On September 29, 2023, the U.S. Food and Drug Administration (FDA) made public a potentially game-changing proposal concerning the regulatory framework for laboratory-developed tests (LDTs). Understanding the nuances and implications of these changes is paramount for specialists in regulatory affairs and the clinical development arena.
“Artificial Intelligence (AI) and Machine Learning (ML) as a branch of computer science, statistics, and engineering that uses algorithms or models to perform tasks and exhibit behaviors such as learning, making decisions, and making predictions. ML is considered a subset of AI that allows models
The pre-IND meeting is an opportunity for highly productive interactions between sponsors and the FDA, allowing for discussion of key material attributes and development strategy plus requests for Agency review and advice on specific topics. In general, such meetings are multidisciplinary and cover the regulatory,
What is the Type D meeting? The FDA introduced the Type D Meeting on October 1, 2022, as part of the Prescription Drug User Fee Act (PDUFA) VII Commitment Letter. This new meeting is designed to make it easier and faster for sponsors to get
During the development of new small molecule drug products, developers must conduct impurity and degradant evaluation at several points in the program and to varying degrees. These evaluations include the active pharmaceutical ingredient (API), also known as the drug substance, and the drug product (formulated
Rare cancers account for 25-30 percent of all new cancer diagnoses and 25 percent of cancer deaths.1 With their poorly understood natural histories, phenotypic heterogeneity, and diverse clinical manifestations, rare cancers pose challenges to drug development and represent a significant unmet need in oncology. Faced with
Progress in advanced computational methods using modeling and simulation has been enabled by advancements in computing technologies and the rise of artificial intelligence and machine learning. This has opened new opportunities in pharmaceutical drug development, such as the ability to evaluate large complex databases and
Premier Consulting’s regulatory strategists specializing in the US FDA’s 505(b)(2) approval pathway are often asked how a sponsor can recover from a pre-IND meeting that doesn’t go as planned. While we firmly believe that setbacks can be turned into opportunities for growth and success, conducting
As a cornerstone of the drug development process, nonclinical investigational new drug (IND)-enabling studies are essential for supporting first-in-human (FIH) dosing for novel therapeutics. High-quality IND-enabling studies demonstrate that a drug is reasonably safe for use in humans and that it exhibits sufficient pharmacological activity
It is an unfortunate reality that many diseases and conditions affect such small numbers of patients that, when a sponsor develops a drug or biological product to treat them, relatively little return on investment is generated to offset the high development costs. As a result,
All clinical trial or marketing applications submitted to the FDA must include a form that summarizes the content of the submission and any relevant information on the sponsor and drug for the reviewers. Periodically, the FDA updates these forms to enhance their usability and incorporate
In this second of our two-part series, we continue our discussion about significant recent developments regarding the regulation of ophthalmic products and discuss what to expect in the months ahead. Unsurprisingly, the U.S. Food and Drug Administration’s (FDA) released updated guidance following the landmark Genus
The global ophthalmic drugs market size was valued at $33.81 billion in 2022 and is expected to grow approximately eight percent from 2023 to 2030[1]. Given this trend, many biopharmaceutical companies are investing in strategies to develop and commercialize new or existing ophthalmic products that
Almost 15 years after its last update, the Electronic Common Technical Document (eCTD)’s latest version has been finalized and is being rolled out internationally. eCTD v4.0 offers significant advancements in the way that sponsors and regulatory bodies handle submissions, and adapting to these improvements will
President Biden of the United States (US) has recently signed into law the Fiscal Year 2023 Omnibus Appropriations Bill, which included the FDA Modernization Act 2.0. This act amends the Federal Food, Drug, and Cosmetic Act (FFDCA), which applies to new drugs, and the Public
For researchers who are developing or working with analytical procedures, the new ICH Q14 Analytical Procedure Development and revised ICH Q2(R2) Validation of Analytical Procedures drafts represent foundational guidance documents. Together, they describe suggested development and validation activities for the lifecycle of an analytical procedure
For researchers who are developing or working with analytical procedures, the new ICH Q14 Analytical Procedure Development and revised ICH Q2(R2) Validation of Analytical Procedures drafts represent foundational guidance documents. Together, they describe suggested development and validation activities for the lifecycle of an analytical procedure
On November 1, 2022, the U.S. Food and Drug Administration (FDA) adopted an addendum to the guidance titled “S1B(R1) Testing for Carcinogenicity of Pharmaceuticals,” which had previously been finalized by the International Council for Harmonization (ICH). The guidance document and integrated addendum detail an integrative,
The Pediatric Research Equity Act (PREA) was signed into law in 2003 to increase pediatric use information in product labeling and close knowledge gaps regarding the safety, efficacy, and appropriate dosing of drugs to treat children. PREA requires new drug applications (NDAs) and biologics license
Digital health products are widely used for the prevention, diagnosis, treatment, and management of health and disease. The introduction of digital medicines—and, more recently, digital therapeutics (DTx)—has begun to influence the treatment and management of certain diseases, both by consumers and by clinicians. Driven by
Computer modeling and simulation of humans, both healthy and with diseases, is a powerful tool. It can augment preclinical and clinical research through mechanistic and predictive investigations that would otherwise be impossible. In recent years, regulatory agencies have begun to accept evidence obtained through modeling
One of the most common formulation issues that sponsors of new drug or biologic products face is the qualification of novel excipients. Although novel excipients can be a part of any new drug application (NDA) or biologics license application (BLA) development program, they seem to
With the promise of simplified and improved treatments, the $118 billion combination-product market is projected to increase at a compound annual growth rate (CAGR) of 8.8%. Working to bring these valuable new therapies to patients, sponsors engaged in strategic development often approach Premier Consulting for
During the development cycle of a regulated therapeutic, the transfer of the manufacturing process is inevitable. The process will be transferred from the development lab to a pilot or small-scale manufacturing facility and, if the program is successful, to a facility for commercial manufacturing. With
Clinical trials for ultra-rare diseases can be particularly challenging to mount due to small, geographically-dispersed patient populations. For such trials, the US Food and Drug Administration (FDA) may allow the use of credible real-world data (RWD) and real-world evidence (RWE) in lieu of data collected
The technology transfer of a manufacturing process to a contract development and manufacturing organization (CDMO) is a key step on the road to developing and commercializing biopharmaceutical products. Successfully executing this step is critical to clearing regulatory expectations, avoiding production delays, and delivering drugs to
A quality electronic Trial Master File (eTMF) is essential to the product development and approval process, as it is the foundation for clinical trial inspections by competent authorities. eTMFs for drug, biologic, and medical device trials should be actively managed as studies progress and should
One of the specialized capabilities in Premier Consulting’s toolbox is coordinating the Active Substance Master File (ASMF) submission process on behalf of sponsors. The ASMF procedure (formerly known as the European Drug Master File [EDMF] procedure) has in recent years become an increasingly utilized instrument
Preparing for regulatory submissions and interactions requires seamless communication and continuity across multiple disciplines. While many consulting companies offer regulatory project management as a capability, Premier Consulting Regulatory Project Managers (PMs) elevate the position by acting a single point of contact for sponsors throughout the
Defined by the US Food and Drug Administration (FDA) as a strategic development process tool, the Target Product Profile (TPP) “embodies the notion of beginning with the goal in mind.”[1] Broadly, the TPP is a template that summarizes key drug labeling concepts to focus discussions
If you develop or manufacture in-vitro diagnostic products, you know the May 2022 roll-out date for the In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (IVDR) is just around the corner. But what, exactly, does that mean? Many of our sponsors have been approaching us
On May 26, 2017, the EU Regulation 2017/746 of the European Parliament and the Council on in vitro diagnostic medical devices (IVDR) became active under the EU Regulation on Medical Devices (MDR). Recertification by May 26, 2022, became required for all previously approved products. The
There are numerous reasons why a sponsor may wish to market a new dosage form of an approved product. Aside from the obvious financial benefits to the sponsor, providing a more convenient and/or faster-acting dosage form of a well-chosen drug provides significant benefits for patients.
