Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explore how those changes could impact your program. Fitbit developing algorithm for early detection of COVID-19 Fitbit recently posted a study that may indicate the company’s
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
This blog features considerations and recommendations for sponsors exploring a 505(b)(2) pathway to drug approval. It was co-written by the Camargo team and the experts at Worldwide Clinical Trials, based on their joint on-demand webinar – 505(b)(2) Planning: Regulatory and Study Conduct Best Practices. In
Hydroxychloroquine. The world rallied around this old drug as a potential treatment of COVID-19 patients. The pharma industry, independent researchers, and governments rushed to conduct trials to see if hydroxychloroquine is safe and effective at any stage of this invasive virus. Though it has now
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 planning a development program. For companies that have not previously interacted with
In 2019, CDER approved 64 NDAs that used the 505(b)(2) pathway, representing important advances in patient care across a wide range of therapeutic areas. The number of 2019 NDA approvals that used the 505(b)(2) pathway fell from 75 in 2018 to 64 in 2019 (Figure 1), in
To succeed in today’s highly competitive pharmaceutical landscape, differentiation is key. In recent years, many generics companies have turned their focus to niche products, complex generics, or biosimilars to achieve this differentiation. During the 3rd Annual Portfolio Management Strategies for Biosimilars and Generics in Barcelona
As part of nationwide efforts to address the opioid crisis, FDA is taking a closer look at the development of critical medications that combat overdose deaths. Most recently, FDA announced its intention to prioritize review of ANDAs for drug products indicated for emergency use in
For the second year in a row, 505(b)(2) FDA approvals grew at double-digit rates according to Camargo’s proprietary database. The number of 505(b)(2) approvals increased 19% from 63 in 2017 to a record-breaking 75 in 2018. *Number to date; however, review documents are not yet available
Last week, FDA published new guidance, Determining Whether to Submit an ANDA or a 505(b)(2) Application (CDER, 2019), to help Sponsors select the best abbreviated approval pathway for their product. While the guidance does not provide any monumental new initiatives, policies or approaches, here are four key
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
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 Clinical Studies Do
It is clear the FDA recognizes the range of development possibilities made possible by the 505(b)(2) pathway, as illustrated by the recently released draft guidance for the development of depot buprenorphine products for treatment of opioid-use disorder. What is striking about this guidance is that
Drug development consultants worldwide promise many things. Traditionally, biotech and pharma companies hire consultants to help guide them through the regulatory process or to fill in where their own companies have a lack of knowledge or resources, but many consultants can do much more than
Generic Firms Looking for Revenue with 505(b)(2) AAM’s Annual Conference is over and most of the generic companies are glad 2017 is over, too. Despite media reports that 2017 was the best year ever for generics, only 3 companies of the top 30 companies reported
Our last blog gave the numbers on 505(b)(2) approvals in 2017, including orphan designations and priority review products. Here we take an in-depth look at what kind of products were approved via the 505(b)(2) pathway, and under which therapeutic areas and FDA Review Divisions they
At the JP Morgan Conference/Biotech Showcase this year, we encountered a record number of companies engaged in 505(b)(2) development. We also had meetings with investors and buyers with their checkbooks open to finance or acquire the more than 80 products we have in development. Unfortunately,
40% Increase in 2017 505(b)(2) Approvals over 2016 The number of 2017 NDA approvals that used the 505(b)(2) regulatory pathway rose dramatically from 45 approvals in each of the last two years to an all-time high of 63 (Figure 1). The median review time for
How to Navigate the Impact of GDUFA From recent news, we know that the FDA has been under increasing pressure to reduce the timing of its reviews while maintaining the highest possible standards for safety and efficacy of the products it approves. This is the
As discussed in a previous blog post (here), the 505(b)(2) development pathway provides a flexible path for developers of new abuse-deterrent formulations. The FDA has shown significant motivation and flexibility in its drive to work with innovators to address the ongoing opioid crisis in the
The overarching goal of the Special Protocol Assessment Draft Guidance for Industry May 2016 (HHS, FDA, CDER, & CBER) is to improve the quality of new drug applications (NDAs) and biologic license applications (BLAs) by providing more certainty in the clinical protocol design process. Among
Several states in the US have already passed laws that remove state restrictions on the medical use of marijuana and its derivatives, and more states are considering such action. The market for medical marijuana in the US is expected to surpass $20 billion by 2020.
