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505(b)(2) Development Articles and Insights

In the News: November 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Voxzogo Approved as a Growth-Improvement Therapy for Children with Dwarfism Biomarin has obtained FDA accelerated approval for Voxzogo (vosoritide), its

In the News: August 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Some Drugs May Require Reclassification to Devices On August 9, the FDA published a Federal Register notice requesting

In the News: June 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Decades-Old Antidepressants Being Repurposed to Treat Cancer  At Camargo, we have worked with hundreds of investigators who have

In the News: May 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Approval of the Month: Non-Opioid for Post-Surgical Pain Gets FDA Nod Heron Therapeutic received FDA approval for its

In the News: March 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Rare Disease Clinical Trials Most Often Terminated Due to Regulatory and Recruitment Issues The difficulty associated with successfully

In the News: August 2020 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Fitbit developing algorithm for early detection of COVID-19 Fitbit recently posted a study that may indicate the company’s

In the News: July 2020 Regulatory and Development Updates

Each month, Camargo’s “In the News” series will highlight important changes and advancements in the regulatory and development space and explore how those changes could impact your program. FDA announces intention to resume domestic inspections Camargo recently examined an FDA Complete Response Letter which required

Repurposing Drugs As an Answer to the COVID-19 Crisis

Hydroxychloroquine. The world rallied around this old drug as a potential treatment of COVID-19 patients. The pharma industry, independent researchers, and governments rushed to conduct trials to see if hydroxychloroquine is safe and effective at any stage of this invasive virus. Though it has now

Three Keys to Preparing Effective Pre-IND Meeting Questions

Updated on: April 19, 2021 Updated by: Taylor Anderson, Content Marketing Associate Asking the appropriate questions during a Pre-IND meeting with the FDA is a critical step in planning a development program. A Pre-Investigational New Drug Application (Pre-IND) meeting can be a valuable component in

2019 505(b)(2) NDA Approvals in Review

In 2019, CDER approved 64 NDAs that used the 505(b)(2) pathway, representing important advances in patient care across a wide range of therapeutic areas. The number of 2019 NDA approvals that used the 505(b)(2) pathway fell from 75 in 2018 to 64 in 2019 (Figure 1), in

ANDAs Prioritized to Combat Opioid Crisis

As part of nationwide efforts to address the opioid crisis, FDA is taking a closer look at the development of critical medications that combat overdose deaths. Most recently, FDA announced its intention to prioritize review of ANDAs for drug products indicated for emergency use in

505(b)(2) or ANDA: Which Pathway is Right for Your Product?

Last week, FDA published new guidance, Determining Whether to Submit an ANDA or a 505(b)(2) Application (CDER, 2019), to help Sponsors select the best abbreviated approval pathway for their product. While the guidance does not provide any monumental new initiatives, policies or approaches, here are four key

505(b)(2) Nonclinical Development: Examples and Advantages

The 505(b)(2) New Drug Application (NDA) pathway can provide unique advantages from the nonclinical development perspective that can save significant amounts of time, money, and resources. Compared to the 505(b)(1) NDA pathway, which is more standardized and follows the general guidance provided by the International

2017 – A Great Year for Generics – Yes or No?

Generic Firms Looking for Revenue with 505(b)(2) AAM’s Annual Conference is over and most of the generic companies are glad 2017 is over, too. Despite media reports that 2017 was the best year ever for generics, only 3 companies of the top 30 companies reported

505(b)(2) Success Requires More Than Just Science

At the JP Morgan Conference/Biotech Showcase this year, we encountered a record number of companies engaged in 505(b)(2) development. We also had meetings with investors and buyers with their checkbooks open to finance or acquire the more than 80 products we have in development. Unfortunately,

505(b)(2) Approval Times: The Real Scoop

The Approval Time for 505(b)(2) and 505(b)(1) NME Products Is Similar A recent article by the Tufts Center for the Study of Drug Development (summarized here) reported that approval times for New Molecular Entities (NMEs) approved via the 505(b)(2) pathway are nearly 5 months longer

Referencing a Listed Drug for the 505(b)(2) Pathway

Section 505(b)(2) of the Food, Drug, and Cosmetic Act describes a 505(b)(2) new drug application (NDA) as an application where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has

On the Rise: 2016 505(b)(2) NDA Approvals

On the Rise: 2016 505(b)(2) NDA Approvals The total number of novel drug approvals in 2016 decreased by approximately half from last year (22 in 2016, from 45 in 2015) and is below the 10-year average of 29 drug approvals per year. Of these, how

505(b)(2) Application Changes: What You Need to Know

505(b)(2) Application Changes: What You Need to Know Title XI of the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 was enacted in order to address concerns that had potential to delay access to more affordable drugs. The FDA has been implementing the

