Drug master files (DMFs) electronic submission deadline extended

FDA DMFs eCTDOn April 7, the Food and Drug Administration (FDA) announced an extension of the compliance date for submitting drug master files (DMFs) in electronic common technical document (eCTD) format. FDA pushed the deadline back one year to May 5, 2018. The compliance date for submitting new drug applications (NDAs), biologics licensing applications (BLAs), and abbreviated new drug applications (ANDAs) electronically remains unchanged (May 5, 2017).

Shifting to the eCTD format represents FDA’s initiative to make the drug application review process more efficient. eCTD standardizes how the life science industry submits applications, amendments, supplements, and reports. FDA states that implementing electronic DMFs will improve the efficiency of the DMF review process. Electronic drug master files allow FDA to review applications more easily and better meet the associated PDUFA and GDUFA performance goals.

Our team of advisors at Pearl Pathways expertly prepare electronic drug master files for FDA submission. We understand the eCTD format and process. We have already helped several life science companies electronically submit DMFs, NDAs, BLAs, and ANDAs. Contact us today to discuss your submission needs.


Here are some helpful resources to prepare for the upcoming deadlines:

Guidance Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the Electronic Common Technical Document (eCTD) Specifications

New Requirements for Electronic Submissions of DMFs

DMF Tip Sheet

eCTD Submission Requirements: What You Need to Know

FDA Electronic Submissions Gateway

21st Century Cures Act deadlines approaching

21st Century Cures ActThe 21st Century Cures Act passed with resounding bipartisan support in the final days of President Barack Obama’s second term. The bill, which includes initiatives impacting several federal organizations and the clinical research ecosystem, will be implemented over the next several years primarily by the US Food and Drug Administration (FDA) and National Institutes of Health (NIH). The Regulatory Affairs Professionals Society (RAPS) recently reported, some provisions of the bill must be implemented in the next two weeks.

March 13, 2017 marks 90 days since the law’s passing and subsequently includes some required actions. The RAPS article points out some of the upcoming deadlines:

  • “Tom Price, the new Secretary of Health and Human Services, shall establish a task force, called the “Taskforce on Research Specific to Pregnant Women and Lactating Women” to provide guidance on “gaps in knowledge and research regarding safe and effective therapies for pregnant women and lactating women, including the development of such therapies and the collaboration on and coordination of such activities.”1
  • Price also must publish a notice in the Federal Register containing a list of each type of Class II device that no longer requires a report “to provide reasonable assurance of safety and effectiveness.”1
  • Another portion of the bill requires NIH officials to “consult with stakeholders, including FDA and the Office of the National Coordinator for Health Information Technology, as well as patients, researchers, physicians, industry representatives, and developers of health information technology to receive recommendations to further enhance ClinicalTrials.gov.”2

These deadlines undoubtedly arrive during a time of change for the FDA and NIH, yet the Cures act was passed with the intention of improving patient care, expanding clinical research programs in the United States, and finding a cure for cancer by the year 2020. With more deadlines approaching at the 180-day mark, or June 13, the new administration officials entering the impacted agencies must come together and work quickly to support the goals of the bill.

Stay tuned to our blog or follow us on Twitter for updates on the 21st Century Cures Act, new legislation, and other current events impacting the life science industry. Do you need assistance with your NIH funded research? Please contact us today.


1 http://docs.house.gov/billsthisweek/20161128/CPRT-114-HPRT-RU00-SAHR34.pdf

2 http://raps.org/Regulatory-Focus/News/2017/02/22/26927/21st-Century-Cures-Act-Deadlines-Approach-in-March-and-June/?utm_source=Email&utm_medium=Informz&utm_campaign=Informz%2DEmails

Obstacles facing biosimilar developers

biosimilar developer stock photo optionThe biosimilars industry is still in its infancy in the U.S. marketplace, resulting in some growing pains for developers of these products. Biosimilars were created under the Biologicals Price Competition and Innovation Act (BCPIA) of 2009 and signed into law through the Patient Protection and Affordable Care Act (Affordable Care Act) on March 23, 20101. Under the BCPIA, a biological product may be demonstrated to be biosimilar if data show the product to be highly similar to a previously-approved biological product. The biosimilar must show no clinically meaningful differences to the reference product and follow the same mechanism of action.

