Skip links

Regulatory Strategy & Submissions Articles and Insights

PDUFA VII: More Changes Coming in the Latest Reauthorization

As we noted in a separate blog post, the forthcoming reauthorization of the FDA’s Prescription Drug User Fee Act (PDUFA VII) includes several provisions that are expected to help advance cell and gene therapy products, as well as therapies designed to treat rare diseases. However,

The Composition and Value of a Portfolio Analysis

One of Camargo’s differentiating offerings is the portfolio analysis, a high-level, integrated evaluation of the scientific, medical, regulatory, and commercial viability of each product within a sponsor’s portfolio. Informed by today’s competitive drug development landscape, as well as by the sponsor’s strategic goals and capabilities,

PDUFA VII: Implications for Developers of Cell and Gene Therapies

One of the biopharmaceutical industry’s most closely watched forthcoming regulatory developments is the FDA’s imminent reauthorization of the Prescription Drug User Fee Act (PDUFA). PDUFA VII, as the reauthorization is commonly known, will cover the fiscal years 2023-2027. Many of the advancements included in PDUFA

In the News: November 2021 Regulatory and Development Updates

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

In the News: October 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. FDA Guidance Addresses Real-World Evidence Data Standards The 21st Century Cures Act generated a good deal of excitement

In the News: September 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. FDA Discusses Focus Areas for PDUFA VII During Public Meeting Following the August publication of the proposed PDUFA

Advancing from Research to Development: What Can Go Wrong?

The drug development process is a long journey, beginning with drug discovery, moving through nonclinical and clinical studies, and ultimately culminating in regulatory approval. With many steps in-between, each just as important as the next, there are many factors regarding development strategy and approach that

In the News: August 2021 Regulatory and Development Updates

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

In the News: July 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Approval of the Month: Repurposed Transplant Drug Approved Based Only on Real-World Evidence In July, Astellas Pharma US

In the News: May 2021 Regulatory and Development Updates

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

In the News: April 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. FDA’s Accelerated Approval Program Comes Under Fire The public’s faith in drugs approved under the FDA’s accelerated approval

In the News: March 2021 Regulatory and Development Updates

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

In the News: February 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. FDA: Sponsors Seldom Disclose RTF Letters’ Existence or Contents and Often Ignore Agency Advice The FDA revealed that

Top 5 Common Misconceptions About Meeting with the FDA

Preparing to meet with the FDA can be challenging and stressful for sponsors, especially when they do not know what to expect. Many have misunderstandings about how meetings should be conducted and what constitutes success. Others find themselves needing to dispel incorrect preconceptions about this

In the News: January 2021 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Approval of the Month: Previously Approved Oncology Drug Cleared for Rare Pediatric Indication Pfizer’s Xalkori (crizotinib) was approved

FDA Designations for Rare Disease Products, Part 1

Comparing Orphan Drug, Rare Pediatric Disease, and Humanitarian Use Device Designations The US FDA offers sponsors a variety of special designation programs to incentivize them to develop and deliver therapies to treat unmet patient needs, such as Fast Track Designation (FTD), Breakthrough Therapy Designation, and

In the News: November 2020 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Remote Document Review Leads to CRL: Be Careful What You Wish for? The FDA’s halt of onsite inspections

In the News: October 2020 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Unpacking the (Black) Box: Antares Licenses Urology Product with Boxed Warning When the FDA requires a product’s labeling

In the News: September 2020 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. FDA Establishes Digital Health Center of Excellence The FDA announced the launch of its Digital Health Center of

In the News: July 2020 Regulatory and Development Updates

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

Patient-Centered Drug Development for Oncology Products

Oncology patients face a difficult journey — a frightening diagnosis followed by intricate and oftentimes burdensome treatment regimens with uncertain outcomes. One patient struggles to take the correct dosage at the prescribed times through the “brain fog” caused by his cancer. Another’s livelihood is at

What to Expect from the FDA During COVID-19 Product Development

As the COVID-19 national emergency stretches on in the United States, the eyes of the pharmaceutical industry are trained on developing diagnostic, therapeutic, and preventive measures to combat the novel disease. Given the significance of the pandemic and the critical need, the FDA has developed

