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LitCovid-sentences  

PMC:7536913 JSONTXT 16 Projects

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Id Subject Object Predicate Lexical cue
T1 0-9 Sentence denotes COVID‐19:
T2 10-67 Sentence denotes A Catalyst to Accelerate Global Regulatory Transformation
T3 68-82 Sentence denotes STEWART et al.
T4 84-195 Sentence denotes A global crisis the magnitude of coronavirus disease 2019 (COVID‐19) can transform drug development and review.
T5 196-437 Sentence denotes It has exposed vulnerabilities and inadequacies in the global healthcare ecosystem as well as spurred innovation, rapid adaption of novel solutions, and unprecedented collaboration among global regulatory agencies, sponsors, and researchers.
T6 438-662 Sentence denotes For the continued and future benefit of patients, it is imperative that all stakeholders leverage the solutions, learnings, and momentum catalyzed by this crisis to advance regulatory science in the drug development process.
T7 664-674 Sentence denotes BACKGROUND
T8 675-771 Sentence denotes Previous public health crises have changed medical product development and regulatory practices.
T9 772-953 Sentence denotes These examples include major legislative amendments and creative application of regulatory paradigms to address HIV, anthrax and other bioterrorism threats, and infectious diseases.
T10 954-1207 Sentence denotes 1 To address the threat of COVID‐19 and simultaneously ensure continuity of development of non‐COVID‐19 treatments, regulators are providing significant regulatory flexibility while maintaining the high standards for quality, safety, and effectiveness.
T11 1208-1440 Sentence denotes As Rasmus Hougaard argued in a recent Forbes article, “The heat of a crisis creates a burning platform, propelling organizations and individuals to make pivots and changes that seemed too hard or overwhelming during normal times.” 2
T12 1441-1625 Sentence denotes Some of the new policies and procedures allowed regulators to completely reprioritize existing high‐priority public health work and reallocate internal resources in unprecedented ways.
T13 1626-1745 Sentence denotes Arguably, such changes should be reserved for public health emergencies because they are unsustainable in the long run.
T14 1746-2132 Sentence denotes However, other interim policies have the potential to endure in a “new normal” way of working to better address public health needs (e.g., repurposed drugs and their combinations with novel therapies), while specific risk‐based policies to accelerate development of potential COVID‐19 therapies and vaccines to an unprecedented level might be applied to other life‐threatening diseases.
T15 2133-2279 Sentence denotes The World Health Organization (WHO) reports, as of August 10, 2020, the total number of global Covid‐19 confirmed deaths is approximately 728,000.
T16 2280-2360 Sentence denotes 3 For perspective, this figure is lower than for other leading causes of death.
T17 2361-2596 Sentence denotes For example, WHO reported the leading causes of global deaths in 2016 were ischemic heart disease and stroke, which claimed 15.2 million lives, and lung cancers (including trachea and bronchus cancers), which caused 1.7 million deaths.
T18 2597-2726 Sentence denotes 4 And as the world has witnessed the economic and societal costs associated with COVID‐19, other diseases share similar burdens.
T19 2727-2846 Sentence denotes These data indicate it would be appropriate to apply the same sense of urgency and innovation to areas beyond COVID‐19.
T20 2847-3051 Sentence denotes We are supportive of many of the proposals being discussed by regulators and other groups identifying transformative practices, e.g., use of digital technologies and flexibility in statistical approaches.
T21 3052-3053 Sentence denotes 5
T22 3054-3224 Sentence denotes Here, we provide an industry regulatory perspective on durable learnings and innovation that may emerge from the COVID‐19 experience; they fall into two major categories.
T23 3225-3415 Sentence denotes First would be innovation in clinical trials and regulatory frameworks, enabled by digital technologies that may increase the efficiency and acceptability to both patients and investigators.
T24 3416-3675 Sentence denotes Second is the application of the same level of regulatory urgency, responsiveness, and flexibility in requirements seen with COVID‐19 solutions to other serious life‐threatening and/or debilitating diseases that remain major causes of mortality and suffering.
T25 3676-3717 Sentence denotes These are described in more detail below.
T26 3719-3774 Sentence denotes TRANSFORM REGULATORY FRAMEWORKS TO STREAMLINE PROCESSES
T27 3775-3961 Sentence denotes First, it is imperative to increase the use of existing electronic‐based tools and accelerate modern digital efforts to improve efficiency of operations for both regulators and industry.
T28 3962-4134 Sentence denotes Outdated technical infrastructure and lack of contemporary digital capabilities present a challenge across many regulatory authorities, regardless of the level of maturity.
T29 4135-4167 Sentence denotes COVID‐19 exposed this shortfall.
T30 4168-4343 Sentence denotes Faster and better‐informed regulatory decisions, coupled with enhanced platforms to enable collaboration and reliance activities among regulators, 6 are critical for success.