Previously on this blog, we have explored the 2020 Chinese export ban on non-human primates (NHPs) and its consequences on pharmaceutical research. In that same post, we explored potential solutions to keep sponsor programs on track. In response to the NHP shortage and the resulting
On the path to U.S. commercialization, every pharmaceutical product makes a stop at the Food & Drug Administration (FDA). Whether that stop becomes a waystation or the end of the line may depend on the degree to which the presenters share the FDA’s understanding of
For developers of new drugs, the Common Technical Document (CTD) is the cornerstone of an Investigational New Drug Application (IND). The CTD is designed to harmonize the submission of data and information to regulatory agencies, reducing the time and resources needed to compile applications for
The 505(b)(2) pathway can yield significant benefits in drug development cost and time. But what are the differences between 505(b)(1) and 505(b)(2)? Drug development pathways in the United States are referred to by their corresponding section in the Food, Drug, and Cosmetics Act: 505(b)(1), 505(b)(2),
Regulatory approval is the final hurdle sponsors face when launching an in vitro diagnostic (IVD). After spending many years and millions of dollars on development, it can prove frustrating when the finish is in sight, but there are barriers to success. Fortunately, many of those
A clinical hold from the U.S. Food and Drug Administration can significantly prolong the time and increase the cost of drug development, a particular concern for emerging and small biotech and specialty pharma companies. In this blog post, we discuss common reasons for clinical holds
As we noted in a separate blog post, the forthcoming reauthorization of the FDA’s Prescription Drug User Fee Act (PDUFA VII) includes several provisions that are expected to help advance cell and gene therapy products, as well as therapies designed to treat rare diseases. However,
One of Premier Consulting’s differentiating offerings is the portfolio analysis, a high-level, integrated evaluation of the scientific, medical, regulatory, and commercial viability of each product within a sponsor’s portfolio. Informed by today’s competitive drug development landscape, as well as by the sponsor’s strategic goals and
One of the biopharmaceutical industry’s most closely watched forthcoming regulatory developments is the FDA’s imminent reauthorization of the Prescription Drug User Fee Act (PDUFA). PDUFA VII, as the reauthorization is commonly known, will cover the fiscal years 2023-2027. Many of the advancements included in PDUFA
Sponsors developing biologics must manage numerous scientific considerations specific to large-molecule products, including biochemical characterization studies to confirm structural identity, biological activity studies to confirm potency, and mechanism of action maintenance. Clinical trials of biologics are designed to determine pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy.
The development of biologics represents a major advancement, enabling the treatment of patients with many illnesses for which no other therapeutics were previously available. When developing biologics, sponsors must manage several scientific considerations specific to large-molecule products, including biochemical characterization studies to confirm structural identity,
“There are only four kinds of people in the world: Those who have been caregivers, those who are currently caregivers, those who will be caregivers, and those who will need caregivers.” — Roslyn Carter Each November, National Family Caregivers Month recognizes and honors all those
The number of approvals for combination products and 505(b)(2) applications has risen in recent years. Combination products consist of at least two constituent parts, each subject to its own statutory and regulatory requirements. Unlike fixed-dose combination therapies, which consist of drug-drug combinations, combination products can
As pharmaceutical science and innovation advance, breakthrough combination products frequently emerge that provide patients with therapeutics comprised of two or more constituents. Combination products can be either two or more active pharmaceutical molecules, combined to address different aspects of a health condition, or the combination
The drug development process is a long journey, beginning with drug discovery, moving through nonclinical and clinical studies, and ultimately culminating in regulatory approval. With many steps in between, each as important as the next, multiple factors regarding development strategy and approach must be considered
When a submission is sent through the FDA’s Electronic Submissions Gateway, it goes through an automated check of many validation rules as specified in the Electronic Common Technical Document (eCTD) submission standards guidance. This validation check determines if the submission is uploaded to the FDA’s
Development and reproductive toxicology studies, or DART studies, are required for most non-oncology programs between IND and NDA filings. Their goal is to detect any effects of a drug within a complete reproductive cycle as relevant to humans — from initial conception to reproductive capacity in
Barry Mangum, Senior Vice President, Pediatrics at Premier Research, talks about the importance of pediatric research, its evolution over the years, and the obstacles and opportunities the industry faces. Q: How long have you been in pediatric clinical research, and how did you enter the
How and When to Incorporate PK Design into Your Gene Therapy Development Plan Gene therapy, which was in its infancy around 30 years ago, is fast gaining prominence in many therapeutic areas, from personalized therapy to mass vaccinations against COVID-19. When developing a clinical development
Incorporating patient-reported outcomes (PROs) into clinical trials can help sponsors better understand patients’ symptoms and how a therapy will affect their quality of life, and these insights can be particularly valuable in oncology research. However, there has been a lack of guidance to help sponsors
For developers seeking to obtain approval for previously approved drug products in the United States, the U.S. Food and Drug Administration offers two abbreviated approval pathways — an abbreviated new drug application (ANDA) and a 505(b)(2) application. Both of these applications rely on the agency’s
While the COVID-19 pandemic has accelerated innovation in many areas, including clinical trial design, many recent advances were already in motion before 2020 as sponsors and CROs sought to improve the patient journey and encourage trial participation. Traditional trials, especially those for pediatric populations, often
Premier Partners has worked on more than 200 nonclinical programs since its inception in 2005, many of which include rare routes of administrations (ROAs) and use of uncommon animal species. We have collaborated with sponsors on many niche programs that have shone a light on both the
This is the final installment in a four-part blog series highlighting FDA designations for products with rare disease indications: orphan drug designation (ODD), rare pediatric disease designation (RPDD), and humanitarian use device (HUD) designation. In this post, we examine the humanitarian use designation. The HUD designation
