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505(b)(2) Approvals for 2017: What Were They and Who Developed Them?

Our last blog gave the numbers on 505(b)(2) approvals in 2017, including orphan designations and priority review products. Here we take an in-depth look at what kind of products were approved via the 505(b)(2) pathway, and under which therapeutic areas and FDA Review Divisions they fell. We look at their review commitments, and at the type of companies that were successful in getting 505(b)(2) products approved in 2017. Ready for the spoiler? It is still small biotechs that dominated the 505(b)(2) scene.

Approvals by Product Type

The following data has been prepared from Camargo’s proprietary 505(b)(2) database, and from the FDA’s public databases including the Orange Book and drugs@FDA.

Last week’s blog included a graph displaying the FDA’s classification of submission type. Seven products were new molecular entities or new active ingredients (the difference is administrative). Most products represented new dosage forms, changes to excipients that prevented approval as a generic, non-bioequivalent differences on pharmacokinetics, etc. Of the new dosage forms, extended release versions of solid oral dosage forms, oral solutions, and injectables were among the approvals.

Four products were drug-device combination products, including a sinus implant and metered dose inhalers. Three products were over-the counter switch (Rx to OTC) versions of prescription products. A further product is a new strength and slightly different indication to the approved products but approved directly as an OTC product. Two products were previously marketed without approval.

These approvals demonstrate the breadth of product types that are suitable for approval via the 505(b)(2) pathway.

Approvals By FDA Review Division

The greatest number of 505(b)(2) approvals in 2017 were from the Division of Pulmonary, Allergy, and Rheumatology (DPARP). Nine products were approved by this Division, however this was likely due to an unusually low number of approvals in 2016 (1 product). Other Divisions that made up a large proportion of approvals include Division of Anesthesia, Analgesia, and Addiction Products (DAAAP), Division of Anti-Infective Products (DAIP), and Division of Hematology Products (DHP).

2017 505(b)(2) Approvals by FDA Review Division

DAAAP = Division of Anesthesia, Analgesia, and Addiction Products; DAIP = Division of Anti-Infective Products; DAVP = Division of Antiviral Products; DBRUP = Division of Bone, Reproductive and Urologic Products; DCaRP = Division of Cardiovascular and Renal Products; DGIEP = Division of Gastroenterology and Inborn Errors Products; DHP = Division of Hematology Products; DMEP = Division of Metabolism and Endocrinology Products; DMIP = Division of Medical Imaging Products; DNDP = Division of Nonprescription Drug Products; DNP = Division of Neurology Products; DOP 1,2 = Division of Oncology Products 1,2 (combined); DPARP = Division of Pulmonary, Allergy, and Rheumatology Products; DPP = Division of Psychiatry Products; DTOP = Division of Transplant and Ophthalmology Products.

Note: One NDA (208400) has been counted twice as it was approved for 2 indications that were each reviewed by different Divisions: Division of Hematology Products and Division of Pulmonary, Allergy, and Rheumatology Products.

Of note, 4 over-the-counter (OTC) products were approved via the 505(b)(2) pathway by the Division of Nonprescription Drug Products in 2017, an increase from 1 product the previous year.

How do non-prescription products end up as 505(b)(2) approvals? If they don’t exactly match the dated OTC drug monographs in every way, they need to be approved under an NDA, usually a 505(b)(2).

Approvals by Therapeutic Area

The greatest number of 505(b)(2) approvals for 2017 occurred in the therapeutic areas of anti-infective and pulmonary (6 products each), followed by cardiovascular, metabolism & endocrinology, and oncology (5 products each).

2017 505(b)(2) Approvals by FDA Review Division

First Cycle Reviews

Approvals achieved in the first cycle were most common in the Division of Nonprescription Drug Products (100%; 4 out of 4 approvals). First cycle reviews were defined as the absence of a complete response letter or the requirement for a major amendment that shifted the PDUFA goal date by 3 or more months. Other Divisions with a high proportion of first reviews were Gastroenterology and Inborn Errors Products (75%; 3 of 4 approvals); Pulmonary, Allergy, and Rheumatology Products (66.7% 6 of 9 approvals); Anti-Infective Products (66.7%; 4 of 6 approvals); and Anesthesia, Analgesia, and Addiction Products (62.5%; 5 of 8 approvals). The Division with the lowest number of 1st cycle reviews was Metabolism and Endocrinology Products (20%; 1of 5 approvals). Note that data in this section are only provided for Divisions in which more 4 or more reviews were conducted.

Post-market Commitments

Of the 63 NDAs approved via the 505(b)(2) pathway, 34 were approved with no post-market commitments, 11 were approved with a Sponsor commitment to conduct deferred studies under the Pediatric Research Equity Act (PREA), and 15 products had commitments for non-PREA studies or assays. Post-market commitments were not listed for 2 products that were only tentatively approved.

Of those products that did not require post-market PREA commitments, 2 had fulfilled PREA commitments prior to approval, 19 were exempt because PREA did not apply, 12 were exempt because the products had been designated orphan, and 22 received a full or partial waiver because studies are impossible or highly impractical (usually due to a small pediatric population), there is evidence strongly suggesting that the product would be ineffective or unsafe in some or all pediatric age groups, or because the product does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients and is not likely to be used in a substantial number of pediatric patients.

Biotechs and Small Pharma Achieve Most of the 505(b)(2) Approvals in 2017

Biotechs dominated 505(b)(2) approvals in 2017. Almost fifty percent (49.2%: 31 of 63) of products approved via the 505(b)(2) pathway in 2017 were submitted by Sponsors that had 4 or fewer approved products (currently market or discontinued) in the US, and for 30% (19 of 63) products, the 505(b)(2) product approval was the only FDA-approved product that the company had. At the other end of the spectrum, 15 of the 505(b)(2) products (23.8%; 15 of 63) were submitted by large pharma (defined as having or having had more than 100 FDA-approved products).

2017 505(b)(2) Drug Product Sponsors by Company Size

As of this week, the marketing rights for at least 7 of the 505(b)(2) products approved in 2017 have already been licensed to other companies. Notably, Marathon Pharmaceuticals LLC, a small privately-held Illinois-based company, sold the US marketing rights to Emflaza (deflazacort oral tablet and suspension, NDA 208684 and NDA 208685, respectively) to PTC Therapeutics for a reported $140 Million plus milestone payment (ref). Marathon is now shutting up shop, but not before making arrangements for the priority review voucher it was granted because Emflaza is indicated for a rare pediatric disease (Duchenne muscular dystrophy). In the previous year, these vouchers have been sold for hundreds of millions of dollars. Not bad for a drug that is believed to have cost much less than that to bring to market.


In 2017, the 505(b)(2) pathway was successfully used to approved a diverse array of new dosage forms, drug-device combinations, and non-prescription products. Most products were approved with less than 1 review cycle. Small biotechs achieved most of the approvals, and the marketing rights for several of these products have already been sold to bigger pharmaceutical companies.

Not sure if your product is appropriate for the abbreviated 505(b)(2) pathway? Contact us to discuss your needs.

Author: Angela Drew, PhD, Product Ideation Consultant, Camargo Pharmaceutical Services