Three Keys to Preparing Effective Pre-IND Meeting Questions

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

The Shutdown From Camargo’s Perspective

Now that the FDA has received at least a temporary reprieve from the longest government shutdown in history, we thought we would share some background and a timeline, along with our experience during the shutdown. Most months, Camargo meets with the FDA at least 4

GDUFA I and II: Considerations for Complex Generics Innovators

The increasing complexity of brand-name drugs has made development of generic alternatives more challenging as well. As complex generic drug products can provide a high-value opportunity for drug development companies, they are similar to 505(b)(2) products in that they may require early and flexible interaction

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

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

Innovative Thinkers: FDA wants YOU

New FDA Guidance on OTC Products FDA just released a very brief (barely three pages of actual text) guidance promoting innovation in new drug applications (NDAs) involving nonprescription (aka over-the-counter, OTC) drug products. In the guidance, “Innovative Approaches for Nonprescription Drug Products, Guidance for Industry’

Nonclinical Study Requirements for 505(b)(2) Development

On June 1, 2018, Camargo Pharmaceutical Services celebrated our 15th Anniversary. For this week’s blog, Camargo co-founders, Dr. Ruth Stevens, Chief Scientific Officer and Executive Vice President, and Ken Phelps, President, discuss an important question Camargo often hears from prospective clients: What Nonclinical Study Requirements

Europe’s Value Added Medicines Initiative

The European Union (E.U.) and the United States (U.S.) both have regulations that allow existing drugs to be improved. The E.U. pathway is limited to improvements of drugs that were approved in the E.U. and that are now generic. Readers of this blog are familiar

505(b)(1) versus 505(b)(2): They Are Not the Same

The 505(b)(2) pathway can yield significant benefits in drug development cost and time. But what are the differences in 505(b)(1) versus 505(b)(2)? They are not the same. Drug development pathways in the United States are referred to by their corresponding section in the Food, Drug,

Rx-to-OTC Switch: Expanding to the US Over-the-Counter Market

Changing the marketing status of a drug from prescription (Rx) to over-the-counter (OTC), known as an Rx-to-OTC switch, can increase drug utilization by an average of 30% (Stomberg et al. 2013). According to the Consumer Healthcare Products Association (CHPA), more than 700 current OTC products

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

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

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

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 Target Product Profile: Your Strategy to Reduce Development and Review Time

Updated on: January 26, 2021 Updated by: Cathy Gatza, PhD, VP of Regulatory and Strategy  It is a story all too common: A drug product is developed, approved, and launched, only to flop in the marketplace. There are various reasons that such products underperform or fail, but frequently the cause is a lack of commercial strategy to help sponsors develop a roadmap to follow from the start through development, approval,

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

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

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

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

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

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

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

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

The GRAS Is Not Always Greener

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

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

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

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

Enforcement Activities: FDA removes unapproved prescription ear drops

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

Examining the Amarin VASCEPA Saga

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

Quality Metrics – Coming Soon to Your Manufacturing Facility

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).

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

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

MAPPing out the timing of a Complete Response submission

A type of FDA document which sometimes slides past under the radar is  MAPP, that is, Manual of Policies and Procedures.  These are actually internal FDA documents which are generally analogous to the SOPs FDA requires that industry have and follow.  However, by virtue of

Extending Exclusivity: How Long Will It Really Last?

Last week at the Generic Pharmaceutical Association (GPhA) Annual Meeting, the 21st Century Cures Act, a proposed bill with bipartisan support, was a topic of discussion. Specifically, subtitle L—Dormant Therapies, which would offer 15 years of exclusivity for drugs and biologics approved as dormant therapies.

2014 505(b)(2) NDA Approvals

2014 drug approvals seem to have rebounded somewhat from the past year. In his annual CDER New Drug Review Update, FDA’s John Jenkins cited 35 NME NDA and BLA approvals (calculated through December 3, 2014), up from 27 in 2013 (see chart below). These approvals

Therapeutic Equivalence Ratings Under 505(b)(2)

The FDA listing of therapeutic equivalence (TE) ratings can be a murky area for products approved under 505(b)(2) applications. The concept of TE ratings emerged from FDA regulations for generics and revolve around the announcement that the FDA would publish a current listing of all

Alkermes Prodrug for Treatment of Multiple Sclerosis: NCE?