Advances in scientific knowledge and growth in the cell and gene therapy space have led to a new and exciting era of medicine for patients, as well as a new motivation for regulators to provide clear, efficient pathways for product developers. These therapies frequently target
Conducting a clinical study in a pediatric patient population requires careful planning, as providing treatment to a child without causing harm is a weighty responsibility. The first tasks in striking this balance are dose selection and dosing interval determination, and this blog post describes how PK modeling
Cancer is not a single disease, but rather hundreds of different diseases. Thus, there will never be a single cure to cancer. As our knowledge of oncology science advances and expands, a growing number of malignancy types and subtypes are constantly being identified, breaking down
In 2020, CDER approved 68 NDAs that used the 505(b)(2) pathway, representing important advances in patient care across a wide range of therapeutic areas. 505(b)(2) Drug Improvement Approvals by Year In spite of an unusual year due to the COVID-19 pandemic, NDA approvals via the
Rare Disease Clinical Trials Most Often Terminated Due to Regulatory and Recruitment Issues The difficulty associated with successfully completing rare disease clinical trials is well-known. Most people believe that recruitment is the primary reason because, by definition, the number of potential trial participants is extremely
In February, the European Medicines Agency (EMA) released the fourth version of its Guidance on the Management of Clinical Trials During the COVID-19 (Coronavirus) Pandemic. As the pandemic continues to impact clinical research worldwide, these updated guidelines reflect the EMA’s evolving stance, clarifying questions raised by
This is the third installment in a four-part blog series highlighting FDA designations for products with rare disease indications: orphan drug designation (ODD), rare pediatric disease designation (RPDD), and humanitarian use device (HUD) designation. Part 2 examined orphan drugs, and in Part 3, we take a detailed
When pitching to investors, a sponsor is not just selling them on the product; it is also promoting its ability to develop that product. Investors want to know the risks involved with the program, but they are also evaluating the sponsor as a risk factor
In 2019, only 1.2 percent of global clinical studies included India, even though the country is estimated to bear 20 percent of the global disease burden. One reason for the slow growth of clinical research in India has been its stringent regulatory requirements. The Ministry
The ultimate goal of any drug development program is to obtain regulatory approval with the desired prescribing information. Beyond that, developers hope to obtain this approval in the shortest amount of time and with the most efficient use of resources. In an article published in
Technology transfer is a critical step in any drug development program, occurring for various reasons and at different development stages. A sponsor may be looking for a contract development and manufacturing organization (CDMO) for clinical trial manufacturing; to transfer a manufacturing process to a larger,
Preparing to meet with the FDA can be challenging and stressful for sponsors, especially when they do not know what to expect. Many have misunderstandings about how meetings should be conducted and what constitutes success. Others find themselves needing to dispel incorrect preconceptions about this
This is the second installment in a four-part blog series highlighting FDA designations for products with rare disease indications: orphan drug designation (ODD), rare pediatric disease designation (RPDD), and humanitarian use device (HUD) designation. Part 1 compared these designations, and in Part 2, we provide a
Drug development is an extremely cumbersome process, requiring the testing of an agent from in vitro studies to in vivo studies to in silico modeling. Given that it can take up to 20 years for a final product to be approved, it is unsurprising that
Comparing Orphan Drug, Rare Pediatric Disease, and Humanitarian Use Device Designations The FDA offers sponsors a variety of special programs to incentivize development of therapies to treat unmet patient needs, including fast track, breakthrough therapy, and qualified infectious disease product designations. This blog post initiates a four-part series
In the first half of 2020, as a direct consequence of the ongoing pandemic, China issued a ban on the export of non-human primates (NHPs), including those used for pharmaceutical research. As this affected COVID-19 research, the NIH later issued a Notice of Limited Availability to prioritize studies requiring
Most people know someone who uses an inhaler to prevent or relieve shortness of breath after exertion or during allergy season. Medicine has been delivered by inhalation for decades to treat human respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and airway
You’ve determined that you need to perform juvenile animal toxicity studies as part of your nonclinical program. The next step is understanding why these studies are required and how they should be designed. Why are juvenile nonclinical studies needed? Drug development programs use safety data
Drug development is a resource-intensive endeavor. Seeking input from the U.S. Food and Drug Administration throughout the journey can help optimize those resources and maximize the likelihood of regulatory approval. When preparing to submit a new drug application, a pre-NDA meeting with the FDA can
Not surprisingly, the majority of nonclinical contract research organizations are not in glamorous locations. So arriving at the front door of one at 7:30 on a snowy or rainy morning isn’t likely on anyone’s bucket list. However, the experienced nonclinical scientist understands that no matter
As a sponsor designs clinical studies, the respective comparison control groups become a critical factor to consider. Often, to gain clinical trial design insights, a sponsor reviews the physician package inserts from approved New Drug Applications (NDAs) and Biologics License Applications (BLAs) with similar indications
Panel Summary from the World Orphan Drug Congress 2020 Last month, executives from leading international biopharma companies came together at the World Orphan Drug Congress 2020 to discuss how they are evaluating new opportunities in the rare disease space. The panel discussion was moderated by
With smartphones now ubiquitous, interest has increased in digital health solutions such as telemedicine platforms and apps used to track symptoms or medication usage. In recent months, the COVID-19 pandemic has only accelerated the adoption of these technologies. While many digital health products are unregulated,
Sponsors and regulators use surrogate endpoints to predict the long-term benefits of drug products that treat serious or life-threatening conditions for which clinical outcomes cannot be rapidly determined. For many conditions, particularly cancers, proving survival or decreased morbidity could require years, so sponsors can use
