Regulatory Strategy & Submissions Resources

Gaining New Indications With Real World Data: The 505(b)(2) Sweet Spot

Gaining approval of new indications for approved or “old” drugs has always been one of the great advantages of the 505(b)(2) regulatory pathway. Couple that with the FDA’s recent enthusiasm for using real world evidence (RWE) to expand a drug’s indications, and you have a strong incentive to get new indications approved particularly, but not […]
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Not a Generic? Must Be a 505(b)(2)?

Generic or 505(b)(2)? The Office of Generic Drugs (OGD) receives many applications under 505(j) that do not meet the statutory definition of a generic drug. The applications reference an approved drug (the referenced listed drug) but differences in formulation, labeling, or other factors cause OGD to recommend that the application be submitted under 505(b)(2). OGD […]
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Drug or Device? – FDA Provides More Clarity – Or Does It?

Drug or Device? – FDA provides more clarity – or does it? Industry has complained for years, and for good reasons, that it is difficult to understand FDA’s determination of whether a combination product would be reviewed as a device or a drug. So, in response to the signing into law of Section 3038 of […]
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Product Selection: Which Product to Develop?

Product Selection and the Importance of Early Strategic Design for Success Why do some new drug products gain approval, but launch with lower-than-anticipated drug sales? Why then can some drug products gain approval and launch and perform well commercially? Is it possible to align a new drug product candidate for success at launch? At Camargo, […]
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Navigating Clinical Holds

Sponsors spend countless hours developing Investigational New Drug (IND) applications, which are the US FDA’s regulatory gateways for conducting clinical trials of investigational drug and drug-device combination products. The stakes are high for companies as they submit their initial IND, as the ability to start clinical trials hinges on the activation of the IND. But […]
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De-risking Drug Development

High-level Reasoning and Technical Methodology for Evaluating a Program’s Risk From a distance, 505(b)(2) product development can seem very straightforward for products that have been on the market or in clinical use for long periods of time. However, these types of products can often present the greatest challenges when trying to modify or improve performance. […]
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Stability Requirements in the 505(b)(2) Space: Why, What, When, How

Stability Requirements in the 505(b)(2) Space: Why, What, When, How Hurry up and wait. That’s the seemingly eternal impact of developmental stability on the new drug development process. The question always asked is: “How can the developer minimize the wait part?” At the top level you can’t. It will always take six months to get […]
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Deuterization: Is it Enough to Get 5- or 7-Year Exclusivity for a 505(b)(2) Product?

Deuterization: Is it Enough to Get 5- or 7-Year Exclusivity for a 505(b)(2) Product? As the 505(b)(2) experts, Camargo has received several enquiries about developing deuterated drugs as a means of achieving sustained-release properties for a product. The approval of Austedo (deutetrabenazine; Teva Pharmaceuticals, Inc.; NDA 208082), marked the first FDA approval of a deuterated […]
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What Went Wrong? Important Outcomes of a Successful Pre-IND Meeting

We are pleased to present the second episode in a new format and series we’re adding to our 505(b)(2) Blog: a video blog / podcast called What Went Wrong? For our second episode, Ken Phelps, CEO, and Dr. Ruth Stevens, CSO, Camargo Pharmaceutical Services, discuss important outcomes for a successful Pre-IND meeting, which is essential […]
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The Value of a Strategic Assessment: Aligning for Success from the Start

The Value of a Strategic Assessment The first step for every wise drug developer beginning a drug development program is to determine the feasibility of a proposed product by asking several high-level questions: Is the product scientifically, medically, and commercially viable? What are the regulatory requirements and potential hurdles? What nonclinical and/or clinical studies will […]
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Shortening the Review Clock: the Latest on Priority Review Vouchers

The Latest on Priority Review Vouchers Priority review vouchers (PRVs) are a valuable incentive available to companies upon approval of novel drugs to treat rare pediatric diseases or certain tropical diseases. These vouchers can be used on a subsequent application to speed the review process and are an asset that can be sold or transferred […]
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Pre-IND Meetings: How to Achieve Success for 505(b)(2)

One of the greatest mistakes that the Sponsor of a 505(b)(2) can make is to have an unsuccessful Pre-IND meeting. Common errors occur at the Pre-IND meeting because Sponsors and CROs that are more familiar with traditional 505(b)(1) drug development programs fail to appreciate the different goals and the impact of a Pre-IND meeting on […]
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Real-World Evidence: Can it Really Be Used For Drug Approvals?