The Approval Time for 505(b)(2) and 505(b)(1) NME Products Is Similar A recent article by the Tufts Center for the Study of Drug Development (summarized here) reported that approval times for New Molecular Entities (NMEs) approved via the 505(b)(2) pathway are nearly 5 months longer
Demystifying Orange Book Designations Since its first appearance in 1980, the Approved Drug Products With Therapeutic Equivalence Evaluations publication (commonly referred to as the Orange Book) has served as a gateway for the emergence of generic drug products via the 505(j) drug approval pathway (and
Section 505(b)(2) of the Food, Drug, and Cosmetic Act describes a 505(b)(2) new drug application (NDA) as an application 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
On the Rise: 2016 505(b)(2) NDA Approvals The total number of novel drug approvals in 2016 decreased by approximately half from last year (22 in 2016, from 45 in 2015) and is below the 10-year average of 29 drug approvals per year. Of these, how
Dramatically Decrease Drug Development Costs Through Literature-Only 505(b)(2) NDA Submissions How would you like to get an NDA approved without conducting any clinical studies? Camargo presented a poster on literature-only 505(b)(2) New Drug Application (NDA) approvals at the recent 2016 AAPS annual meeting and exposition
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
Time to Pick the Low-Hanging Fruit: Improving Drug Development ROI in 2017 With forecasts of decreasing peak sales for late pipeline drugs, a logical way to increase the return on investment (ROI) for pharmaceutical companies is to develop products with lower research and development (R&D)
A significant part of the FDA’s charge is ensuring the safety of drugs available to the public. While a substantial part of the FDA’s efforts in guaranteeing public safety go into the safety assessment process during drug development, the process does not end with NDA
Tropical or Rare Pediatric Disease Priority Review Vouchers: Update and Use of the 505(b)(2) Pathway While the United States market for drugs and biologics targeting tropical or rare pediatric diseases is very small, developing novel therapies for patients in these underrepresented groups can be advantageous
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
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
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
Statistical Bootstrapping Method Using a Bias-Corrected Acceleration Approach Well-reasoned and properly conducted statistical analyses can be essential to successful drug development, particularly in the context of manufacturing scale-up, process and component changes, and in comparisons with a reference product. Similarity tests between dissolution profiles steer
Many fixed-dose drug-drug combination products arise from an observation that a synergistic effect occurs when two drugs are administered together, or that both drugs are frequently taken together for convenience. As one or both drugs are typically already approved, the 505(b)(2) pathway is the obvious
On April 11 and 12, 2016, Ken Phelps, President and CEO of Camargo Pharmaceutical Services, spoke at the 505(b)(2) Forum and CTrials Conference in Tel Aviv, Israel, on the topic of 505(b)(2) Combination Drug Products. What is attractive about the 505(b)(2) regulatory pathway, and specifically,
It’s a familiar story: Pharmaceutical Company X spends years developing Product Y only to discover at a crucial point in the process that Product Y will not succeed. The result is often millions of dollars and development years wasted. But could drug development failure be
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
Last month CDER/CBER released a short, final guidance, “Determining the Extent of Safety Data Collection Needed in Late Stage Premarket and Postapproval Clinical Investigations.” (CDER/CBER, 2016) While brief, the guidance could provide a significant reduction in safety data collection for NDA sponsors. This could
Return on Investment for 505(b)(2) Products: Is an “AB” Rating Possible? As new generic product options become more scarce and the competition more fierce, generic manufacturers have recently become very interested in the 505(b)(2) regulatory pathway. The benefits of the 505(b)(2) pathway are well known,
2015 was a big year for FDA, with 45 novel new therapies approved — much higher than 28, the average number approved in the past decade. Of the 45 approved in 2015, how many were approved through the 505(b)(2) pathway? And how does the number
It is a widely held tenet that market exclusivity is essential for the successful launch of a new drug. But is this always the case? For products approved through the FDA 505(b)(2) pathway, is pursuing the 3-year period of exclusivity available through Hatch-Waxman always necessary?
