Camargo 505(b)(2) Blog

Active Ingredients vs. Active Moieties – Perplexity of Understanding the Relationship or Distinction

Recently a federal district court spotlighted FDA’s apparently inconsistent definitions of what constitutes an “active ingredient (AI)”  in rejecting the Agency’s rationale for denying Amarin Pharmaceuticals Inc.’s fish oil capsule Vascepa (icosapent ethyl) (NDA 202057 approved July 26, 2012), request for 5 years of market exclusivity as a New Chemical Entity (NCE).  On Feb. 21, […]
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To List or Not to List – That is the Question

A 505(b)(2) may rely on the FDA’s previous findings of safety and efficacy  of an approved drug product. It is possible to rely on more than one approved drug product.  It is also possible that a 505(b)(2) applicant does not have to rely on any approved drug. The correct choice of listed drug product may allow  […]
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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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Priority Review Vouchers are a Big Carrot for Hungry Companies

Priority review vouchers (PRVs), which are fast-becoming a powerful incentive for drug companies, were originally based on a publication (Ridley et al. 2006) from a group at Fuqua School of Business at Duke University in NC. The idea behind PRVs was that developers of treatments for neglected infectious diseases (and later, rare pediatric diseases) would […]
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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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Opportunities in Orphan Drug Development for Investors, Pharma and CROs

Orphan drugs, defined in the Orphan Drug Act as drugs developed to treat rare diseases that affect fewer than 200,000 people in the U.S., have begun to make their mark for patients and drug companies. As the number of orphan drugs has increased over the past 30 years, many patients with rare diseases have benefited […]
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REMS/ETASU and Safe Use in Bioequivalence trials

We’ve previously commented regarding the predilection of RLD holders whose product approvals include a Risk Evaluation and Mitigation Strategy (REMS) and Elements To Assure Safe Use (ETASU) to use the REMS/ETASU as a barrier to entry for generic completion.  Specifically, the RLD holder will refuse to sell their product to the prospective generic manufacturers, who […]
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MAPPing out the timing of a Complete Response submission

A type of FDA document which sometimes slides past under the radar is  MAPP, that is, Manual of Policies and Procedures.  These are actually internal FDA documents which are generally analogous to the SOPs FDA requires that industry have and follow.  However, by virtue of the various requirements for transparency placed on FDA, they are […]
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Extending Exclusivity: How Long Will It Really Last?

Last week at the Generic Pharmaceutical Association (GPhA) Annual Meeting, the 21st Century Cures Act, a proposed bill with bipartisan support, was a topic of discussion. Specifically, subtitle L—Dormant Therapies, which would offer 15 years of exclusivity for drugs and biologics approved as dormant therapies. From the House Committee on Energy and Commerce’s bill summary/discussion […]
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2014 505(b)(2) NDA Approvals

2014 drug approvals seem to have rebounded somewhat from the past year. In his annual CDER New Drug Review Update, FDA’s John Jenkins cited 35 NME NDA and BLA approvals (calculated through December 3, 2014), up from 27 in 2013 (see chart below). These approvals include 505(b)(1) NDAs as well as BLAs . Some interesting stats […]
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Manufacturing Support for “Breakthrough Therapy” Designation for Solid Oral Dosage Forms

In November, this author participated in an open forum at the AAPS Annual Meeting focused on streamlining manufacturing and scale up to support ‘breakthrough therapy’ designation for solid oral dosage forms. The goal was to provide clarity for breakthrough therapies and chemistry, manufacturing and controls (CMC) challenges to develop a quality submission in a shortened timeframe where […]
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Therapeutic Equivalence Ratings Under 505(b)(2)

The FDA listing of therapeutic equivalence (TE) ratings can be a murky area for products approved under 505(b)(2) applications. The concept of TE ratings emerged from FDA regulations for generics and revolve around the announcement that the FDA would publish a current listing of all of its approved drugs together with TE ratings. This was […]
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Orphan Drug Exclusivity for a Previously Approved Drug: a 505(b)(2) Conundrum