The Food and Drug Administration (FDA) began requiring drug efficacy, in addition to safety, for approval in 1962 based on the Kefauver-Harris Amendment. Despite this requirement, many drugs that have been approved by FDA have limited efficacy (eg, drugs that treat cancer or Alzheimer’s disease).

Paper Submissions: Going, going…away

In order to fulfill a requirement specified in Section 745A(a) of the Food and Drug Administration Safety and Innovation Act (aka FDASIA), FDA recently issued a draft guidance directing mandatory use of electronic filing and formatting for most regulatory submissions which currently can still be submitted

MannKind Breathes Easier – Inhaled Insulin Finally Approved

MannKind’s Afrezza Receives FDA Approval In June of this year, MannKind Corporation announced that they received FDA approval for Afrezza®, their rapid-acting inhaled insulin product. MannKind is currently working to identify a pharma partner to manufacture and distribute Afrezza, and the product could be available

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

2013 505(b)(2) NDA Approvals

2013 appears to be a challenging year for FDA NDA approvals.  FDA’s John Jenkins reviewed the  NME NDA and BLA approvals through November 2013, showing that 25 such products were approved (see chart below).  These 25 approvals are 505(b)(1)NDA and BLA’s.  Generally, this performance was seen as

Expensive, cheap, value? CMO costs.

Contract manufacturing organization (CMO) A bids $600,000.  CMO B bids $450,000.  Which bid is cheaper? Assume for the moment that both CMOs provide equal service parameters: skill, capacity, timelines, regulatory history, experience, etc. and we are judging both based only on price. No, this is a not trick question. 

ANDA but No NDA – What to Rely on?

Camargo participates in 2-5 PIND meetings each month and one thing we notice in the FDA minutes is that the boilerplate answer to ‘does the Agency agree this ….. is appropriate for filing under 505(b)(2)?’ keeps getting longer.  Recently, the Agency (or, at least, some divisions) is

PREA – Pediatric Plan Timing Changed by PDUFA V

The Food and Drug Administration Safety and Innovation Act (FDASIA; also known as PDUFA V), signed into law on July 9, 2012, contains amendments to the Pediatric Research Equity Act (PREA) that specifically detail the timing of the submission of a Pediatric Study Plan (PSP). In

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

505(b)(2) Prodrug Fails Phase III Study

Development of drugs for new indications entails more risk of failure than simply changing formulations.  Just ask XenoPort, which announced May 19th that its prodrug of R-baclofen, arbaclofen placarbil,   failed to show efficacy in a Phase III clinical trial. Arbaclofen placarbil was being studied for multiple sclerosis-related

Don’t conduct unneeded tox studies

In April I presented a webinar under the auspices of the DIA concerning preclinical bridging. During this webinar, we discussed the need to fill the toxicology gaps that may have been created during the time since the original reference listed drug was approved. These gaps,

Merck Uses 505(b)(2) for New Combo

On May 3, 2013 FDA approved Merck’s  Liptruzet, which combines the its Zetia (ezetimibe) and atorvastatin – Pfizer’s Lipitor which has gone generic.  According to the Merck press release, Liptruzet was approved “for the treatment of elevated low-density lipoprotein (LDL) cholesterol in patients with primary or

New PDUFA V Meeting Timelines

PDUFA V ushered in new industry and FDA commitments.  Among these are changes in meeting timelines. A significant change from PDUFA IV is the timeline for Type A meetings. Under PDUFA IV the meeting package was due 30 days in advance of the meeting.  Now,

Advisory Committee Cool on Non-Steroid Hot Flash Treatments

The Camargo team got its start in the 505(b)(2) process at Duramed Pharmaceuticals with the 1990’s development and approval of Cenestin (synthetic conjugated estrogens, A).  The product was approved based on a Phase 3 clinical study demonstrating the treatment of moderate to severe vasomotor symptoms (VMS)

Are 505(b)(2)’s “Super Generics” or what do we call them?

