Sayler Interviewed for Food Processing Magazine Article on Trump’s Effect on Food Industry

EAS Senior Director for Food Consulting Services, Allen Sayler, was interviewed for an article published in Food Processing Magazine on the regulatory state of the food industry under the Trump administration. Published during Scott Gottlieb’s tenure as FDA commissioner, Sayler discussed how Gottleib appeared to have the full confidence of the Trump administration. EAS continues to monitor Agency updates under the acting commissioner, Norman Sharpless.

Big Data, Real World Evidence and The Digital Revolution – Hang On!

By: John Brennan

Executives from AbbVie, AstraZeneca, Bristol-Myers Squibb, Merck and Co., Johnson and Johnson, Pfizer and Sanofi were grilled on Capital Hill in February on topics ranging from drug pricing, reimbursement, rebates and patent extensions to executive compensation. Senators called for new actions to address the high cost of prescription drugs in America.

Costs to the consumer and healthcare systems are immense. The US spent 345 billion USD on prescription drugs in 2018 and growth estimates could reach 500 billion by 2025. Although not discussed at the hearing, a significant portion (15% to 20%) of the pharma revenue stream is used for pharmaceutical R and D. This investment is the lifeblood of the global pharmaceutical industry. However, discovery, development and commercialization of a NCE or biologic could cost as much as 2.0 billion USD when failures and opportunity costs are taken into consideration. Adding to the cost and risk is the complexity of modern drug development. Establishing drug safety, determining efficacy and ensuring product quality are expensive tasks that must be monitored by sponsors and regulatory agencies. Then, there is the issue of reimbursement: market access, value proposition and pricing are the domain of the commercial payers, the new stakeholder with requirements that must be addressed in all development and commercialization scenarios.

Designing and aligning the appropriate regulatory strategy for each development asset is a critical component of program success. Here are a few of the emerging topics in drug development that should be contemplated when constructing the regulatory pathway for a NCE or biologic.

“Big Data” is a term used to describe large complex historical data sets that can be extracted and analyzed using methods that are different from traditional data management procedures. One application of “big data” gaining some traction in clinical trial design is the use of historical information to create a “synthetic” control arm instead of a traditional placebo treatment. The use of synthetic controls will never replace the randomized controlled study design but the new analysis tools for complex “big data” sets could cut control groups in half or replace them altogether, especially when traditional designs become prohibitive or historical data is complete and well-characterized.

Real World Evidence (RWE) and Patient Centricity. RWE is information collected outside of a formal clinical trial. It includes electronic medical records, claims and billing data, patient and disease registries and data gathered through wearable digital devices. In a recent address to the National Academy of Sciences and in a subsequent publication, CDER’s Janet Woodcock advocated for the use of RWE as a way of collecting and using patient data in clinical trials. Woodcock noted there has been little use of RWE in drug regulatory decisions regarding drug effectiveness. A draft guidance on RWE and a framework for its use is in the works at FDA and scheduled for release in 2020. Further, regulatory agencies have been asking for information on how clinical trials can be “fit for purpose” “with the patient population. Sponsors are now checking protocol design and interventions with patients, not just investigators, KOLs and internal experts. Patient centricity will be very relevant in future regulatory dossier reviews and approvals.

The Digital Health Revolution. Ten years ago it was hard to envision that connectable biosensors, wearables, implantables, smartphone applications, artificial intelligence, remote patient monitoring and machine learning would impact data collection and enable the emergence of personalized medicine. Now, many study protocols use digital and mobile technology as an integral part of study execution.

Value Proposition and Reimbursement. The “fee for care” model used in healthcare is shifting to value-based reimbursement. While regulatory approval requires demonstration of patient safety and efficacy, payer access requires a clear demonstration of a value proposition to qualify for reimbursement. Pipeline commercial development centered on pricing, market access and payer acceptance are now built into development programs long before final investment decisions are made at the governance level. Elements of the value proposition could include differentiation over standard-of-care, price, ease of use and innovative packaging.