Last month, BioPharmaDive published a series on biosimilars, one of which addressed “5 hurdles facing biosimilar developers.” With only four biosimilars currently approved in the U.S. market, there is plenty of room for growth. That is, of course, if developers can navigate the hurdles facing them as they jump into this young, bourgeoning industry.

BioPharmaDive listed the following challenges for developers:

  1. Pricing Pressures
  2. Legal battles
  3. Reimbursement
  4. Education
  5. Manufacturing

Regarding pricing pressures, all too often we can see various news organizations covering the backlash from consumers, government, and key stakeholders towards the biopharmaceutical industry regarding pricing. Biosimilars are not immune to this scrutiny. The expectation exists that biosimilars will play a similar role on the market as generic drugs. Generics “revolutionized the way drugs were sold in the U.S., offering an 80% to 90% discount to branded drugs…yet, Pfizer priced its Remicade (infliximab) biosimilar Inflectra (Infliximab-dyyb) at only a 15% discount – raising the issue of whether biosimilars will have their desired impact on the market.”2

A few key legal battles have already broken out since the BPCIA paved the way for biosimilars, potentially creating an unsettling precedent for this new industry. As for reimbursement challenges, locations where nurses or physicians infuse drugs typically use a “complicated reimbursement formula based on average sales price.”2 The BioPharmaDive article goes on to explain the pushback from reference product developers and biosimilar developers about Centers for Medicare & Medicaid Services (CMS) using codes that do not specifically identify the maker of the product. The product payment and required modifiers for biosimilars outlined by CMS can be found here.

A lot of questions still exist surrounding biosimilars, which the FDA began addressing last year through advisory committee meetings. Education for developers, health care professionals, and patients will continue to contribute to the success of the industry moving forward. The drug industry is far from immune to manufacturing setbacks, and biosimilar developers must account for these issues as well. Biosimilars, like the reference biologics they mimic, are derived from living cells “with inherent variability and therefore are incredibly complex to manufacture.”2

Pearl Pathways employs a team of experts with decades of experience across all of the life science industries. Our team has helped several life science companies develop their products and navigate through the challenges detailed above. Please contact us today to begin a conversation.




Save the date: RAPS Indiana Chapter hosts a senior FDA representative to speak about drug safety lifecycle management

RAPS IndianaOn March 9th, the RAPS Indiana Chapter, chaired by Pearl Pathways COO Gretchen Bowker, will host an interactive presentation from a senior FDA representative. The FDA representative, Jill R. Bourdage, RPh, PMP, will speak about processes and procedures of the Office of Surveillance and Epidemiology (OSE) within the Center of Drug Evaluation and Research (CDER). The presentation will provide an overview of the OSE and its role in the continuum of drug safety lifecycle management. Anticipated updates from PDUVA VI will be covered and the audience will learn how the role of the OSE Safety Regulatory Project Manager and regulatory expert as point of contact for industry can help achieve optimal communication.

Presentation title: Optimizing Communications with the Office of Surveillance & Epidemiology

Date: March 9, 2017

Time: 5:30 – 8:00pm EST

Location: Purdue University: Seng Liang Wang Hall

West Lafayette, IN

Registration and more information about the content can be found here.

CDER’s novel drug approvals for 2016: a review

Last week, John Jenkins, M.D. issued a review of the FDA’s new drugs program in the Center for Drug Evaluation and Research (CDER). The total number of new drug approvals decreased dramatically in 2016 versus the previous year; however, Jenkins, who is the Director of the Office of New Drugs in FDA’s CDER, approaches the numbers with optimism (fda.gov). Twenty-two novel drugs received approval by CDER, and most of these drugs could add “significant clinical value” to the care of thousands of patients with serious and life-threatening illnesses.