Earlier this month FDA (CDER and CBER) issued a new draft guidance, Best Practices for Communication Between IND Sponsors and FDA During Drug Development. Based on Camargo’s frequent communications with the Agency during product development, the guidance does not present any profound or significant changes
On October 15, 2015, the United States Food and Drug Administration (FDA) issued a new guidance for industry and review staff with more uniform recommendations for the nonclinical safety evaluation of approved drug substances that are reformulated or in which a new route of administration
As I walked the floor at the International Generic Pharmaceutical Alliance (IGPA) conference in Toronto, I couldn’t help but feel a little gratified. Companies that were once disavowing the 505(b)(2) approval pathway are now driving the conversation. Investors that once shied away from 505(b)(2) products
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
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
Shifting views on the safety of drug substances at FDA are not uncommon with the advent of new scientific findings or upon better understanding of physiological processes or disease states. With time, these shifting views may manifest as differences in policies or requirements for drug
Extrusion-enabled pharmaceutical processing (E2P2) has long been employed in pharmaceutical development (Drug Development and Industrial Pharmacy. 33:909-926,1043-1057 (2007)). Reasons for utilizing E2P2 include: Enhancing physico-chemical properties of APIs such as solubility and stability Modifying in vivo release of a drug to enhance bioavailability and clinical
Drug shortages can have serious and immediate effects on providing needed therapies to patients, and preventing shortages is a current priority for FDA. FDA has taken a variety of actions to eliminate, mitigate, and prevent shortages (Executive Order 13588; Interim Final Rule; and Draft Guidance
Recently a federal district court spotlighted FDA’s apparently inconsistent definitions of what constitutes an “active ingredient (AI)” in rejecting the Agency’s rationale for denying Amarin Pharmaceuticals Inc.’s fish oil capsule Vascepa (icosapent ethyl) (NDA 202057 approved July 26, 2012), request for 5 years of market
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
As we have noted in this blog previously, under the Pediatric Research Equity Act (PREA), all new drug applications for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration are required to contain an assessment of the
The “cliff” has passed for pharma but has just begun for generics companies that have benefited from the high number of drugs going off patent. CEOs of generics companies report they are considering a spectrum of solutions to bridge the revenue gap, but perhaps none
Priority review vouchers (PRVs), which are fast-becoming a powerful incentive for drug companies, were originally based on a publication (Ridley et al. 2006) from a group at Fuqua School of Business at Duke University in NC. The idea behind PRVs was that developers of treatments
FDA held a public hearing this past Friday (27March2015) to air their proposal that generic companies be responsible for updating their labeling whenever ‘new safety information’* is available. Generic companies argue against such a proposal because it would lead to confusion about safety warnings if
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
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
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.
The FDA recently provided a summary of new drug approvals in 2014 pointing to an 18-year high. According to its website, the FDA approved 41 novel medicines in 2014, 14 more than in 2013. Nearly 40% of the new drugs approved in 2014 were for
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
In November, this author participated in an open forum at the AAPS Annual Meeting focused on streamlining manufacturing and scale up to support ‘breakthrough therapy’ designation for solid oral dosage forms. The goal was to provide clarity for breakthrough therapies and chemistry, manufacturing and controls (CMC) challenges
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
The FDA recently posted new Guidance on its website awarding certain fixed-combination drug products (fixed-combinations) 5-year new chemical entity (NCE) exclusivity. While the Agency held previously that these products were ineligible for NCE exclusivity (5 years) if one component is already approved, with this new
The Food and Drug Administration (FDA) began requiring drug efficacy, in addition to safety, for approval in 1962 based on the Kefauver-Harris Amendment. Despite this requirement, many drugs that have been approved by FDA have limited efficacy (eg, drugs that treat cancer or Alzheimer’s disease).
In 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’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
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.