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

KV Appeals Makena Decision

We have followed the saga of KV’s Makena for two reasons.  The most important reason is that the submission, review and approval of Makena is perhaps the best example of using a publicly funded clinical study for NDA approval, despite the clinical trial material not being sourced

No 5-Year Exclusivity for Combinations Drugs with an NCE

One anomaly to the exclusivity rules is that a combination drug product containing a new chemical entity (NCE) and one or more previously approved drugs does not receive the 5-year exclusivity that a single-component NCE drug would receive. Thus, Ferring Pharmaceuticals Prepopik (sodium picosulfate, citric acid and

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.

Suit to challenge use of REMS to block generics and 505(b)(2)

Innovators have used REMS to block generic and 505(b)(2) developers from gaining access to the reference listed drugs (RLD), effectively blocking their development.  The 2012 Congress failed to pass legislation to force innovators to provide access to the RLD’s.  FDA believes it has no authority

Orphan Designation without Exclusivity: Court asked to decide

Yesterday, Depomed filed suit against the FDA requesting the Court to order FDA to grant their product Gralise (gabapentin) 7 years of exclusivity since it was granted Orphan status; upon approval, Gralise was granted 3 years of exclusivity. Depomed licensed the product to Solvay which

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

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

Stability Changes coming to ANDAs

This post comes from D.C. where I am attending the GPhA Fall Technical Conference.  We just completed a presentation by FDA’s Glen Smith.  He  detailed the proposed new stability requirements for ANDA drug products.  It is essentially the adoption of ICH Q1A.  For readers of this

Don’t launch unapproved products after 9/19/2011

I had a call from a client who wondered if he could launch a new ‘DESI’ product. He had just read the FDA’s recent announcement that it would take immediate enforcement action on any unapproved drug introduced into the market after September 19, 2011. So,

AB Rated 505(b)(2)’s

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

2012 PDUFA User Fees

The 2012 PDUFA User Fees have been announced in the Federal Register.  In summary, the fees are: Applications: Full – requiring clinical data (e.g., Phase 2 or 3):  $1,841,500 Not requiring clinical data                                 :         920,750 Supplements requiring clinical data                  :         920,750 Establishment fee:

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

Why generic companies might like 505(b)(2)

How would you like to spend a couple of hundred thousands of dollars (or equivalent local currency) and countless months getting FDA approval and patent expiration and then face 14 competitors?  What’s the ROI for that? June 1, 2011 Donepezil Hydrochloride Tablets, Matrix Laboratories Ltd.,

Ophthalmics: 21 CFR 314 94(a)(9)(iv) no longer applies

Who would have guessed that 21 CFR 314.94(a)(9)(iv) no longer applies to ophthalmics?  You wouldn’t generally have expected it to just be cancelled – normally FDA must go through notice and comment, but apparently the FDA can make a regulation disappear by decree. 21 CFR

KV’s Makena Part 2: Accelerated Approval Subpart H

In a previous posting, I provided background on KV’s Makena (17a-hydroprogesterone caproate injection aka 17P). The development and regulatory history contains many lessons. In this posting I’d like to examine the accelerated approval process. Makena was approved under 505(b)(2) as seen from the approval letter

KV’s Makena® Part 1: 505(b)(1) or 505(b)2)?

In a previous posting, I provided background on KV’s Makena (17?-hydroprogesterone caproate injection aka 17P). The development and regulatory history contains many lessons. In this posting I’d like to examine the choice of regulatory route. Makena was approved under 505(b)(2) as seen from the approval

KV’s Makena®: A trove of 505(b)(2) Lessons

On February 3, 2011 Hologic, Inc. (subsequently sold assets to KV Pharmaceuticals) received 505(b)(2) approval of Makena®, its 17?-hydroxyprogesterone caproate injection (17P) to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. The

