Which of the following is considered a “substantive” change in drug manufacturing?

A substantive change in drug manufacturing refers to modifications that can significantly impact the drug's attributes, safety, or effectiveness. When looking at the choice that defines such a change, the one that describes a modification affecting the identity, strength, quality, purity, or stability of a drug product is correct.

This is because any alteration that affects these critical attributes directly impacts how the drug functions and is perceived by regulatory bodies and healthcare providers. For instance, a change in strength could lead to ineffective treatment or increased risk of side effects, while changes to quality or purity could affect the drug's safety profile. These aspects are pivotal not just for compliance with regulatory standards, but also for ensuring patient safety and drug efficacy.

In contrast, the other options do not imply changes that could substantively alter the drug’s characteristics. Minor label updates and changes in packaging design, while they may be important for compliance and marketing, do not significantly affect the core properties of the drug. Similarly, alterations in advertising strategies are more about marketing than the essence of the drug's formulation or manufacturing process.