With the signing of the 21st Century Cures Act, the US Congress tasked the FDA with developing a framework to evaluate how the use of data from sources other than traditional clinical trials may be used to support drug approvals. This framework will apply to post-market commitments and to new indications for approved drugs. This […]
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Unforced Errors: FDA Refusal to File or Receive Letters

UNFORCED ERRORS: FDA Refusal to File or Receive Letters Few things can be more damaging to a pharmaceutical company than the refusal by the Food and Drug Administration (FDA) to review their New Drug Application (NDA) or Abbreviated New Drug Application (ANDA). When a company submits their application for authorization to market a new or […]
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Improving NDA Approval Odds for New Dosage Forms of Approved Products

Improving NDA Approval Odds for New Dosage Forms of Approved Products There are numerous reasons why a Sponsor may wish to market a new dosage form of an approved product. Aside from the obvious financial benefits to the sponsor, providing a more convenient and/or faster-acting dosage form of a well-chosen drug provides significant benefits for […]
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Dramatically Decrease Drug Development Costs Through Literature-Only 505(b)(2) NDA Submissions

Dramatically Decrease Drug Development Costs Through Literature-Only 505(b)(2) NDA Submissions How would you like to get an NDA approved without conducting any clinical studies? Camargo presented a poster on literature-only 505(b)(2) New Drug Application (NDA) approvals at the recent 2016 AAPS annual meeting and exposition in Denver, Colorado. Individuals from the FDA and the pharmaceutical […]
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PRO-CTCAE: Improving Oncology Drug Development

Patient-reported outcomes (PROs) provide valuable tools for collecting information on subjective symptomatic effects during clinical trials. They are considered the gold standard for the assessment of health-related quality of life, treatment preferences, and satisfaction with care. PRO results from a well-defined and reliable PRO instrument can be used to support claims in product labeling, which […]
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Expedited Approval of FDA-approved Drugs in Australia

Expedited Approval of FDA-approved drugs in Australia: New Market Opportunities for Drugs and Devices In the past, after gaining approval for a drug/device in the United States, subsequent approval in Australia involved significant duplicated effort and additional regulatory hurdles. This has resulted in a lack of incentive for pharmaceutical companies and delays of up to […]
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505(b)(2) Application Changes: What You Need to Know

505(b)(2) Application Changes: What You Need to Know Title XI of the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 was enacted in order to address concerns that had potential to delay access to more affordable drugs. The FDA has been implementing the MMA via the statute since it was enacted in 2003. […]
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Extrapolation of Clinical Data for Pediatric Uses: Application for Medical Devices and Drug Products

Extrapolation of Clinical Data for Pediatric Uses: Application for Medical Devices and for Drug Products Extrapolation of Clinical Data for Medical Devices1 The Food and Drug Administration released the revised draft guidance entitled ‘‘Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices” on June 21, 2016 (Docket No. FDA–2015–D–1376). This guidance explains […]
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Risk Evaluation and Mitigation Strategies (REMS) Basics

The Food and Drug Administration is responsible for ensuring that human drugs are safe and effective, while also advancing public health by helping to speed product innovations. In determining if a drug should be marketed, the Agency must weigh the benefits of the therapy against its potential risks to the patient. If a drug or […]
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Effects on Exclusivity: The Biologics Price Competition and Innovation Act of 2009

On March 23, 2010, the U.S. FDA enacted the Biologics Price Competition and Innovation Act of 2009 (BPCIA) as part of the Patient Protection and Affordable Care Act (Public Law 111-148). The passing of BPCIA amended the definition of a “biological product” to include a “protein (except any chemically synthesized polypeptide)”, altering the way that […]
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Leveraging Postmarketing Safety Data in 505(b)(2) Drug Development Programs