Approvals of ANDAs slows

I attended the 2011 Generic Pharmaceutical Association (GPhA) meeting last week. There was lots of useful information from several speakers. One area in particular stood out to me — the approvals of ANDAs are slowing and there is a growing awareness that the root cause

Contrave® Rejection: The Long and the (Too) Short of it

On February 1st Orexigen(R) Therapeutics, Inc. and Takeda Pharmaceutical Company Limited (Takeda) announced that the FDA issued a complete response letter dated January 31, 2011 regarding the New Drug Application for Contrave® (naltrexone HCl/bupropion HCl) extended-release tablets for the treatment of obesity, including weight loss

Injectables: 505j or 505(b)(2)?

Generic injectable drug products are treated differently than other routes of administration when it comes to permitted differences from the RLD. For most dosage forms, the sponsor is allowed to change excipients as long as the test product is bioequivalent to the RLD. No so

REMS for 505(b)(2) products?

Camargo has been involved in the development of several opioids and is often contacted by new sponsors to develop alternate formulations. One question often brought up is: does a 505(b)(2) approved opioid require a REMS (Risk Evaluation and Mitigation Strategies — for more information on

2010 505(b)(2) Approvals

We join everyone else this time of year and develop a list – ours is a list of FDA approvals made under 505(b)(2). As widely reported (WSJ article here) FDA reported that approvals were down in 2010. Frankly, it’s hard to tell what the figures

PDUFA Fee Waiver: Plan Ahead

For an original NDA, whether it is a 505(b)(1) or 505(b)(2), there is a PDUFA fee to be paid at the time of the submission of the application or the FDA will refuse to file it. For a small business ( a company of less

Safety Studies for 505(b)(2) Applications

The 505(b)(2) pathway is very often cost efficient and lower risk because the NDA application can reference existing preclinical and even human safety studies for the active ingredient. Most often, the excipients used are GRAS-listed. Thus, the applicant doesn’t have to conduct much additional preclinical

Company Officials Personally Liable

As part of what appears to be an increasingly aggressive enforcement stance, there have recently been a number of statements coming from FDA in several settings suggesting that an increase in the number of prosecutions of senior corporate individuals is imminent. In the past, FDA

When is an IND required?

Most of us know that a BA/BE study of a generic can be done without an IND (the exception, called a Bio-IND, is when the drug being studied is cytotoxic or a radioactive labeled drug). In 505(b)(2) drug development we often are studying the BA/BE

505(b)(2)s with Minimal Sponsor Studies

The power of the 505(b)(2) process is realized when the sponsor has to conduct few, if any, studies to get their drug product approved. For many drugs there is wealth of data available in the public domain. The challenge is locating the data and then

FDA Places Hold on all ANDA PAS & CBE Reviews

In a blog posting earlier this year, we discussed the then median 26 month ANDA approval time and how it was getting longer. We now know that the Office of Generic Drugs (OGD) currently has over 3000 ANDA post-approval supplements (PAS) waiting for action, of

Failed 505(b)(2)?: Vivus™ Qnexa

I am often asked about 505(b)(2) drug development failures. After all, 505(b)(2) is a regulatory pathway that is chosen because it is lower cost and has lower risk than a 505(b)(1). The lower risk is attributable to the reliance on the known safety and efficacy

Lannett’s Morphine Sulfate Oral Solution: 505(b)(2) or 505j?

Lannett Co., Inc. and its subsidiary Cody Laboratories manufacture Morphine Sulfate Immediate Release Concentrated Oral Solution 20mg/mL. Readers will remember that the various manufacturers of morphine solution were the first to receive FDA enforcement letters based on the Agency’s Unapproved Drugs Initiative. Roxane Laboratories filed

Generic Lovenox: 505j or 505(b)(2)

Today, Marwood Group Advisory Services broadcast an e-mail giving its thoughts on the approval of Momenta Pharmaceutical’s generic of Lovenox®. This is a very nice write up of the regulatory history, including the summary of the Citizen Petition filed by Sanofi- Aventis challenging such approval,

New User Fees for 2011

FDA announced the new PDUFA user fees for fiscal year 2011 (starts October 1, 2010). The fee for a full application containing clinical data is $1,542,000.   For a supplement or an NDA not requiring clinical data, the fee is $771,000. A clinical study is generally

Still submitting paper ANDA applications?