These are just a few of the issues that impact strategic regulatory drug development right now. There are others: biosimilars, regulatory guidance for cell and gene therapy and precision medicine applications to minimize patient variability and improve response rate. On top of all this, regulators and sponsors will have to guide new product promotion to be consistent with product labeling as drug development and regulatory approval become more complex.

EAS offers a wealth of knowledge, enabling the development of regulatory strategies that best position your products in today’s environment. For more information or to discuss your product’s challenges contact Bryan J. Coleman, Senior Director for Pharmaceuticals and Medical Devices at bcoleman@easconsultinggroup.com. We also invite you to view our industry services sheet or the pharmaceutical tab on the EAS website.

Coleman to Present at CHPA Regulatory and Scientific Affairs Committee Meeting

Senior Director for Pharmaceutical and Device Consulting Services, Bryan Coleman, will speak on recent inspection trends for cosmetic to OTC crossover products at the upcoming CHPA Regulatory and Scientific Affairs Committee Meeting on May 20 in Bethesda, MD. In addition, EAS is a proud sponsor of the Regulatory and Scientific Quality conference which takes place May 21-22, also in Bethesda.

EAS to Sponsor, Exhibit and Participate on Panel at Upcoming FDLI Annual Meeting

EAS is a proud sponsor of the FDLI Annual Conference, taking place in Washington, D.C. May 2-3. In addition, Senior Director Tara Couch will be participating in a breakout session on day one covering a status update on Modified Risk Tobacco Applications. Also in attendance at the conference, Allen Sayler, Senior Director for Food Consulting Services and Cathryn Sacra, Director of Labeling and Cosmetics Cosmetic Consulting Services. Stop by the EAS table to learn more about our services.

Meet May 2019 Issue of the Month Author

John J Brennan Ph.D.

John J. Brennan, Ph.D. is a former Senior Project Leader in Global Pharmaceutical Research and Development at AbbVie in North Chicago, Illinois. At Abbvie he served as the Enterprise Leader for 3 Global Asset Development teams accountable for creating and executing development strategies in several therapeutic disciplines including exocrine pancreatic insufficiency, cystic fibrosis and diabetic nephropathy. His areas of interest include First-in-Man, Proof-of-Concept, Proof-of-Principle, and late-stage registration studies and lifecycle management. Prior to joining AbbVie, he worked at Solvay Pharmaceuticals, Inc. in Global Project Management and as a Therapeutic Area Leader in Women’s Health, Men’s Health and Clinical Pharmacology. Dr. Brennan is a graduate of Temple University and received the Ph.D. degree in Pharmaceutical Sciences from the Philadelphia College of Pharmacy and Science (now University of the Sciences).

Pharma’s Big Data, Real World Evidence and The Digital Revolution

Dear Reader,

Edward A. Steele

Welcome to the May 2019 edition of EAS-e-News, the free newsletter dedicated to FDA regulated industries. It has been a busy month at EAS, with the release of new complimentary On-Demand webinars, announcements of new training seminars, publication of numerous articles on a wide-variety of subjects as well as a fantastic attendance at the EAS booth during the recent Supplyside East. For those of you who had an opportunity to meet with Tara Couch, our senior director for dietary supplements and Heather Fairman, one of our expert independent consultants I am sure you came away with a lot of great information on EAS and how we can begin to assist your company with any number of FDA requirements. For those who were unable to attend, I invite you to take a look at our quick reference information sheets to learn more about EAS. We are always glad to speak with you about your GMP questions or concerns.

If you will be in Geneva for Vitafoods Europe, May 7-9 we invite you to come by the EAS booth, B149, to meet Tara Couch and Charles Breen, our Independent Advisor for FSMA. In addition to exhibiting at Vitafoods, EAS is a proud training partner for the show, offering a one-day comprehensive look at GMPs for the dietary supplement industry. Registration for this seminar, taking place May 6, the day before the official start of Vitafoods, is being handled through Vitafoods directly. In addition, Charles Breen will be speaking as part of the technical sessions on hygienic commitments for food safety.

