Commercialization Resources

3-Year Exclusivity May Not Be Worth as Much as You Think

It is a widely held tenet that market exclusivity is essential for the successful launch of a new drug. But is this always the case? For products approved through the FDA 505(b)(2) pathway, is pursuing the 3-year period of exclusivity available through Hatch-Waxman always necessary? Or is it possible that a product may succeed without […]
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Pediatrics – What are the appropriate age ranges?

As we have noted in this blog previously, under the Pediatric Research Equity Act (PREA), all new drug applications for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication(s) […]
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PhRMA and GPhA team up (!) to offer their EAR proposal to solve generic safety labeling issue

FDA held a public hearing this past Friday (27March2015) to air their proposal that generic companies be responsible for updating their labeling whenever ‘new safety information’* is available. Generic companies argue against such a proposal because it would lead to confusion about safety warnings if every multisource product has different labeling (coincidentally, and privately,  they […]
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Paper Submissions: Going, going…away

In order to fulfill a requirement specified in Section 745A(a) of the Food and Drug Administration Safety and Innovation Act (aka FDASIA), FDA recently issued a draft guidance directing mandatory use of electronic filing and formatting for most regulatory submissions which currently can still be submitted in paper format.  The change is not exactly imminent, but […]
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MannKind Breathes Easier – Inhaled Insulin Finally Approved

MannKind’s Afrezza Receives FDA Approval In June of this year, MannKind Corporation announced that they received FDA approval for Afrezza®, their rapid-acting inhaled insulin product. MannKind is currently working to identify a pharma partner to manufacture and distribute Afrezza, and the product could be available as soon as January 2015. This approval has been a […]
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Importing pre-launch products with a bit of PLAIR

With the tsunami of activities connected with the initial implementation of all the GDUFA requirements, another change made by FDA went largely under the radar.  FDA released the draft guidance, “Pre-Launch Activities Importation Requests (PLAIR)”. (CDER July 2013) which describes how an NDA/ANDA applicant may import finished dosage forms into the United States prior to […]
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The Road to Commercial Success – The Target Product Profile

The goal of drug product development is commercial success.  If this statement wasn’t true, how would patients access the live-saving or life-enhancing drugs we are developing.  Yet, all too many companies focus just on FDA approval, which in our view should be just a very important milestone. When embarking on the drug development journey, it is […]
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FDA Goes Against Advisory Committee and Approves Low Dose Paroxentine for Hot Flashes

On 6/30/2013, FDA approved Noven Pharmaceuticals Brisdelle (paroxetine) for the treatment of vasomotor symptoms (hot flashes).  This 505(b)(2)  approval is notable since it is the first non-hormonal product product approved for this indication. But from a regulatory point of view, it is even more interesting – FDA went against a 10-4 Advisory Committee vote against […]
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Advisory Committee Cool on Non-Steroid Hot Flash Treatments

The Camargo team got its start in the 505(b)(2) process at Duramed Pharmaceuticals with the 1990’s development and approval of Cenestin (synthetic conjugated estrogens, A).  The product was approved based on a Phase 3 clinical study demonstrating the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause –   (known as ‘hot flashes’).  For decades, estrogens have […]
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Are 505(b)(2)’s “Super Generics” or what do we call them?

When we started Camargo almost 10 years ago, products approved under 505j were called ‘generics’ and 505(b)(1) ‘new drugs’.  We could find no consensus of a name for products approved via 505(b)(2). Of course, when Camargo started business, there had been very few 505(b)(2) products approved.  Fast forward 10 years and we have seen an explosion of 505(b)(2) products […]
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No 5-Year Exclusivity for Combinations Drugs with an NCE

One anomaly to the exclusivity rules is that a combination drug product containing a new chemical entity (NCE) and one or more previously approved drugs does not receive the 5-year exclusivity that a single-component NCE drug would receive. Thus, Ferring Pharmaceuticals Prepopik (sodium picosulfate, citric acid and magnesium oxide) was approved as a 505(b)(2) in July, 2012, […]
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Off-label promotion: Free Speech?

Announcement of the decision from the US Court of Appeals for the Second Circuit in the United States v. Alfred Caronia generated a lot of discussion this past week, as well it might.  The appellate court overturned the criminal conviction of pharmaceutical sales representative Alfred Caronia for off-label promotion of Xyrem, prescribed primarily to prevent narcolepsy.  […]
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Generic of 505(b)(2)

There are not many instances of a generic version of a reference drug approved via the 505(b)(2) pathway.  Last Friday, FDA approved Watson’s generic of Teva’s Plan B One-Step [progestin].  Watson will call its version Next Choice One Dose. For history and industry buffs, Plan B was originally developed under the Duramed brand Barr Pharmaceuticals, […]
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ViroPharma loses exclusivity appeal

