Have you ever wondered about the difference between preclinical and nonclinical studies? While those in scientific fields like pharmaceutical development are accustomed to words with specific agreed-upon definitions to facilitate communication and minimize misunderstandings, these two terms seem to have slipped through the cracks. Their
A lot of our focus in previous blogs has been on how to best negotiate regulatory hurdles to get your product approved as quickly and cheaply as possible, and how to differentiate your product from the marketed products. And as we have previously blogged, to
Electronic Submissions Update: the end of paper submissions looms closer, and requirements for Standardized Study Data go into effect: What that means for industry Under section 745A(a) of the FD&C Act, no earlier than 24 months after FDA issued the final guidance on December 2014,
Importing Investigational Pharmaceuticals to the U.S.? Changes Are Coming The United States government is making ongoing, concerted efforts to improve the importation process for many products, including pharmaceuticals and medical devices. It’s important to stay on top of the new importation changes and their effect
Drug repositioning, also known as drug reprofiling or repurposing, has become an increasingly important part of the drug development process. This book examines the business, technical, scientific, and operational challenges and opportunities that drug repositioning offers. Readers will learn how to perform the latest experimental
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
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
Last week the “Dormant Therapies Act” (DTA), a companion piece to the Modernizing our Drug & Diagnostics Evaluation and Regulatory Network Cures Act (also known as the MODDERN Cures Act of 2013), was introduced in the U.S. Senate. The Act would provide a drug maker
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
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
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
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
Development stage companies are seeing more opportunities to license their products to generic companies. Recently, generic company CEOs reinforced the importance of 505(b)(2)-developed products to their financial future. The 2014 Generic Pharmaceutical Association (GPhA) annual meeting concluded this pastweek in Orlando. This is the largest gathering of C-level
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
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.
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
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
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 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
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,
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)
Camargo is privileged to work with many clients to develop Orphan drugs. In order to obtain an Orphan drug approval the sponsor must first request that the drug and indication be granted orphan-drug designation. This process requires research into both the indication and the potential
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
Nice going! 2012 saw a record number of 505(b)(2) drugs approved – 47. As is usual at this time of the year, I have prepared a listing of all of the approvals. This year, I have made the listing more useful – the table is
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
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
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
It’s happened in most generic product development programs: A likely looking drug product candidate is selected and the due diligence begins. A review of the Orange Book shows one or more “use code” patents listed for the RLD. A review of the actual patent reveals
How many drug development companies leave it up to the CRO or CMO to design or execute their studies or formulation/manufacturing without oversight? Like those who boarded the Titantic 100 years ago, they seem to trust the mantra that their contractor’s work is unsinkable. MAP Pharmaceuticals
In a speech at yesterday’s 2012 TEDMED conference, the head of the NIH, Dr. Francis Collins, said that there is a big gap between basic research and drugs for patients. To bridge this gap he suggested ‘some of those old drugs could be re-purposed —
A recent editorial (may need subscription) in the New York Times opined that a recent Supreme Court decision – a “bizarre outcome” – “makes it virtually impossible to sue generic manufacturers for failing to provide adequate warning of a prescription drug’s dangers.” The court case the Times
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
I am hesitant to contribute more information about so-called DESI drugs at the risk of further confusion. My goal is always to provide clarity, so here goes. Fundamental to any discussion about DESI products is the definition of a drug product. Let’s just focus on
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
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,
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
Yesterday (08Jun11) The Wall Street Journal reported (subscription may be required) that Pfizer will cut an additional $1 Billion – mostly in administrative costs. These cuts come after cuts to sales and R&D. What’s driving all of these cuts is two-fold: loss of sales of
We believe that the 505(b)(2) drug development pathway is best used when we can improve the safety and/or efficacy of an existing drug product. We see many opportunities to improve clinical effectiveness, but before trying to prove this in a clinical setting – which is time-consuming
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.,
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
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
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
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
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 §§
As part of the PDUFA V reauthorization discussions, the FDA and industry are talking about better approaches to rare disease drug development and orphan drugs. Public interests and Congress have mandated that FDA develop new guidances on the required studies needed for NDA approval. In
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
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
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
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
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
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
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
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
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
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
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
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
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 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
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
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
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
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:
Cheaper is not always better. The cost of drug development demands that the pharmaceutical industry review the cost of all components of the program. In doing this, often the choice of the active pharmaceutical ingredient (API) manufacturer is driven by cost. Many of the API’s
This past Tuesday (6/8/2010), we participated in a DIA-sponsored webinar entitled Understanding the Development and Label Allowances for 505(b)(2) Abuse-Deterrent Products. Joining me, Ruth Stevens our CSO and Cindy Phurrough, our Clinical Operations head, was Dr. Lynn Webster, Chief Medical Officer of Lifetree Clinical Research
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
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
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
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
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
Last week I made a presentation at the Society of Biomolecular Sciences (SBS) 2010 Annual Meeting in Phoenix (due to the Iceland volcano eruption, many participants are still there). The occasion was the inaugural meeting of the newly formed Special Interest Group for Repositioning Drugs
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”.