Improving Drug Development ROI in 2017

Time to Pick the Low-Hanging Fruit: Improving Drug Development ROI in 2017 With forecasts of decreasing peak sales for late pipeline drugs, a logical way to increase the return on investment (ROI) for pharmaceutical companies is to develop products with lower research and development (R&D)

The GRAS Is Not Always Greener

  The GRAS Is Not Always Greener: Why GRAS Status Does Not Guarantee Excipient Safety Many, if not most, 505(b)(2) submissions represent a change to an approved drug, usually involving a formulation change. Understandably, the focus of sponsors is often primarily on supporting the safety

Back to Basics: 505(b)(2) FAQs Part 1

As the 505(b)(2) expert, Camargo is frequently asked questions about how to get a product approved via the 505(b)(2) regulatory pathway and if this pathway is appropriate. Given the growing popularity of the 505(b)(2) pathway for approval of repurposed, reformulated, or unapproved marketed products, we

Statistical Bootstrapping Method To Take the Uncertainty out of Drug Development

Statistical Bootstrapping Method Using a Bias-Corrected Acceleration Approach Well-reasoned and properly conducted statistical analyses can be essential to successful drug development, particularly in the context of manufacturing scale-up, process and component changes, and in comparisons with a reference product. Similarity tests between dissolution profiles steer

Pediatric Applicability or Not–This Revised Guidance Is for You

Since 1994, the statutory and regulatory requirements for drug product labeling for pediatric populations have been evolving. The FDA Modernization Act of 1997 (FDAMA) contained incentives for conducting pediatric studies on drugs that had exclusivity or patent protection. In 2003, the Pediatric Research Equity Act

Additional 505(b)(2) Benefits: Selective Safety Data Collection

  Last month CDER/CBER released a short, final guidance, “Determining the Extent of Safety Data Collection Needed in Late Stage Premarket and Postapproval Clinical Investigations.” (CDER/CBER, 2016) While brief, the guidance could provide a significant reduction in safety data collection for NDA sponsors. This could

2015 505(b)(2) NDA Approvals

2015 was a big year for FDA, with 45 novel new therapies approved — much higher than 28, the average number approved in the past decade. Of the 45 approved in 2015, how many were approved through the 505(b)(2) pathway? And how does the number

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?

Encounters of the Third Sector

As I walked the floor at the International Generic Pharmaceutical Alliance (IGPA) conference in Toronto, I couldn’t help but feel a little gratified. Companies that were once disavowing the 505(b)(2) approval pathway are now driving the conversation. Investors that once shied away from 505(b)(2) products

Enforcement Activities: FDA removes unapproved prescription ear drops

For years FDA has threatened to remove unapproved products (so-called DESI products) from the marketplace. Recently, the FDA took enforcement action against  several unapproved prescription ear drops.  What products will be next?  DESI producers can use the 505(b)(2) pathway to avoid such actions on their products. Let’s take a

Examining the Amarin VASCEPA Saga

The headlines and newscasts reported Amarin’s success in wining off-label promotion, but behind the scenes, another noteworthy action took place – in a very rare action, the FDA rescinded a special protocol assessment (SPA) that would have enabled Amarin to promote the new indication. In

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

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

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

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.

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

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

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

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).

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

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

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

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. 

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

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

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

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,

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

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

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,

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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 —

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

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

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

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,

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

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:

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

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.,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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,

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

Labeling for Abuse-Deterrent Drugs

This past Tuesday (6/8/2010), we participated in a DIA-sponsored webinar entitled Understanding the Development and Label Allowances for 505(b)(2) Abuse-Deterrent Products. Joining me, Ruth Stevens our CSO and Cindy Phurrough, our Clinical Operations head, was Dr. Lynn Webster, Chief Medical Officer of Lifetree Clinical Research

Pro-Drug Denied

I am frequently asked if 505(b)(2) projects fail or whether any NDA submissions are rejected. My answer is that the vast majority succeeds and are eventually approved. Those that fail more often are due to money or design issues, not execution risks. Today I discuss

505(b)(2) Product Gains Revenue with FDA Actions Against DESI’s

Eurand reported improved financial performance for the 1st quarter of 2010. CEO Gearoid Faherty indicated the majority of the revenue gains could be attributed to Zenpep®, Eurand’s delayed-release pancreatic insufficiency drug. Zenpep was approved in August 2009. The FDA has recently clamped down on unapproved

Target Product Profile

Today’s blog courtesy of Lynn Gold, Ph.D. Camargo’s VP of CMC. In any project development program an understanding of the program goal is critical to finding the shortest path to the final result. Generation of a Target Product Profile early in a development program facilitates

505(b)(2): Repositioning, Repurposing or What?