Experience that shows electronic filing of NDA’s, IND’s and ANDA’s helps speed up the review and approval of these applications. Perhaps because of the software cost and extensive training needed some companies still submit paper applications. Effective today, August 1, 2010, the address to submit

What should a license cost?

Many drug development projects stem from licensing an invention or product. Agreeing on the cost of the license is critical to the licensee to assure that the project is economically feasible. The licensor is interested in maximizing the value of the invention. How do you

Avandia: Who Won?

The media has been very involved in the Avandia case. Headlines or page 1 stories in the New York Times, Wall Street Journal and the British press seemed to take sides rather than report the facts (okay, I shouldn’t be surprised). Today, the day after

Advisory Committee Meeting: Rosiglitazone

The media is crazed with interpretations of the FDA and GSK briefing materials for the Advisory Committee meeting this week regarding the safety of Avandia (rosiglitazone). For those readers who’d like to read the original documents themselves, here are the links.   July 13—14, 2010:

The Skinny On a Potential New Treatment of Obesity

Orexigen® Therapeutics is developing a new fixed dose sustained-release (SR) combination of naltrexone and bupropion for the treatment of obesity. The rationale behind the two active ingredients is stated to be: Bupropion acts on the weight control circuit by stimulating the POMC neuron. Naltrexone prevents

Pro-Drug Denied

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

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

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

Target Product Profile

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

CMC Issues Again

Several previous blogs have discussed the importance of maintaining quality oversight of a contract facility to the drug development timeline. Below is an example of a generic manufacturer with problems maintaining quality oversight of its own multiple sites. Apotex, the Canadian generic manufacturer received a

Manufacturing Problems for Intravenous Emulsions

Many of the drug products manufactured by Hospira, including intravenous nutritional emulsions and propofol have been on the market for years. Hospira received a warning letter on April 12th citing two of its intravenous drug product manufacturing plants in North Carolina. The sites were inspected

Biosimilars or Biodissimilars?

On March 19 and 20th the University of Washington School of Pharmacy hosted “The Biosimilars Conference”. This conference prompted some interesting discussions. A good background of the current legal status and issues around biosimilars can be found in the September 30th blog “Biosimilars; an Introduction”.

FDA Removes Unapproved Nitroglycerin Tablets

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

FDA’s Determination of Vyvanse as NME Upheld

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

FDA’s DAARP is now DAAP, DPAP is now DPARP

Effective March 15th, the FDA’s Division of Anesthesia, Analgesia, and Rheumatology Products is being reorganized. This reorganization is part of some other reassignments announced yesterday (3/09/2010) by the FDA. The “R” part – Rheumatology, will move to the Division of Pulmonary and Allergy Products, which

Exalgo Approved

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

Do Not Neglect Your Third-Party Drug Substance Manufacturer

Another example of the importance CMC was reported in January. Warner Chilcott plc received a complete response letter from the FDA. The “low dose” oral contraceptive NDA was the file in question. The FDA inspection of the third-party drug substance manufacturing facility and control testing

Generic Approvals Taking Longer

I attended the Annual GPhA meeting this past week.  This event is attended by the CEO’s and other top brass of most of the major generic pharmaceutical companies. This year was highlighted by a presentation from the FDA Commissioner, Dr. Margaret Hamburg.  In her remarks, Dr.

Can and Should ANDA Labeling Differ from the RLD?

In the past two months, two appellate courts, the Fifth Circuit and the Eighth Circuit have handed down decisions which essentially state that generic pharmaceutical companies can be sued in state courts for failure-to-warn regarding serious side effects, where the generic companies had conformed their

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

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.

