Camargo 505(b)(2) Blog

Advisory Committee Meeting: Rosiglitazone

The media is crazed with interpretations of the FDA and GSK briefing materials for the Advisory Committee meeting this week regarding the safety of Avandia (rosiglitazone). For those readers who’d like to read the original documents themselves, here are the links.   July 13—14, 2010: Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee […]
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The Skinny On a Potential New Treatment of Obesity

Orexigen® Therapeutics is developing a new fixed dose sustained-release (SR) combination of naltrexone and bupropion for the treatment of obesity. The rationale behind the two active ingredients is stated to be: Bupropion acts on the weight control circuit by stimulating the POMC neuron. Naltrexone prevents inhibition of POMC neurons by blocking the action of β-endorphin […]
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India Tightening Inspections on Raw Materials

Cheaper is not always better. The cost of drug development demands that the pharmaceutical industry review the cost of all components of the program. In doing this, often the choice of the active pharmaceutical ingredient (API) manufacturer is driven by cost. Many of the API’s and raw materials are now coming from China. Any company […]
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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 and Pain Clinic. Ruth reviewed the regulatory background, the types […]
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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 an example of a failure based, in large part, on […]
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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 pancreatic enzymes that have been on the market for years. […]
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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 reaching the goal of a marketed drug product. It provides […]
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CMC Issues Again

Several previous blogs have discussed the importance of maintaining quality oversight of a contract facility to the drug development timeline. Below is an example of a generic manufacturer with problems maintaining quality oversight of its own multiple sites. Apotex, the Canadian generic manufacturer received a CMC based warning letter on March 29th. This recent warning […]
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Manufacturing Problems for Intravenous Emulsions

Many of the drug products manufactured by Hospira, including intravenous nutritional emulsions and propofol have been on the market for years. Hospira received a warning letter on April 12th citing two of its intravenous drug product manufacturing plants in North Carolina. The sites were inspected by the FDA in April 2009, and the violations cited […]
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Oxycodone + Niacin Voted Down 19-1

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

On March 19 and 20th the University of Washington School of Pharmacy hosted “The Biosimilars Conference”. This conference prompted some interesting discussions. A good background of the current legal status and issues around biosimilars can be found in the September 30th blog “Biosimilars; an Introduction”. When talking about biologics it is important to remember that […]
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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 Agency will not always indicate whether it is under (b)(1) […]
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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 can be thought of as unauthorized generics.
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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 2/23/2007 approval, FDA determined that the API was a new molecular […]
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FDA’s DAARP is now DAAP, DPAP is now DPARP

Effective March 15th, the FDA’s Division of Anesthesia, Analgesia, and Rheumatology Products is being reorganized. This reorganization is part of some other reassignments announced yesterday (3/09/2010) by the FDA. The “R” part – Rheumatology, will move to the Division of Pulmonary and Allergy Products, which will be renamed the Division of Pulmonary, Allergy, and Rheumatology […]
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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 drug. When we last heard, FDA had told CombinatoRx/Covidien/Alza (clinical […]
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Do Not Neglect Your Third-Party Drug Substance Manufacturer

Another example of the importance CMC was reported in January. Warner Chilcott plc received a complete response letter from the FDA. The “low dose” oral contraceptive NDA was the file in question. The FDA inspection of the third-party drug substance manufacturing facility and control testing laboratory used to support the application reported outstanding deficiencies which […]
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Spending on DTC Advertisements

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

I attended the Annual GPhA meeting this past week.  This event is attended by the CEO’s and other top brass of most of the major generic pharmaceutical companies. This year was highlighted by a presentation from the FDA Commissioner, Dr. Margaret Hamburg.  In her remarks, Dr. Hamburg admitted to a need for FDA to step up […]
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Can and Should ANDA Labeling Differ from the RLD?

