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Applied Clinical Trials June 2021

Egnyte commissioned GatePoint Research to query 152 executives in Regulatory Affairs, R&D, Clinical and Quality about the challenges facing data-driven, mission-critical companies as they try to maintain GxP compliance, specifically around data integrity and data privacy and security.

The report looks at how the biotechs efficiently and securely manage collaboration and data and unveils some interesting results. One of the findings is that the most popular applications used to manage regulated data are not designed for life sciences specifically. In such a specialized field, this can lead to trouble.

Another finding the report points to is a divide developing amongst life scenes organizations. There are technology adopters and there are organizations that still operate from manual processes leading to friction in collaborating with partners and difficulty maintaining compliance with regulations.

Articles

Egnyte Releases Life Science Data Management Trends Report

Despite the pressures and added regulatory challenges imposed by the COVID-19 pandemic, and the uproar over its surprise approval of Biogen’s new Alzheimer’s therapy Aduhelm, FDA is on track this year to authorize a notable number of new molecular entities (NMEs) and important biotech therapies. In the first half of 2021, the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) gave the nod to 29 novel therapies, slightly ahead of last year’s pace that saw the approval of a near-record 53 new drugs.

CDER’s list of novel new drug added up to 27 NMEs and biologics as of June 30, 2021, with several more additions in July.

 AndCBER okayed a new pneumococcal vaccine and new treatments for multiple myeloma and for lymphoma.

Almost half of the new drugs are treatments for cancer and related conditions, many benefitting from priority review and accelerated approval programs. That includes Jazz Pharmaceuticals’ new blood cancer therapy, a treatment for non-small cell lung cancer from Amgen, and Bristol Myers Squibb’s new CART-T therapy for multiple myeloma plus a cell therapy for large B-cell lymphoma.

Important non-cancer approvals also include the first new treatment for vaginal yeast infections in two decades and the first therapy for chronic weight management authorized since 2014, arising from approval of an added indication for Novo Nordisks’s type 2 diabetes injectable Wegovy (semaglutide) for obese or overweight adults. FDA also okayed new therapies for Duchenne muscular dystrophy, lupus nephritis, chronic heart failure and, notably, an extended release injectable to manage HIV, replacing daily pills with monthly injections.

There were advances in the over-the-counter drug world, too. In June, FDA approved the first nonprescription nasal antihistamine to expand treatment options for patients age six and older; younger children still have to obtain Bayer Healthcare’s Astepro (0.15% azelastine hydrochloride nasal spray) on a prescription basis.

Important news on the approvals front continued in July, as FDA authorized its first interchangeable biosimilar—Mylan’s Semglee once-daily insulin therapy, biosimilar to Sanofi’s Lantus.

 FDA also approved an important treatment for high-risk, early-stage, triple-negative breast cancer, giving the nod to Merck’s Keytruda (pembrolizumab) to be used in combination with chemotherapy for this serious condition.

On the downside, FDA halted use of a treatment approved in February for relapsed or refractory multiple melanoma, Pepaxto from the Swedish firm Oncopeptides, based on evidence from ongoing clinical studies of higher death rates among patients treated with the new drug vs. an earlier therapy. Pepaxto gained accelerated approval, but now FDA has alerted patients and health professionals to the potential risk and has suspended enrollment in postapproval studies pending further examination of the safety signal.

CDER officials attribute their ability to maintain a fairly normal advise and consent process for innovative drugs over the past 18 months on the hard work of its dedicated staff, as well as efficiencies gained from the recent reorganization of its Office of New Drugs (OND). CDER director Patrizia Cavazzoni noted increases in staff hiring and retention at the May 2021 annual meeting of the Food and Drug Law Institute (FDLI), attributing this surprising development to new remote work flexibilities due to COVID-19 restrictions. She also cited the success of large platform trials and clinical networks, as well as increased sponsor use of decentralized trials. The structural overhaul of OND has resulted in smaller, more flexible review offices with clearer areas of expertise and greater alignment of interrelated disease areas, Cavazzoni explained in recent testimony to the House Energy & Commerce Health subcommittee, which held a hearing to explore the lack of new therapies for neurogenerative diseases.

https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2021

https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2021-biological-license-application-approvals

https://www.fda.gov/news-events/press-announcements/fda-approves-first-interchangeable-biosimilar-insulin-product-treatment-diabetes?utm_medium=email&utm_source=govdelivery

https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-patients-and-health-care-professionals-about-clinical-trial-results-showing-increased?utm_medium=email&utm_source=govdeliver

https://www.fda.gov/news-events/congressional-testimony/path-forward-advancing-treatments-and-cures-neurodegenerative-diseases-07292021

FDA is on track this year to authorize a notable number of new molecular entities and important biotech therapies.