A significant part of the FDA’s charge is ensuring the safety of drugs available to the public. While a substantial part of the FDA’s efforts in guaranteeing public safety go into the safety assessment process during drug development, the process does not end with NDA approval. Postmarketing assessments such as pharmacovigilance programs play a critical […]
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Pitfalls of Changing the Salt of a Listed Drug

Pitfalls of Changing the Salt of a Listed Drug The 505(b)(2) registration pathway for new drug products allows the applicant of the new drug product to reference the literature and the FDA’s findings of safety and/or effectiveness (e.g., as listed on the Listed Drug product’s label) to fulfill various registration requirements. From a nonclinical perspective, […]
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Abuse Deterrence Labeling – Generic vs 505(b)(2) Drug Development

Abuse Deterrence Labeling – Generic vs 505(b)(2) Drug Development With the ongoing opioid epidemic, drug abuse, diversion, and misuse are significant concerns for the FDA. The current opioid abuse problems also present significant opportunities for companies willing to explore new formulation technologies to deter abuse. Camargo has significant experience in opioid abuse and abuse-deterrent labeling. […]
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Protein Product 505(b)(2)s Face a Looming Application “Dead Zone”

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) was enacted on March 23, 2010 as part of the Patient Protection and Affordable Care Act (Public Law 111-148). The BPCIA changed the regulation of certain protein products by amending the definition of a “biological product” to include a “protein (except any chemically synthesized polypeptide)”, […]
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The New FDA Draft Guidance on Chewables

An idea for a more convenient dosage form for an existing drug product often presents an opportunity for a commercial advantage. Fortuitously, it also presents the possibility for using the 505(b)(2) regulatory pathway to product approval, which is often faster and less expensive than the 505(b)(1) route. Recently, FDA issued a brief draft guidance describing […]
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The GRAS Is Not Always Greener

The GRAS Is Not Always Greener: Why GRAS Status Does Not Guarantee Excipient Safety Many, if not most, 505(b)(2) submissions represent a change to an approved drug, usually involving a formulation change. Understandably, the focus of sponsors is often primarily on supporting the safety and efficacy of the active ingredient(s). However, the safety of the […]
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Back to Basics: 505(b)(2) FAQs Part 3: Regulatory Strategies

As the 505(b)(2) expert, Camargo is frequently asked questions about how to get a product approved via the 505(b)(2) regulatory pathway and if this pathway is appropriate. Given the growing popularity of the 505(b)(2) pathway for approval of repurposed, reformulated, or unapproved-marketed products, we thought it would be worth providing a refresher. Here is Part […]
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Key Inflection Point in a Drug’s Time to Market: Choice of Regulatory Pathway

Traditional drug development follows a standard process beginning with nonclinical studies and moving into clinical studies, all with the purpose of proving a new drug candidate is safe and effective. When the U.S. opened up an alternate path, 505(b)(2), the primary purpose was to utilize existing data and knowledge, minimize costly animal and human studies, […]
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The Regulation of Follow-On Biological Products via 505(b)(2)

Strike While the Iron is Hot In December 2015, the U.S. FDA granted approval for Eli Lilly and Company’s Basaglar (insulin glargine injection), a long-acting human insulin product indicated for glycemic control in patients with diabetes mellitus. Basaglar marked the first “follow-on” insulin therapy to be approved in the U.S. through a truncated review pathway […]
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Pediatric Applicability or Not–This Revised Guidance Is for You

Since 1994, the statutory and regulatory requirements for drug product labeling for pediatric populations have been evolving. The FDA Modernization Act of 1997 (FDAMA) contained incentives for conducting pediatric studies on drugs that had exclusivity or patent protection. In 2003, the Pediatric Research Equity Act (PREA) was signed into law requiring, for certain drugs, sponsors […]
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Is a Reference Listed Drug Mandatory in the 505(b)(2) Pathway?