Readers of this blog and Camargo clients know that a 505(b)(2) does not have to reference a listed drug (LD) but may do so. Also, we have submitted many applications that do not reference the ‘obvious’ LD because doing so would trigger patent challenges and
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
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
On 6/30/2013, FDA approved Noven Pharmaceuticals Brisdelle (paroxetine) for the treatment of vasomotor symptoms (hot flashes). This 505(b)(2) approval is notable since it is the first non-hormonal product product approved for this indication. But from a regulatory point of view, it is even more interesting
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,
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
Again we have the media troubled by new, improved drugs that cost more than the generic they are based on rather than trumpeting the improvements. Raptor Pharmaceutical received approval of its Procysbi (cysteamine bitartrate) for the treatment of nephropathic cystinosis, an orphan disease affecting an estimated 500 patients
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
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
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
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
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
K-V Pharmaceuticals filed for Chapter 11 bankruptcy. After years of GMP issues narrowed the product offering to just one product, Makena (17-hydoxyprogesterone caproate), poor sales of the product couldn’t sustain the company. In this blog I have discussed the filing and approval of Makena, a product
There are not many instances of a generic version of a reference drug approved via the 505(b)(2) pathway. Last Friday, FDA approved Watson’s generic of Teva’s Plan B One-Step [progestin]. Watson will call its version Next Choice One Dose. For history and industry buffs, Plan
I’m not into politics, but maybe some of my readers are and wish to contact their representative in the U.S. House of Representatives to share your thoughts on a pending issue. With the introduction of REMS, innovator companies have used the restricted distribution feature to
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
ViroPharma has pulled out all stops to prevent generic copies of its off-patent Vancocin® capsule (vancomycin hydrochloride) including the use of the Citizen Petition process. Recently, FDA denied most of the requests in their Citizen Petition and simultaneously approved generics from 3 companies. ViroPharma immediately responded
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
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:
A lot of generic companies are breathing easier today. As we discussed in this blog before, two district courts ruled that generic companies must comply with state laws and add warnings to the label even if it differs from that of the brand product (the
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 (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
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
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
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 FDA has approved NuedextaÃ’(Avanir Pharmaceuticals Inc.), a drug that curbs involuntary and uncontrolled crying and laughing episodes (known as pseudobulbar affect (PBA)) that are experienced by patients with some neurological disorders. Nuedexta is the first drug to be approved to treat patients with these
NSAIDs are known to induce gastrointestinal (GI) tract toxicity, notably upper GI tract. Drugs that suppress gastric acid secretion such as histamine type 2 receptor antagonists, proton pump inhibitors (PPIs), NSAIDs (e.g., COX-2 selective drugs), and misoprostol (a prostaglandin E analog that also has mucosal
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
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
On the new drug side we have had user fees since 1992. The Prescription Drug User Fee Act (PDUFA) has been renewed many times. The Act provides that FDA will adhere to certain goals in return for fees levied on industry. The pharmaceutical industry has
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
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,
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
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
An FDA advisory meeting is scheduled tomorrow (4/22/2010) to review Acura Pharmaceuticals proposed Acurox® (oxycodone + niacin) immediate release tablets. Acura had submitted and NDA in December 2008 and received a Complete Response letter from FDA in June 2009 (a Complete Response letter is a
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
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
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
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
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
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
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
FDA is trying to remove unapproved new drugs from the market. This past year the FDA approved URL’s colchicine. Previously, FDA announced it was taking action against unapproved colchicine on the market. We have commented on these actions in this blog. A recent article in
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
The trend in Big Pharma continues to shift from small molecules to biologics. PhRMA announced that it added seven (7) new members to its roster at the end of the year. The new PhRMA members are Cubist Pharmaceuticals, Inc., Lexington, MA; OSI Pharmaceuticals, Inc., Melville,
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
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
Xanodyne obtained 505(b)(2) approval for tranexamic acid for use in treating heavy menstrual bleeding (menorrhagia). The RLD is Cyklokapron(R) which is used to treat hemophilia and to reduce the need for replacement therapy during and following tooth extraction. The RLD received orphan approval in 1986.