Last week I made a presentation at the Society of Biomolecular Sciences (SBS) 2010 Annual Meeting in Phoenix (due to the Iceland volcano eruption, many participants are still there).  The occasion was the inaugural meeting of the newly formed Special Interest Group for Repositioning Drugs

505(b)(2) Approvals

I have seen various postings and articles on the number of 505(b)(2) approvals.  The numbers do not always agree.  Why don’t they agree?  Many people look only at the approval letter.  The FDA will always indicate that the NDA was submitted as a 505(b).  But the

FDA Removes Unapproved Nitroglycerin Tablets

On March 16, 2010 FDA ordered Glenmark Generics and Konec to cease manufacturing and distribution of nitroglycerin tablets.  These actions are part of the FDA program to remove unapproved products from the market.  In this case, Pfizer makes the approved product, so these removed products

FDA’s Determination of Vyvanse as NME Upheld

On March 4, 2010 the U.S. District Court for the District of Columbia agreed that FDA was within its rights to grant Shire’s Vyvanse (lisdexamfetamine dimesylate) NME status and thus, 5-years exclusivity. New Rivers Pharmaceuticals (NRP) was the original sponsor of the lisdexamfetamine NDA. During the

Exalgo Approved

Exalgo, hydromorphone extended release tablet was approved March 1, 2010. I waited a couple of days to see if it was approved under 505(b)(1) or 505(b)(2). At this writing, we don’t know. We have previously detailed in this blog the regulatory approval saga for this

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

Once Daily Trazodone Approved

Yesterday, 2/3/10, FDA approved under 505(b)(2) Canadian-based Labopharm’s once-daily version of trazodone HCl for the treatment of depression (as of this writing, this approval is not posted on the FDA web site). The initial PDUFA date was July 18, 2009 but this was missed because

505(b)(2) NDA Preparation Process

Camargo is fully prepared to create, submit and manage the review of an NDA, either 505(b)(1) or 505(b)(2). Generally, we submit the NDA electronically, so we’re submitting an eCTD. 1. An individualized secure shared website for Camargo and the Client’s project is created for document

DESI to 505(b)(2) Raises Drug Costs

FDA is trying to remove unapproved new drugs from the market. This past year the FDA approved URL’s colchicine. Previously, FDA announced it was taking action against unapproved colchicine on the market. We have commented on these actions in this blog. A recent article in

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

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

PhRMA Adds New Bio Companies

The trend in Big Pharma continues to shift from small molecules to biologics. PhRMA announced that it added seven (7) new members to its roster at the end of the year. The new PhRMA members are Cubist Pharmaceuticals, Inc., Lexington, MA; OSI Pharmaceuticals, Inc., Melville,

Start Your New Year Right

Do not start the New Year off with CMC issues. Take the time to follow-up on your subcontractors before the FDA finds problems and delays submission approval. Pharmaxis Ltd. just found out the hard way that poor oversight of manufacturing and testing subcontractors will be

Getting Unapproved Drugs (DESI, etc.) Approved

FDA uses the term ‘Unapproved Drugs’ to refer to any drug that is marketed in the U.S. without FDA approval.  There are hundreds, maybe thousands of these drugs in the U.S..  We have written about the efforts of FDA to remove them from the market. 

505(b)(2) Approval Standards – Referenced Studies

Awareness of current FDA and its Division standards is important when preparing a new submission. A basic premise for a 505(b)(2) submission to the Agency is that the application contains full reports of investigations of safety and effectiveness but where at least some of the

505(b)(2) – Giving Thanks

No turkey, no Black Friday specials, just a thank you note. Little did we know that in 1984 Congress would provide for a regulatory pathway that would provide such a cornucopia of beneficial products that we see under development today. US consumers should give thanks


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

Qutenza: Approval of a “DESI-inspired” Drug

This week, NeurogesX, Inc. announced the FDA 505(b)(2) approval of Qutenza(TM), its 8% capsaicin patch, for management of post-herpetic neuralgia (PHN) – the nerve pain that can follow an attack of shingles. While not strictly speaking a DESI product, Qutenza can be considered “DESI-inspired,” because

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. 

A New Paradigm for the Development of Drugs for Type 2 Diabetes

Due to Camargo’s on-going client projects in this area, our chief medical officer, Dr. Sam Kaba recently attended a DIA-sponsored conference in Washington, D.C. entitled Cardiovascular Safety and Development of Type 2 Diabetes Mellitus Medications: Current State of the Art and Opportunities to Advance the

FDA Refuse to File: Merck Zetia & Pfizer Lipitor

Merck disclosed that FDA refused to file its 505(b)(2) NDA for the combination of Pfizer’s Lipitor (atorvastatin) with Zetia (ezetimibe).  According to Merck’s disclosure, the FDA reason for he refusal is: The FDA has identified additional manufacturing and stability data that are needed and the

FDA warns P&G over use of Drug + Vitamin C

Last Thursday, 10/29/2009, FDA sent P&G a warning letter regarding Vicks DayQuil Plus Vitamin C and Vicks NyQuil Plus Vitamin C. The FDA takes the position that these two products are unapproved drugs because they combine a (OTC) drug and a dietary supplement.  The relevant passage

REMS or RiskMAP or what?