As I wrote last week, on 4/9/12 the FDA denied ViroPharma’s request for 3-year exclusivity for its antibiotic Vancocin and approved three generics.  ViroPharma immediately sued the heads of FDA and HHS and their Agencies.  In a U.S. District Court decision, the judge denied ViroPharma’s motions to grant a  preliminary injunction to require that FDA withdraw the ANDA […]
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ViroPharma denied request for 3-year exclusivity

ViroPharma has pulled out all stops to prevent generic copies of its off-patent Vancocin® capsule (vancomycin hydrochloride) including the use of the Citizen Petition process.  Recently, FDA denied most of the requests  in their Citizen Petition and simultaneously approved generics from 3 companies.  ViroPharma immediately responded by filing a suit against the FDA. A reading of the […]
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NIH Head Urges Repositioning/Repurposing

In a speech at yesterday’s 2012 TEDMED conference, the head of the NIH, Dr. Francis Collins, said  that there is a big gap between basic research and drugs for patients.  To bridge this gap he suggested ‘some of those old drugs could be re-purposed — or taught new tricks’ – hey, that’s our tag line! […]
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Generic vs. 505(b)(2) Failure-to-Warn Liability

A recent editorial (may need subscription) in the New York Times opined that a recent Supreme Court decision – a “bizarre outcome” – “makes it virtually impossible to sue generic manufacturers for failing to provide adequate warning of a prescription drug’s dangers.”   The court case the Times is referring to is Pliva Inc. v. Mensing .   In […]
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Don’t launch unapproved products after 9/19/2011

I had a call from a client who wondered if he could launch a new ‘DESI’ product. He had just read the FDA’s recent announcement that it would take immediate enforcement action on any unapproved drug introduced into the market after September 19, 2011. So, the question he asked was, is his “DESI” drug an […]
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Whew! Supreme Court rules generic labels must track RLD

A lot of generic companies are breathing easier today. As we discussed in this blog before, two district courts ruled that generic companies must comply with state laws and add warnings to the label even if it differs from that of the brand product (the Reference Listed Drug – RLD). The cases went to the […]
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Why generic companies might like 505(b)(2)

How would you like to spend a couple of hundred thousands of dollars (or equivalent local currency) and countless months getting FDA approval and patent expiration and then face 14 competitors?  What’s the ROI for that? June 1, 2011 Donepezil Hydrochloride Tablets, Matrix Laboratories Ltd., Approval Donepezil Hydrochloride Tablets, Cipla Ltd., Approval Donepezil Hydrochloride Tablets, Wockhardt […]
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KV’s Makena: Part 3: Use of Public Information for 505(b)(2) approvals

In previous postings (Intro, Part 1, Part 2), I provided background on KV’s Makena (17a-hydroxyprogesterone caproate injection aka 17P). The development and regulatory history contains many lessons. In this posting I’d like to examine the use of public information to substitute for sponsors’ studies. By definition, the 505(b)(2) application must contain information to which the […]
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KV’s Makena® Part 1: 505(b)(1) or 505(b)2)?

In a previous posting, I provided background on KV’s Makena (17?-hydroprogesterone caproate injection aka 17P). The development and regulatory history contains many lessons. In this posting I’d like to examine the choice of regulatory route. Makena was approved under 505(b)(2) as seen from the approval letter (at this writing the approval documents are not posted […]
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2010 505(b)(2) Approvals

We join everyone else this time of year and develop a list – ours is a list of FDA approvals made under 505(b)(2). As widely reported (WSJ article here) FDA reported that approvals were down in 2010. Frankly, it’s hard to tell what the figures are, let alone mean. The Agency sometimes includes approval of […]
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Safety Studies for 505(b)(2) Applications

The 505(b)(2) pathway is very often cost efficient and lower risk because the NDA application can reference existing preclinical and even human safety studies for the active ingredient. Most often, the excipients used are GRAS-listed. Thus, the applicant doesn’t have to conduct much additional preclinical or safety studies except where needed, such as, to support […]
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Will We Have Generic User Fees? Public Meeting To Be Held.

On the new drug side we have had user fees since 1992. The Prescription Drug User Fee Act (PDUFA) has been renewed many times. The Act provides that FDA will adhere to certain goals in return for fees levied on industry. The pharmaceutical industry has benefited from PDUFA in greater certainty of the timeframe for […]
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Lannett’s Morphine Sulfate Oral Solution: 505(b)(2) or 505j?

Lannett Co., Inc. and its subsidiary Cody Laboratories manufacture Morphine Sulfate Immediate Release Concentrated Oral Solution 20mg/mL. Readers will remember that the various manufacturers of morphine solution were the first to receive FDA enforcement letters based on the Agency’s Unapproved Drugs Initiative. Roxane Laboratories filed an NDA for its product which was approved January 25, […]
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New User Fees for 2011

FDA announced the new PDUFA user fees for fiscal year 2011 (starts October 1, 2010). The fee for a full application containing clinical data is $1,542,000.   For a supplement or an NDA not requiring clinical data, the fee is $771,000. A clinical study is generally Phase 2 or Phase 3, so a 505(b)(2) approved based […]
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What should a license cost?