New Drug Approvals On Track at FDA

ACRO has released its DCT Toolkit, which lays out a vision for how decentralized clinical trials can be planned and executed now and in the future. Decentralized clinical trials (DCTs) have been an innovative resource during the pandemic, and DCTs will continue to be an important, patient-centric clinical trial design.

The DCT Toolkit is now available on ACRO’s website and contains four resources:

Bringing the Trial to the Patient: A Quality-by-Design Manual for Decentralized Clinical Trials

QbD Manual for Decentralized Clinical Trials: The Quick Reference Guide

Decentralized Clinical Trials Risk Assessment Considerations

Decentralized Clinical Trials Data Flow Maps

ACRO Releases DCT Toolkit

MMS Holdings announced that its learning arm, MMS Academy, has expanded its global training portfolio with the launch of new courses in inspection readiness and clinical programming. These new courses will give students and working professionals the opportunity to gain the knowledge that the pharmaceutical, biotechnology, and medical device industries require.

In the 14-week inspection readiness course, students will gain an understanding of global health authority (i.e. FDA, EMA, etc.) inspection processes, targeted industry-specific guidance, and important regulations and guidelines that allow teams to ensure successful regulatory authority inspections.

Mini courses are also available, each lasting three to four hours, and have been prepared with consideration for a variety of specific inspection needs, including: remote inspections, regulatory agency and ISO basics, post inspection management, GMP, Sponsor and CRO inspections, and more.

Intermediate Fundamentals of Clinical Programming, an 8-week course, is designed for intermediate SAS programmers looking to learn more about the CDISC SDTM model. Those taking this course will gain the confidence to model clinical trial data into SDTM domains and a level of expertise to draw upon when engaged in real-world projects.

This course provides an understanding of:

Converting clinical data into SDTM format by understanding the required modeling of the General Observation Class and targeted domains

The components included in define.xml v2.0

The process of third-party validation of the define application

How to resolve and apply corrective measures to ensure modeling is in compliance with SDTM standards

MMS Adds New Inspection and Programming Courses to MMS Academy

Congressional leaders, as well as regulated industry, want more information from FDA on its strategy for resuming inspections of manufacturing facilities to better assure the quality, safety and efficacy of medical products. The suspension of in-person field inspections in March 2020 has resulted in a huge backlog of delayed site visits, as FDA sent investigators only to those operations deemed “mission critical.”

FDA acting commissioner Janet Woodcock recently confirmed that the agency is returning to normal procedures for domestic inspections, although foreign inspections still will be limited to mission-critical situations. In testimony before the Senate Health, Education, Labor and Pensions (HELP) Committee on July 20, 2021, Woodcock outlined FDA’s plan to “transition to standard operations” for U.S. inspections, which still means focusing on higher-risk establishments and scheduling postponed surveillance inspections based on risk.

Meanwhile, Congressional leaders continue to demand more information on how and when FDA will resume standard operating procedures for inspections, reflecting concerns that postponed oversight may delay the approval of new drugs and biologics. In a lengthy letter to Woodcock dated July 22, 2021, Republicans and Democrats on the House Energy and Commerce Committee requested details on the status of foreign inspections; whether delayed inspections are hindering the approval of applications for new drugs, generics and biosimilars; FDA’s ability to utilize inspection reports from trusted inspectorates; and how FDA’s data modernization initiative will improve its inspection program. The legislators also want to know how much of the $38.3 million provided FDA to help address the pandemic is being used to support the resumption of domestic and foreign inspections, and the impact of FDA’s decision to pre-announce all inspections for the foreseeable future.

FDA normally conducts nearly 1,000 foreign and domestic inspections a year for medical products, but has made less than 100 critical site visits in the U.S. in the last two years, and only a handful overseas. In its “Resiliency Roadmap for FDA Inspectional Oversight” issued May 5, 2021, FDA acknowledged that it had postponed most inspections in 2020 due to the pandemic, focusing primarily on manufacturing operations producing drugs needed to prevent critical shortages and to support the approval of novel drugs or treatments for COVID-19.