On 30 September 2009, the FDA issued a new draft guidance for industry: Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications. The guidance describes the content and format of a REMS, which the FDA was authorized

505(b)(2) Submissions: No RLD

Two weeks ago (10/14/09) I had the pleasure to present at the Drug Repositioning Summit in Boston.  I started my talk by asking the audience if a 505(b)(2) application required a Reference Listed Drug (RLD).  Most replied affirmatively. My talk was on 505(b)(2)’s without an RLD. Let’s take

FDA Reaffirms 5-year Exclusivity for a Pro-drug

FDA has reaffirmed its prior assignment of 5 years exclusivity to Vyvance (lisdexamfetamine dimesylate).  When Vyvance was approved in 2007, this prodrug of dextramphetamine was given NCE status with a 5 year exclusivity.  With this exclusivity, the FDA may not accept an ANDA before the

Preemption: New Hampshire 1, Sanity 0

On September 30, U.S. District Court (New Hampshire)  judge Joseph Laplante decided that Mutual Pharmaceutical was obligated by New Hampshire law to include warnings on its ANDA products not included on the reference listed drug’s labeling.  The judge ruled that, although the Hatch-Waxman amendment clearly stated

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

Comparability Protocols

What do you need to do when you need to change suppliers or manufacturing sites?  Among the many choices is a formal FDA Comparability Protocol.  Our VP CMC, Lynn Gold explains. Advance planning can improve the possibility of FDA accepting your proposed change. One alternative that can streamline

DESI Presentation: Q&A

Today I conducted an audio conference entitled: FDA banning DESI Drugs-Submissions Strategies to Keep Yours on the Market.  I know, a bit aggressive, but it’s also a crowded market.  Judging from the questions, most attendees are current DESI producers looking to gain knowledge of the

Test Specifications for Stability Studies

Pivotal stability programs that are used to generate stability data for NDA submissions are different than research stability programs used to design the drug product, explore packaging configurations, etc.  This is common sense, but we have seen instances of pivotal stability programs that have been

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

BDSI’s buccal fentanyl 505(b)(2) NDA approved

BioDelivery Sciences International received FDA approval of its 505(b)(2) NDA for buccal fentanyl on July 16, 2009.  Most notable about this approval is the first REMS (Risk Evaluation and Mitigation Strategies).  The FDA cautioned that this REMS shouldn’t be used as an example for other

AstraZeneca ends collaboration with MAP Pharmaceuticals

MAP Pharmaceuticals announced yesterday (7/9/09) that AstraZeneca has ended its collaboration on unit dose budesonide (UDB).  This past February, MAP reported that the Phase 3 study had failed to reach its primary endpoints.  Apparently, further analysis failed to support continued development of UDB. We seldom

Benzyl Alcohol- NME approved under 505(b)(2)

The source of NMEs (new molecular entities) for use in 505(b)(2) drug development programs is vast.  A major benefit of an NME is the 5 year data exclusivity. Sciele Pharma recently (4/9/09) obtained 505(b)(2) approval for a 5% benzyl alcohol lotion for the treatment of head lice in

ADVENTRX restarts 505(b)(2) development

Today June 29, ADVENTRX Pharmaceuticals announced plans to use their recent financing to finish the development of ANX-530 (vinorelbine emulsion) and submit a 505(b)(2) NDA by the end of the year. Careful readers of this blog may remember a January 2008 posting citing ADVENTRX ANX-530 as an

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

Electronic filing of eCTD INDs

As large amount of documentation and data are required in IND submissions, the Electronic Common Technical Document (eCTD) format is a wise choice for the submission of INDs to the FDA. Camargo’s experience with filing INDs in the eCTD format includes a very recent eCTD

Writing and submitting electronic 505(b)(2) INDs

Any use of a drug product not previously authorized for marketing in the United States first requires submission of an Investigational New Drug Application (IND) to the FDA. To date, the FDA accepts IND submissions in the ‘old format‘ and in the Common Technical Document

Melphalan – New 505(b)(2) Orphan Designation

Delcath Systems Inc. announced that the FDA has granted an additional orphan designation for melphalan for the treatment of neuroendocrine tumours metastatic to the liver.  Delcath uses a proprietary system they call the Percutaneous Hepatic Perfusion (PHP) System to deliver high doses of existing drugs

What are DESI Drugs?