Many drug development projects stem from licensing an invention or product. Agreeing on the cost of the license is critical to the licensee to assure that the project is economically feasible. The licensor is interested in maximizing the value of the invention. How do you arrive at the terms? One handy source to learn how […]
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Avandia: Who Won?

The media has been very involved in the Avandia case. Headlines or page 1 stories in the New York Times, Wall Street Journal and the British press seemed to take sides rather than report the facts (okay, I shouldn’t be surprised). Today, the day after the 2-day FDA Advisory Committee met to review the safety […]
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Advisory Committee Meeting: Rosiglitazone

The media is crazed with interpretations of the FDA and GSK briefing materials for the Advisory Committee meeting this week regarding the safety of Avandia (rosiglitazone). For those readers who’d like to read the original documents themselves, here are the links.   July 13—14, 2010: Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee […]
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Oxycodone + Niacin Voted Down 19-1

In an overwhelming 19-1 vote , the FDA joint advisory committee meeting held yesterday (4/22/2010) recommended that the FDA not approve Acura/King’s proposed oxycodone + niacin tablet.  As we commented on Wednesday of this week, the sponsor’s data showed that about 16% of the  intended patients would experience flushing at a normal dose of oxycodone.  Yet, […]
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Spending on DTC Advertisements

At GPhA last week, one of the CEO’s on an industry panel said that big pharma spent more on DTC (direct-to-consumer) advertising than on R&D.  Clearly, generic companies don’t like this promotional activity, but I was skeptical of the facts.  A quick Google of DTC costs brought an article in the New England Journal of Medicine with […]
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Generic Approvals Taking Longer

I attended the Annual GPhA meeting this past week.  This event is attended by the CEO’s and other top brass of most of the major generic pharmaceutical companies. This year was highlighted by a presentation from the FDA Commissioner, Dr. Margaret Hamburg.  In her remarks, Dr. Hamburg admitted to a need for FDA to step up […]
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Roche’s Actemra Approved For RA After Year’s Delay

John Jenkins, Office of New Drugs Director, remarked on the low rate (30 percent) of firstcycle approvals for standard review applications (‘The Pink Sheet,’ Dec. 7, 2008). He attributed the low approval rate in part to the submission of applications that require amendments, often because the original submissions were incomplete or incorrect. A recent example […]
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Competition for 505(b)(2) Approvals

Yesterday I presented an audioconference on 505(b)(2) candidate selection. A participant posed the following question: What if our company is developing a drug product (A) and a competitor is also developing a similar product (A’). Can both be approved? The way this would normally work at FDA is that it would approve the first product […]
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2009 505(b)(2) Approvals

2009 saw a record number of 505(b)(2) approvals. A total of thirty-three (33) 505(b)(2) NDA’s were approved by FDA in calendar 2009: 23 new formulations 1 New Molecular Entity 5 new combinations of existing drugs 4 drugs already marketed, but without an approved NDA We track approvals on this blog as they occur. Approvals that […]
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PCID Summary

The FDA issued a draft guidance “Draft Guidance for Industry: Incorporation of Physical-Chemical Identifiers (PCID) into Solid Oral Dosage Form Drug Products for Anticounterfeiting” on July 13, 2009. This PCID guidance focuses on the use of inks, pigments, flavors and other physical-chemical identifiers that can be used by manufacturers of solid oral dosage forms (SODF) […]
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Generic or 505(b)(2)?

Is an opioid product that has abuse resistant characteristics but otherwise the same as the RLD a generic or 505(b)(2)? Readers will know that Camargo has been involved in many opioid-related projects. We have been to FDA’s DAARP 13 times this past year alone. What is the objective of most of these meetings? For the […]
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EXAL-still-GO-ing

At first, Monday’s (11/16/09) news from CombinatoRx said that the FDA had told the company “that the NDA in its current form would not be sufficient to form the basis for approval of Exalgoâ„¢ under Section 505(b)(1)”. Then, on Friday (11/20/09), the company said that the FDA had extended the PDUFA review date by 3 […]
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FDA approves Xanodyne’s tranexamic acid

Xanodyne obtained 505(b)(2) approval for tranexamic acid for use in treating heavy menstrual bleeding (menorrhagia).  The RLD is Cyklokapron(R) which is used to treat hemophilia and to reduce the need for replacement therapy during and following tooth extraction.  The RLD received orphan approval in 1986.  Initially, both tablet and injectable dosage forms  were approved but […]
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505(b)(2) For Formulation Changes