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
Due to Camargo’s on-going client projects in this area, our chief medical officer, Dr. Sam Kaba recently attended a DIA-sponsored conference in Washington, D.C. entitled Cardiovascular Safety and Development of Type 2 Diabetes Mellitus Medications: Current State of the Art and Opportunities to Advance the
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
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
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
It is important to give the FDA credit for admitting mistakes. Yesterday’s posting in this blog concerned Vyvance’s NCE and 5 year exclusivity status. The thorough response by the FDA to the Actavis request for reconsideration of the new chemical entity (NCE) 5 year exclusivity
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
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
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
Yesterday, October 13, FDA sent Warning Letters to four manufacturers of Codeine Sulfate tablets, 30 and 60 mg: Lehigh Valley Technologies, Inc., Cerovene Inc., Dava International, Inc., and Glenmark Generics, Inc., for marketing a product without an approved application. The manufacturers have 15 days to cease
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
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
MAP Pharmaceuticals announced yesterday (7/9/09) that AstraZeneca has ended its collaboration on unit dose budesonide (UDB). This past February, MAP reported that the Phase 3 study had failed to reach its primary endpoints. Apparently, further analysis failed to support continued development of UDB. We seldom
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
Today June 29, ADVENTRX Pharmaceuticals announced plans to use their recent financing to finish the development of ANX-530 (vinorelbine emulsion) and submit a 505(b)(2) NDA by the end of the year. Careful readers of this blog may remember a January 2008 posting citing ADVENTRX ANX-530 as an
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
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
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
During the Q&A after my audioconference yesterday a participant asked if a proposed drug product containing 1 new drug and 2 already approved drugs would be a 505(b)(2). Although she didn’t say so, I assumed that the 2 approved drugs did not belong to her
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
Media is reporting that BTG’s Phase IIa study of a novel gel formulation of paxclitaxel showed tumor reduction in 70% of patients. In effect, BTG is taking a known agent and directly targeting the affected tissues; BTG is also reportedly in later phase trials looking
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
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
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,
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
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)
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
For the first time, FDA’s new drug division has approved more 505(b)(2) drugs than those submitted via 505(b)(1). In 2006 and 2007, the percentage of 505(b)(2) drug approvals went from 20 to 43%, respectively. The FDA publishes a list of drugs approved each year and
This past Friday, 1/30/2009, the FDA approved Takeda Pharmaceuticals North America Kapidex (dexlansoprazole) for the treatment of gastroesophageal reflux disease (GERD). Kapidex is an enantiomer of lansoprazole (Prevacid). In addition to the change in enantiomer, Kapidex is formulated with two type of enteric-coated granules to
On 1/27/2009 Watson Pharmaceuticals announced that the FDA had approved its GELNIQUE(tm) (oxybutynin chloride) Gel 10% for the treatment of overactive bladder. The gel product supplements a transdermal patch made by Watson (Oxytrol) which has not had the marketing success one might expect, perhaps due
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
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
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
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
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
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.
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
FDA inspections and citations sometimes take a few weeks to appear on the FDA website. So, “news” is a erlative term here. Nonetheless, activity related to DESI drugs has a keen interest to us because they represent FDA thinking and potential 505(b)(2) projects. A July
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.
Shionogi, a Japan-based pharmaceutical company, announced yesterday (9/1/2008) that it would buy Atlanta-based Sciele Pharma for $1.42 billion – 57% premium to the current share price. Shionogi’s analysis of the purchase is here. Sciele’s business strategy relies on 505(b)(2) drug development. Sciele in-licenses products in a
Transcept Pharmaceuticals (formerly TransOral) announced today (9/2/2008) that it is merging with Novacea. Transcept is a privately held company while Novacea is NASDQ-listed, so the merged company will be a public company. Novacea had 2 cancer therapies that didn’t meet expectations. Transcept has a 505(b)(2)
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’:
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
Last week (7/30/2008) , FDA announced that it seized timed-release guaifenesin products from KV Pharmaceutical. In 2002 the FDA determined this DESI product to be a safety hazard to children. The manufacturers, including KV Pharmaceutical (Warning Letters: see page 23) were told to stop manufacturing by November 2003
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
Hospira, best known as a generic injectable pharmaceutical company, is going to start developing a transdermal product. Yesterday (7/2/2008), Altea Therapeutics announced a partnership with Hospira for the development and commercialization of an undisclosed product. Altea is best known for its transdermal delivery system. You can
We have all been confronted with the issue of patents and exclusivity for 505(b)(2) product development projects. Financial backers, VC’s, private equity are fixated on the ruggedness of patents – no patent = no money. Biomarin Pharmaceuticals made a presentation at the 2008 BIO conference