A reader pointed out that I have never defined DESI drugs, despite several posts that contained references to them.  DESI drugs are a great source for 505(b)(2) development since many will qualify for 5 years data exclusivity. Once upon a time…. In 1938 the FD&C

505(b)(2) IV Acetaminophen

Cadence Pharmaceuticals announced yesterday 5/14/2009 that it had submitted an NDA for Acetavance(TM) – intravenous acetaminophen.  It is instructive to look at the clinical development plan for this 505(b)(2) product.  According to the company, the FDA required 2 pivotal Phase 3 trials: one clinical trial for

Multiple Dosage Strength Products – CMC Considerations

Developing a product with multiple strengths?  How do you go about filing multiple strengths in an IND?  Lynn Gold, Ph.D., Camargo VP of CMC explains: How and when to draft one CMC section covering multiple drug strengths for the same dosage form? Long-term drug development goals

505(b)(2) Combination Products

During the Q&A after my audioconference yesterday a participant asked if a proposed drug product containing 1 new drug and 2 already approved drugs would be a 505(b)(2).  Although she didn’t say so, I assumed that the 2 approved drugs did not belong to her

Polypill: a 505(b)(2) candidate

FDA approved Novartis’ Exforge HCT on April 30, 2009 for the second-line treatment of hypertension.  Exforge, approved in 2007, contains the calcium channel blocker amlodipine and the angiotensin receptor blocker valsartan.  The new product adds to Exforge the well known diuretic HCTZ – hydrochlorothiazide.  The

505(b)(2) Head Lice Treatment approved

FDA announced on April 9 that it had approved Sciele Pharma’s benzyl alcohol lotion, 5% for the first-line treatment of head lice.  Sciele was recently acquired by Shionogi Company. Sciele licensed this product in July 2007 from Summers Laboratories.  The product had a PDUFA date

FDA Stops DESI Unapproved Rx Narcotics

Yesterday, 3/31/09, FDA sent warning letters to nine pharmaceutical companies  to stop manufacturing 14 unapproved narcotic drugs.  These drugs are unapproved because they were made without NDA or ANDA approvals, falling under the category of DESI or grandfathered drugs. Warning letters were sent to the

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

Generic Cliff

At the recent Generic Pharmaceutical Association (GPhA) 2009 annual meeting, several presenters discussed what was termed the “generic cliff” – a time in the near future when there will be no small molecules left to copy.  According to the CEOs of Watson, Mylan and Teva,

505(b)(2) Development Risks

We know that 505(b)(2) drug development is chosen because it is lower cost, lower risk and faster than traditional new drug development and offers the potential of greater ROI than generics.  But, it is not without any risks. On 3/06/2009, Takeda announced “that although the

Generic Biologics

This past week I attended the 2009 Generic Pharmaceutical Association annual meeting.  Much time was devoted to the issue of generic versions of biologics.  Adding to the debate was the what to call these drugs.  The GPhA prefers to call them biosimilars (nice ring to sameness)

Use of Foreign Trial Data

No, I don’t have a  crystal ball.  Yesterday, I posted comments on the factors FDA can use to determine what foreign trial data it can use (extrapolate) to US populations and medical practice.  Today, an article entitled “Ethical and Scientific Implications of the Globalization of

2008 505(b)(2) Approvals

For the first time, FDA’s new drug division has approved more 505(b)(2) drugs than those submitted via 505(b)(1). In 2006 and 2007, the percentage of 505(b)(2) drug approvals went from 20 to 43%, respectively.  The FDA publishes a list of drugs approved each year and

Dexlansoprazole approved for the treatment of GERD

This past Friday, 1/30/2009, the FDA approved Takeda Pharmaceuticals North America Kapidex (dexlansoprazole) for the treatment of gastroesophageal reflux disease (GERD).  Kapidex is an enantiomer of lansoprazole (Prevacid).  In addition to the change in enantiomer, Kapidex is formulated with two type of enteric-coated granules to

Watson’s 505(b)(2) Overactive Bladder Gel Approved by FDA

On 1/27/2009 Watson Pharmaceuticals announced that the FDA had approved its GELNIQUE(tm) (oxybutynin chloride) Gel 10% for the treatment of overactive bladder.  The gel product supplements a transdermal patch made by Watson (Oxytrol) which has not had the marketing success one might expect, perhaps due

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

Fenofibrate (TriCor) active metabolite approved

In a previous posting we commented on the battle between Abbott and Teva over Abbott’s generic defense strategy.  Yesterday (12/15/2008), FDA approved Abbott’s TriLipix – fenofibric acid.  Fenofibric acid is the active metabolite of fenofibrate.  The approval includes an indication to allow use in combination

What is an NME?

People are often surprised when I tell them that 505(b)(2) applications can contain a new molecular entity (NME).  In fact, a 505(b)(2) covers any NDA application that relies on pivotal efficacy or safety information that the sponsor does not own the rights to. So what

505(b)(2) Combination Meets Phase 3 Goals

Horizon Therapeutics announced yesterday that its “fixed-dose combination product containing ibuprofen and famotidine, demonstrated a statistically significant reduction in the incidence of non-steroidal anti-inflammatory drug (NSAID)-induced upper gastrointestinal (gastric and/or duodenal) ulcers in patients with mild-to-moderate pain when compared to ibuprofen alone.”  Note that the

Sertraline + CBT – a new 505(b)(2) Combo

Several news sources report today (10/31/2008) that a new study shows that sertraline in combination with CBT eases anxiety in children.  A number of 505(b)(2) development projects arise from observing these kinds of trials:  an efficacy study shows that two (or more) concurrent treatments are

Just a BE study for 505(b)(2) approval? Likely not!

