What FDA finalized on August 24
FDA published its final Evaluation of Therapeutic Equivalence guidance on August 24, 2026. The document replaces a July 2022 draft and explains the scientific principles FDA uses when it evaluates approved multisource prescription drug products for the Orange Book. It is final guidance, not a regulation, and FDA describes its recommendations as nonbinding.
The agency says the final version adds a request route in certain circumstances, when the sole difference from a listed drug relied upon in a 505(b)(2) application is an inactive-ingredient difference not permitted under 21 CFR 314.94(a)(9)(iii) or (iv). FDA also made minor changes to improve clarity and update the guidance. The notice does not announce a new code for any named product, revise a state pharmacy-practice law, set an implementation date, or direct a pharmacist to make a particular substitution.
1. Read the code as a product relationship
FDA calls approved drug products therapeutically equivalent when they are pharmaceutical equivalents and have demonstrated bioequivalence, so they can be expected to have the same clinical effect and safety profile when used under their labeling. That assessment belongs to the products and grouping shown in the Orange Book. It is not a free-standing grade for an ingredient, manufacturer, or dosage form.
An A-first code means FDA considers the products therapeutically equivalent within the relevant grouping. AB means actual or potential bioequivalence concerns have been resolved with adequate evidence; other A codes address dosage forms for which FDA sees no known or suspected bioequivalence problem. A B-first code means actual or potential bioequivalence issues have not been resolved. BX, for example, means the available data are insufficient for FDA to determine therapeutic equivalence.
The rest of the code matters. Three-character codes such as AB1 and AB2 separate equivalence groups under the same product heading, often because more than one reference listed drug is involved. Recording only 'AB' can erase the distinction the code was designed to preserve. Capture the dispensed package's NDC, labeler or distributor, strength, dosage form, and route; then document how it maps to the Orange Book applicant, application number, product grouping, full code, and check date.
2. Do not turn a missing code into a verdict
A blank TE field can reflect several different situations: no therapeutically equivalent product may be listed in the Active section; FDA may not have evaluated a 505(b)(2) product, may still be evaluating it, or may have found it non-equivalent; a petitioned ANDA may not be pharmaceutically equivalent to its reference drug; or the product may be in the Discontinued Drug Product List.
A blank field therefore does not, by itself, establish poor quality, lack of approval, clinical inferiority, or therapeutic nonequivalence. It also does not establish that substitution is permitted. Record what the current Orange Book shows and identify any unresolved question. FDA may revise an A code to a B code when new information creates a concern, or remove a code when no therapeutically equivalent products remain in the Active section, so the check date belongs in the evidence.
3. Keep FDA science separate from substitution authority
FDA's TE decision is a scientific judgment, while the Orange Book preface says generic-substitution policy is administered by the states. An A code is not a national instruction to substitute. A consultant pharmacist's record should distinguish what FDA concluded from who is authorized to act, which product is available, and what the prescriber, pharmacy, facility, payer, or resident must confirm under the governing process.
Therapeutically equivalent products can still differ in characteristics such as shape, scoring, release mechanism, packaging, excipients, expiration, storage conditions, and some labeling. A difference is not automatically clinically important, but neither should it disappear behind a two-letter code. If administration, allergy or intolerance history, feeding-tube use, identification, storage, or another resident-specific issue makes a characteristic relevant, place that fact beside the equivalence check and route it to the responsible decision-maker.
Build one four-field handoff
A practical handoff can stay short. Put these four fields together rather than passing along a screenshot or a copied letter:
- Actual product: dispensed NDC, labeler or distributor, strength, dosage form, route, and the source used to identify it.
- Orange Book match: applicant, application number, product grouping, full TE code, source, and check date.
- Authority: the state substitution rule and any prescriber, pharmacy, facility, payer, or resident approval still required by the local process.
- Resident decision: any product-specific difference that matters, the decision owner, and the next action. Recheck when the dispensed product, Orange Book entry, or product availability changes.