Whether you plan to out-license or commercialize your product, getting the label right matters. When putting together a comprehensive drug development plan, it’s important to remember one of Premier Consulting’s key approaches to drug development: “Begin with the end in mind.” This is a multifactorial
Between 2010 and 2018, 33.8 percent of the 402 orphan indications approved by the FDA were approved for children only or targeted pediatric diseases.1 The rare pediatric disease priority review voucher program is one incentive that’s helped to spur research and development in this area
Have you ever wondered about the difference between preclinical and nonclinical studies? While those in scientific fields like pharmaceutical development are accustomed to words with specific, agreed-upon definitions to facilitate communication and minimize misunderstandings, these terms seem to have slipped through the cracks. Their similar meanings often make it
The Electronic Common Technical Document (eCTD) is the standard format for submitting applications, amendments, supplements, and reports to the Food and Drug Administration. The eCTD harmonizes the regulatory review process for global drug development, as its structure is based on the International Council for Harmonisation
In an era of pandemic urgency, repurposed drugs may be our first, best hope to finding effective treatments for COVID-19. Dozens of sponsors are now seeking efficient, streamlined processes to test and establish the safety and efficacy of existing products for the treatment of the novel
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
Oncology patients face a difficult journey — a frightening diagnosis followed by intricate and oftentimes burdensome treatment regimens with uncertain outcomes. One patient struggles to take the correct dosage at the prescribed times through the “brain fog” caused by his cancer. Another’s livelihood is at
As the COVID-19 national emergency stretches on in the United States, the eyes of the pharmaceutical industry are trained on developing diagnostic, therapeutic, and preventive measures to combat the novel disease. Given the significance of the pandemic and the critical need, the FDA has developed
In a previous blog post, we discussed some significant changes to over-the-counter (OTC) product regulations put into place by the passage and signing into law of the CARES Act. The previous post focused on the most attention-getting OTC component of the new law: the introduction
Research into drugs and vaccines to combat the COVID-19 pandemic caused by the SARS-CoV-2 virus has been and remains in full swing. With that as backdrop, how do you choose the right animal model for your nonclinical research? To begin with, defining precise and clear
Updated on: April 19, 2021 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
In an effort to maintain the continuity of our clinical trials during the COVID-19 pandemic, Premier Consulting is helping sponsors take steps to safeguard the well-being of patients who were previously expected to go to a medical facility to receive treatment. A Direct-to-Patient (DTP) model
Tucked away in the nearly 900 pages of the Coronavirus Aid, Relief, and Economic Security (CARES) Act just passed is the addition of Section 505G to the Food, Drug, and Cosmetic Act. This section makes substantial changes to the statutory structure and requirements for over-the counter (OTC)
As a regulatory affairs professional advising various stakeholders on the interpretation and implementation of guidance documents from the FDA, I can safely say that the task is challenging in the best of cases. FDA guidance documents have a tendency to be vague and difficult to
In response to the newly released U.S. Food and Drug Administration (FDA) guidance on COVID-19, the Statistics Department at Premier Research has committed to highlight specific and necessary actionable considerations that directly address key FDA recommendations in the guidance. These considerations call attention to some general actions required
On January 31, 2020, the Secretary of Health and Human Services (HHS) declared a national emergency to combat the COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2. As a result, the FDA is authorized to grant Emergency Use Authorizations (EUAs) for any medical countermeasure (MCM)
During these challenging times when the world is focused on COVID-19 and the matters at hand, it’s understandable if you didn’t take much notice of March 23 as a significant date – one that’s been on the FDA’s radar for a while. March 23, 2020,
In response to the Coronavirus Disease 19 (COVID-19) pandemic, the scientific community, industry, and regulatory agencies are pulling together to facilitate the development of diagnostic tests, drugs, and vaccines to help prevent the spread of the disease. The timelines for development of new drugs and
In March 2020, at the start of the COVID-19 pandemic, the FDA issued guidance on the conduct of clinical trials. “The FDA released this guidance to emphasize that at all times, patients’ safety should continue to be at the forefront of considerations,” said Anand Shah, M.D., FDA
As those working in the development of combination products likely know, the Food and Drug Administration (FDA) issued two new draft guidances in December 2019. The guidances – Requesting FDA Feedback on Combination Products and Bridging for Drug-Device and Biologic-Device Combination Products – were published in response to the 21st Century
Transdermal and topical delivery systems (TDS) are important dosage forms that allow delivery of a drug to local tissue or provide systemic delivery through the skin. These drug products provide a number of advantages for patients, but can be challenging to develop. In November 2019,
In October 2018, the Food and Drug Administration (FDA) issued Standard Operating Policy and Procedure (SOPP) – SOPP 8214 Version 1.0: INTERACT Meetings with Sponsors for Drugs and Biological Products. This document details recommendations for the Center for Biologics Evaluation and Research (CBER)’s engagement 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
If you are planning to submit a New Drug Application (NDA) for an oncology drug product in 2020, revised pediatric study plan requirements could have an impact on the submission. FDA recently released draft guidance on changes to pediatric study requirements put in place by Section
Fueled by unprecedented medical, technological and social advancements of the past century, it should be no surprise that we are living longer than ever before. By 2030, more than one in four people in Europe and North America will be 60 years or older. And
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
Thought leaders in the world of biotherapeutics development converged on Carlsbad, California this September for the 25th Annual Charles River Biotech Symposium. Aptly titled, “Biotechnology-Derived Therapeutics Perspectives on Nonclinical Development,” this forum gave Sponsors developing novel biologic-based therapies (e.g. therapeutic vaccines, mAbs, Bs/TsAbs, oligos, peptides,
With drug discovery completed and your lead asset identified, it’s time to initiate IND-enabling activities, moving one step closer to clinical deployment. According to the Tufts Center for the Study of Drug Development, fewer than 10 percent of nonclinical lead assets move into the clinic.