If you are a frequent reader of our blog, you know that the 505(b)(2) pathway can facilitate a cheaper, faster drug approval route. This is accomplished by relying on: 1) safety and efficacy data from published literature and/or 2) the agency’s assessment of safety and efficacy of a FDA-approved product, known as the “reference listed […]
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Drug Development Question? Here’s how to communicate with the FDA!

Earlier this month FDA (CDER and CBER) issued a new draft guidance, Best Practices for Communication Between IND Sponsors and FDA During Drug Development. Based on Camargo’s frequent communications with the Agency during product development, the guidance does not present any profound or significant changes in how they conduct and or prefer communicating with IND […]
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Enforcement Activities: FDA removes unapproved prescription ear drops

For years FDA has threatened to remove unapproved products (so-called DESI products) from the marketplace. Recently, the FDA took enforcement action against  several unapproved prescription ear drops.  What products will be next?  DESI producers can use the 505(b)(2) pathway to avoid such actions on their products. Let’s take a look at the recent action and show an example of  […]
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Examining the Amarin VASCEPA Saga

The headlines and newscasts reported Amarin’s success in wining off-label promotion, but behind the scenes, another noteworthy action took place – in a very rare action, the FDA rescinded a special protocol assessment (SPA) that would have enabled Amarin to promote the new indication. In this post, we’ll examine the reasons for FDA’s action and […]
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Quality Metrics – Coming Soon to Your Manufacturing Facility

In the July 28th, Federal Register, (Under “Meetings”) FDA announced the availability of the draft guidance “Request for Quality Metrics-Guidance for Industry.” Although there are “requests” for quality metrics in the guidance, the bulk of the document tells industry what quality metrics they will be reporting, at least initially. FDA primarily cites Sections 706 and […]
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Use of Extrusion-Enabled Pharmaceutical Processes in Drug Development via a Streamlined Regulatory Pathway

Extrusion-enabled pharmaceutical processing (E2P2) has long been employed in pharmaceutical development (Drug Development and Industrial Pharmacy. 33:909-926,1043-1057 (2007)). Reasons for utilizing E2P2 include: Enhancing physico-chemical properties of APIs such as solubility and stability Modifying in vivo release of a drug to enhance bioavailability and clinical efficacy Facilitating development and manufacture of fixed combination drug products […]
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Active Ingredients vs. Active Moieties – Perplexity of Understanding the Relationship or Distinction

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

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

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

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

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

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

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

2014 drug approvals seem to have rebounded somewhat from the past year. In his annual CDER New Drug Review Update, FDA’s John Jenkins cited 35 NME NDA and BLA approvals (calculated through December 3, 2014), up from 27 in 2013 (see chart below). These approvals include 505(b)(1) NDAs as well as BLAs . Some interesting stats […]
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Therapeutic Equivalence Ratings Under 505(b)(2)

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

Until now, if a Sponsor intended to request orphan designation with 7 years of marketing exclusivity for a drug that has already been granted orphan designation, FDA has followed the Code of Federal Regulations (CFR), including the condition described in 21CFR §316.34(c): “If a drug is otherwise the same drug as a previously approved drug […]
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Alkermes Prodrug for Treatment of Multiple Sclerosis: NCE?

The Food and Drug Administration (FDA) began requiring drug efficacy, in addition to safety, for approval in 1962 based on the Kefauver-Harris Amendment. Despite this requirement, many drugs that have been approved by FDA have limited efficacy (eg, drugs that treat cancer or Alzheimer’s disease). In many cases, some portion of the limited efficacy is […]
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Paper Submissions: Going, going…away

In order to fulfill a requirement specified in Section 745A(a) of the Food and Drug Administration Safety and Innovation Act (aka FDASIA), FDA recently issued a draft guidance directing mandatory use of electronic filing and formatting for most regulatory submissions which currently can still be submitted in paper format.  The change is not exactly imminent, but […]
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MannKind Breathes Easier – Inhaled Insulin Finally Approved