A couple of weeks ago I was invited to present at the 2009 Nebraska Research and Innovation Conference.  The theme of my talk was “The Case for Improving Existing Drugs”. There are several factors driving people to the 505(b)(2) development pathway, a couple of which are: Generic cliff.  By about 2017 there will be very […]
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Allergan sues FDA to allow off-label promotion

Late last week Allergan initiated a novel approach to avoiding FDA regulatory action on off label promotions:  a lawsuit, complete with a request for an injunction against FDA.  Specifically, Allergan alleges that because FDA prohibits promotion of off label uses for Botox, Allergan’s First Amendment right of free speech is being violated.  Allergan would like the […]
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Colchicine Tablets Approved

Colchicine Tablets were approved by FDA on 7/29 & 7/30/09 (approval letters not yet posted as of this writing).  Two NDA’s were submitted, one for the treatment of acute gout and the other for familial Mediterranean fever (FMF). Pretty amazing and interesting for a number of reasons.  First, it is a DESI (meaning, a previously unapproved […]
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ANDA Suitability Petition vs 505(b)(2)

I was honored to be invited to speak at the FDA-OCRA 12th Annual Educational Conference in Irvine California on June 10, 2009.  I was asked to discuss and compare the 505(b)(2) and ANDA Suitability Petition.  I thought I should share this topic with the readers of this blog. Why make the comparison between an ANDA […]
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Cheerios®: breakfast cereal or drug?

Cheerios® – venerable breakfast cereal or…drug? Last month the FDA issued a warning letter to General Mills CEO Ken Powell, informing him that the cholesterol-lowering claims on the Cheerios label transformed it from food product to unapproved drug.  The Food and Drug Administration Modernization Act of 1997 allows for certain authoritative health claims to be […]
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Quick-release bromocriptine mesylate approved

The FDA approved VeroScience’s Cycloset (bromocriptine mesylate) 0.8mg tablets on May 5 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The NDA was first submitted in 1997 – before the 505(b)(2) guidance.  The API, bromocriptine mesylate was approved under NDA 017962 in 1978 as Parlodel […]
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What to develop?

Not all clients come to us with product ideas.  Indeed, they want us to help identify a short list of suitable candidates.  Example companies might include technology platform companies. How do we go about helping these clients? We have a four-step process: Criteria Selection, Criteria Evaluation, Candidate Narrowing, Candidate Selection. 1. Criteria Selection.  Every company will use […]
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505(b)(2) NDA Labeling

All NDA submissions require that a draft label be included. For a 505(b)(2) NDA, where do you get the information for this label? What labeling is required? What is labeling?  Well, the “label” is what is on the immediate container of the drug product and can contain printed or graphic information.  “Labeling” is all other […]
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What is a ‘483?

You may read in the news or a company press release that a manufacturing site has received a ‘483.  This is usually considered bad news. Indeed, failure to remedy observations in a ‘483 can lead to withheld product approvals or even plant closure. When the FDA makes a visit to inspect a facility (manufacturer, lab, […]
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Brand-name drugs no better than generics

Read the headline again – ‘Brand-name drugs no better than generics’.  This headline was on MSNBC/MSN web site and originated from a Reuters article reporting on a study conducted by Dr. Aaron Kesselheim of Brigham and Women’s Hospital and Harvard Medical School in Boston.  The study concluded that there is no evidence that brand-name drugs given […]
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Creating a safer NSAID

Many companies are attempting to reduce the GI bleeding, ulcers and perforations caused by administration of NSAIDS (e.g., ibuprofen, naproxen, aspirin).  Since Vioxx was removed from the market (and it was a safer NSAID with respect to GI), there has been an surge of NSAID activity around these existing actives.  We understand that the FDA’s […]
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505(b)(2) Patent & Marketing Exclusivity

IP attorney Stephen Albainy-Jenai and I just concluded a webinar hosted by DIA entitled 505(b)(2) Patent & Exclusivity.  23 different companies attended, showing the increasing interest in 505(b)(2) issues.  Earlier this year, DIA hosted my overview of the 505(b)(2) drug development process where the attendees had many questions asking specifically about patents and exclusivity, many of which I couldn’t […]
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New Safety Reporting Requirements for Unapproved OTC products

We’ve been observing the FDA crackdown on unapproved DESI and OTC drugs.  The reason that Congress and FDA have made these moves is a concern for safety.  Industry counters that these drugs have been used safely for years.  Frankly, there is a lack of data to support either side.  Approved drugs have always been subject […]
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505(b)(2) – Part 2: The Assessment: Preclinical Review/Preclinical Plan

Rats, mice, dogs, pigs – ANDA folks don’t have to deal with testing generic products in animals.  As long as the excipients are previously approved, generic drugs don’t have to conduct any preclinical studies. 505(b)(2) development programs may need to include some preclinical studies depending mainly on whether the route of administration changes or FDA […]
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