Camargo 505(b)(2) Blog

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 […]
Read More

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 […]
Read More

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 […]
Read More

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.
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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!
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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, […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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, […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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.  […]
Read More

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 […]
Read More

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 […]
Read More

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 […]
Read More

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 wide range of therapeutic categories. Products include fenofibrate (lower doses), […]
Read More

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) strategy which we have reviewed in this blog before.  The […]
Read More

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 modified release drug where the RLD is an immediate release […]
Read More

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 services ‘page’: The chart is a result of pharmacokinetic modeling.  Note the […]
Read More

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 FDA issued a draft guidance stating that all NDA and […]
Read More

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 unless they received NDA approval.  Adams Respiratory Therapeutics obtained NDA […]
Read More

$1,247,200 PDUFA Fees for FY 2009

FDA announced on August 1, 2008 the user fees for fiscal year 2009 (the U.S. government 2009 fiscal year start on October 1, 2008).  The fees are based on PDUFA IV approved last year.  The application fee for an application requiring clinical data is $1,247,200, for an application not requiring clinical data or a supplement […]
Read More

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 word) when they learn about the studies need to get […]
Read More

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 claimed indication(s) in pediatric patients unless this requirement in waived, […]
Read More

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 see where this business deal is going.  Hospira many injectables, many […]
Read More

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 to encourage others that patents are not always needed.  The […]
Read More

BIO – User’s Manual

I attended the 2008 BIO Annual convention, my first.  More than 20,000 registrants.  There were the usual plenary sessions with lots of wonderful, flowery, well-meaning platitudes and well-deserved awards.  The luncheons had the current governors of Massachusetts and California and Jeb Bush, the former governor of Florida (unabashedly representing John McCain), Colin Powell and other […]
Read More

Orphan’s turn 25

I attended a session at the 2008 BIO convention in San Diego celebrating the 25th anniversary of the Orphan Drug Act.  Before the Act, there were almost no orphan drugs.  The exemption from the PDUFA user fees (running $1.175MM today), 50% tax credit for clinical studies and a 7 year marketing exclusivity are powerful incentives […]
Read More

Creating a safer NSAID

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

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 appears that Raptor is also trying to improve on the […]
Read More

Indevus’ Stock drops 70% on FDA’s request for more safety data

On June 4, Indevus Pharmaceuticals reported that the FDA is likely to request additional safety data before approving NEBIDO®, its depot testosterone product for the treatment of male hypogonadism.  The news sent the stock on a  tumble – losing $2.46 to $1.26/share (a 70% decline) in the subsequent trading period (it has since recovered a bit, Friday’s […]
Read More

Suicidal behavior: Ignore therapeutic area at your own risk

We hope a common theme emerges from this blog and our public interactions: it is vital when planning 505(b)(2) drug development to look at the entire therapeutic class to learn what studies are needed for approval of the drug .  Not including the class in your background of public information can be suicidal. FDA regulates […]
Read More

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 can be used to develop your own strategy. Recall that […]
Read More

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 therapeutic indication(s)?  Why would the medical profession select yours? Generic […]
Read More

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 than one RLD.  As long as the information is supprortive of […]
Read 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 same, even has the same marking.  But are they same?  […]
Read More

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 submit a patent certification, regardless of the submission route, generic […]
Read More

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 would reduce the likelihood of sudden and unexpected general anesthesia.  […]
Read More

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 that primarily provide convenience and compliance benefits is not a […]
Read More

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 of an example.  Generally, an Orphan drug fulfills an unmet […]
Read More

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 approval was based on replicate clinical studies.  On 1/28/2008 UCB obtained […]
Read More

Trade secrets

According to some observers, the US Patent system is undermining innovation.   In KSR International versus Teleflex Inc., the US Supreme Court ruled that  patents must be “more than the predictable use of prior art elements according to their established functions” or  in my layman’s words, you can’t patent something that should have been obvious.  The drug […]
Read More

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 certify against both RLDs? A: If you reference a RLD, […]
Read More

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 this blog know is wrong.  We have discussed the use […]
Read More

505(b)(2) Patent & Marketing Exclusivity

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

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 long enough in 12 of 18 patients to receive a […]
Read More

505(b)(2) Pre-IND Meetings Denied

Yikes!  For the first time, Camargo has two (yes, 2!) pre-IND meetings denied. Same week.  Not cancelled, not postponed, not re-scheduled – denied!  In both cases, the review divisions said we were on the right track, no controversy exists and that we should simply file the IND. Wow.  The purpose of the pre-IND meeting is much […]
Read More

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 the question: is any data essential for approval being obtained […]
Read More

505(b)(2) Patent & Exclusivity

We gets lots of questions about how the patent system works for 505(b)(2)’s and how it relates (or not) to exclusivity provisions.  A good friend and colleague who is an expert in patent law is going to join me on  a webinar sponsored by DIA.  It will be held April 22 from 11:00 to 12:30.  […]
Read More

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 are now stretching to 20+ months.  Now comes the news […]
Read More

Metabolites: New safety testing requirements – impact on 505(b)(2)

For Valentine’s Day, FDA issued a new guidance on metabolite safety testing.  Essentially, it outlines the non-clinical testing that may be required when the metabolism in humans produces significantly higher amounts of the same metabolites in the animal species where the toxicology was assessed. As the guidance points out, recent advances in analytical technology have […]
Read More

A single Phase 3 trial needed for 505(b)(2) approval of a combination drug

Alchemia Ltd., an Australian pharmaceutical company, announced that it had gained agreement with FDA that a single Phase 3 trial would suffice for approval of its chemotherapeutic drug HA-irinotecan (a new drug containing irinotecan (Pfizer’s Camptosar®) formulated with hyaluronic acid (HA).   Alchemia has conducted phase 1 and 2 studies outside the U.S.  It presented the results […]
Read More

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 6, FDA announced it was taking enforcement action because the […]
Read More

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: Prepare a pre-IND submission package. This package outlines where we […]
Read More

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 a “statistically significant reduction in injection site reactions”.  The company further […]
Read More