30 prodrugs have been approved by the FDA. Seven prodrugs were approved in 2015 and six in 2017. Examples of recently approved prodrugs are such as dabigatran etexilate (approved in 2010), gabapentin enacarbil (2011), sofosbuvir (2013), tedizolid phosphate (2014), isavuconazonium (2015), aripiprazole lauroxil (2015), selexipag (2015), latanoprostene bunod (2017), benzhydrocodone (2018), and tozinameran (2020). Classification Prodrugs can be classified into two major types, based on how the body converts the prodrug into the final active drug form: Type I prodrugs are bioactivated inside the cells (intracellularly). Examples of these are anti-viral nucleoside analogs that must be phosphorylated and the lipid-lowering statins. Type II prodrugs are bioactivated outside cells (extracellularly), especially in digestive fluids or in the body's circulatory system, particularly in the blood. Examples of Type II prodrugs are salicin (described above) and certain antibody-, gene- or virus-directed enzyme prodrugs used in chemotherapy or immunotherapy. Both major types can be further categorized into subtypes, based on factors such as (Type I) whether the intracellular bioactivation location is also the site of therapeutic action, or (Type 2) whether or not bioactivation occurs in the gastrointestinal fluids or in the circulation system. Subtypes Type IA prodrugs include many antimicrobial and chemotherapy agents (e.g., 5-flurouracil). Type IB agents rely on metabolic enzymes, especially in hepatic cells, to bioactivate the prodrugs intracellularly to active drugs. Type II prodrugs are bioactivated extracellularly, either in the milieu of GI fluids (Type IIA), within the systemic circulation and/or other extracellular fluid compartments (Type IIB), or near therapeutic target tissues/cells (Type IIC), relying on common enzymes such as esterases and phosphatases or target directed enzymes. Importantly, prodrugs can belong to multiple subtypes (i.e., Mixed-Type). A Mixed-Type prodrug is one that is bioactivated at multiple sites, either in parallel or sequential steps. For example, a prodrug, which is bioactivated concurrently in both target cells and metabolic tissues, could be designated as a "Type IA/IB" prodrug (e.g., HMG Co-A reductase inhibitors and some chemotherapy agents; note the symbol " / " applied here). When a prodrug is bioactivated sequentially, for example initially in GI fluids then systemically within the target cells, it is designated as a "Type IIA-IA" prodrug (e.g., tenofovir disoproxil; note the symbol " - " applied here). Many antibody- virus- and gene-directed enzyme prodrug therapies (ADEPTs, VDEPTs, GDEPTs) and proposed nanoparticle- or nanocarrier-linked drugs can understandably be Sequential Mixed-Type prodrugs. To differentiate these two Subtypes, the symbol