MannKind’s Afrezza Receives FDA Approval In June of this year, MannKind Corporation announced that they received FDA approval for Afrezza®, their rapid-acting inhaled insulin product. MannKind is currently working to identify a pharma partner to manufacture and distribute Afrezza, and the product could be available as soon as January 2015. This approval has been a […]
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Importing pre-launch products with a bit of PLAIR

With the tsunami of activities connected with the initial implementation of all the GDUFA requirements, another change made by FDA went largely under the radar.  FDA released the draft guidance, “Pre-Launch Activities Importation Requests (PLAIR)”. (CDER July 2013) which describes how an NDA/ANDA applicant may import finished dosage forms into the United States prior to […]
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The Road to Commercial Success – The Target Product Profile

The goal of drug product development is commercial success.  If this statement wasn’t true, how would patients access the live-saving or life-enhancing drugs we are developing.  Yet, all too many companies focus just on FDA approval, which in our view should be just a very important milestone. When embarking on the drug development journey, it is […]
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2013 505(b)(2) NDA Approvals

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

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

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

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

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

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

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

On May 3, 2013 FDA approved Merck’s  Liptruzet, which combines the its Zetia (ezetimibe) and atorvastatin – Pfizer’s Lipitor which has gone generic.  According to the Merck press release, Liptruzet was approved “for the treatment of elevated low-density lipoprotein (LDL) cholesterol in patients with primary or mixed hyperlipidemia as adjunctive therapy to diet when diet alone […]
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Non-clinical bridging – Most 505(b)(2)’s Don’t Require Full Tox Package

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

PDUFA V ushered in new industry and FDA commitments.  Among these are changes in meeting timelines. A significant change from PDUFA IV is the timeline for Type A meetings. Under PDUFA IV the meeting package was due 30 days in advance of the meeting.  Now, under PDUFA V, this package is due at the time of […]
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Advisory Committee Cool on Non-Steroid Hot Flash Treatments

The Camargo team got its start in the 505(b)(2) process at Duramed Pharmaceuticals with the 1990’s development and approval of Cenestin (synthetic conjugated estrogens, A).  The product was approved based on a Phase 3 clinical study demonstrating the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause –   (known as ‘hot flashes’).  For decades, estrogens have […]
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Are 505(b)(2)’s “Super Generics” or what do we call them?

When we started Camargo almost 10 years ago, products approved under 505j were called ‘generics’ and 505(b)(1) ‘new drugs’.  We could find no consensus of a name for products approved via 505(b)(2). Of course, when Camargo started business, there had been very few 505(b)(2) products approved.  Fast forward 10 years and we have seen an explosion of 505(b)(2) products […]
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KV Appeals Makena Decision

We have followed the saga of KV’s Makena for two reasons.  The most important reason is that the submission, review and approval of Makena is perhaps the best example of using a publicly funded clinical study for NDA approval, despite the clinical trial material not being sourced by the sponsor of the NDA.  The other reason is […]
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No 5-Year Exclusivity for Combinations Drugs with an NCE

One anomaly to the exclusivity rules is that a combination drug product containing a new chemical entity (NCE) and one or more previously approved drugs does not receive the 5-year exclusivity that a single-component NCE drug would receive. Thus, Ferring Pharmaceuticals Prepopik (sodium picosulfate, citric acid and magnesium oxide) was approved as a 505(b)(2) in July, 2012, […]
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2013 GDUFA Fees

FDA has published the 2013 GDUFA fees: Finished Dosage Form (FDF) :  Domestic: $175,389  Foreign: $190,389 API:                                       Domestic: $26,458    Foreign: $41,458 These fees are due by March 4, 2013.
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Suit to challenge use of REMS to block generics and 505(b)(2)

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

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

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

As I wrote last week, on 4/9/12 the FDA denied ViroPharma’s request for 3-year exclusivity for its antibiotic Vancocin and approved three generics.  ViroPharma immediately sued the heads of FDA and HHS and their Agencies.  In a U.S. District Court decision, the judge denied ViroPharma’s motions to grant a  preliminary injunction to require that FDA withdraw the ANDA […]
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2011 505(b)(2) Approvals Now Exceed 505(b)(1) NDA Approvals

