Camargo 505(b)(2) Blog

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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CMC Bridging Studies

We have discussed bridging studies in this blog before in the context of the phase 1 bridging study to link the safety and efficacy of the RLD to the proposed drig product.  So, what is meant by a bridging study for CMC* purposes?During the 505(b)(2) drug development process we often change the formulation, components or API. […]
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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 alogliptin NDA was filed prior to issuance of FDA’s December […]
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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) or biogenerics and BIO prefers to call them follow-on biologics […]
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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 Clinical Research” appears in the New England Journal of Medicine […]
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Use of Data from Foreign Clinical Studies for US Approval

Two major factors drive clients to consider running trials in foreign countries – cost and recruitment.  The question we often get is: can we use the data from such trials in a US submission?   The answer is: quite possibly.  I won’t address the conduct of supporting trials in foreign countries, rather, this post addresses the conduct […]
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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 this list for approvals through November, 2008 has a column […]
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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 provide two separate releases of medication.  According to the Takeda […]
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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 to the acceptance of the patch form by patients. So […]
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505(b)(2) NDA Labeling

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

You may read in the news or a company press release that a manufacturing site has received a ‘483.  This is usually considered bad news. Indeed, failure to remedy observations in a ‘483 can lead to withheld product approvals or even plant closure. When the FDA makes a visit to inspect a facility (manufacturer, lab, […]
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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 with a statin.  In fact, it was announced that Abbott […]
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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 is an NME? Under FD&C 505(c)(3)(D) and 505(j)(5)(D) “a new […]
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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 drug development program contained two Phase 3 trials, one examining gastric […]
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Brand-name drugs no better than generics

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

A minor ripple in the media, the Associated Press reviewed Medicaid records and found that since 2004, Medicaid has paid at least $200 million for unapproved drugs (perhaps $50MM per year).  “Unapproved” sounds scary, right?  These drugs are DESI drugs that are not normally reimbursed.  $200 million pales in comparison to the amounts that Medicaid has paid.  For […]
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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 safe and effective for a given set of indications.  It […]
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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. The sponsor believe or has designed the product to have […]
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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 over the last few years that the FDA has made […]
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Another DESI in Discretion

Ever since FDA gave notice about Marketed Unapproved Drugs, manufacturers of these drugs have been wondering when the shoe would drop on their products.  Basically, the FDA has said that eventually these products must be removed from the market.  Since the FDA does not have sufficient resources, it will remove products it deems most hazardous.  […]
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FDA Bans 30+ Ranbaxy Generic Drugs – except 1 Sole Source

Today’s (9/17/08) news headlines include reporting on FDA’s ban on the import of more than 30 generic drugs made by Ranbaxy at two manufacturing sites in India.  The ban is based on FDA’s adverse inspection findings (the notorious Inspectional Observations (FDA-483 form)) at Ranbaxy’s Dewas and Sahib facilities.. FDA has a wide degree of power to exclude […]
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More DESI-products cited. Exceptions are noted for unique products.

FDA inspections and citations sometimes take a few weeks to appear on the FDA website. So, “news” is a erlative term here.  Nonetheless, activity related to DESI drugs has a keen interest to us because they represent FDA thinking and potential 505(b)(2) projects. A July 24 Warning Letter was issued by FDA to G & W […]
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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.  A recent Google search on an RLD yielded almost 40,000 […]
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