In the past two months, two appellate courts, the Fifth Circuit and the Eighth Circuit have handed down decisions which essentially state that generic pharmaceutical companies can be sued in state courts for failure-to-warn regarding serious side effects, where the generic companies had conformed their labeling to that of the current Reference Listed Drug. For […]
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Roche’s Actemra Approved For RA After Year’s Delay

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

Tuesday, February 2nd, Teva Pharmaceuticals announced that the FDA will review its new biologic license application (BLA) to sell a biotechnology medicine, Neutroval, to boost white blood cells, which is “similar” to Amgen Inc’s Neupogen®(filgrastim). The new product is already marketed as TevaGrastim in Europe. There is a regulatory pathway for approving generic versions of […]
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Pediatric Assessments in Drug Development: Timing in Europe vs. US

As we have noted in this blog on several occasions, under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), 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 […]
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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 FDA found issues when inspecting the API manufacturing facility — […]
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It’s Budget Time at the FDA!

In a time where there are going to be government spending caps and cuts, the Administration is proposing a 23% increase in FDA’s 2011 budget (see pages 19-21). Some of this additional money is proposed to come from new fees on food facilities ($220 million) and generic drug makers ($38 million in user application fees […]
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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 control. A folder structure is set up according to the […]
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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 Kaiser Health News questions whether the approval of these DESI […]
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Could This NDA Delay Have Been Avoided?

Once a new drug application (NDA) has been accepted by the agency for filing, the PDUFA review clock starts. We all know the importance of the shortest time to market. Recently MannKind Corporation issued a press release stating that the FDA will not be able to complete the review of MannKind’s NDA for its ultra […]
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Competition for 505(b)(2) Approvals

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

2009 saw a record number of 505(b)(2) approvals. A total of thirty-three (33) 505(b)(2) NDA’s were approved by FDA in calendar 2009: 23 new formulations 1 New Molecular Entity 5 new combinations of existing drugs 4 drugs already marketed, but without an approved NDA We track approvals on this blog as they occur. Approvals that […]
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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, NY; Alexion Pharmaceuticals, Inc., Cheshire, CT; Ferring Pharmaceuticals, Inc., Parsippany, […]
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Analytical Requirements for Oral Solutions

Analytical requirements for the NDA submission of an oral solution to the FDA are very similar to those requirements for any new drug product. The analytical methods that are used for the testing of an oral solution at the NDA stage of development should be fully validated per the ICH guidelines, Q2A and Q2B, now […]
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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 a concern for the FDA. This concern translates into approval […]
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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.  But also FDA has devoted a lot of resources to […]
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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 information required for approval comes from studies not conducted by […]
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Questions and Answers On the Topic of Authorized Generics

What would be the regulatory path for an Authorized generic, in general? Authorized Generics (AG) are prescription drugs that are produced by the NDA holder and marketed under a private label, at generic prices. This circumstance typically presents itself when the NDA holder still has patent protection for the product on the market. Authorization of […]
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PCID Summary

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

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

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

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

GTx announced 11/2/2009 that it has received a Complete Response Letter from the FDA concerning its NDA for TOREMIFENE CITRATE 80 mg (ACAPODENE®). The NDA, filed in late December 2008, sought approval for use of toremifene 80 mg to reduce fractures in men with prostate cancer receiving androgen deprivation therapy (ADT). The NDA was based on […]
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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 Science. His report: The FDA Guidance for Industry on Evaluating […]
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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 Company is assessing the FDA’s response in order to determine […]
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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 from the FDA warning letter is: Notwithstanding your attempt to […]
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Reference Listed Drugs (RLDs):Can More Than One Be Used?

