Blog & Resources Camargo Blog March 30th, 2009

Botanicals: What is the Starting Material for the API?

We typically work with small molecules of synthetic origin, but occasionally are retained to work with products that have active ingredients from botanical (plant) sources. Lynn Gold, our VP of CMC provides the following discussion on how to define the starting material for the Active Pharmaceutical Ingredient (API).

The definition of the starting material for any API is a negotiation process with the agency. This begins with your pre-IND meeting discussions and will continue as the program progresses through development. It is helpful in this negotiation process to provide as much information to the agency as you can. Clearly map your thoughts and key points for the agency to follow.

There is a guidance that can be helpful when beginning this process. The “ICH Q7A Good Manufacturing Practice for Active Pharmaceutical Ingredients” defines raw material, intermediate and API.

When dealing with an API extracted from plant origin there are two important points; the starting material is always the plant source and the API starting material can be different as shown in Table 1 from the ICH Q7A guidance.

Table 1: Application of this Guidance to API Manufacturing (Ref. ICH Q7A)

Type of Manufacturing

Application of this guidance to steps (shown in gray) used in this type of manufacturing

Chemical ManufacturingProduction of the API starting materialIntroduction of the API starting material into processProduction of Intermediate(s)Isolation and purificationPhysical processing, and packaging
API derived from animal sourcesCollection of organ, fluid, or tissueCutting, mixing, and/or initial processingIntroduction of the API starting material into processIsolation and purificationPhysical processing, and packaging
**API extracted from plant sources** Collection of plantCutting and initial extraction(s)Introduction of the **API starting material** into processIsolation and purificationPhysical processing, and packaging
Herbal extracts used as APICollection of plantsCutting and initial extractionFurther extractionPhysical processing, and packaging
API consisting of comminuted or powdered herbsCollection of plants and/or cultivation and harvestingCutting/ comminutingPhysical processing, and packaging
Biotechnology:fermentation/cell cultureEstablishment of master cell bank and working cell bankMaintenance of working cell bankCell culture and/or fermentationIsolation and purificationPhysical processing, and packaging
“Classical” Fermentation to produce an APIEstablishment of cell bankMaintenance of the cell bankIntroduction of the cells into fermentationIsolation and purificationPhysical processing, and packaging

The botanical starting material, the plant being harvested, should be documented and should be subject to change control procedures. Multiple sources can be identified with the proper documentation.

The API starting material as defined in Table 1, is the material obtained from the first extractions. From this point in the process forward, GMP documentation and procedures should be in place. The in-process controls and testing should be well defined and documented. The components incorporated from this point forward should be clearly defined and received under GMP’s, tested per internal SOP’s and released prior to use in the manufacturing process.

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