I have seen various postings and articles on the number of 505(b)(2) approvals. The numbers do not always agree. Why don’t they agree? Many people look only at the approval letter. The FDA will always indicate that the NDA was submitted as a 505(b). But the
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
On February 19th, 2010, FDA published a proposed rule in the Federal Register to revise 21 CFR §§ 16, 58, 71, 101, 171, 190, 312, 511, 571 and 812 to require Sponsors of the various impacted regulatory applications to file a report with FDA providing
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
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
As we have noted in this blog on several occasions, under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all new drug applications for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration are required to contain
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
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)
Although morphine sulfate oral solution has been used for many years in pain management, it had never been approved by the FDA. As part of their ongoing unapproved drugs initiative, the FDA announced on March 30, 2009 that it was taking enforcement action against Roxane
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
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
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 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 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
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
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.
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
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
No turkey, no Black Friday specials, just a thank you note. Little did we know that in 1984 Congress would provide for a regulatory pathway that would provide such a cornucopia of beneficial products that we see under development today. US consumers should give thanks
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
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
As readers of this blog will know, a 505(b)(2) application is a US NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of
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
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
Recently we considered the case of a 505(b)(2) NDA without an RLD. So let’s ask if a 505(b)(2) NDA have more than one RLD? In a word, the answer is “yes”! When using the 505(b)(2) regulatory pathway, Sponsors may rely on the Agency’s previous findings
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 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
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
At Camargo, we can help clients evaluate the market potential of their proposed drug product by examining factors that might influence the resulting medical position at the time of product launch. When desired or needed for potential fund-raising, we can also perform a full marketing
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
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
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
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
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
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 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
I have added a new page to this blog to track 505(b)(2) approvals. Please note the tab named Scorecard. It will be organized by calendar year. I am currently catching up on 2009 to date. Enjoy and give feedback when needed!
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
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
Any meeting with the FDA is critically important to Sponsors. We all know that a tremendous amount of time and effort goes into planning for these meetings. But even before this step the decision to ask for a meeting and the contents of the meeting
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
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
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
Camargo is working with several clients in developing better treatments for pain. Unfortunately, the active substances that supress pain also can be abused. The FDA and DEA are trying to find ways to allow access to these medicines while imimizing the inherent risks of drug
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
A reader pointed out that I have never defined DESI drugs, despite several posts that contained references to them. DESI drugs are a great source for 505(b)(2) development since many will qualify for 5 years data exclusivity. Once upon a time…. In 1938 the FD&C
MAP Pharmaceuticals recently reported good Phase 3 data on its new product in development, Levadex – dihydroergotamine (DHE) orally inhaled. DHE is an old drug that has been used for a long time as an injectable – a couple of generics exist. MAP says that
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
Developing a product with multiple strengths? How do you go about filing multiple strengths in an IND? Lynn Gold, Ph.D., Camargo VP of CMC explains: How and when to draft one CMC section covering multiple drug strengths for the same dosage form? Long-term drug development goals
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
We typically work with small molecules of synthetic origin, but occasionally are retained to work with products that have active ingredients from botanical (plant) sources. Lynn Gold, our VP of CMC provides the following discussion on how to define the starting material for the Active Pharmaceutical Ingredient (API).
