identification of other substances
  In addition to APIs and excipients, the RLDs often contain a class of other substances that are low in content but may have an important impact on the quality of the preparation. There are three main sources of these substances:



① Substances introduced during API synthesis

② Substances produced by the interaction between APIs and excipients

③ Substances produced by the degradation of the API itself

In the consistency evaluation, Alfa Chemistry helps you confirm the requirements for the quality of raw materials, excipients and key process parameters of drug production, and control these substances to ensure the safety and quality of your manufactured generic drug are well controllable.

Compound Structure Confirmation

• Single crystal preparation
• Infrared and Raman spectroscopy
• NMR and Mass spectra: Structural analysis