A pharmaceutical company is granted orphan designation for a medicine that treats Hunter Syndrome. The company goes on to receive marketing approval for the medicine. The approved medicine is administered through intravenous infusion. This route of administration, while effective for some, does not address the
Yesterday, FDA released draft guidance on the use of the Inactive Ingredient Database (IID) in drug development. The guidance is one step FDA is taking to address feedback from the generics industry that IID enhancements are needed to help sponsors make the right formulation decisions. What is the IID?
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
From fitness tracking to healthy eating to virtual doctor visits, mobile technology places an ever-expanding selection of health management tools and information at our fingertips. With clear benefits, it is no surprise that the Food and Drug Administration (FDA) is encouraging the development of mobile
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
It has recently been reported that drugmakers have argued against broad orphan exclusivity for Eagle Pharmaceuticals, Inc.’s Bendeka® product. This was in response to the FDA’s invitation to applicants of certain products containing bendamustine to share how broad of a scope they believe Eagle’s seven-year
To get a successful return on investment (ROI) for your product, it is essential to establish early in the process: Is there an unmet need for the product? Which attributes will the product need to access the market? Will providers and patients be receptive to
Breakthrough therapy designation will speed the development and review of your 505(b)(2) product Breakthrough therapy designation is the most recent addition to the suite of expedited programs offered by the FDA. Compared to fast track designation (discussed in a prior blog post), the qualifying criteria for
One of the tenets of the FDA is to get safe and effective drugs to market as soon as possible. To expedite approval of products for which there is the greatest clinical need, the FDA offers four expedited programs to get beneficial therapies to patients
For centuries, botanical remedies have been used in many cultures to treat various diseases. In recent years, pharmaceutical companies have turned to botanical drugs for alternative medicines to treat diseases with unmet medical needs. The FDA also recognizes the interest in developing botanical products and
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
We decided to mention some noteworthy firsts from the FDA during August 2018 and a change in the FDA’s policy on obtaining orphan incentives via pediatric-subpopulation designation. Competitive Generic Therapy Designation The FDA granted Competitive Generic Therapy (CGT) designation for the first time for Potassium
The increasing complexity of brand-name drugs has made development of generic alternatives more challenging as well. As complex generic drug products can provide a high-value opportunity for drug development companies, they are similar to 505(b)(2) products in that they may require early and flexible interaction
Last month the US District Court for the District of Columbia ordered the FDA to grant Eagle Pharmaceuticals, Inc., 7-years of marketing exclusivity for Bendeka® (bendamustine). This was the second loss for the FDA regarding orphan exclusivity for the ‘same drug’ that is not clinically
The 505(b)(2) new drug application (NDA) pathway can provide unique advantages from the nonclinical development perspective that can save significant time, money, and resources. Compared to the 505(b)(1) NDA pathway, which is more standardized and follows the general guidance provided by the International Conference on
Innovative Thinkers: FDA wants YOU FDA just released a very brief (barely three pages of actual text) guidance promoting innovation in new drug applications (NDAs) involving nonprescription (aka over-the-counter, OTC) drug products. In the guidance, “Innovative Approaches for Nonprescription Drug Products, Guidance for Industry’ (CDER
Updated on: February 9, 2021 Updated by: Stacey A. Ayres, PhD, VP of Regulatory and Strategy While the analysis in this blog post was conducted in 2018, the takeaway still rings true today: CRLs can have a devastating impact on emerging biopharma development programs, and
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
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
The recent key decision by the FDA for Exparel® stresses the importance of reevaluating 505(b)(2) strategy throughout a product development lifecycle. A solid, data-driven development strategy is important from the beginning; however, new data, including related regulatory actions, must be considered and incorporated to realign
Additional Indications: Advantages of QIDP Designation The benefits of early strategy for 505(b)(2) drug development programs are numerous, but none as substantial as market exclusivity. Incentives available to sponsors of QIDP include fast track designation, priority review designation, and 5 years of additional market exclusivity.
2017 was a big year for orphan designations and approvals. Sixteen of the sixty-three (25%) products approved via the 505(b)(2) pathway in 2017 received orphan designation. Importantly, more than half of the approved 505(b)(2) products with orphan designation received seven years of orphan exclusivity. That’s
As Sponsors become more aware of the benefits and risks of developing products in the current market, their focus often turns to Product Ideation and how this process can help develop smarter products. Here the answers to some key questions about Product Ideation and the
If you think regulatory pharmacokinetics requirements are just a box-checking exercise then you may be throwing away money and time on unnecessary studies. At Premier Consulting, we have always focused on innovative approaches for the most challenging drug development programs, but our cutting-edge pharmacokinetics strategies
Updated on: March 9, 2021 Emerging biopharma companies play a big role in overall drug development—the percentage of new therapies both originated and launched by these companies has increased over the last decade, in an industry that is growing at the same time. As drivers
A New Draft Guidance Provides In Vitro Diagnostic Device Requirements That May Impact Therapeutic Drug Trials Did you know that an assay used in a clinical trial designed to study an investigational drug may be considered an investigational In Vitro Diagnostic (IVD) Device, and therefore
The FDA just released a new draft guidance on developing fixed-dose combination antihypertensive products. While the clarification for industry is good, the strategy is not new to Premier Consulting. Gaining approval of a combination product that is made up of approved, single-entity drugs is achieved
A prodrug developed via the 505(b)(2) pathway can improve an existing therapeutic while increasing the value of the asset. The therapeutics which excite us most here at Premier Consulting are drugs which deliver effective therapies to patients in need, including therapies improved by utilizing prodrugs.