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

This post comes from D.C. where I am attending the GPhA Fall Technical Conference.  We just completed a presentation by FDA’s Glen Smith.  He  detailed the proposed new stability requirements for ANDA drug products.  It is essentially the adoption of ICH Q1A.  For readers of this blog, we know that 505(b(2) NDA’s must have 12 months […]
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Don’t launch unapproved products after 9/19/2011

I had a call from a client who wondered if he could launch a new ‘DESI’ product. He had just read the FDA’s recent announcement that it would take immediate enforcement action on any unapproved drug introduced into the market after September 19, 2011. So, the question he asked was, is his “DESI” drug an […]
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AB Rated 505(b)(2)’s

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

The 2012 PDUFA User Fees have been announced in the Federal Register.  In summary, the fees are: Applications: Full – requiring clinical data (e.g., Phase 2 or 3):  $1,841,500 Not requiring clinical data                                 :         920,750 Supplements requiring clinical data                  :         920,750 Establishment fee: $520,100 Product: $98,970 For those doing the math, the cost […]
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Whew! Supreme Court rules generic labels must track RLD

A lot of generic companies are breathing easier today. As we discussed in this blog before, two district courts ruled that generic companies must comply with state laws and add warnings to the label even if it differs from that of the brand product (the Reference Listed Drug – RLD). The cases went to the […]
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KV’s Makena Part 4: Statistical versus Clinical Significance

In previous postings (Intro, Part 1, Part 2, Part 3), I have provided background on KV’s Makena (17a-hydroxyprogesterone caproate injection aka 17P).  The development and regulatory history contains many lessons. In this posting I’d like to examine the difference between statistical and clinical significance.  Please note that this is not meant as a rigorous statistics […]
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Why generic companies might like 505(b)(2)

How would you like to spend a couple of hundred thousands of dollars (or equivalent local currency) and countless months getting FDA approval and patent expiration and then face 14 competitors?  What’s the ROI for that? June 1, 2011 Donepezil Hydrochloride Tablets, Matrix Laboratories Ltd., Approval Donepezil Hydrochloride Tablets, Cipla Ltd., Approval Donepezil Hydrochloride Tablets, Wockhardt […]
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Ophthalmics: 21 CFR 314 94(a)(9)(iv) no longer applies

Who would have guessed that 21 CFR 314.94(a)(9)(iv) no longer applies to ophthalmics?  You wouldn’t generally have expected it to just be cancelled – normally FDA must go through notice and comment, but apparently the FDA can make a regulation disappear by decree. 21 CFR 314(a)(9)(iv) states: (iv)Inactive ingredient changes permitted in drug products intended […]
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KV’s Makena: Part 3: Use of Public Information for 505(b)(2) approvals

In previous postings (Intro, Part 1, Part 2), I provided background on KV’s Makena (17a-hydroxyprogesterone caproate injection aka 17P). The development and regulatory history contains many lessons. In this posting I’d like to examine the use of public information to substitute for sponsors’ studies. By definition, the 505(b)(2) application must contain information to which the […]
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KV’s Makena Part 2: Accelerated Approval Subpart H

In a previous posting, I provided background on KV’s Makena (17a-hydroprogesterone caproate injection aka 17P). The development and regulatory history contains many lessons. In this posting I’d like to examine the accelerated approval process. Makena was approved under 505(b)(2) as seen from the approval letter (at this writing the approval documents are not posted at […]
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KV’s Makena® Part 1: 505(b)(1) or 505(b)2)?

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

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

On September 29, 2010 FDA published a Final Rule revising the requirements for safety reporting for INDs and other BE/BA studies. At the same time FDA issued an accompanying draft guidance to assist in interpreting the new rule. The Final Rule, revising 21 CFR §§ 312.32, 312.64 and 320.31, becomes effective March 28, 2011. The […]
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User Fee Waivers: What is an Affiliate? New Guidance Issued

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