Pre-prescription Research of Generic Drug

A more comprehensive and deeper understanding of the critical properties and characteristics of the Reference Listed Drugs (RLDs) is necessary to develop successful (consistent quality and efficacy) generic drug formulations. The purpose of pre-prescription studies is to provide a basis for generic drug formulation process design, and to provide reliable solutions to problems that arise during the formulation process studies. In addition, another important aim of pre-prescription research is to provide a proof for preliminary risk assessment for formulation studies and to determine the direction of formulation studies. As an important part of the consistency evaluation, the results of pre-prescription studies also offer indispensable evidence for passing the review of CDER. Alfa Chemistry offers reliable pre-prescription studies, providing studies on the physicochemical properties of active ingredients and excipients, reverse engineering of the RLDs, quality control methods, product life cycle management, etc.

Alfa Chemistry's Services

At Alfa Chemistry, the content of pre-prescription research includes:

• Determine the prescription dosage of the generic drug
• Determine the key quality attributes of the RLDs such as:
1. Physical properties of the RLDs: solubility, crystal shape, particle size, crystallinity, etc.
2. Chemical properties of the RLDs: stability, excipient compatibility, etc.
3. Mechanical properties of the RLDs: fluidity, compressibility (plasticity and elasticity), density, etc.
• Demonstrate the consistency of the important properties of the relevant substances of the manufactured generic drug

RLD Information Research

We conduct a comprehensive research on the RLDs, mainly to determine:

• Whether the RLD is provided with legal raw materials
• Clinical information, product specification of the RLDs
• Formulation dosage form and specification
• Product quality standards of the RLDs
• RLD prescription composition and process research information
• Stability information of the RLDs
• The patent status and production registration status of the RLDs

Figure 1. Evaluation of various parameters in a prescription. (Gari, M.; et al. 2019)

Determination and Quality Assurance of Reference Preparations & Raw Materials

• Investigation of reference formulation: determination of reference formulation
• Investigation of raw materials: source of API and excipient, comparison with API and excipient of the RLD, determination and screening of key raw material
• Quality control: comprehensive testing of the reference preparation (identify a series of quality attributes of the reference preparation such as components, crystal form, moisture content, solubility, content, related substances, etc.; intra- and inter-batch uniformity of the reference preparation) and raw materials

Quality by Design (QbD) for Generic Drug

We use the QbD strategy to fully investigate the target RLD products, and conduct a comprehensive analysis to clarify the QTPP (Quality Target Product Profile) profile, including key quality attributes, dosage form, prescription composition, preparation process, physical and chemical properties of active ingredients, crystal forms, eutectic and solvent compounds, particle shape and size, quality standards, etc.

Reverse Engineering of RLD

Reverse engineering refers to the reverse analysis of preparation design and manufacturing technology based on the premise of full research on the RLDs. At Alfa Chemistry, the purpose of reverse engineering services is to determine the components, technical specifications and other critical attributes of RLDs to ensure the manufactured generic drug with similar efficacy.