FDA has OMB approval to initiate a short voluntary survey of the cosmetics industry, which will assess a variety of GMP aspects. This survey is important to help FDA gain a better understanding of the current state of industry GMPs, and the results provided to FDA will have no identifying information, nor will responses be used by the agency to initiate enforcement actions. A Federal Register notice regarding the survey can be found here and we encourage cosmetics firms to participate in this effort.

In other FDA news, a new effort to bolster the collaboration between FDA and the Customs and U.S. Border Patrol (CBP) is underway to better protect against illegal and harmful products from gaining entry into the U.S. through the mail system, or other ports of entry. More information on this effort can be found in the What’s New at FDA section of this edition.

As mentioned earlier, we are pleased that numerous compliance seminars are both approaching and new on the horizon. Our next GMP One-day Refresher training will take place in Denton, TX on May 7, and then Andover, MA on August 13, just outside of Boston. This one-day session is designed as an opportunity to outsource your department’s GMP refresher training. At just $300 per registration it is a great and cost-effective opportunity for your entire team to learn from our experts. More information can be found on the EAS website.

Additionally, we have two complimentary webinars coming up in May. On May 7 join Norma Skolnik for a look at how FDA eyes certain cosmetics claims and on May 14 join Jeff Roberts for a look at compliance with 21 CFR Part 11. Also, on June 13 we invite you to join EAS Senior Director for Pharmaceuticals and Devices, Bryan Coleman for a look at GMPs for OTCs.

Our issue of the month is written by John Brennan and looks at pharma big data, real world evidence and the Digital Revolution and our Ask the Expert on FDA’s plans to revamp the 510(k) process is answered by George Yanulis. Finally, I am pleased to welcome a new independent consultant, Dennis Gaalswyck and a new office manager, Kate Gibson. Learn more in our Who’s Who section of this edition.

As always, thank you for your interest in EAS and we invite you to share this newsletter with your colleagues.

Sincerely,

Edward A. Steele Signature

Ed Steele
Chairman and CEO

510(k) Guidance and Substantial Equivalence Discussed in MedTech Intelligence

Independent Consultant, Jay Mansour, discussed the movement away from substantial equivalence in favor of performance testing for the 510(k) application process in a recent MedTech Intelligence. “Expanding on the Abbreviated 510(k) Program for demonstrating substantial equivalence for 510(k) premarket submissions, FDA is identifying certain “well understood” medical devices that may be cleared based on performance criteria,” he says.

April 2019 Drug and Device Corner

It has come to EAS’s attention that there is significant confusion regarding the exemption of Class 1 Medical Device products to comply with the 21 CFR 801.20 requirement for the label of a medical device to bear a unique device identifier. Per 21 CFR 801.30 A class I device that FDA has by regulation exempted from the good manufacturing practice requirements found at 21 CFR 801.20 is not required to comply with the UDI label requirement. You can check the FDA’s Medical Device Exemptions 510(k) and GMP Requirements webpage for more specific information to determine if your product is indeed exempt. All other Class I devices will be required to bear the UDI number on the packaging/device beginning no later than September 24, 2020. If you have questions on UDI requirements, please contact EAS.

Guidance Document updates on the FDA website

Immediately in effect Guidance Document

Compliance Policy for Combination Product Postmarketing Safety Reporting: This guidance document is intended to assist Combination Product Applicants who are subject to the Combination Product Postmarketing Safety Reporting Final Rule issued on December 20, 2016, and codified in 21 CFR Part 4, Subpart B. This guidance document discusses FDA’s compliance policy for the rule. The Federal Registernotification can be found at this link.

CDER & CBER

Bispecific Antibody Development Programs: This guidance provides recommendations to assist industry and other parties involved in the development of bispecific antibodies. This guidance does not discuss development considerations for other multitarget therapies that are combinations of monoclonal antibodies or are antibody cocktails or polyclonal antibodies. Although this guidance is specific to bispecific antibodies, the principles discussed in this guidance may also be applicable to the development of other types of bispecific protein products. 