 For 2021 the agency has some 15,000 domestic surveillance inspections on its to-do list, most of those involving food and other products, but a third related to drugs.

To better manage this considerable volume of inspection work, FDA is aims to enhance the Office of Regional Affairs (ORA) field inspection program through the agency’s data modernization initiative to provide cross-program interoperability, Woodcock reported to the Senate panel. This includes new technology supporting regulatory assessments to improve the receipt, review and analysis of industry data and records, including a review of inspectional approaches using next-generation assessment technologies.

Furthermore, FDA has established a new agency-wide Inspectional Affairs Council to better coordinate inspection approaches and assessments across product centers. This panel aims to “optimize the inspection process,” explained Judith McMeekin, associate commissioner for regulatory affairs, in a presentation July 14, 2021 to the Alliance for a Stronger FDA. McMeekin, who manages ORA’s 5000 inspectors and other staffers, noted that the Council will provide a forum for the leadership of FDA centers to jointly assess strategies and policy issues across operations to ensure optimal use of resources.

McMeekin reported that ORA has conducted about 30 mission critical foreign inspections during the pandemic, which has involved a tremendous effort to mitigate risks to investigators. ORA also worked to facilitate the emergency approval of vital vaccines to combat the pandemic by devising methods to inspect key vaccine clinical research sites, collaborating with the Center for Biologics Evaluation and Research (CBER) to plan the visits. In just four weeks, a team of more than 50 ORA investigators inspected 26 clinical research facilities to ensure the accuracy and reliability of data to be considered by FDA’s vaccine advisory committee. Here, FDA sent in two inspectors, instead of one, to assess data in the shortest amount of time, supplying them with portable projectors able to review documents from a distance.

McMeekin also highlighted ORA’s need for additional funding, particularly to enhance its operations related to drugs and medical products. Only 10% of its budget is supported by user fees, she explained, and most of its appropriated funds are allotted to food safety and oversight. To expand its drug inspection activities, lab capacity and scrutiny of more imported packages containing drugs, ORA is looking to tap more medical product user fee funds, while also increasing appropriated support to bolster its staff dealing with medical devices and biologics, as well as its cadre of foreign inspectors.

In going forward with scheduling of site visits in the U.S., FDA is utilizing a rating system to assess the number of COVID-19 cases in the local area and risks to personnel, in consultation with state and local authorities. And for now, the agency also is pre-announcing domestic inspections to ensure a facility is available and safe for FDA staffers to visit. But FDA officials recognize that it will take some time to restart its foreign drug inspection program due to the more extensive planning required to arrange for safe travel and site visits.

https://www.help.senate.gov/imo/media/doc/Woodcock%20Testimony.pdf

https://energycommerce.house.gov/sites/democrats.energycommerce.house.gov/files/documents/07.22.21-EC-Letter-to-FDA.pdf

https://www.fda.gov/media/148197/download

FDA acting commissioner Janet Woodcock has outlined FDA’s plan to “transition to standard operations” for U.S. inspections.

FDA Under Pressure to Restore “Normal” Drug Inspections

Mike Rea, CEO and Founder of IDEA Pharma, speaks about how his newly launched sister company—Protodigm—takes lessons learned from IDEA, combined with ideas borrowed from engineering and tech development, to form a new concept in pharma and biotech to innovate drug development with minimized risk and without bias.

Podcasts

Nuance in the CRO World

 addressed the first two elements necessary in 

Figure 1) to help sponsors derive the greatest benefits from eCOA technology: involving all key stakeholders in the earliest stages of designing and implementing eCOA solutions and carefully considering your data NEEDS versus “nice-to-haves.” Part 2 addresses the next four crucial elements: implementing best practices in design, taking advantage of your solution provider’s experience, relying on configurable platforms not customized solutions, and focusing on user experience (UX).

Patient-centric design is the most critical factor in eCOA design. Members of the Transcelerate Biopharma’s Patient Technology Initiative spoke with a diverse group of patients to understand what they would like sponsors to consider when designing studies using patient technology. Among those were patient burden, UX, and patient comprehension

and it is well known within the eCOA industry that best practices should be followed to minimize compromising patients’ comprehension of electronic versions of questionnaires originally developed for paper administration.