T31 4344-4478 Sentence denotes We discuss the following recommendations, recognizing that certain areas are more practiced, while others require further examination.
T32 4480-4533 Sentence denotes Virtual clinical trials and digital health technology
T33 4534-4678 Sentence denotes By far, the biggest innovation emerging from the COVID‐19 crisis is the virtualization of many aspects of clinical trials by digital enablement.
T34 4679-4859 Sentence denotes By utilizing various digital health technologies, patients can participate in one or more aspects of a trial without visiting a clinical site as part of “routine” drug development.
T35 4860-5041 Sentence denotes We commend the regulators for developing much needed guidance during the pandemic, allowing for remote monitoring and other alternatives to help sponsors continue to conduct trials.
T36 5042-5401 Sentence denotes While decentralized clinical trials and digital health technologies have been critical during the current pandemic, the increased use of telemedicine creates opportunities to reform the clinical trial paradigm by implementing digitally enabled tools in areas such as patient screening, informed consent, telemedicine‐facilitated visits, and remote monitoring.
T37 5402-5671 Sentence denotes The International Council for Harmonization (ICH) is currently revising the E6 Guideline Good Clinical Practice, and we believe this is an ideal opportunity to support the development of a responsive guideline with stakeholders’ perspectives and advances in technology.
T38 5672-5673 Sentence denotes 7
T39 5675-5721 Sentence denotes Alternatives to on‐site regulatory inspections
T40 5722-5850 Sentence denotes The idea of a virtual regulatory inspection seemed reserved for the next generation of regulatory professionals, until COVID‐19.
T41 5851-6008 Sentence denotes Our experience with remote Good Clinical Practice and pharmacovigilance inspections by regulators during the pandemic has been both positive and encouraging.
T42 6009-6149 Sentence denotes The challenges of COVID‐19 underscore the importance of achieving process efficiency while at the same time ensuring high‐quality standards.
T43 6150-6356 Sentence denotes To date, the remote inspections have demonstrated efficiencies for regulators and sponsors by eliminating travel, enhancing document management systems, and fostering disciplined and focused communications.
T44 6357-6688 Sentence denotes We recognize the broader practice of virtual inspections is untested, but it’s an area worth exploring, where regulatory inspections of investigator sites and sponsors are digitally enabled (e.g., secure video conferencing), allowing inspectors to interview personnel, review procedures, and validate data against source documents.
T45 6690-6756 Sentence denotes A global platform to accelerate real‐time data and insight sharing
T46 6757-6899 Sentence denotes The pandemic has galvanized a renewed call for knowledge and voluntary data sharing as researchers race to find solutions to end the pandemic.
T47 6900-7088 Sentence denotes While stakeholders are committed to facilitating effective data sharing of COVID‐19 research findings, the types of data and the methods of sharing should be harmonized, where appropriate.
T48 7089-7335 Sentence denotes Forums such as ICH and the International Coalition of Medicines Regulatory Authorities can play an important role in convening stakeholders to navigate the various challenges and avoid the emergence of fragmented, potentially conflicting systems.
T49 7336-7558 Sentence denotes Beyond data sharing to accelerate development, cloud‐based systems have the potential to accelerate and streamline regulatory review and enhance regulatory decision making, encompassing parallel agency review and reliance.
T50 7559-7560 Sentence denotes 8
T51 7562-7619 Sentence denotes Universal acceptance of electronic regulatory submissions
T52 7620-7756 Sentence denotes As noted above, we have seen a wide range of flexibility by regulators to avoid delays in patient access to new and existing treatments.
T53 7757-7990 Sentence denotes Regulators around the world have permitted electronic files for Certificates of Pharmaceutical Products and Good Manufacturing Practices, and accepted all regulatory filings electronically (e.g., meeting packages and annual reports).
T54 7991-8204 Sentence denotes This reduction in administrative burden—without reduction in quality of information being provided—has simplified regulatory processes while maintaining compliance, and facilitated more efficient use of resources.
T55 8205-8323 Sentence denotes Moreover, COVID‐19 has revealed the advantages to having real‐time and accurate product information for all countries.
T56 8324-8469 Sentence denotes Electronic labeling provides the opportunity to immediately share with patients and healthcare providers changes in approved product information.
T57 8470-8679 Sentence denotes While we recognize many regulators have already taken steps toward implementing electronic labeling, it is important to do so in a consistently accessible manner, seeking standards and interoperable solutions.
T58 8680-8681 Sentence denotes 9
T59 8683-8761 Sentence denotes ADVANCE MORE RISK‐BASED REGULATORY DECISIONS TO ADDRESS OTHER SERIOUS DISEASES
T60 8762-8970 Sentence denotes In order to rapidly accelerate the development and manufacturing scale‐up of COVID‐19 therapeutics, industry and regulators continue to partner in quick fashion to adopt fit‐for‐purpose regulatory strategies.