A 505(b)(2) with 8 years of exclusivity. That is the prize that Calla Therapeutics will receive upon approval of its innovative vaginal cream drug candidate for the treatment of recurrent vulvovaginitis (RVVC). Premier Consulting helped Calla obtain Qualified Infectious Disease Product (QIDP) designation for its
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 the Inactive
Changing the marketing status of a drug from prescription (Rx) to over-the-counter (OTC), known as an Rx-to-OTC switch, can increase drug utilization by an average of 30% (Stomberg et al. 2013). According to the Consumer Healthcare Products Association (CHPA), more than 700 current OTC products
With a recent update from the United States Food and Drug Administration (US FDA), the quest for abuse-deterrent opioids has taken another step. But will the new Guidance lead developers forward or backward? We previously commented on the Draft Guidance for generic abuse-deterrent opioids in
Finally there is hope for Sponsors of complex generics with the new Pre-ANDA program outlined in GDUFA II. More good news: the 505(b)(2) experts have got you covered for the development of complex generics. Until now, Sponsors of complex generic products either submitted an NDA
While the old adage “It’s easier to beg forgiveness than to ask permission” might have worked well as a child, it rarely applies when dealing with the FDA. The FDA recently published a final guidance titled “Formal Dispute Resolution: Sponsor Appeals Above the Division Level”,
Earlier this year, the U.S. Food and Drug Administration (FDA) announced its Drug Competition Action Plan, which aims to bring more competition to the drug market and improve consumer access to drugs. As part of this effort, the Agency is focusing on ways to help
Dogma says that a compound used for a nutrition, such as a vitamin, cannot be a drug. Such dogma prevents the development of many good drugs. The FDA just approved vitamin C – ascorbic acid as a drug. Read on to learn how this came
Gaining approval of new indications for approved or “old” drugs has always been one of the great advantages of the 505(b)(2) regulatory pathway. Couple that with the FDA’s recent enthusiasm for using real world evidence (RWE) to expand a drug’s indications, and you have a
Drug or Device? – FDA provides more clarity – or does it? Industry has complained for years, and for good reasons, that it is difficult to understand FDA’s determination of whether a combination product would be reviewed as a device or a drug. So, in
Product Selection and the Importance of Early Strategic Design for Success Why do some new drug products gain approval, but launch with lower-than-anticipated drug sales? Why then can some drug products gain approval and launch and perform well commercially? Is it possible to align a
Seamless clinical trials have become the new buzz word in drug development since FDA Commissioner Scott Gottlieb promoted their use this month. But are they new, and which products are best suited to this style of clinical trial? Oncology drugs are the obvious examples of
Sponsors spend countless hours developing Investigational New Drug (IND) applications, which are the US FDA’s regulatory gateways for conducting clinical trials of investigational drug and drug-device combination products. The stakes are high for companies as they submit their initial IND, as the ability to start
From a distance, 505(b)(2) product development can seem very straightforward for products that have been on the market or in clinical use for long periods of time. However, these types of products can often present the greatest challenges when trying to modify or improve performance.
At Premier Consulting, we are often asked for strategic advice on drug development programs seeking approval in not only the United States (US), but also approval from other regulatory agencies, including the hybrid application in the European Union (EU). It is useful at the beginning
Updated on: January 26, 2021 It is a story all too common: A drug product is developed, approved, and launched, only to flop in the marketplace. There are various reasons that such products underperform or fail, but frequently the cause is a lack of commercial strategy to help sponsors develop a roadmap to follow from the start through development, approval, and launch. While a focus on FDA
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 you can’t. It will always take six months to get
As the 505(b)(2) expert, Premier Consulting is exposed to many projects in which sponsors have attempted to leverage the 505(b)(2) pathway as a way to utilize information obtained from studies not conducted by or for the Sponsor. For the 505(b)(2) pathway, the strategic leveraging of
As the 505(b)(2) experts, Premier Consulting has received several enquiries about developing deuterated drugs as a means of achieving sustained-release properties for a product. The approval of Austedo (deutetrabenazine; Teva Pharmaceuticals, Inc.; NDA 208082), marked the first FDA approval of a deuterated drug. A recently
The requirements for abuse-deterrent opioids are in flux as the FDA grapples with what they can do to address the ongoing opioid epidemic. As part of their efforts in promoting the development of abuse-deterrent opioids, the Agency has required that manufacturers demonstrate that their product
The provision of Written Responses Only (WRO) by the FDA in response to Pre-IND meeting requests is here to stay. While rarely requested or preferred by Sponsors, this meeting response format is being used with increasing frequency by many Divisions at the FDA since the
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 reason for the PDUFA and now the
In general, under the Pediatric Research Equity Act (PREA), submission of an initial pediatric study plan (iPSP) is required for a drug or biological product that includes a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration. Submission
After months of speculation, the first round of changes for pharmaceutical manufacturers arising from the planned withdrawal of the United Kingdom of Great Britain and Northern Ireland (UK) from the European Union (EU) have arrived. And the changes are major for companies based in the
The risk involved with an asset needs to be assessed before a sale. Whether from the buy or sell side, it pays to understand how much an asset is worth. For those involved with in-licensing or out-licensing, a properly performed due diligence assessment places a more
The first step for every wise drug developer beginning a drug development program is to determine the feasibility of a proposed product by asking several high-level questions: Is the product scientifically, medically, and commercially viable? What are the regulatory requirements and potential hurdles? What nonclinical
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 Latest on Priority Review Vouchers Priority review vouchers (PRVs) are a valuable incentive available to companies upon approval of novel drugs to treat rare pediatric diseases or certain tropical diseases. These vouchers can be used on a subsequent application to speed the review process
Drugs that are on the market but are not approved by the FDA are more common than you might think. Even some physicians might be unaware that the drug they are prescribing has not been approved, meaning it has not undergone the rigorous standards of
Fixed-dose combination products (FDCs), or drugs containing multiple active ingredients, offer benefits to pharmaceutical companies and patients. For Pharma, creative matching of multiple APIs can open new markets, while for patients, FDCs can offer convenience and therapeutic benefits. Often, FDCs are composed of previously approved
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
One of the greatest mistakes the sponsor of a 505(b)(2) product can make is to have an unsuccessful pre-IND meeting. Errors often occur at the pre-IND meeting because sponsors and CROs that are more familiar with traditional 505(b)(1) development programs fail to appreciate the different
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 some new drug products
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
Randomized controlled Phase 3 (and some Phase 2) studies are clinical trials that are designed to answer specific questions, such as whether the proposed drug is effective in treatment or prevention of a particular disease. As such, the primary endpoint is the most important one