Uncomplicated design is crucial in ensuring:

All information can be understood by all end users (sites and patients)

Simplicity of use regardless of technical literacy

One of the easiest ways to ensure simplicity of design is to rely on your solution provider’s previous experience. Typically, they have experience with diverse sponsors, geographic locations, indications, and study parameters. They have spent time extracting lessons learned from post-study discussions with sponsors. Their clinical, scientific, regulatory, project management, and technology expertise is vital in designing and implementing eCOA solutions. Combined with your internal key stakeholders’ project-specific knowledge and their experience with internal processes, systems, and technology, the collaboration will yield a design that makes sense for your study.

Configurable platform vs. customized solutions

Let us first clarify what we mean by “configurable” and “customized.”

 To use existing code from within an application to meet specific requirements.

 To write new software code to meet specific requirements.

In Table 1, we describe the benefits of the configurable platform and potential challenges of customized solutions.

Table 1: Configurable versus Customized Software

Consider configurable solutions that allow you to build your study using a standardized library of assessments to meet study goals. For example, the YPrime StudyBuilder solution offers a range of development settings and outputs a study design that is pre-validated and ready for use. Features of YPrime’s StudyBuilder include:

Thoughtful design requires us to consider the burden this technology may place on patients and sites. It is important that sponsors and solution providers remember to stick to the basics and keep simple the UX design. Some factors to consider:

Amount of time the patient must invest to set up, use, close out, and return the device

Keeping it simple with easy-to-understand user guides, login screen, and other navigation

Amount of disruption to the patient’s daily activities

Level of comfort as patients wear or carry the device throughout their day

Direct patient interaction versus passive data collection and transmission

By investing time and resources upfront on 

 (see Figure 1), sponsors can streamline and gain efficiencies during the study development process, reduce time to first-patient-in, increase site satisfaction, and ensure patient compliance.

TransCelerate Bio Pharma Inc. Patient Considerations: A patient perspective on key considerations for sponsors implementing patient technology in clinical trials. Available from: https://transceleratebiopharmainc.com/patient-technology-implementation-framework/patient-technology-assets/. (Accessed April 19, 2021)

Critical Path Institute ePRO Consortium. Best Practices for Electronic Implementation of Patient-Reported Outcome Response Scale Options. Available from https://c-path.org/wp-content/uploads/2014/05/BestPracticesForElectronicImplementationOfPROResponseScaleOptions.pdf. (Accessed April 19, 2021).

Critical Path institute ePRO Consortium. Best Practices for Migrating Existing Patient-Reported Outcome Instruments to a New Data Collection Mode. Available from: https://c-path.org//wp-content/uploads/2014/05/BestPracticesForMigratingExistingPROInstrumentstoaNewDataCollectionMode.pdf. (Accessed April 19, 2021).

To derive the greatest benefits from eCOA technology, several elements must work together to create a strong foundation for sponsor success.

Thoughtful Design in eCOA Development: Part 2

WCG has announced the acquisition of VeraSci, a global provider of specialty scientific and eClinical software to support the design and execution of clinical trials focused on central nervous system disorders.

VeraSci provides clients with solutions that aim to improve data quality in clinical trials, including endpoint and assessment services, rater training and certification, language and translation support, and eCOA and ePRO technologies. With its Pathway technology platform, VeraSci enables the collection of data that can be used to assess symptoms, cognition, and functional capacity in a wide range of therapeutic indications.

Moving forward, VeraSci will be known as WCG VeraSci. The organization will retain its leadership structure and continue to operate from its headquarters in North Carolina.

WCG Acquires VeraSci

ACM Global Laboratories, Inc. has announced the rebranding of ABS Laboratories to ACM Bioanalytical Services.

Founded over two decades ago by Drs. Colin Feyerabend and Mira Doig, ABS Laboratories was purchased by ACM Global Laboratories in 2018 as it expanded its central laboratory testing offerings for clinical trials to include bioanalytical services. ABS Laboratories, now ACM Bioanalytical Services, specializes in complex assay development and validation for the quantification of drugs, metabolites and biomarkers in biological samples used in pharmaceutical research and development.

ACM Bioanalytical Services will maintain all of its employees, equipment, and location in York, UK.

ABS Laboratories Becomes ACM Bioanalytical Services

Thursday, July 22, from 4:30 to 6:00 p.m. CDT

 – Midwest educational event will cover the Chicago, Columbus, Detroit, Indianapolis, and Minneapolis areas with a specific focus on these therapeutic areas and medical conditions:

https://www.ciscrp.org/event/aware-for-all-midwest-virtual-event/

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Applied Clinical Trials June 2021