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5 Essentials for Building a Robust Target Product Profile

A Target Product Profile (TPP) serves as the primary strategic framework that aligns commercial and clinical workstreams. When properly defined, the TPP enables drug developers to manage the development equation of risk x cost x time = success, and it starts by keeping the end

Do Your Biologics Assays Tell the Whole Story?

Adherence to cGMP regulations assures the identity, potency, purity and quality of biologics or advanced therapeutics and helps ensure adequate control of manufacturing operations. A primary way to demonstrate these attributes for a biologic product under development is through assays. Stages of Assay Development Design

Analytical Testing Considerations for Gene Therapy Products

The FDA’s January 2020 guidance, Chemistry, Manufacturing and Control (CMC)[1] Information for Human Gene Therapy Investigational New Drug Applications (INDs), outlines the analytical methods that define the quality, safety and efficacy of gene therapy therapeutics. The analytical package, consisting of release, stability, and characterization tests,

Artificial Intelligence (AI), Machine Learning (ML) and the FDA

“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

CMC Considerations for Pre-IND Meetings

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,

Early FDA Feedback with Type D Meetings

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

Evaluating Impurities in New Drugs to Prevent Delays in Development

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

In Silico Modeling Unveils a New Era in Rare Disease Drug Development

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

Strategies for Recovering from an Unsatisfactory Pre-IND Meeting

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

Understanding the Elements of a Typical IND-Enabling Package

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

Transitioning to eCTD v4.0

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

What You Need to Know About ICH Q14 and ICH Q2(R2), Part 2

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

What You Need to Know About ICH Q14 and ICH Q2(R2), Part 1

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

PREA and Fixed-Dose Combinations: When Things Get Complicated

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

Three Keys to a Successful Process Technology Transfer

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

Mastering the Active Substance Master File (ASMF) Submission Process

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

The Target Product Profile: Basics and Benefits

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

Next Step in the NHP Shortage: New FDA Guidelines

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

505(b)(1) versus 505(b)(2): They Are Not the Same

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),

The Key to Streamlining Regulatory Approval for IVDs

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

PDUFA VII: More Changes Coming in the Latest Reauthorization

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,

The Composition and Value of a Portfolio Analysis

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

PDUFA VII: Implications for Developers of Cell and Gene Therapies

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

Biologic Therapeutics Development, Part 2: Regulatory Pathways and Pharmacometric Analysis

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.

Biologic Therapeutics Development, Part 1: Definition and Distinct Characteristics

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,

Advancing from Research to Development: What Can Go Wrong?

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

Gene Therapy and Pharmacokinetics

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

In the News: Regulatory and Development Updates

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

Key Changes in the Revised EMA Guidance on Clinical Trials During COVID

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

Technology Transfer: What Is It, and How Is It Done?

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,

Top 5 Common Misconceptions About Meeting with the FDA

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

FDA Designations for Rare Disease Products, Part 1

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

Don’t Underestimate the Value of a Pre-NDA Meeting

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

Anatomy of a Nonclinical Study Monitoring Report

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

Multidisciplinary Team Advances Immuno-Oncology Development

Developing a product from concept to commercialization is a multi-faceted and risky process. Particularly for complex programs, development plans must be customized based on real-world patient experience and optimized for a product’s post-approval success. A cross-disciplinary team is essential for crafting and assessing complex development

Repurposing Drugs As an Answer to the COVID-19 Crisis

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

Patient-Centered Drug Development for Oncology Products

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

What to Expect from the FDA During COVID-19 Product Development

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

CARES Act Introduces OTC Administrative Order Process

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

Three Keys to Preparing Effective Pre-IND Meeting Questions

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

COVID-19 Stimulus Legislation Will Cost OTC Manufacturers

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)

Snapshot: A New Guidance Document Program From the FDA

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

Statistical Considerations for FDA COVID-19 Guidance

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

Why Did My NDA Become a BLA on March 23, 2020?

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,

FDA Issues Guidance on Clinical Trials During COVID-19

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

UPDATE – Draft FDA Guidance Concerning Combination Products

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

Streamline Early Clinical Development With an INTERACT Meeting

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

2019 505(b)(2) NDA Approvals in Review

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

Drug Development for an Aging Population

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

3 Key Takeaways from the 25th Annual Charles River Biotech Symposium

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,

Nonclinical Development Strategy and Study Design

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.

Rare and Orphan Drug Development in the EU

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

The Missing Parts of the Inactive Ingredient Database (IID)

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?

ANDAs Prioritized to Combat Opioid Crisis

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

Digital Health: FDA Regulation of Mobile Medical Apps

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

Is the 505(b)(2) or ANDA Pathway Right for Your Product?

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

Scope of Orphan Drug Exclusivity – How Broad is Broad?

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

GDUFA I and II: Considerations for Complex Generics Innovators

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

Advantages of the 505(b)(2) Pathway in Nonclinical Development

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

New FDA Guidance on OTC Products

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

How to Get Orphan Status for 505(b)(2) Drugs

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

Rx-to-OTC Switch: Expanding to the US Over-the-Counter Market

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

Product Selection: Which Product to Develop?