With the signing of the 21st Century Cures Act, the US Congress tasked the FDA with developing a framework to evaluate how the use of data from sources other than traditional clinical trials may be used to support drug approvals. This framework will apply to
The end of paper submissions looms closer, and requirements for Standardized Study Data go into effect. What does that means for industry? Under section 745A(a) of the FD&C Act, no earlier than 24 months after FDA issued the final guidance on December 2014, “Providing Regulatory
Few things can be more damaging to a pharmaceutical company than the refusal by the Food and Drug Administration (FDA) to review their New Drug Application (NDA) or Abbreviated New Drug Application (ANDA). When a company submits their application for authorization to market a new
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 had become an issue as excipient suppliers recommend the
Desmopressin (DDAVP®; Ferring Pharmaceuticals Inc) was approved in the US in 1978. DDAVP is currently approved to treat central diabetes insipidus, hemophilia A, type 1 von Willebrand’s disease, nocturnal enuresis (bedwetting) in children, and as a diagnostic test to measure renal concentrating abilities. Desmopressin is
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? Premier Consulting presented a poster on literature-only 505(b)(2) New Drug Application (NDA) approvals at the recent 2016 AAPS annual meeting and
Patient-reported outcomes (PROs) provide valuable tools for collecting information on subjective symptomatic effects during clinical trials. They are considered the gold standard for the assessment of health-related quality of life, treatment preferences, and satisfaction with care. PRO results from a well-defined and reliable PRO instrument
As part of the 505(b)(2) drug development and registration process, the applicant of the new drug product can reference the literature and the FDA’s findings of safety and/or effectiveness (e.g., as listed on the Listed Drug product’s label) to fulfill various registration requirements.[1] Since many
In the past, after gaining approval for a drug/device in the United States, subsequent approval in Australia involved significant duplicated effort and additional regulatory hurdles. This has resulted in a lack of incentive for pharmaceutical companies and delays of up to 2 years to bring
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 MMA via the statute since it was enacted
The Food and Drug Administration released the revised draft guidance entitled ‘‘Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices” on June 21, 2016 (Docket No. FDA–2015–D–1376). This guidance explains the circumstances in which appropriate extrapolation of medical device data (either from
On March 23, 2010, the U.S. FDA enacted the Biologics Price Competition and Innovation Act of 2009 (BPCIA) as part of the Patient Protection and Affordable Care Act (Public Law 111-148). Under BPCIA, applications for biological protein products, which were previously approved as New Drug
The United States government is making ongoing, concerted efforts to improve the importation process for many products, including pharmaceuticals and medical devices. It’s important to stay on top of the new importation changes and their effect on business. Foreign biotech, device manufacturers, API producers, and
The Food and Drug Administration is responsible for ensuring that human drugs are safe and effective, while also advancing public health by helping to speed product innovations. In determining if a drug should be marketed, the Agency must weigh the benefits of the therapy against
On March 23, 2010, the U.S. FDA enacted the Biologics Price Competition and Innovation Act of 2009 (BPCIA) as part of the Patient Protection and Affordable Care Act (Public Law 111-148). The passing of BPCIA amended the definition of a “biological product” to include a
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
The Benefits of 505(b)(2) for Orphan Drug Development The Orphan Drug Designation Program, created by the Orphan Drug Act of 1983, provides significant financial incentives for the development of drugs for rare diseases. The potential incentives include tax credits for clinical trial costs, waiver of
The 505(b)(2) registration pathway for new drug products allows the applicant of the new drug product to reference the literature and the FDA’s findings of safety and/or effectiveness (e.g., as listed on the Listed Drug product’s label) to fulfill various registration requirements. From a nonclinical
On May 27, 2016, AstraZeneca announced they received a Complete Response Letter (CRL) from the FDA for their sodium zirconium cyclosilicate (ZS-9) New Drug Application (NDA) (reference link). This hyperkalemia drug was developed by ZS Pharma and was generally expected to receive FDA approval when
With the ongoing opioid epidemic, drug abuse, diversion, and misuse are significant concerns for the FDA. The current opioid abuse problems also present significant opportunities for companies willing to explore new formulation technologies to deter abuse. Premier Consulting has significant experience in opioid abuse and abuse-deterrent
Premier Consulting is known for its expertise in the 505(b)(2) pathway. But, in a global pharmaceutical business, many clients are looking to develop drugs for both the US and EU markets. We’ve written before about the EU process that is similar to the U.S. 505(b)(2)
The Biologics Price Competition and Innovation Act of 2009 (BPCIA) was enacted on March 23, 2010 as part of the Patient Protection and Affordable Care Act (Public Law 111-148). The BPCIA changed the regulation of certain protein products by amending the definition of a “biological
As the 505(b)(2) expert, Premier Consulting 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
Designing a new drug from scratch is costly and time-consuming. One attractive option to differentiate from currently marketed products is to chemically modify the characteristics of an existing drug to create a prodrug. Often a prodrug can improve the safety and efficacy of an approved
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 for both patients and Sponsors. A number of incentives exist to encourage companies to apply
An idea for a more convenient dosage form for an existing drug product often presents an opportunity for a commercial advantage. Fortuitously, it also presents the possibility for using the 505(b)(2) regulatory pathway to product approval, which is often faster and less expensive than the
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 and efficacy of the active ingredient(s). However, the safety of the inactive ingredients (excipients) needs
As the 505(b)(2) expert, Premier Consulting 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
Traditional drug development follows a standard process beginning with nonclinical studies and moving into clinical studies, all with the purpose of proving a new drug candidate is safe and effective. When the U.S. opened up an alternate path, 505(b)(2), the primary purpose was to utilize
As the 505(b)(2) expert, Premier Consulting 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
As the 505(b)(2) expert, Premier Consulting 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,
Strike While the Iron is Hot In December 2015, the U.S. FDA granted approval for Eli Lilly and Company’s Basaglar (insulin glargine injection), a long-acting human insulin product indicated for glycemic control in patients with diabetes mellitus. Basaglar marked the first “follow-on” insulin therapy to
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 the development path forward based on the quality
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, Strategic Advisor at Premier Consulting, 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, why is
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
If you are a frequent reader of our blog, you know that the 505(b)(2) pathway can facilitate a cheaper, faster drug approval route. This is accomplished by relying on: 1) safety and efficacy data from published literature and/or 2) the agency’s assessment of safety and
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 be
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
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, such as a potentially lower cost and accelerated path to market.