I have addressed this topic before but from several recent discussions I thought it useful to repeat this here. A number of companies hope to do just BE studies to obtain approval.  The proposed changes to the RLD are formulation, dosage form, IR to ER, etc.

Drug Repositioning Summit 2008

Camargo was one of the sponsors of Cambridge Healthtech Institute’s Drug Repositioning Summit last week (Oct. 6-7, 2008).  I woke the group up on the second day with a breakfast talk entitled “505(b)(2) Experiences – The Journey Continues”.  I reviewed some of the important changes

505(b)(2) Literature Searches – Too much or too little?

A 505(b)(2) submission relies on information in the public domain to fulfill some of the information required in an NDA for approval.  This information comes from more than the reference drug’s NDA review documents.  In fact, for older drugs, the amount of information can be overwhelming. 

Shionogi to Buy Sciele Pharma

Shionogi, a Japan-based pharmaceutical company, announced yesterday (9/1/2008) that it would buy Atlanta-based Sciele Pharma for $1.42 billion –  57% premium to the current share price.  Shionogi’s analysis of the purchase is here.  Sciele’s business strategy relies on 505(b)(2) drug development.  Sciele in-licenses products in a

Transcept and Novacea to Merge

Transcept Pharmaceuticals (formerly TransOral) announced today (9/2/2008) that it is merging with Novacea.  Transcept is a privately held company while Novacea is NASDQ-listed, so the merged company will be a public company.  Novacea had 2 cancer therapies that didn’t meet expectations.  Transcept has a 505(b)(2)

Modeling using Dissolution Data

Not only pharmacokineticists get to have fun in the modeling sandbox.  Chemists and formulators get to have their fun synthesizing data.  Let’s use an example of how dissolution data can be used for modeling.  The example is taken from a project to develop a oral

PK Modeling, not just any pretty face

We recently changed the navigation and look of our website to show that we are a full-service drug development company.  505(b)(2) drug development is so much more than just regulatory submissions!  I was asked to explain what the chart is on the pharmacokinetics (PK) services

Residual Solvents – New FDA Draft Guidance

The USP established a new test requirement for control of residual solvents in finished dosage forms. The new test is in the General Chapter <467> “Residual Solvents”  [Sorry no link – password protected].  The test became official July 1, 2008.  In turn, on August 5, 2008 the

KV’s DESI Guaifenesin Trumped by Adam’s 505(b)(2) Product

Last week (7/30/2008) , FDA announced that it seized timed-release guaifenesin products from KV Pharmaceutical.  In 2002 the FDA determined this DESI product to be a safety hazard to children.  The manufacturers, including KV Pharmaceutical (Warning Letters: see page 23)  were told to stop manufacturing by November 2003

Current versus RLD approval requirements

A 505(b)(2) NDA has the same approval requirements as a 505(b)(1) NDA, the only difference is where the pivotal data comes from .  505(b)(2) is not a shortcut in the sense that you can get by with less information.  Clients are often amazed (the polite

PREA and 505(b)(2)

Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the

Hospira expands into 505(b)(2) development

Hospira, best known as a generic injectable pharmaceutical company, is going to start developing a transdermal product.  Yesterday (7/2/2008), Altea Therapeutics announced a partnership with Hospira for the development and commercialization of an undisclosed product.  Altea is best known for its transdermal delivery system.  You can

505(b)(2) – No patent, just exclusivity

We have all been confronted with the issue of patents and exclusivity for 505(b)(2) product development projects.  Financial backers, VC’s, private equity are fixated on the ruggedness of patents – no patent  = no money.  Biomarin Pharmaceuticals made a presentation at the 2008 BIO conference

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

Raptor announces Orphan designation for cysteamine bitartate

Raptor Pharmaceuticals announced that the FDA has granted orphan drug designation for cysteamine bitartrate for the treatment of Huntington’s disease. Cysteamine is currently approved by the FDA and European Medicines Agency to treat nephropathic cystinosis*, also an orphan designation. In addition to the targeted orphan designation, it

Fenofibrate in the news (again)

I recently used the saga of Abbott’s TriCor (fenofibrate) product life extension tactics for an FDA citation to support the use of multiple RLD’s in a 505(b)(2) application.  I also think the story is instructive to the 505(b)(2) industry as to how even slight changes

What’s the competition?

