Throughout our years of preparing and filing FDA submissions, Camargo has often encountered sponsors who cannot file an NDA or BLA within expected timeframes, most commonly due to a failure to start and complete prerequisite activities before the targeted filing date. In this post, we
Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Fitbit developing algorithm for early detection of COVID-19 Fitbit recently posted a study that may indicate the company’s
This week the FDA released a new draft Guidance for Industry entitled “Post-approval Changes to Drug Substances” as part of the FDA’s commitment to the reauthorization of the Generic Drug User Fee Amendments (GDUFA II). The new draft Guidance fills an important void as the
Liposome drug products frequently contain an already-approved drug, and can utilize the 505(b)(2) pathway to approval. Liposomal drug products are a sub-group of Non-biological Complex Drugs (NBCD) and contain greater complexity in characterization and approval than small-molecule drugs. Further, their generic follow-on products, ‘nanosimilars’ or
One of the main causes of Refusal to File / Receive actions by the US FDA is due to inadequate Chemistry, Manufacturing, and Controls (CMC) data. This missing data relates to formulation issues, incomplete stability data, and inactive ingredients listed above the limits found in
Stability Requirements in the 505(b)(2) Space: Why, What, When, How Hurry up and wait. That’s the seemingly eternal impact of developmental stability on the new drug development process. The question always asked is: “How can the developer minimize the wait part?” At the top level
Make Sure Your Bridge Stays Intact: CMC and Dissolution in 505(b)(2) Development One of the most common reasons for a company developing a drug to receive a Refuse to File letter from the FDA is for problems with Chemistry, Manufacturing, and Controls (CMC). Camargo has
Improvements and Updates to the FDA Inactive Ingredient Database The FDA recently announced it has made corrections, updates, and additions of a backlog of formulations to the Inactive Ingredient Database (IID), an important modification for drug developers and development. The previous state of the IID
Aligning Chemistry, Manufacturing, and Controls with Clinical Trials Nine times out of ten, a sponsor approaches their 505(b)(2) drug development process without a clear plan for Chemistry, Manufacturing, and Controls (CMC). What does that do to a development plan? When a 505(b)(2) drug does not
At the recent GPhA meeting in Orlando, Florida, Dr. Kathleen Uhl from the FDA Office of Generic Drugs (OGD) spoke about the quality of Abbreviated New Drug Application (ANDA) submissions and highlighted the detriments of a poor quality submission. All would agree that a poor
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).
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
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
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.
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
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
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
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
Mobius Therapeutics announced that it has received orphan drug status for Mitosol to prevent the recurrence of pterygium after surgical excision. The active ingredient, mitomycin has been used without FDA approval for eye surgeries since the mid 1960’s. Due to its long history of use,
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
The Quality Module (Module 3 or Chemistry, Manufacturing and, Controls section (CMC)) in the eCTD format serves as the backbone of any regulatory submission, an IND or NDA. We have discussed this in a previous blog posting. There is debate about the usefulness of the
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
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
Another example of the importance CMC was reported in January. Warner Chilcott plc received a complete response letter from the FDA. The “low dose” oral contraceptive NDA was the file in question. The FDA inspection of the third-party drug substance manufacturing facility and control testing
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
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
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
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
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
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
Camargo is often called on to write and/or assemble NDAs. When we get to prepare an NDA from the beginning, all of the information builds and the resulting ‘story’ is easy for the FDA to understand. Often we are retained to write portions and just
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
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).
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
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
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 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
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.
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
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