2016 could be viewed as a year of “firsts” for new drug approvals. Spinal muscular atrophy and Duchenne muscular dystrophy both received first treatments. Parkinson’s disease related hallucinations and delusions, primary biliary cirrhosis, and hepatitis C each received new treatments. Several new oncology drugs obtained approval to help patients with ovarian cancer, bladder cancer, soft tissue sarcoma, and chronic lymphotic leukemia. CDER approved two new diagnostic agents used to detect certain forms of cancer as well. Jenkins notes that 73% of the 22 novel products benefited from at least one of the FDA’s programs to expedite new drug development and review. Another promising statistic from the CDER review team is that 95% of the novel drug products they reviewed last year were “first cycle” products. This means that CDER did not need to request additional information from submitters to approve the product. Find an extensive look at all of last year’s new drug approvals in the FDA’s 2016 Novel Drugs summary.

The high usage rate of an FDA fast-track program indicates efficiency within the approval process. The nearly 100% “first cycle” approvals suggests that life science companies are submitting accurate and comprehensive clinical trial data. Pearl Pathways prides itself on helping companies and researchers successfully expedite the product development life cycle. Last year alone, our team provided expert insight into the FDA’s Fast Track, Breakthrough Therapy, and priority review designations to several of our clients. Please contact us today to find out how we can help you with your new treatments in 2017 and beyond.

21st Century Cures Act: potential impact on the clinical research landscape

clinical trialsThe historic 21st Century Cures Act, written into law last December, is a 362-page bill comprised of several initiatives impacting the life sciences industry. The allocation of $4.8 billion for the “Cancer Moonshot” portion of the bill won over most headlines during news cycles leading up to the bill’s signing, but several other sections will impact the clinical research ecosystem over the next several years. An article published in this month’s volume of the Journal of Clinical Research Best Practices outlines the major sections of the Cures Act that affect clinical trials.

The aforementioned Cancer Moonshot leads the bill, creating a $4.8B “NIH Innovation Account” that will allocate funds to the Precision Medicine Initiative, BRAIN Initiative, Cancer, and Adult Stem Cells research. Another $500M will be set aside for an “FDA Innovation Account.” The Eureka Prize Competition section allocates prize money for significant advancements in biomedical sciences and/or improving health outcomes in serious yet disproportionate research areas. Three sections address confidentiality of personal health information for study participants: Privacy Protection for Human Research Subjects, Protection of Identifiable and Sensitive Information, and Data Sharing.

To support emerging scientists, the NIH will develop and prioritize policies that promote opportunities for new researchers. The NIH also addresses Educational loan repayment addresses by increasing repayments from $35k to $50k in exchange for research work in the areas of basic science, AIDS, and emerging needs. This section also instructs the NIH to prioritize research conducted by professionals from disadvantaged backgrounds.

Reducing administrative burden for researchers also makes up a large section of the bill. Within two years, HHS is to “harmonize and eliminate duplicative Conflict of Interest reporting… [and] examine the varying minimum thresholds, consider allowing for just in time reporting, and consider redefining which investigators and sub-investigators need to report.” Several sections address the patient experience during clinical trial studies. The FDA will create guidance explaining the use and requirement of patient experience data such as data collected by non-clinicians (e.g. patients, family, etc.), the impact of disease and therapy on patient lives, and patient treatment preferences.

The bill would not be complete without detailing the penalties for violation of grants, contracts, and other agreements created under the 21st Century Cures Act. The bill outlines fines from $10k-$50k for each false statement or omission in addition to $10k-$15k fines per day for delays in the transfer of funds to HHS.

Do you need assistance with your NIH funded research? Please contact us at Pearl Pathways.

New drug approvals stumble, total filings hit mark in 2016

new drug approvals 2016Record approvals of new drugs in 2014 and 2015 likely won’t continue in 2016. Even so, the total number of filings remains just above the average. FierceBiotech examined the numbers yesterday and tried to uncover the meaning.

According to John Jenkins, the soon-to-be retired director of the Center for Drug Evaluation and Research (CDER) at the FDA, approvals of new molecular entities (NMES) currently stand at 19, well below the 45 NMEs approved in 2015. Novel drugs and biologics currently being reviewed by the FDA will also fall short of the 2015 numbers but align close with 2014. Jenkins attributes 2016’s underwhelming numbers in part due to five drugs that were slated for 2016 approval that received a green light ahead of schedule in 2015. A significant increase in applications resulting in a complete response letter (CRL), meaning they did not achieve the adequate approval mark, also increased from 2 in 2015 to 12 this year (so far). The FierceBiotech article notes that the hike in CRLS could be the effect of a “greater use of speedier approval pathways designed to accelerate access to new medicines [that] is raising the risk of failure at the first hurdle.”