Until now, if a Sponsor intended to request orphan designation with 7 years of marketing exclusivity for a drug that has already been granted orphan designation, FDA has followed the Code of Federal Regulations (CFR), including the condition described in 21CFR §316.34(c): “If a drug is otherwise the same drug as a previously approved drug […]
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5-Year Exclusivity for Certain Fixed-Combination Drugs with an NCE

The FDA recently posted new Guidance on its website awarding certain fixed-combination drug products (fixed-combinations) 5-year new chemical entity (NCE) exclusivity. While the Agency held previously that these products were ineligible for NCE exclusivity (5 years) if one component is already approved, with this new Guidance in effect, a drug product will be eligible for […]
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Alkermes Prodrug for Treatment of Multiple Sclerosis: NCE?

The Food and Drug Administration (FDA) began requiring drug efficacy, in addition to safety, for approval in 1962 based on the Kefauver-Harris Amendment. Despite this requirement, many drugs that have been approved by FDA have limited efficacy (eg, drugs that treat cancer or Alzheimer’s disease). In many cases, some portion of the limited efficacy is […]
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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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Top Generic CEO’s confirm importance of 505(b)(2) in their company’s financial future

Development stage companies are seeing more opportunities to license their products to generic companies.  Recently, generic company CEOs reinforced the importance of 505(b)(2)-developed products to their financial future. The 2014 Generic Pharmaceutical Association (GPhA) annual meeting concluded this pastweek in Orlando.  This is the largest gathering of C-level executives from the generic industry.  Camargo has exhibited and I […]
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2013 505(b)(2) NDA Approvals

2013 appears to be a challenging year for FDA NDA approvals.  FDA’s John Jenkins reviewed the  NME NDA and BLA approvals through November 2013, showing that 25 such products were approved (see chart below).  These 25 approvals are 505(b)(1)NDA and BLA’s.  Generally, this performance was seen as disappointing, but readers of this blog know that the number […]
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Expensive, cheap, value? CMO costs.

Contract manufacturing organization (CMO) A bids $600,000.  CMO B bids $450,000.  Which bid is cheaper? Assume for the moment that both CMOs provide equal service parameters: skill, capacity, timelines, regulatory history, experience, etc. and we are judging both based only on price. No, this is a not trick question.  But the result is not obvious. Even with a detailed […]
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ANDA but No NDA – What to Rely on?

Camargo participates in 2-5 PIND meetings each month and one thing we notice in the FDA minutes is that the boilerplate answer to ‘does the Agency agree this ….. is appropriate for filing under 505(b)(2)?’ keeps getting longer.  Recently, the Agency (or, at least, some divisions) is informing sponsors that they cannot use a product approved under […]
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PREA – Pediatric Plan Timing Changed by PDUFA V

The Food and Drug Administration Safety and Innovation Act (FDASIA; also known as PDUFA V), signed into law on July 9, 2012, contains amendments to the Pediatric Research Equity Act (PREA) that specifically detail the timing of the submission of a Pediatric Study Plan (PSP). In order to direct greater adherence to the PREA requirements before […]
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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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FDA Rejects Depomed’s Gabapentin for Menopausal Symptoms

FDA concurred with its Advisory Committee’s recommendations and has turned down Depomed’s application seeking a new indication for gabapentin.  Depomed has sought approval to use the drug in the treatment of menopausal symptoms – ‘hot flashes’. We reviewed the Advisory Committee’s deliberations in this blog this past April.  The drug failed to show superiority over placebo.  […]
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505(b)(2) Prodrug Fails Phase III Study

Development of drugs for new indications entails more risk of failure than simply changing formulations.  Just ask XenoPort, which announced May 19th that its prodrug of R-baclofen, arbaclofen placarbil,   failed to show efficacy in a Phase III clinical trial. Arbaclofen placarbil was being studied for multiple sclerosis-related spasticity. Racemic baclofen,  now generic, is indicated for treating muscle […]
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Don’t conduct unneeded tox studies