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: Why Didn’t We Think of That?

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

Navigating Clinical Holds

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

The Target Product Profile: Your Strategy to Reduce Development and Review Time

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

The New Reality of Generics under GDUFA

From recent news, we know that the FDA has been under increasing pressure to reduce the timing of its reviews while maintaining the highest possible standards for safety and efficacy of the products it approves. This is the reason for the PDUFA and now the

Brexit and EMA: The Changes Have Begun

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

DESI Drugs: Potential Targets for Quick Approvals

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 – Navigating the Combination Rule

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

505(b)(2) Approval Times: The Real Scoop

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

Pre-IND Meetings: How to Achieve Success for 505(b)(2)

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

Referencing a Listed Drug for the 505(b)(2) Pathway

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

Unforced Errors: FDA Refusal to File or Receive Letters

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

A New Indication for an Old Drug. What Could Go Wrong?

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

PRO-CTCAE: Improving Oncology Drug Development

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

505(b)(2) Application Changes: What You Need to Know

Title XI of the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 was enacted in order to address concerns that had potential to delay access to more affordable drugs. The FDA has been implementing the MMA via the statute since it was enacted

Risk Evaluation and Mitigation Strategies (REMS) Basics

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

Improving Drug Development ROI in 2017

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)

Orphan Drug Development: Ensuring Best Time to Market

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

Pitfalls of Changing the Salt of a Listed Drug

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

Abuse Deterrence Labeling – Generic vs 505(b)(2) Drug Development

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

The Prodrug Benefit of Utilizing the 505(b)(2) Pathway

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

The New FDA Draft Guidance on Chewables

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

Back to Basics: 505(b)(2) FAQs Part 3: Regulatory Strategies

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

Back to Basics: 505(b)(2) FAQs Part 1

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,

The Regulation of Follow-On Biological Products via 505(b)(2)

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

Pediatric Applicability or Not–This Revised Guidance Is for You

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

Additional 505(b)(2) Benefits: Selective Safety Data Collection

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

3-Year Exclusivity May Not Be Worth as Much as You Think

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?

Enforcement Activities: FDA removes unapproved prescription ear drops

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

Examining the Amarin VASCEPA Saga

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

Quality Metrics – Coming Soon to Your Manufacturing Facility

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).

To List or Not to List – That is the Question

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

Pediatrics – What are the appropriate age ranges?

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

REMS/ETASU and Safe Use in Bioequivalence trials

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

MAPPing out the timing of a Complete Response submission

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

Extending Exclusivity: How Long Will It Really Last?

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.

Therapeutic Equivalence Ratings Under 505(b)(2)

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

5-Year Exclusivity for Certain Fixed-Combination Drugs with an NCE

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

Alkermes Prodrug for Treatment of Multiple Sclerosis: NCE?

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).

Paper Submissions: Going, going…away

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

Importing pre-launch products with a bit of PLAIR

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

ANDA but No NDA – What to Rely on?

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

PREA – Pediatric Plan Timing Changed by PDUFA V

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

New PDUFA V Meeting Timelines

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,

Are 505(b)(2)s “Super Generics,” or what do we call them?

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

No 5-Year Exclusivity for Combinations Drugs with an NCE

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

Off-label promotion: Free Speech?

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

Orphan Designation without Exclusivity: Court asked to decide

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

New Generic Stability Requirements

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

ViroPharma Denied Request for 3-year Exclusivity

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

Drug Development Planned Like the Titanic

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

Generic vs. 505(b)(2) Failure-to-Warn Liability

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

When is an IND required?

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

Labeling for Abuse-Deterrent Drugs

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

Target Product Profile

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

505(b)(2): Repositioning, Repurposing or What?

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

FDA’s Determination of Vyvanse as NME Upheld

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

Can and Should ANDA Labeling Differ from the RLD?

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 Oral Solutions

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

505(b)(2) Approval Standards – Referenced Studies

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

Authorized Generics Q&As

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

Reference Listed Drugs (RLDs): Can More Than One Be Used?

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

REMS or RiskMAP or what?

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

Is There a Market For Your Drug?

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

Biosimilars: An Introduction

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

Comparability Protocols

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

DESI Products: Q&A

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

Test Specifications for Stability Studies

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

ANDA Suitability Petition vs 505(b)(2)

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

Risk Evaluation Mitigation Strategy (REMS) for long-acting opioids

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

What are DESI Drugs?

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

Multiple Dosage Strength Products – CMC Considerations

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

Botanicals: What is the starting material for the API?

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).

One vs. Two Batches for Single-Dose and Multiple-Dose Studies

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

505(b)(2) NDA Labeling

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

505(b)(2) Literature Searches – Too much or too little?

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

PREA and 505(b)(2)

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

What Is the Competition for Your Product?

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

Paragraph IV Certifications under 505(b)(2)

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

505(b)(2) Patent & Marketing Exclusivity

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