Jenkins felt encouraged by this year’s large share of innovative medicines in the total number of approvals. Over one third are designated for rare diseases, 37% are first-in-class drugs, and 8/10 received clearance in the US ahead of other markets. Pearl Pathways is well equipped to support your NME NDAs/BLAs submissions to help your organization receive approval efficiently and expedite your product’s pathway to market.

The 21st Century Cures Act passes through the House with resounding support

The 2st Century Cures Act, a nearly 1,000 page bill that details changes for the Food and Drug Administration (FDA) and National Institute of Health (NIH), passed by a vote of 392-26 today in in the House of Representatives. A Senate vote could come as soon as next week.

Assuming the bill prevails in the Senate, the NIH will be the recipient of $4.8 billion in funding over the next 10 years, though money allocation must be reauthorized each year. This money is “earmarked for the three landmark big science initiatives of President Obama’s time in office: the cancer moonshot, the BRAIN Initiative, and the Precision Medicine Initiative” (FierceBiotech).

The passing vote of 392-26 came as a shock to some critics of the bill, “showing a bipartisan spirit that has been rare in recent years” (statnews.com). If the bill passes, it would also “gives states $1 billion to fight the opioid crisis, and deliver an additional $500 million to the FDA.”

FDA’s list of emerging tech requests topped by continuous manufacturing and sterile production innovations

The US FDA’s Emerging Technology program was established as a catalyst for new technologies to help modernize pharmaceutical development and manufacturing in areas where the FDA has limited review or inspection experience. Thomos O’Connor from the FDA’s Office of Pharmaceutical Quality explains that “this is technology with the potential to modernize the body of knowledge associated with pharmaceutical development to support more robust, predictable, and cost-effective processes or novel products… our vision is to have a maximally efficient, agile, flexible pharmaceutical manufacturing  sector that reliably produces high quality drugs without extensive regulatory oversight ” (in-PharmaTechnologist.com).

O’Connor is a member of the committee formed to facilitate the program and assist the industry with applications. The committee, known as the Emerging Technology Team (ETT), has already received 20 applications this year, doubling the number requested last year. The in-PharmaTechnologist article breaks down the submissions: continuous manufacturing technologies for drug product, substance, and biologics represent 30% of all requests, another 30% consists of the use of robotics and container closure systems for sterile injectable production, biotechnology processes and analysis represent 22%, and the final 17% include other areas of innovation such as new dosage forms and 3D printing.

What implications, if any, do these numbers say about the future of the life sciences industry? One could look at the breakdown as a compass for where future demand (and funding) will be. Though continuous manufacturing and robotic/container closure technologies led the way with a majority share of submissions, the numbers represent a fairly even and robust spread of emerging technologies. If your firm is looking to participate in the Emerging Technology program and need guidance with your IND, NDA, ANDA, or BLA application, our dedicated team of experts at Pearl Pathways is here to help.

FDA Halts Finalization of Lab-Developed Test Draft Guidance

Last Friday, the FDA halted the finalization of guidance that would have changed the way lab-developed tests (LDTs) are regulated. The reason? The presidential election. The current administration now enters its waning hours and the FDA decided to suspend guidance until the new regime takes office.

As RAPS reported, the press office for the FDA, Tara Goodin, defended this position because the “FDA believes that patients and health care providers need accurate, reliable, and clinically valid tests to make good health care decisions – inaccurate or false tests results can harm individual patients. We have been working to develop a new oversight policy for laboratory developed tests… and realize just how important it is that we continue to work with stakeholders, our new Administration, and Congress to get our approach right. We plan to outline our view of an appropriate risk-based approach in the near future.”

The agency released draft guidelines two years ago outlining a risk-based framework for regulating LDTs that would be phased in over nine years. LDTs have historically been regulated by the Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments. The FDA’s decision, though praised by some, creates uncertainty for the industry and may leave a lot of companies in limbo. To learn more about this topic, see our industry whitepaper. Need assistance navigating the regulatory guidance for IVDs or LDTs, contact us and our experts can help.