Instead, the Orange Book Preface instructs: “We recognize that certain drug products approved in 505(b)(2) applications may not have therapeutic equivalence codes, and that FDA may undertake therapeutic equivalence evaluations with respect to such drug products. A person seeking to have a therapeutic equivalence rating for a drug product approved in a 505(b)(2) application may petition the Agency through the citizen petition procedure (see 21 CFR 10.25(a) and 21 CFR 10.30).”All of the above factors, when taken together, mean that 505(b)(2) NDA holders will be facing a higher PDUFA user fee burden. To that end, 505(b)(2) NDA holders should review their Orange Book listings and request (or petition) FDA for changes/corrections, and, when appropriate, request an “A” therapeutic equivalence rating.

At the end of Section 1.10, FDA adds a new paragraph:We recognize that certain drug products approved in 505(b)(2) applications may not have therapeutic equivalence codes, and that FDA may undertake therapeutic equivalence evaluations with respect to such drug products. A person seeking to have a therapeutic equivalence rating for a drug product approved in a 505(b)(2) application may petition the Agency through the citizen petition procedure (see 21 CFR 10.25(a) and CFR 10.30).You may recall that in recent years there’s been a decent amount of controversy over the issue of therapeutic equivalence rating assignment to 505(b)(2)-approved drug products, from citizen petitions (see our previous post here), to a lawsuit against FDA that was later dropped (see our previous post here). In addition to substitutability, the assignment of therapeutic equivalence ratings to drug products approved under 505(b)(2) NDAs has an effect on whether or not a manufacturer is subject to annual PDUFA user fees.

These cases have also challenged the “natural” labeling of foods containing genetically modified organisms (“GMOs”), which are increasingly prevalent in our food supply but need not be labeled as such under current FDA rules.[1] Faced with these class actions, several federal judges reached out to the FDA for an administrative determination under 21 C.F.R. § 10.25(c), asking whether manufacturers can label food products containing bioengineered ingredients as “natural” or “all natural” or “100% natural”.[2] The judges then stayed or dismissed pending class action suits while they awaited the FDA’s decision.A Definition’s Natural Benefits If the FDA provided a formal, regulatory definition of “natural” for food products, that definition could establish a bright line for compliance.