In April I presented a webinar under the auspices of the DIA concerning preclinical bridging. During this webinar, we discussed the need to fill the toxicology gaps that may have been created during the time since the original reference listed drug was approved. These gaps, I stated, has led to the unfounded belief that the […]
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Merck Uses 505(b)(2) for New Combo

On May 3, 2013 FDA approved Merck’s  Liptruzet, which combines the its Zetia (ezetimibe) and atorvastatin – Pfizer’s Lipitor which has gone generic.  According to the Merck press release, Liptruzet was approved “for the treatment of elevated low-density lipoprotein (LDL) cholesterol in patients with primary or mixed hyperlipidemia as adjunctive therapy to diet when diet alone […]
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Raptor’s Procysbi Costs More Than A Generic (!)

Again we have the media troubled by new, improved drugs that cost more than the generic they are based on rather than trumpeting the improvements.  Raptor Pharmaceutical received approval of its Procysbi (cysteamine bitartrate) for the treatment of  nephropathic cystinosis, an orphan disease affecting an estimated 500 patients in the U.S.  FDA approved Procysbi under 505(b)(2) on April […]
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Non-clinical bridging – Most 505(b)(2)’s Don’t Require Full Tox Package

I have just finished a webinar under the sponsorship of the DIA dealing with non-clinical bridging. In this post, I’d like to share one of the case studies from my presentation to illustrate what should be considered during development. The example is the development of gabapentin enacarbil by XenoPort/GSK for restless leg syndrome. Gabapentin enacarbil […]
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New PDUFA V Meeting Timelines

PDUFA V ushered in new industry and FDA commitments.  Among these are changes in meeting timelines. A significant change from PDUFA IV is the timeline for Type A meetings. Under PDUFA IV the meeting package was due 30 days in advance of the meeting.  Now, under PDUFA V, this package is due at the time of […]
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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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Orphan Designation Granted Letter

Camargo is privileged to work with many clients to develop Orphan drugs.  In order to obtain an Orphan drug approval the sponsor must first request that the drug and indication be granted orphan-drug designation.  This process requires research into both the indication and the potential population.  If the FDA’s Office of Orphan Products Development agrees, […]
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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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KV Appeals Makena Decision

We have followed the saga of KV’s Makena for two reasons.  The most important reason is that the submission, review and approval of Makena is perhaps the best example of using a publicly funded clinical study for NDA approval, despite the clinical trial material not being sourced by the sponsor of the NDA.  The other reason is […]
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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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2013 GDUFA Fees

FDA has published the 2013 GDUFA fees: Finished Dosage Form (FDF) :  Domestic: $175,389  Foreign: $190,389 API:                                       Domestic: $26,458    Foreign: $41,458 These fees are due by March 4, 2013.
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2012 505(b)(2) Approvals – Record Year

Nice going!  2012 saw a record number of 505(b)(2) drugs approved – 47.  As is usual at this time of the year, I have prepared a listing of all of the approvals. This year, I have made the listing more useful – the table is now sortable and now contains a hyperlink to both the […]
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Suit to challenge use of REMS to block generics and 505(b)(2)

Innovators have used REMS to block generic and 505(b)(2) developers from gaining access to the reference listed drugs (RLD), effectively blocking their development.  The 2012 Congress failed to pass legislation to force innovators to provide access to the RLD’s.  FDA believes it has no authority to assist.  In fact, FDA refuses to reveal if the […]
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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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Orphan Designation without Exclusivity: Court asked to decide

Yesterday, Depomed filed suit against the FDA requesting the Court to order FDA to grant their product Gralise (gabapentin) 7 years of exclusivity since it was granted Orphan status; upon approval, Gralise was granted 3 years of exclusivity. Depomed licensed the product to Solvay which became Abbott via acquisition.  Thus the majority of NDA-related regulatory […]
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New Generic Stability Requirements

