Camargo 505(b)(2) Blog

505(b)(2) – Part 2: The Assessment: Timeline, Cash Flows

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 the sponsor to determine if the project is financially feasible. […]
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PDUFA 2008 – New Submisison Fees for 505(b)(2) Applications

FDA announced that for 2008 the full application fee for a 505(b)(2) that requires a clinical study will be $1,178,000.  In addition, the establishment fee is $392,700 and the product fee is $65,030.  Small  businesses (defined as entities, including affiliates, with less than 500 employees) may request a  waiver of the PDUFA review fee for […]
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FDA takes action against compounding pharmacies’ estriol-containing hormone products

On January 7, 2008, the FDA issued warning letters to several compounding pharmacies (example) advising them stop compounding hormone products contain estriol, an unapproved new drug.  This activity has been going on since the mid-1990’s, popularized by the actress Suzanne Somer’s books. The general term used by this industry is bio-identical hormone replacement therapy – BHRT. […]
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New Safety Reporting Requirements for Unapproved OTC products

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 to support either side.  Approved drugs have always been subject […]
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505(b)(2) – Part 2: The Assessment: CMC Development Plan

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.  Most often, the focus of the company is the clinical […]
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505(b)(2) – Part 2: The Assessment: Clinical Marketing Assessment

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 means that simply getting FDA approval isn’t enough.  The drug […]
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505(b)(2) – Part 2: The Assessment: Regulatory Strategy

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 be supplied using information from published literature and/or the Agency’s […]
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505(b)(2) – Part 2: The Assessment: Clinical Development Plan

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 documents as applicable. The plan consists of the outline of […]
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505(b)(2) – Part 2: The Assessment: Clinical Pharmacology

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 the reference listed drug (RLD) as well as other drugs […]
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505(b)(2) – Part 2: The Assessment: Pharmacokinetic Review

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 multiple-dose administration Dose proportionality Bioavailability Dose-ranging studies Drug-drug interaction studies […]
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New MAPP for FDA Accepting Alternate Compendia for CMC standards

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 the use of BP, EP and JP grade excipients and […]
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505(b)(2) Combo Plavix/Prilosec

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 overcoming their well understood limitations. By combining complementary characteristics of […]
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505(b)(2) – Part 2: The Assessment: Preclinical Review/Preclinical Plan

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 mainly on whether the route of administration changes or FDA […]
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505(b)(2) – Part 2: The Assessment: Safety Review

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 RLD are we proposing to make in this development […]
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P&G Drops out of a 505(b)(2) Development

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 have had to be extended, meaning that the product may […]
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505(b)(2) – Part 2: The Assessment: Efficacy Review

One of the key attractions to the 505(b)(2) route is the potential of gaining approval with only one Phase 3 study.  Moreover, this Phase 3 study is often small, at least compared to the thousands of patients in 505(b)(1) submissions.  There are exceptions, to be sure.  For example, 2 or more trials may be needed […]
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Foreign Inspections by FDA

The US General Accounting Office (GAO) criticised what it concluded is a lack of FDA inspection of foreign API and finished dosage form manufacturers.  This has received a lot of coverage in the lay and professional press, especially since a huge increase in API’s is coming from China; FDA has only 13 inspections scheduled in China, a country […]
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505(b)(2) – Part 2: The Assessment: Competitive Product(s) Review

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 drugs are being studied for eventual marketing? This comparative review […]
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505(b)(2) – Part 1: The overall process

Our process for developing a drug product to be submitted to the US FDA under the 505(b)(2) process has been validated during many meetings with FDA.  I want to share important aspects of this process with the community. This is the first post of several parts.  I will use the following flow diagram as our road […]
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Adams “DESI” Product Approvable

Adams Respiratory Therapeutics announced that it received an Approvable letter from FDA on 10/29/07 for its guaifenesin 600/1200 mg and codeine phosphate 30/60 mg extended-release bi-layer tablets.  The release indicates that the FDA needed additional data to support the use of the product with food. The proposed product is one of several currently on the market […]
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505(b)(2) – Freedom from Generic Competition – Exclusivity Issues

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 obtain a market free from a duplicate: patent protection and […]
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Drug Repositioning: 2 Flavors

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 drug and make significant changes to it (formulation, dose, route […]
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First Generic FDA Review Time to Drop

Maybe the title should have a question mark after it – will the review time for a first generic drop?  FDA plans to do so – it announced the Generic Initiative for Value and Efficiency (GIVE). Basically, the Office of Generic Drugs will try to review within 6 months an application for a first generic […]
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FDA moving against unapproved Hydrocodone products

FDA is announcing that it intends to remove all unapproved products containing hydrocodone from the market. The FDA intends to swiftly move against products labeled for use in children under 6 years of age and allow 90-180 days for products not labeled for use in children under 6 years of age. Manufacturers wishing to market these […]
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CNN Story on “Unapproved Drugs”

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 the DESI review process, but it is well known that […]
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PDUFA 2007 – New Submisison Fees for 505(b)(2) Applications

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 rush experienced with this re-authorization, provisions for an extra 3 […]
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505(b)(2) of Withdrawn Product

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 can check to see if the FDA has made this […]
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Use CMO’s Labs or Outside Labs

Why does Camargo recommend not to use a CMO’s testing lab for development?  CMO labs are tailored for commercial production, characterized by many SOP’s and schedules. During early drug development we need answers quickly, sometimes even approximate answers.  We’re not bound at this stage by GMPs.  We have several outside labs, so we can select one that is […]
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Inactive ingredients exposed

You’re choosing excipients and determining amounts, so you go to the IAG (Inactive Ingredient Guide) look up the approved amounts and you’re good to go.  Right? Maybe not…  You need to consider EXPOSURE.  Exposure is amount over time.  Look at the IAG and determine what products have this excipient/inactive ingredient and compute the potential exposure […]
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MDS Bioanalytical Audits

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 were used to approve many ANDA’s. FDA required the ANDA […]
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