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 Premier Consulting’s frequent communications with the Agency during product development, the guidance does not present any profound or significant
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
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
On July 2, 2015 the House passed the 21st Century Cures Act . The focus is on expediting research and development on debilitating diseases, and smoothing the process to get important therapeutic options to patients who need them quickly. The Senate has not yet approved
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
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
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
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
We’ve previously commented regarding the predilection of RLD holders whose product approvals include a Risk Evaluation and Mitigation Strategy (REMS) and Elements To Assure Safe Use (ETASU) to use the REMS/ETASU as a barrier to entry for generic completion. Specifically, the RLD holder will refuse
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.
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
With the tsunami of activities connected with the initial implementation of all the GDUFA requirements, another change made by FDA went largely under the radar. FDA released the draft guidance, “Pre-Launch Activities Importation Requests (PLAIR)”. (CDER July 2013) which describes how an NDA/ANDA applicant may
The goal of drug product development is commercial success. If this statement wasn’t true, how would patients access the life-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
Readers of this blog and Premier Consulting 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
Premier Consulting participates in multiple pre-IND (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
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
In this blog post, we will examine a case study that illustrates various factors that should be considered during development. The example is the development of gabapentin enacarbil by XenoPort/GSK for restless leg syndrome. Gabapentin enacarbil is a prodrug of Pfizer’s gabapentin, approved in 1993,
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,
When Premier Consulting was young, products approved under 505j were called “generics” and 505(b)(1) “new drugs.” There was no consensus name for products approved via 505(b)(2). Of course, at the time there had been very few 505(b)(2) products approved. By now, we have seen an
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
Announcement of the decision from the US Court of Appeals for the Second Circuit in the United States v. Alfred Caronia generated a lot of discussion this past week, as well it might. The appellate court overturned the criminal conviction of pharmaceutical sales representative Alfred
Yesterday, Depomed filed suit against the FDA requesting the Court to order FDA to grant their product Gralise (gabapentin) seven years of exclusivity since it was granted Orphan status; upon approval, Gralise was granted three years of exclusivity. Depomed licensed the product to Solvay which became
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
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
How many drug development companies leave it up to the CMO to design or execute their formulation and 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 seemed
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
At Premier Consulting, 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
On September 29, 2010 FDA published a Final Rule revising the requirements for safety reporting for INDs and other BE/BA studies. At the same time FDA issued an accompanying draft guidance to assist in interpreting the new rule. The Final Rule, revising 21 CFR §§
As part of the PDUFA V reauthorization discussions, the FDA and industry are talking about better approaches to rare disease drug development and orphan drugs. Public interests and Congress have mandated that the FDA develop new guidances on the required studies needed for NDA approval.
Under the current PDUFA regulations, a small business can request a waiver of the normal review fees for an NDA if it is the first NDA submitted by the small business. The definition of a small business is fewer than 500 employees. In determining the
Sponsors and their investors continue to seek cost efficient ways to meet their financial milestones. Modeling can be used as a cost effective way to estimate the effect of changing an oral product from immediate release to extended release. Modeling avoids the cost of making
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 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 post. There is debate about the usefulness of the
From a technological standpoint, it is understood that the goal of developing 505(b)(2) abuse-deterrent products is to make changes to the API or formulation of a drug that has abuse potential in such a way that it dissuades the abuser from wanting to use the
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 reaching the goal of a marketed drug product. It provides a
Some define repositioning as the process of examining alternate indications for drugs that have failed in the clinic. Others say that repurposing (with or without the hyphen; re-purposing) is interchangeable with repositioning. When many people think of repositioning drugs, they expect the outcome to be
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
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
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 an assessment of the safety and effectiveness of the
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
Awareness of current FDA standards and those of its various divisions 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. However, for 505(b)(2) applications, at least
What would be the regulatory path for an authorized generic, in general? Authorized generics (AG) are prescription drugs that are produced by the NDA holder and marketed under a private label, at generic prices. This circumstance typically presents itself when the NDA holder still has
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
Can 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 of safety and/or efficacy of an already approved product which is termed the reference listed
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
At Premier Consulting, we can help clients evaluate the market potential of their proposed drug product by examining factors that might influence the resulting medical position at the time of product launch. When desired or needed for potential fund-raising, we can also perform a full
Related to the current frantic activity regarding health care in the US, there is a smaller struggle concerning biosimilars that in many ways mirrors the larger health care struggle. Drug products made from small molecules are regulated primarily by the Food, Drug and Cosmetic Act
What do you need to do when you need to change suppliers or manufacturing sites? Among the many choices is a formal FDA comparability protocol. Advance planning can improve the possibility that the FDA accepts your proposed change. One alternative that can streamline the process
The FDA is moving against DESI drugs and DESI producers are wondering if their products are next on the chopping block. Here are a few commonly asked questions about how that will affect DESI producers. Will a 505(b)(2) of a DESI receive exclusivity? Yes, 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
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
Premier Consulting 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
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
The Food and Drug Administration (FDA) heard testimony on May 27 and 28, 2009, regarding the effort to develop a class-wide Risk Evaluation Mitigation Strategy (REMS) for long-acting opioids products that contain fentanyl, hydromorphone, methadone, morphine, oxycodone or oxymorphone. The public hearing was held to
DESI drugs are a great source for 505(b)(2) development since many will qualify for 5 years data exclusivity. In this post, we will define what they are. Once upon a time…. In 1938 the FD&C Act was established that required that drugs be proven safe
Developing a product with multiple strengths? How do you go about filing multiple strengths in an IND? How and when do you draft one CMC section covering multiple drug strengths for the same dosage form? Long-term drug development goals may include multiple strengths of a
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
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
A draft label be included with all NDA submissions. 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 can
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
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
In speaking with sponsors, 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. Existing products What other drugs are available for the same therapeutic indication(s)? Why would the medical
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
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
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