In speaking with prospective clients, we often discuss the potential competition to their proposed drug product. In order to have success in the market, the proposed product needs market differentiation. Some thoughts on a couple of categories: Existing Products – What other drugs are available for the same

Multiple RLD’s under 505(b)(2)

I enjoy eating Chinese food with a group, because I can get a sample from each person’s plate.  Such as in 505(b)(2) submissions, you can pick and choose parts of different RLD’s for your submission. A reader was surprised when I previously commented that a 505(b)(2) submission can have more

RLD – Born in the USA

You have a global perspective and drug development program.  You want to conduct studies in the US and an international location.  You’re going to use an RLD from Big Pharma – you know, the global giants.  The RLD bought in the US and Europe looks the

Paragraph IV Certifications under 505(b)(2)

What is the difference between a Paragraph IV certification between the 505j (ANDA, generic) and 505(b)(2)? None.  The difference is the exclusivity outcome – 505(b)(2) never gets any exclusivity based on patent certification. In a U.S. drug application, in Module 1, Administrative Documents, you must

Fospropofol turned down or approved by FDA Advisory Committee?

MGI Pharma’s Aquavan(R) (fospropofol) is a phosphate prodrug of the anesthetic propofol.  Propofol  must be administered by an anesthesiologist because of its rapid onset. The phosphate prodrug’s time to onset is delayed due to the conversion to the active moiety.   A slow onset of sedation

Biovail to reduce 505(b)(2) development

Biovail joined the increasing list of pharma companies that are downsizing or eliminating their 505(b)(2) development programs.  As reported in the Wall Street Journal* Biovail CEO William Wells, in a conference call announcing a  change in company focus,  said “Focusing on the development of products

505(b)(2) Orphan Drug Approval with only a BE study?

A reader recently inquired about Orphan drugs and asked me if I thought an Orphan drug developed under 505(b)(2) could be approved based on just a Phase 1 study – a pharmacokinetic or pharmacodynamic comparison to the RLD. At first I thought I couldn’t think

Racemate > Isomer Approval under 505(b)(2)

The 505(b)(2) process is used to obtain approval of an isomer of an already approved racemate.  An example is cetirizine.  The original product approved (Zyrtec)  is a racemate.  In May 2007, UCB, Inc. obtained approval for levocetirizine dihydrochloride 5 mg tablets, using the 505(b)(2) process.  That

505(b)(2) RLD Patent Certification

In our webinar last week on Patent & Marketing Exclusivity we received an interesting question that I would like to pass along to readers of this blog. Q: If there are two RLDs, one with IP and one without IP, does a Sponsor have to

505(b)(2) with Orphan Indication

I was recently asked how you can have a 505(b)(2) application for an Orphan drug.  The reasoning behind the query was that Orphan drugs are new chemical entities (NCE).  This perpetuates the misconception that 505(b)(2) cannot be used for NCEs, which by now readers of

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

NanoNews – Beads deliver drug to site of action

In another fine example of a formulation change, Biocompatibles International reported that its very small beads were used to sequester Doxorubicin (adriamycin).  The resulting beads were delivered via a catheter directly into the liver of patients with liver tumors.  The tumor growth was suppressed for

Is your drug project a 505(b)(2), ANDA or OTC?

I get a lot of requests to assure people that their project is, or is not, a 505(b)(2). A few questions about whether it is an OTC candidate. The question about whether the proposed drug is a 505(b)(1) or 505 (b)(2) is readily answered by

Approval delays at FDA

One of the expected benefits of the new drug approval process under PDUFA is that drugs get approved within a certain timeframe, today about 10 months after submission. This often cited as a reason why generic companies are looking at 505(b)(2) – generic approval times

Another “unapproved” drug needs a 505(b)(2) approval

FDA is continuing to act on its promise made in January 2007 to remove products from the market that it considers unapproved.  These products, some stemming from the DESI process, have been with us many years. The latest casualty is Colchicine for Injection.  On February

505(b)(2) – Part 3: Pre-IND submission & meeting

Before filing an IND, it is desirable (we counsel imperative) to have a pre-IND meeting with the FDA.  The goal is to get FDA’s concurrence with the proposed development plan and regulatory submission pathway.  The steps for this meeting (known as a Type B meeting) include:

505(b)(2) with Only Phase 1 Study

We are often asked if a 505(b)(2) application always requires a clinical study (i.e., Phase 2 or 3 in patients).  The answer is a resounding NO. On January 14, 2008 ADVENTRX Pharmaceuticals announced the successful completion of a bioequivalence study that demonstrated similar blood levels and

505(b)(2) – Part 2: The Assessment: Timeline, Cash Flows

Once the clinical development plan is established, the CMC, regulatory and medical communication plans can be matched up. We use MS Project to develop a high-level overall plan.  MS Project then can be used to generate cash flows and Gantt charts.  This information can be used by

505(b)(2) – Part 2: The Assessment: CMC Development Plan

CMC Development Plan All too often we see plans that don’t integrate the clinical trial materials with the clinical development plan.  This is usually because the people and organizations responsible for each area don’t interact well and there is a lack of overall project management. 