Not all clients come to us with product ideas. Indeed, they want us to help identify a short list of suitable candidates. Example companies might include technology platform companies. How do we go about helping these clients? We have a four-step process: Criteria Selection, Criteria
At the recent Generic Pharmaceutical Association (GPhA) 2009 annual meeting, several presenters discussed what was termed the “generic cliff” – a time in the near future when there will be no small molecules left to copy. According to the CEOs of Watson, Mylan and Teva,
Today’s posting stems from a client question. The client’s product candidate is an oral product that requires both single- and multiple dose pharmacokinetic studies. Question: Do companies ever use one pivotal batch for single-dose (SD) study and another batch for the multi-dose (MD) study? What
We know that 505(b)(2) drug development is chosen because it is lower cost, lower risk and faster than traditional new drug development and offers the potential of greater ROI than generics. But, it is not without any risks. On 3/06/2009, Takeda announced “that although the
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
Two major factors drive clients to consider running trials in foreign countries – cost and recruitment. The question we often get is: can we use the data from such trials in a US submission? The answer is: quite possibly. I won’t address the conduct of
During drug development and/or during the review of a submission, FDA regulations may change. Changes can be made immediately or they can appear as drafts. Proposed regulations or guidances are presented in draft form to seek public comment. In any case, it is important to monitor any
All NDA submissions require that a draft label be included. For a 505(b)(2) NDA, where do you get the information for this label? What labeling is required? What is labeling? Well, the “label” is what is on the immediate container of the drug product and
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
Camargo was one of the sponsors of Cambridge Healthtech Institute’s Drug Repositioning Summit last week (Oct. 6-7, 2008). I woke the group up on the second day with a breakfast talk entitled “505(b)(2) Experiences – The Journey Continues”. I reviewed some of the important changes
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.
Not only pharmacokineticists get to have fun in the modeling sandbox. Chemists and formulators get to have their fun synthesizing data. Let’s use an example of how dissolution data can be used for modeling. The example is taken from a project to develop a oral
We recently changed the navigation and look of our website to show that we are a full-service drug development company. 505(b)(2) drug development is so much more than just regulatory submissions! I was asked to explain what the chart is on the pharmacokinetics services ‘page’:
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
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
I attended the 2008 BIO Annual convention, my first. More than 20,000 registrants. There were the usual plenary sessions with lots of wonderful, flowery, well-meaning platitudes and well-deserved awards. The luncheons had the current governors of Massachusetts and California and Jeb Bush, the former governor
On June 4, Indevus Pharmaceuticals reported that the FDA is likely to request additional safety data before approving NEBIDO®, its depot testosterone product for the treatment of male hypogonadism. The news sent the stock on a tumble – losing $2.46 to $1.26/share (a 70% decline) in the
In speaking with prospective clients, we often discuss the potential competition to their proposed drug product. In order to have success in the market, the proposed product needs market differentiation. Some thoughts on a couple of categories: Existing Products – What other drugs are available for the same
I enjoy eating Chinese food with a group, because I can get a sample from each person’s plate. Such as in 505(b)(2) submissions, you can pick and choose parts of different RLD’s for your submission. A reader was surprised when I previously commented that a 505(b)(2) submission can have more
You have a global perspective and drug development program. You want to conduct studies in the US and an international location. You’re going to use an RLD from Big Pharma – you know, the global giants. The RLD bought in the US and Europe looks the
MGI Pharma’s Aquavan(R) (fospropofol) is a phosphate prodrug of the anesthetic propofol. Propofol must be administered by an anesthesiologist because of its rapid onset. The phosphate prodrug’s time to onset is delayed due to the conversion to the active moiety. A slow onset of sedation
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
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
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
Yikes! For the first time, Camargo has two (yes, 2!) pre-IND meetings denied. Same week. Not cancelled, not postponed, not re-scheduled – denied! In both cases, the review divisions said we were on the right track, no controversy exists and that we should simply file the
We gets lots of questions about how the patent system works for 505(b)(2)’s and how it relates (or not) to exclusivity provisions. A good friend and colleague who is an expert in patent law is going to join me on a webinar sponsored by DIA.
