The information below represents an outline of the FDA’s current thinking on Q7A Good Manufacturing Guidance for Active Pharmaceutical Ingredients. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.

• Section XIX (19) contains guidance that only applies to the manufacture of API’s used in the production of drug (medicinal) products specifically for clinical trials (investigational medicinal products)
• An API starting material is a raw material, an intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API.
• An API starting material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in house.
• API starting materials normally have defined chemical properties and structure.
• The company should designate the rational for the point at which production of the API begins
• For synthetic processes, this is known as the point at which API starting materials are entered into the process.
• From this point on, appropriate GMP should be applied to these intermediate and/or API manufacturing steps, including validation of critical process steps determined to impact the quality of the API.
• However, the fact that a company chooses to validate a process step does not necessarily define a step as critical.
• The stringency of GMP in API manufacturing should increase as the process proceeds from early API steps to final steps, purification, and packaging.
• Physical processing of API’s, such as granulation, coating or physical manipulation of particle size (e.g., milling, micronizing) should be conducted according to this guidance.

This table gives guidance on the point at which the API starting material is normally introduced into the process.