Recently we considered the case of a 505(b)(2) NDA without an RLD.  So let’s ask if  a 505(b)(2) NDA have more than one RLD? In a word, the answer is “yes”! When using the 505(b)(2) regulatory pathway, Sponsors may rely on the Agency’s previous findings of safety and/or efficacy of an already approved product which […]
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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 to require by provisions of the FDA Amendments Act (FDAAA) […]
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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 a look at the regulation itself: Notice that there is […]
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Did FDA Make a Mistake? Prodrug Emend Exclusivity Reconsidered

It is important to give the FDA credit for admitting mistakes. Yesterday’s posting in this blog concerned Vyvance’s NCE and 5 year exclusivity status. The thorough response by the FDA to the Actavis request for reconsideration of the new chemical entity (NCE) 5 year exclusivity granted to Vyvanse (lisdexamfetamine dimesylate) Capsules, the prodrug of dexamphetamine, […]
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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 exclusivity expires unless a paragraph IV is filed, in which […]
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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 that the the ANDA must contain the same wording as […]
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505(b)(2) For Formulation Changes

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

At Camargo, we can help clients evaluate the market potential of their proposed drug product by examining factors that might influence the resulting medical position at the time of product launch.  When desired or needed for potential fund-raising, we can also perform a full marketing forecast.  One aspect of this is to look at market […]
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Codeine Sulfate: FDA continues drive to remove unapproved products, with a twist

Yesterday, October 13, FDA sent Warning Letters  to four manufacturers of Codeine Sulfate tablets, 30 and 60 mg:  Lehigh Valley Technologies, Inc., Cerovene Inc., Dava International, Inc., and Glenmark Generics, Inc., for marketing a product without an approved application.   The manufacturers have 15 days to cease manufacturing, and distributors have 180 days to cease further shipment.  […]
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Allergan sues FDA to allow off-label promotion

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

  Related to the current frantic activity regarding health care in the US, there is a smaller struggle concerning biosimilars that in many ways mirrors the larger health care struggle. Drug products made from small molecules are regulated primarily by the Food, Drug and Cosmetic Act (FD&CA) and through regulations promulgated by the FDA Center […]
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More DESI Tannates removed from market

FDA continues to remove unapproved DESI products from the market.  Generally, it appears that the removals occur when the manufacturing site is inspected and the FDA identifies unapproved products being made.  The latest manufacturer to be hit is ANIP Acquisition Company.  During an inspection of the firms facilities in Gulfport, MS this past February, the […]
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A Treatment IND is NOT the same as an IND

In this blog I seldom quote or provide hyperlinks to press reports because they too often contain misleading information.  Yet, today’s DIA web summary contained an article that I just have to correct.  The article was a  summary of a report on Medpage’s website.  The report’s heading is inadvertently correct: “FDA Finds Oral Insulin Spray […]
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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 the process of change and add clarity to the requirements […]
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2010 PDUFA Fee: $1,405,500

Costs keep rising at FDA and for 2010 this is reflected in a 12.7% increase in user fees.  The new user fee for a full NDA submission is $1,405,500.  The fee for 2009 is $1,247,200.  Remember, for the federal government, 2010 starts October 1, 2009.
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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 pathway to FDA approval.  As we have tracked in this […]
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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 performed for clients with no defined specifications.  A stability protocol […]
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FDA halts marketing of topical ibuprofen products

Noting that topical ibuprofen drugs are not included in any OTC monograph or the subject of any approved NDA, the FDA has issued warning letters (click hyperlink to FDA warning letter) to eight manufacturers/distributors.  This action is continuing good news to DESI producers who worry that getting an NDA may not cause FDA to remove non-NDA […]
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FDA requests melamine testing of ingredients

U. S. government officials both inside and outside of FDA have acknowledged that the Agency currently lacks the resources, both financial and human, to adequately monitor the materials going into products being used in the United States.  The answer?  In the case of the somewhat notorious contaminant melamine, the answer is to make regulated industry […]
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Colchicine Tablets Approved

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

I have added a new page to this blog to track 505(b)(2) approvals.  Please note the tab named Scorecard.  It will be organized by calendar year.  I am currently catching up on 2009 to date. Enjoy and give feedback when needed!
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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 opioid products.  The reason is that the product is indicated […]
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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 see failed 505(b)(2) development projects.  This case is interesting because […]
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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 patients 6 months of age and older.  Benzyl alcohol is […]
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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 example of where a single pk study might be sufficient […]
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Make the Most of Your Interactions with the FDA: FDA Meeting Requests