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:
Once the clinical development plan is established, the CMC, regulatory and medical communication plans can be matched up. We use MS Project to develop a high-level overall plan. MS Project then can be used to generate cash flows and Gantt charts. This information can be used by
We’ve been observing the FDA crackdown on unapproved DESI and OTC drugs. The reason that Congress and FDA have made these moves is a concern for safety. Industry counters that these drugs have been used safely for years. Frankly, there is a lack of data
CMC Development Plan All too often we see plans that don’t integrate the clinical trial materials with the clinical development plan. This is usually because the people and organizations responsible for each area don’t interact well and there is a lack of overall project management.
Competitive Products Review/Clinical Marketing Assessment This section includes an assessment of the existence of a medical need and the ability of the proposed drug to compete with existing and pipeline agents. At Camargo we deeply believe that good science = good business. In practice, this
Regulatory Strategy This section provides analysis of pertinent regulatory information to produce a recommended regulatory pathway. A thorough search of regulatory documents supports the regulatory recommendations (e.g., Dockets Management; HeinOnline[1]). The 505(b)(2) regulatory pathway may be appropriate if part of the NDA application requirements can
Clinical Development PlanThe proposed Clinical Development Plan is dependent on the selected regulatory pathway. The Clinical Development Plan is based on available Agency study recommendations provided in the FDA Guidance for Industry documents, information in the public domain (e.g., PubMed), and information obtained from SBA
Clinical Pharmacology An overview of the proposed product’s absorption, distribution, metabolism, and excretion (ADME) is detailed in this section obtained from various resources. An important source of information for this and other sections is the FDA reviewer summaries (Summary Basis of Approval – SBA) for
A comprehensive search of the literature is performed to obtain published pharmacokinetic (PK) data for the proposed product (dependent on selected regulatory pathway). This review compares the PK profiles for all available routes and conditions of administration and dose strengths. This review includes studies assessing: Single- and
Of course my product is safe! – the RLD was shown to be safe. Perhaps so. The FDA approves products based on a risk/benefit; is the risk of taking the drug outweighed by the benefit? Would FDA approve the RLD using today’s standards? What changes from
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;
We investigate major factors that influence the potential clinical evidence required and the likelihood of a product’s acceptance in the market. Having established a working draft of our labeled indication(s), we look at the therapeutic category. What drugs have been used, are currently used and what
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.
Well, freedom from generic competition for a while at least. Generally, most companies business plans specify some means to keep the competition at bay until the product can make a profit : when revenues start to exceed investments. There are two ways for 505(b)(2) applications to
Last week’s Drug Repositioning Summit was attended by more than 150 people. The Summit started with my 3-hour workshop on 505(b)(2) drug development. Several attendees were seemingly confused about what “drug repositioning” means. There are two distinct ‘flavors’ of drug repositioning: Take a currently US-approved
A source of 505(b)(2) opportunities comes from products that have been discontinued. One of the first things that must be done is to determine why it was discontinued – by law, the product must not have been discontinued for reasons of safety or efficacy. You
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
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
MDS Pharma is back to profitability after shedding its bioanalytical facility in Montreal. This lab conducted analyses of 100’s of bioequivalence studies. FDA audited the lab several times, effectively shut down the lab and called into question the acceptability of the BE study conclusions that