This guidance focuses on general regulatory and scientific considerations for bispecific antibodies, not on development of a particular bispecific antibody. Industry and other stakeholders are encouraged to engage FDA to discuss their individual bispecific antibody development program.

REMS: FDA’s Application of Statutory Factors in Determining When a REMS Is Necessary: This guidance is intended to clarify how the FDA applies the factors set forth in section 505-1 of the FD&C Act (21 U.S.C. 355-1) in determining whether a risk evaluation and mitigation strategy (REMS) is necessary to ensure that the benefits of a drug outweigh its risks.

CDER, CDRH & CBER

Guidance for Industry Pharmacogenomic Data Submissions: This guidance is intended to facilitate scientific progress in the field of pharmacogenomics and to facilitate the use of pharmacogenomic data in drug development.

CDRH

Technical Considerations for Non-Clinical Assessment of Medical Devices containing Nitinol: The 25 purpose of this draft guidance is to outline technical considerations associated with medical devices that have at least one patient contacting component comprised of nitinol. Due to the unique properties of nitinol, the Agency has developed this draft guidance to provide FDA’s current thinking on technical considerations specific to devices using nitinol. These recommendations are intended to be general and not product-specific and should be evaluated in conjunction with the intended use and technological characteristics of your device and any relevant device-specific guidances.

Technical Performance Assessment of Quantitative Imaging in Device Premarket Submissions: This draft guidance document is applicable to all devices that generate quantitative imaging values across the information, a wide range of imaging modalities, intended uses, levels of automation, and complexity of algorithms. This guidance document provides FDA’s recommendations on technical performance assessment, and user information that should be included in a premarket submission for devices that include quantitative imaging functions. 

Class II Special Controls Guideline: In Vitro Diagnostic Devices for Bacillus spp. Detection: Guideline for Industry and FDA staff. This special controls guideline was developed to establish special controls for in vitro diagnostic devices for Bacillus species (spp.) detection. This guideline identifies measures that FDA believes are necessary to mitigate the risks to health associated with devices of this type and provide a reasonable assurance of safety and effectiveness. Following the effective date of the final rule classifying the device,1 manufacturers of in vitro diagnostic devices for Bacillusspp. detection2 will need either to (1) comply with the particular mitigation measures set forth in the special controls guideline or (2) use alternative mitigation measures, which demonstrate to the Agency’s satisfaction that those alternative measures identified by the firm will provide at least an equivalent assurance of safety and effectiveness.

Surgical Staplers and Staples for Internal Use – Labeling Recommendations: The Food and Drug Administration (FDA) is issuing this guidance to provide labeling recommendations for surgical staplers and staples for internal use. These labeling recommendations are being issued because malfunctions and misuse associated with these devices have resulted in serious adverse events, including deaths.

DCRH & CBER

Review and Update of Device Establishment Inspection Processes and Standards: FDA is issuing this draft guidance to comply with section 702(b)(1) of the FDA Reauthorization 77 Act of 2017 (FDARA) (Public Law 115-52), which directs FDA to issue draft guidance that specifies how the Agency will implement uniform processes and standards that are applicable to inspections (other than for-cause) of foreign and domestic medical device establishments. FDA updated processes and standards as needed, to address the new provisions in section 704(h)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) that were added by FDARA section 702(a), and to establish a standard timeframe for inspections. This draft guidance also describes standardized methods of communication during the inspection process, and identifies practices for investigators and device establishments to facilitate the continuity of inspections of such establishments.