After much delay, FDA just released the new Guidance on the stability requirements to file and obtain approval of a generic drug product and API under 505j.  The new requirements bring ANDAs closer in line with NDAs and ICH.  The new requirements as summarized in the Guidance are: 1. Submit data from three pilot scale batches […]
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Court dismisses KV’s suit against FDA

Yesterday 9/6/2012, the U.S. District Court for the District of Columbia dismissed KV Pharmaceutical’s suit against the FDA.  KV had asked the Court to force FDA to stop the marketing of compounded versions of 17-hydroxyprogesterone caproate cream and related imported API.  FDA countered with the argument that the Courts cannot force the FDA to take […]
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K-V Pharma bankrupt – Claims FDA Doesn’t Back Makena

K-V Pharmaceuticals filed for Chapter 11 bankruptcy. After years of GMP issues narrowed the product offering to just one product, Makena (17-hydoxyprogesterone caproate), poor sales of the product couldn’t sustain the company. In this blog I have discussed the filing and approval of Makena, a product for pre-term labor.  Prior to this approval, the product had been available […]
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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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REMS in Congress

I’m not into politics, but maybe some of my readers are and wish to contact their representative in the U.S. House of Representatives to share your thoughts on a pending issue. With the introduction of REMS, innovator companies have used the restricted distribution feature to prevent other pharmaceutical companies from obtaining drug supplies that can […]
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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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Drug Development Planned Like the Titanic

How many drug development companies leave it up to the CRO or CMO to design or execute their studies or formulation/manufacturing without oversight?   Like those who boarded the Titantic 100 years ago, they seem to trust the mantra that their contractor’s work is unsinkable.  MAP Pharmaceuticals seemed to do just that – the approval of their […]
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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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2011 505(b)(2) Approvals Now Exceed 505(b)(1) NDA Approvals

What a year for 505(b)(2) drug development!  In 2011 FDA approved 44 505(b)(2) NDA submissions.  Various authors have reported that FDA approved 34 or 35 drugs in 2011 (505(b)(1) NDA + BLA).  I had speculated a couple of years ago that perhaps 80% of new drugs approved  in 2012 would be 505(b)(2)’s, based on botha  […]
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What is an Approved DESI Product?

I am hesitant to contribute more information about so-called DESI drugs at the risk of further confusion.  My goal is always to provide clarity, so here goes. Fundamental to any discussion about DESI products is the definition of a drug product.  Let’s just focus on one part of the definition – the labeling.  A drug […]
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Stability Changes coming to ANDAs

This post comes from D.C. where I am attending the GPhA Fall Technical Conference.  We just completed a presentation by FDA’s Glen Smith.  He  detailed the proposed new stability requirements for ANDA drug products.  It is essentially the adoption of ICH Q1A.  For readers of this blog, we know that 505(b(2) NDA’s must have 12 months […]
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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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AB Rated 505(b)(2)’s

Can you have an “AB” rated 505(b)(2)?  Yes, as well as other Therapeutic Equivalent (TE) codes that are most often associated with the TE codes for generics in the Orange Book. Several years ago when I was speaking about the potential products that qualified under 505(b)(2) I had a line in a PowerPoint slide for […]
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2012 PDUFA User Fees

The 2012 PDUFA User Fees have been announced in the Federal Register.  In summary, the fees are: Applications: Full – requiring clinical data (e.g., Phase 2 or 3):  $1,841,500 Not requiring clinical data                                 :         920,750 Supplements requiring clinical data                  :         920,750 Establishment fee: $520,100 Product: $98,970 For those doing the math, the cost […]
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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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KV’s Makena Part 4: Statistical versus Clinical Significance

In previous postings (Intro, Part 1, Part 2, Part 3), I have 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 difference between statistical and clinical significance.  Please note that this is not meant as a rigorous statistics […]
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Patent Cliff Causes Pfizer Cuts

