From printing to approval: which routes are open to printed drugs

The precedent: Spritam®

In August 2015, Aprecia Pharmaceuticals announced FDA approval of Spritam® (levetiracetam), the first drug manufactured with a 3D printing process. The antiepileptic is approved as adjunctive therapy for partial-onset, myoclonic and primary generalized tonic-clonic seizures. The underlying ZipDose® technology produces a porous tablet that disintegrates with a sip of liquid and still carries a high drug load, according to the manufacturer “up to 1,000 mg in a single dose”.

This showed that an additive manufacturing process can meet the requirements of a drug regulator. For every new technology, however, the question remains which route is the most sensible one for submitting a product.

505(b)(2): new formulation, known active ingredient

In the US, the 505(b)(2) route is often the obvious choice for newly formulated, already known active ingredients. It goes back to the Hatch-Waxman Amendments of 1984. It is a full New Drug Application, but one that may rely in part on data the applicant did not generate itself, such as published studies or earlier FDA findings on an approved reference product.

Typical use cases are new dosage forms, strengths or formulations, new combinations and changed dosing regimens. The route sits between the 505(b)(1) application, which rests largely on the applicant’s own studies, and the generic application (ANDA), which mainly requires proof of bioequivalence. It is considered faster and less costly than a full procedure; complete evidence of safety and efficacy is still required. If a change meets certain conditions, approval can bring three years of market exclusivity.

Adare and Laxxon name the 505(b)(2) route as a possible path for products made with SPID®. According to the company, Laxxon is pursuing it for LXM.2, for example, an oral tablet with a GLP-1 receptor agonist.

New programs for new manufacturing technologies

Besides the application route, early dialogue with the agency is gaining importance. The Food and Drug Omnibus Reform Act (FDORA), part of the Consolidated Appropriations Act 2023, required the FDA to set up a designation program for Advanced Manufacturing Technologies (AMT). The agency published the draft guidance in December 2023.

An AMT designation is meant to allow earlier and more frequent interaction with the FDA. According to the draft, priority goes to technologies that substantially improve product quality or can help address supply shortages. The program is also of interest to technology developers and contract manufacturers who do not file applications themselves.