Any meeting with the FDA is critically important to Sponsors.  We all know that a tremendous amount of time and effort goes into planning for these meetings.  But even before this step the decision to ask for a meeting and the contents of the meeting package should be carefully considered. Typically, a meeting is requested […]
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ANDA Suitability Petition vs 505(b)(2)

I was honored to be invited to speak at the FDA-OCRA 12th Annual Educational Conference in Irvine California on June 10, 2009.  I was asked to discuss and compare the 505(b)(2) and ANDA Suitability Petition.  I thought I should share this topic with the readers of this blog. Why make the comparison between an ANDA […]
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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 IND application accepted by the FDA’s Division of Anesthesia, Analgesia […]
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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 (CTD) format. The CTD is maintained by the International Conference […]
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Risk Evaluation Mitigation Strategy (REMS) for long-acting opioids

Camargo is working with several clients in developing better treatments for pain.  Unfortunately, the active substances that supress pain also can be abused.  The FDA and DEA are trying to find ways to allow access to these  medicines while imimizing the inherent risks of drug abuse. In order to properly advise clients, Camargo attends various […]
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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 directly to the site of the tumor.  Melphalan was first […]
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Cheerios®: breakfast cereal or drug?

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

The FDA approved VeroScience’s Cycloset (bromocriptine mesylate) 0.8mg tablets on May 5 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The NDA was first submitted in 1997 – before the 505(b)(2) guidance.  The API, bromocriptine mesylate was approved under NDA 017962 in 1978 as Parlodel […]
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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 the treatment of acute pain in patients following orthopedic surgery […]
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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 may include multiple strengths of a drug product to support […]
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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 company. The answer is yes, the inclusion of these 2 […]
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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 product was approved based on a single “8-week, multi-center, randomized, […]
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DESI + non-cGMP = Recall

FDA is clamping down  on DESI’s, but to date we have seen FDA only stop manufacturing and distibution.  Until now.  On April 20, 2009, Neilgen Pharmaceuticals and its parent Advent Pharmaceuticals were forced into a recall of 13 cough/cold medications.  All of the cough cold medications are tannate salts of common ingredients.  It is one […]
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505(b)(2) Program: BTG’s Paxclitaxel Gel for Oesophageal Cancer

Media is reporting that BTG’s Phase IIa study of a novel gel formulation of paxclitaxel showed tumor reduction in 70% of patients.  In effect, BTG is taking a known agent and directly targeting the affected tissues;  BTG is also reportedly in later phase trials looking at this gel product in brain cancer – placing the […]
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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 of April 2008 but closure issues led to a revised […]
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Morphine Solution – FDA Changes its decision

We recently discussed FDA’s decision to remove morphine-containing products from the market.  Unfortunately, this decision was made without the benefit of an NDA-approved product being available. This left a void in the market – no oral morphine solution was available for home care.  Give some credit to the FDA – they swiftly reversed their decision […]
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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 following companies (I have listed the affected drug products for […]
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Botanicals: What is the starting material for the API?

We typically work with small molecules of synthetic origin, but occasionally are retained to work with products that have active ingredients from botanical (plant) sources.  Lynn Gold, our VP of CMC provides the following discussion on how to define the starting material for the Active Pharmaceutical Ingredient (API). The definition of the starting material for any API is […]
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What to develop?

Not all clients come to us with product ideas.  Indeed, they want us to help identify a short list of suitable candidates.  Example companies might include technology platform companies. How do we go about helping these clients? We have a four-step process: Criteria Selection, Criteria Evaluation, Candidate Narrowing, Candidate Selection. 1. Criteria Selection.  Every company will use […]
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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, this period is 2017-2019. What’s leading people to see the […]
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One vs. Two batches for single-dose and multiple dose studies

Today’s posting stems from a client question.  The client’s product candidate is an oral product that requires both single- and multiple dose pharmacokinetic studies. Question:  Do companies ever use one pivotal batch for single-dose (SD) study and another batch for the multi-dose (MD) study?  What are the pros and cons of doing this? See the […]
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