CVM

#120 Veterinary Feed Directive Regulation Questions and Answers (Revised)

FDA to Begin Inspections for Intentional Adulteration in March 2020

FDA recently announced that verification of compliance with the Intentional Adulteration (IA) rule will begin in March 2020. Addressing hazards that may be intentionally introduced to foods, including by acts of terrorism, with the intent to cause wide-spread harm to public health, the IA rule requires the food industry to implement risk-reducing strategies for processes in food facilities that are significantly vulnerable to intentional adulteration. Those food facilities covered by the rule will be required to develop and implement a food defense plan, (which is part of the Food Safety Modernization Act (FSMA) requirements), identifying vulnerabilities and mitigation strategies for those vulnerabilities. Additionally, facilities will be required to ensure that the mitigation strategies are working. The first compliance date arrives in July 2019. EAS Consulting Group’s FSMA team can help assess current food defense strategies and strengthen those that do not meet FDA’s stringent requirements.

Insider Podcast on 25 Years of DSHEA Features Senior Director, Tara Lin Couch, Ph.D.

Tara Lin Couch was interviewed for a Natural Products Insider podcast on her reflections of 25 years of DSHEA. Recorded at SupplySide East, she discusses how the dietary supplement industry, pre-DSHEA, was the “wild, wild west” and that 21 CFR 111, Current Good Manufacturing Practices, completely changed the way the dietary supplement industry operates, with “current” processes adapting as technology advances.

FDA Proposing to Change the 510(k) Submission Process for Medical Devices

By George Yanulis

Each month, EAS selects one question sent in by readers to be answered by one of our experts. This month’s question is answered by George Yanulis D.Eng., an expert in medical device safety and the 510(k) process.

Question: Why is FDA proposing to change the 510(k) submission process for medical devices?

Yanulis: The rapid technological advances in the medical device arena have been dramatic. A 510(k), otherwise known as a Premarket Notification, is the mechanism by which device manufacturers notify FDA of their intent to market a medical device at least 90 days in advance of doing so. By reviewing the data in a 510(k), FDA is able to determine whether the device is equivalent to a device already placed into one of the three classification categories, Class I (General Controls requiring the least amount of regulatory control because they present minimal harm to users), Class II, (General Controls with Special Controls that must comply with specific labeling requirements, mandatory performance standards and postmarket surveillance) or Class III, (those devices requiring a PMA due to insufficient information to assure the safety and effectiveness solely through general or special controls. As a consultant, Class III medical devices have been my primary focus, particularly in the ICD and cardiac pacemaker device areas.

On November 26, 2018, then FDA Commissioner Scott Gottlieb announced changes to the process for approving medical devices for the U.S. market aimed at dramatically revamping the popular 510(k) clearance pathway which enables approvals based on predicates. FDA recognizes its current approach has the potential to limit advancing technological innovation and FDA is now looking to limit the age of predicates to ten years in order to avoid using outdated technologies as older predicates are less relevant to today’s requirements of interconnectivity and complexity.

FDA is proposing an approval outside of the 510(k) process if the comparable device being used is older than a decade, a change that would significantly disrupt the current process through which the vast majority, (80%) of devices are approved. FDA proposes creating a new alternative 510(k) pathway that will focus on objective safety and performance criteria. While devices more than 10 years old are not believed to be unsafe, nor would those devices need to be removed from the market, the change will encourage use of more modern predicates and as such encourage competition to adopt modern technologies and features while improving overall standards and improving outcomes.

As an expert who has collaborated directly with the FDA and particularly with CDRH, I welcome these changes. My expectation is that all devices will continue to be safe and effective, and substantially equivalent as dictated in the 510(k).

You may find some of the below FDA resources to be helpful, and please contact EAS with specific questions regarding your 510(k) filing.

https://www.fda.gov/medicaldevices/productsandmedicalprocedures/deviceapprovalsandclearances/510kclearances/

https://www.fda.gov/downloads/Training/CDRHLearn/UCM421766.pdf

New EAS Complimentary On-Demand Webinars Available

EAS recently presented three complimentary webinars that are now available for on-demand viewing. The first, on the challenges of preparing infant formula notifications presented by EAS Independent Advisor Robert Martin, Ph.D., Independent Consultants Timothy Morck and Robbie Burns and Senior Director for Food Consulting Services Allen Sayler, covered an overview of filing and safety study requirements. It can now be viewed on-demand on the EAS website.