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

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)

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

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

Competition for 505(b)(2) Approvals

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

2009 505(b)(2) Approvals

2009 saw a record number of 505(b)(2) approvals. A total of thirty-three (33) 505(b)(2) NDA’s were approved by FDA in calendar 2009: 23 new formulations 1 New Molecular Entity 5 new combinations of existing drugs 4 drugs already marketed, but without an approved NDA We

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

Start Your New Year Right

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

Getting Unapproved Drugs (DESI, etc.) Approved

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

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

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

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

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


At first, Monday’s (11/16/09) news from CombinatoRx said that the FDA had told the company “that the NDA in its current form would not be sufficient to form the basis for approval of Exalgoâ„¢ under Section 505(b)(1)”. Then, on Friday (11/20/09), the company said that

Qutenza: Approval of a “DESI-inspired” Drug

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

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

FDA Refuse to File: Merck Zetia & Pfizer Lipitor

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

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

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

REMS or RiskMAP or what?

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

505(b)(2) Submissions: No RLD

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

FDA Reaffirms 5-year Exclusivity for a Pro-drug

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

Preemption: New Hampshire 1, Sanity 0

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

505(b)(2) For Formulation Changes

A couple of weeks ago I was invited to present at the 2009 Nebraska Research and Innovation Conference.  The theme of my talk was “The Case for Improving Existing Drugs”. There are several factors driving people to the 505(b)(2) development pathway, a couple of which

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

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

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

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

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.

DESI Presentation: Q&A

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

Test Specifications for Stability Studies

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

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

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

Colchicine Tablets Approved

Colchicine Tablets were approved by FDA on 7/29 & 7/30/09 (approval letters not yet posted as of this writing).  Two NDA’s were submitted, one for the treatment of acute gout and the other for familial Mediterranean fever (FMF). Pretty amazing and interesting for a number of

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

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

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

ANDA Suitability Petition vs 505(b)(2)

I was honored to be invited to speak at the FDA-OCRA 12th Annual Educational Conference in Irvine California on June 10, 2009.  I was asked to discuss and compare the 505(b)(2) and ANDA Suitability Petition.  I thought I should share this topic with the readers

Electronic filing of eCTD INDs

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

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

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

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

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

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

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

Polypill: a 505(b)(2) candidate

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

505(b)(2) Head Lice Treatment approved

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

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

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

Generic Biologics

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

Use of Foreign Trial Data

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

2008 505(b)(2) Approvals

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

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

Fenofibrate (TriCor) active metabolite approved

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

What is an NME?

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

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

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

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

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

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

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

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

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. 

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

$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,

Current versus RLD approval requirements

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

PREA and 505(b)(2)

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

Raptor announces Orphan designation for cysteamine bitartate

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

Fenofibrate in the news (again)

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

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

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

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

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

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

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:

PDUFA 2008 – New Submisison Fees for 505(b)(2) Applications

FDA announced that for 2008 the full application fee for a 505(b)(2) that requires a clinical study will be $1,178,000.  In addition, the establishment fee is $392,700 and the product fee is $65,030.  Small  businesses (defined as entities, including affiliates, with less than 500 employees)

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

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

Foreign Inspections by FDA

The US General Accounting Office (GAO) criticised what it concluded is a lack of FDA inspection of foreign API and finished dosage form manufacturers.  This has received a lot of coverage in the lay and professional press, especially since a huge increase in API’s is coming from China;

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

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

Adams “DESI” Product Approvable

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

First Generic FDA Review Time to Drop

Maybe the title should have a question mark after it – will the review time for a first generic drop?  FDA plans to do so – it announced the Generic Initiative for Value and Efficiency (GIVE). Basically, the Office of Generic Drugs will try to

FDA moving against unapproved Hydrocodone products

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

Use CMO’s Labs or Outside Labs

Why does Camargo recommend not to use a CMO’s testing lab for development?  CMO labs are tailored for commercial production, characterized by many SOP’s and schedules. During early drug development we need answers quickly, sometimes even approximate answers.  We’re not bound at this stage by GMPs.  We have

Inactive ingredients exposed

You’re choosing excipients and determining amounts, so you go to the IAG (Inactive Ingredient Guide) look up the approved amounts and you’re good to go.  Right? Maybe not…  You need to consider EXPOSURE.  Exposure is amount over time.  Look at the IAG and determine what