Yesterday (08Jun11) The Wall Street Journal reported  (subscription may be required) that Pfizer will cut an additional $1 Billion – mostly in administrative costs.  These cuts come after cuts to sales and R&D. What’s driving all of these cuts is two-fold:  loss of sales of their products to generics and failure to obtain approval for […]
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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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Ophthalmics: 21 CFR 314 94(a)(9)(iv) no longer applies

Who would have guessed that 21 CFR 314.94(a)(9)(iv) no longer applies to ophthalmics?  You wouldn’t generally have expected it to just be cancelled – normally FDA must go through notice and comment, but apparently the FDA can make a regulation disappear by decree. 21 CFR 314(a)(9)(iv) states: (iv)Inactive ingredient changes permitted in drug products intended […]
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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 2: Accelerated Approval Subpart H

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

On February 3, 2011 Hologic, Inc. (subsequently sold assets to KV Pharmaceuticals) received 505(b)(2) approval of Makena®, its 17?-hydroxyprogesterone caproate injection (17P) to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. The subsequent announcement that the price would be set at $1500 […]
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Revised Safety Reporting for BE/BA Studies Effective March 28, 2011

On September 29, 2010 FDA published a Final Rule revising the requirements for safety reporting for INDs and other BE/BA studies. At the same time FDA issued an accompanying draft guidance to assist in interpreting the new rule. The Final Rule, revising 21 CFR §§ 312.32, 312.64 and 320.31, becomes effective March 28, 2011. The […]
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What is the Pediatric Drug Development Approach for Rare Diseases and Orphan Drugs?

As part of the PDUFA V reauthorization discussions, the FDA and industry are talking about better approaches to rare disease drug development and orphan drugs. Public interests and Congress have mandated that FDA develop new guidances on the required studies needed for NDA approval. In these discussions, participants refer to the “pediatric drug development approach” […]
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User Fee Waivers: What is an Affiliate? New Guidance Issued

Under the current PDUFA regulations, a small business can request a waiver of the normal review fees for an NDA if it is the first NDA submitted by the small business. The definition of a small business is fewer than 500 employees. In determining the 500 employee limit FDA also considers the affiliates of the […]
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Approvals of ANDAs slows

I attended the 2011 Generic Pharmaceutical Association (GPhA) meeting last week. There was lots of useful information from several speakers. One area in particular stood out to me — the approvals of ANDAs are slowing and there is a growing awareness that the root cause is not just the Office of Generic Drugs (OGD). As […]
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Contrave® Rejection: The Long and the (Too) Short of it

On February 1st Orexigen(R) Therapeutics, Inc. and Takeda Pharmaceutical Company Limited (Takeda) announced that the FDA issued a complete response letter dated January 31, 2011 regarding the New Drug Application for Contrave® (naltrexone HCl/bupropion HCl) extended-release tablets for the treatment of obesity, including weight loss and maintenance of weight loss (http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irol-newsArticle&ID=1522207&highlight=). In the letter, FDA […]
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Mitosol – an Orphan & 505(b)(2) without clinical studies

Mobius Therapeutics announced that it has received orphan drug status for Mitosol to prevent the recurrence of pterygium after surgical excision. The active ingredient, mitomycin has been used without FDA approval for eye surgeries since the mid 1960’s. Due to its long history of use, the FDA did not require that Mobius conduct clinical trials. […]
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Injectables: 505j or 505(b)(2)?

Generic injectable drug products are treated differently than other routes of administration when it comes to permitted differences from the RLD. For most dosage forms, the sponsor is allowed to change excipients as long as the test product is bioequivalent to the RLD. No so for injectables, the excipients must be the same. If the […]
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REMS for 505(b)(2) products?