Next, The FSMA Foreign Supplier Verification Program requires a Qualified Individual, who has the pertinent education and on the job experience enabling him or her to perform their duties, overseeing FSVP. EAS Independent Advisors, Charles Breen and Domenic Veneziano presented an overview of the program as well as addressed common questions asked by the exporters of food products into the U.S. marketplace. Find this on-demand webinar here.

Finally, in late March, Susan Crane, EAS Independent Advisor for OTC Drugs and Labeling discussed cosmetics labeling and claims requirements. Those wishing for a deeper dive into Cosmetics Claims regulations are invited to join Norma Skolnik on May 7 for a look at how words do matter when it comes to marketing a product.

Final Rule on OTC Hand Sanitizers Issued

FDA issued a Final Rule, effective April 13, 2019, which aims to ensure the safety and effectiveness of OTC hand sanitizers, formally known as topical consumer antiseptic rub products. These products are intended for use without water and marketed under the FDA’s OTC Drug Review.

Active ingredients of ethanol, isopropyl alcohol, benzalkonium chloride, which the majority of hand sanitizer rubs on the market contain, have deferred action to allow for the ongoing study and submission of additional safety and effectiveness data to enable FDA’s safety determination for use in OTC consumer antiseptic rub products.  At this time, FDA states that it does not intend to take action to remove hand sanitizers containing these three active ingredients from the market and their status will be addressed either after completion and analysis of the studies or at another time, if these studies are not completed.

However, 28 other active ingredients, identified in the 2016 Consumer Antiseptic Rub proposed rule, including triclosan and benzethonium chloride, are no longer eligible for inclusion in any future OTC monograph.

This long awaited rule finalizes a June 30, 2016 proposed rule on consumer antiseptic rubs, where FDA requested additional scientific data to support the safety and effectiveness of active ingredients used in OTC consumer antiseptic rubs. FDA has determined that less than 3% of the marketplace will be affected by the issuance of this final rule, as most OTC consumer antiseptic rubs use ethyl alcohol as the active ingredient.

Concerned companies may contact EAS to learn more about how this Final Rule impacts product formulations and compliance with the OTC monograph.

Did You Know? EAS Offers Verification and Validation Services of Electronic Signatures Under 21 CFR Part 11

Increasing usage of electronic methods to capture and produce critical data, which are subject to regulatory scrutiny led to the effect of Title 21 CFR Part 11. This part of the Code of Federal Regulations establishes the United States Food and Drug Administration (FDA) regulations on electronic records and electronic signatures.

The aim of this regulation is to define the criteria under which the agency will consider electronic records, electronic signatures, and handwritten signatures executed to electronic records to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper.

The FDA released a guidance document in 2003 to clarify how part 11 should be implemented and enforced. This has been updated many times, partly due to the fast-emerging changes in technology. In June 2017, the FDA also issued a draft guidance on the use of Electronic Records and Electronic Signatures in Clinical Investigations.

The FDA takes accountability of electronic signatures very seriously and upon inspection of these records deficiencies may result in a warning letter.

These constantly evolving rules can be daunting to understand and implement. EAS’ team of experts is available to assist your firm in understanding your requirements under 21 CFR Part 11 as well as assess your compliance.  Areas in need of strengthening will be addressed giving your firm a detailed action plan for maintaining compliance for both signatures and storage of electronic data.

Meet New Office Manager, Kate Gibson

Kate Gibson is a graduate of UNC Chapel Hill with a degree in Psychology and Peace, War and, Defense. While at university, Kate was involved in the Triangle Institute for Security Scholars and UNC Neural Connections and has a passion for inclusive STEM Education. Prior to EAS she held a position at the UNC Gillings School of Global Public Health, specializing in tobacco marketing regulation research. Kate is originally from Denver, North Carolina.