505(b)(2) – Part 2: The Assessment: Regulatory Strategy

Regulatory Strategy This section provides analysis of pertinent regulatory information to produce a recommended regulatory pathway.  A thorough search of regulatory documents supports the regulatory recommendations (e.g., Dockets Management; HeinOnline[1]). The 505(b)(2) regulatory pathway may be appropriate if part of the NDA application requirements can

505(b)(2) – Part 2: The Assessment: Clinical Development Plan

Clinical Development PlanThe proposed Clinical Development Plan is dependent on the selected regulatory pathway.  The Clinical Development Plan is based on available Agency study recommendations provided in the FDA Guidance for Industry documents, information in the public domain (e.g., PubMed), and information obtained from SBA

505(b)(2) – Part 2: The Assessment: Clinical Pharmacology

Clinical Pharmacology An overview of the proposed product’s absorption, distribution, metabolism, and excretion (ADME) is detailed in this section obtained from various resources.  An important source of information for this and other sections is the FDA reviewer summaries (Summary Basis of Approval – SBA) for

505(b)(2) – Part 2: The Assessment: Pharmacokinetic Review

A comprehensive search of the literature is performed to obtain published pharmacokinetic (PK) data for the proposed product (dependent on selected regulatory pathway). This review compares the PK profiles for all available routes and conditions of administration and dose strengths. This review includes studies assessing: Single- and

New MAPP for FDA Accepting Alternate Compendia for CMC standards

On 11/3/2007 FDA issued a new MAPP* entitled “Acceptability of Standards from Alternative Compendia (BP/EP/JP)”.  Although directed at new drugs, one can probably argue that the policy should also apply to the Office of Generic Drugs.  Up to now, reviewers seemed arbitrarily accepting or denying

505(b)(2) Combo Plavix/Prilosec

Cogentus Pharmaceuticals is working on a combination tablet that combines clopidogrel, the active ingredient in Plavix, with omeprazole, the API in Prilosec. Cogentus’s business strategy is to: “… improv[e] the therapeutic profiles of existing, proven drugs in ways that take full advantage of their strengths while

505(b)(2) – Part 2: The Assessment: Safety Review

Of course my product is safe! – the RLD was shown to be safe. Perhaps so.  The FDA approves products based on a risk/benefit; is the risk of taking the drug outweighed by the benefit?  Would FDA approve the RLD using today’s standards?  What changes from

P&G Drops out of a 505(b)(2) Development

Nastech announced on 11/7/2007 that P&G had dropped out of their co-development of a nasally delivered version of Lilly’s osteoporosis drug Forteo (teriparatide).  As reported, the Nastech CEO speculated that the reason for P&G’s termination of its participation was that original timescales for product development

505(b)(2) – Part 2: The Assessment: Efficacy Review

One of the key attractions to the 505(b)(2) route is the potential of gaining approval with only one Phase 3 study.  Moreover, this Phase 3 study is often small, at least compared to the thousands of patients in 505(b)(1) submissions.  There are exceptions, to be

505(b)(2) – Part 1: The overall process

Our process for developing a drug product to be submitted to the US FDA under the 505(b)(2) process has been validated during many meetings with FDA.  I want to share important aspects of this process with the community. This is the first post of several parts. 

Adams “DESI” Product Approvable

Adams Respiratory Therapeutics announced that it received an Approvable letter from FDA on 10/29/07 for its guaifenesin 600/1200 mg and codeine phosphate 30/60 mg extended-release bi-layer tablets.  The release indicates that the FDA needed additional data to support the use of the product with food. The

Drug Repositioning: 2 Flavors

Last week’s Drug Repositioning Summit was attended by more than 150 people.  The Summit started with my 3-hour workshop on 505(b)(2) drug development.  Several attendees were seemingly confused about what “drug repositioning” means.  There are two distinct ‘flavors’ of drug repositioning: Take a currently US-approved

FDA moving against unapproved Hydrocodone products

FDA is announcing that it intends to remove all unapproved products containing hydrocodone from the market. The FDA intends to swiftly move against products labeled for use in children under 6 years of age and allow 90-180 days for products not labeled for use in children

CNN Story on “Unapproved Drugs”

CNN ran a story today to  increase public awareness that there are hundreds of drugs consumed in the U.S. that have never been formally approved by the FDA. For professionals, the FDA has a web page devoted to this topic.  Some of these products were subject to

505(b)(2) of Withdrawn Product

A source of 505(b)(2) opportunities comes from products that have been discontinued.  One of the first things that must be done is to determine why it was discontinued – by law, the product must not have been discontinued for reasons of safety or efficacy.  You