Camargo has been involved in the development of several opioids and is often contacted by new sponsors to develop alternate formulations. One question often brought up is: does a 505(b)(2) approved opioid require a REMS (Risk Evaluation and Mitigation Strategies — for more information on REMS see a previous posting)? The short answer is: of […]
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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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PDUFA Fee Waiver: Plan Ahead

For an original NDA, whether it is a 505(b)(1) or 505(b)(2), there is a PDUFA fee to be paid at the time of the submission of the application or the FDA will refuse to file it. For a small business ( a company of less than 500 employees) the fee can be waived for its […]
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Nuedexta® – Smart Pharmacology to Treat a Unique Disorder

The FDA has approved NuedextaÃ’ (Avanir Pharmaceuticals Inc.), a drug that curbs involuntary and uncontrolled crying and laughing episodes (known as pseudobulbar affect (PBA)) that are experienced by patients with some neurological disorders. Nuedexta is the first drug to be approved to treat patients with these symptoms. Nuedexta is a combination product containing dextromethorphan hydrobromide […]
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Endpoint for GI Toxicity Clarified

NSAIDs are known to induce gastrointestinal (GI) tract toxicity, notably upper GI tract. Drugs that suppress gastric acid secretion such as histamine type 2 receptor antagonists, proton pump inhibitors (PPIs), NSAIDs (e.g., COX-2 selective drugs), and misoprostol (a prostaglandin E analog that also has mucosal protective properties) have been studied for their ability to protect […]
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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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Company Officials Personally Liable

As part of what appears to be an increasingly aggressive enforcement stance, there have recently been a number of statements coming from FDA in several settings suggesting that an increase in the number of prosecutions of senior corporate individuals is imminent. In the past, FDA and the Department of Justice have initiated a fair number […]
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When is an IND required?

Most of us know that a BA/BE study of a generic can be done without an IND (the exception, called a Bio-IND, is when the drug being studied is cytotoxic or a radioactive labeled drug). In 505(b)(2) drug development we often are studying the BA/BE of a test drug versus an RLD as part of […]
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505(b)(2)s with Minimal Sponsor Studies

The power of the 505(b)(2) process is realized when the sponsor has to conduct few, if any, studies to get their drug product approved. For many drugs there is wealth of data available in the public domain. The challenge is locating the data and then preparing it for the FDA in such a way that […]
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Why have a Quality Overall Summary for the Quality Module?

The Quality Module (Module 3 or Chemistry, Manufacturing and, Controls section (CMC)) in the eCTD format serves as the backbone of any regulatory submission, an IND or NDA. We have discussed this in a previous blog posting. There is debate about the usefulness of the Quality Overall Summary (QOS or Module 2.3 of eCTD) with […]
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FDA Places Hold on all ANDA PAS & CBE Reviews

In a blog posting earlier this year, we discussed the then median 26 month ANDA approval time and how it was getting longer. We now know that the Office of Generic Drugs (OGD) currently has over 3000 ANDA post-approval supplements (PAS) waiting for action, of which 1500 have been pending for over 6 months. In […]
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Failed 505(b)(2)?: Vivus™ Qnexa

I am often asked about 505(b)(2) drug development failures. After all, 505(b)(2) is a regulatory pathway that is chosen because it is lower cost and has lower risk than a 505(b)(1). The lower risk is attributable to the reliance on the known safety and efficacy of the reference drug product. Indeed, one of the strategies […]
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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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Generic Lovenox: 505j or 505(b)(2)

Today, Marwood Group Advisory Services broadcast an e-mail giving its thoughts on the approval of Momenta Pharmaceutical’s generic of Lovenox®. This is a very nice write up of the regulatory history, including the summary of the Citizen Petition filed by Sanofi- Aventis challenging such approval, but it contains a glaring error. Upon approval and an […]
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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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Still submitting paper ANDA applications?

Experience that shows electronic filing of NDA’s, IND’s and ANDA’s helps speed up the review and approval of these applications. Perhaps because of the software cost and extensive training needed some companies still submit paper applications. Effective today, August 1, 2010, the address to submit the paper ANDA is: Office of Generic Drugs (HFD—600) Center […]
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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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