Many companies are attempting to reduce the GI bleeding, ulcers and perforations caused by administration of NSAIDS (e.g., ibuprofen, naproxen, aspirin). Since Vioxx was removed from the market (and it was a safer NSAID with respect to GI), there has been an surge of NSAID
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
We hope a common theme emerges from this blog and our public interactions: it is vital when planning 505(b)(2) drug development to look at the entire therapeutic class to learn what studies are needed for approval of the drug . Not including the class in
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
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
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
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
Biovail joined the increasing list of pharma companies that are downsizing or eliminating their 505(b)(2) development programs. As reported in the Wall Street Journal* Biovail CEO William Wells, in a conference call announcing a change in company focus, said “Focusing on the development of products
A reader recently inquired about Orphan drugs and asked me if I thought an Orphan drug developed under 505(b)(2) could be approved based on just a Phase 1 study – a pharmacokinetic or pharmacodynamic comparison to the RLD. At first I thought I couldn’t think
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
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
I was recently asked how you can have a 505(b)(2) application for an Orphan drug. The reasoning behind the query was that Orphan drugs are new chemical entities (NCE). This perpetuates the misconception that 505(b)(2) cannot be used for NCEs, which by now readers of
IP attorney Stephen Albainy-Jenai and I just concluded a webinar hosted by DIA entitled 505(b)(2) Patent & Exclusivity. 23 different companies attended, showing the increasing interest in 505(b)(2) issues. Earlier this year, DIA hosted my overview of the 505(b)(2) drug development process where the attendees had many questions asking
In another fine example of a formulation change, Biocompatibles International reported that its very small beads were used to sequester Doxorubicin (adriamycin). The resulting beads were delivered via a catheter directly into the liver of patients with liver tumors. The tumor growth was suppressed for
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
I get a lot of requests to assure people that their project is, or is not, a 505(b)(2). A few questions about whether it is an OTC candidate. The question about whether the proposed drug is a 505(b)(1) or 505 (b)(2) is readily answered by
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
For Valentine’s Day, FDA issued a new guidance on metabolite safety testing. Essentially, it outlines the non-clinical testing that may be required when the metabolism in humans produces significantly higher amounts of the same metabolites in the animal species where the toxicology was assessed. As
Alchemia Ltd., an Australian pharmaceutical company, announced that it had gained agreement with FDA that a single Phase 3 trial would suffice for approval of its chemotherapeutic drug HA-irinotecan (a new drug containing irinotecan (Pfizer’s Camptosar®) formulated with hyaluronic acid (HA). Alchemia has conducted phase 1
FDA is continuing to act on its promise made in January 2007 to remove products from the market that it considers unapproved. These products, some stemming from the DESI process, have been with us many years. The latest casualty is Colchicine for Injection. On February
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:
We are often asked if a 505(b)(2) application always requires a clinical study (i.e., Phase 2 or 3 in patients). The answer is a resounding NO. On January 14, 2008 ADVENTRX Pharmaceuticals announced the successful completion of a bioequivalence study that demonstrated similar blood levels and
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
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
On 11/3/2007 FDA issued a new MAPP* entitled “Acceptability of Standards from Alternative Compendia (BP/EP/JP)”. Although directed at new drugs, one can probably argue that the policy should also apply to the Office of Generic Drugs. Up to now, reviewers seemed arbitrarily accepting or denying
Cogentus Pharmaceuticals is working on a combination tablet that combines clopidogrel, the active ingredient in Plavix, with omeprazole, the API in Prilosec. Cogentus’s business strategy is to: “… improv[e] the therapeutic profiles of existing, proven drugs in ways that take full advantage of their strengths while
Rats, mice, dogs, pigs – ANDA folks don’t have to deal with testing generic products in animals. As long as the excipients are previously approved, generic drugs don’t have to conduct any preclinical studies. 505(b)(2) development programs may need to include some preclinical studies depending
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
Nastech announced on 11/7/2007 that P&G had dropped out of their co-development of a nasally delivered version of Lilly’s osteoporosis drug Forteo (teriparatide). As reported, the Nastech CEO speculated that the reason for P&G’s termination of its participation was that original timescales for product development
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
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.
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
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
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
CNN ran a story today to increase public awareness that there are hundreds of drugs consumed in the U.S. that have never been formally approved by the FDA. For professionals, the FDA has a web page devoted to this topic. Some of these products were subject to
Congress just passed the Food and Drug Administration Amendments Act of 2007. Most of us in 505(b)(2) drug development will think of it as the PDUFA 2007 (Prescription Drug User Fee Amendments of 2007). This amendment covers the period from 2008-2012 (plus, to circumvent the
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