T61 8971-9186 Sentence denotes Similar to how we take such exceptional action for COVID‐19 patients, we need to advance regulatory policy for patients with life‐limiting autoimmune conditions, late‐stage heart failure, or other serious illnesses.
T62 9187-9428 Sentence denotes Such life‐threatening diseases will continue long after COVID‐19 is managed, and it will be important not to revert to previous practices and to emerge from the current situation with enduring solutions for the benefit of patients, globally.
T63 9429-9629 Sentence denotes This objective will challenge each stakeholder to implement processes that enable regulators to prioritize and focus on the most important, unmet needs with the most substantial public health impacts.
T64 9631-9670 Sentence denotes Innovative clinical evidence generation
T65 9671-9888 Sentence denotes The pandemic has underscored the premium for speed of success and the acceptability by regulators of the use of innovative trial strategies with a quantitative decision‐making framework to support regulatory approval.
T66 9889-10180 Sentence denotes We have seen the benefit of streamlining trial protocols and embracing novel trial designs such as platform approaches to simultaneously test multiple assets in the clinic, using historical data for predictive analyses, or borrowing information on placebo/standard of care from other trials.
T67 10181-10353 Sentence denotes 10 These mechanisms, together with use of real‐world data on external controls and adaptive clinical designs are not new and are increasingly well understood and accepted.
T68 10354-10428 Sentence denotes They should be leveraged where similar benefit/ risk considerations apply.
T69 10430-10472 Sentence denotes Risk‐based preclinical safety requirements
T70 10473-10797 Sentence denotes The global support for drug and vaccine development, including streamlining nonclinical requirements, has allowed candidates, such as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) antibodies, to move quickly into the clinic to most efficiently determine if the experimental treatment is effective for patients.
T71 10798-11015 Sentence denotes The practice of deferring or eliminating certain preclinical studies while there is a degree of uncertainty in the experimental candidate for specific life‐threatening illnesses with no effective treatment is not new.
T72 11016-11164 Sentence denotes ICH S9 Guideline “Nonclinical Evaluation for Anticancer Pharmaceuticals” provides for such regulatory flexibility for advanced oncology indications.
T73 11165-11323 Sentence denotes We encourage regulators to apply this approach to other life‐threatening illnesses across therapeutic areas, and to model a global harmonized approach as ICH.
T74 11324-11498 Sentence denotes The benefits to society could be significant—by reducing the need to use animals, modernize drug development, and potentially make new therapies available to patients faster.
T75 11500-11547 Sentence denotes Fit for purpose and risk‐based CMC requirements
T76 11548-11680 Sentence denotes As preclinical and clinical phases are streamlined, chemistry and manufacturing controls (CMC) data must equally be fit for purpose.
T77 11681-11925 Sentence denotes In order to rapidly accelerate the development and manufacturing scale‐up of COVID‐19 treatments and vaccines, regulators have employed risk‐based decisions to defer certain CMC requirements to later stages of development or even post approval.
T78 11926-12118 Sentence denotes There are long‐standing challenges to accelerating manufacturing aspects under expedited programs, and the COVID‐19 experience further emphasizes the need for analogous regulatory flexibility.
T79 12119-12260 Sentence denotes For instance, using judgment‐based clinically meaningful specifications or deferring longer‐term stability data until the postmarket setting.
T80 12261-12631 Sentence denotes Moreover, allowing companies to report more postapproval changes within their quality system (vs. submitting for regulatory approval) would allow for more manufacturing flexibility and ability to react to supply challenges globally more quickly, as outlined in ICH Q12 Guideline “Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Development.”
T81 12633-12653 Sentence denotes POTENTIAL CHALLENGES
T82 12654-12714 Sentence denotes These proposals are not without their respective challenges.
T83 12715-12880 Sentence denotes Technological solutions need to account for issues like privacy, security, and platform stability; likewise, expanded training for personnel might also be necessary.
T84 12881-13028 Sentence denotes Unintended consequences can also result, e.g., the possible development of diverging drug review processes under various global health authorities.
T85 13029-13080 Sentence denotes But these challenges can be addressed and overcome.
T86 13081-13254 Sentence denotes Considering the significant benefit these transformative initiatives bring to patients, we support near‐term implementation with reviews and future adjustments as necessary.
T87 13256-13266 Sentence denotes CONCLUSION
T88 13267-13342 Sentence denotes This paper touches on some critical innovations deployed during the crisis.
T89 13343-13646 Sentence denotes It is not comprehensive, but there is little reason not to immediately begin exploring these initiatives as part of the “new normal.” We are committed to working with stakeholders around the world to transform regulatory frameworks using new technologies while maintaining the gold standard of approval.
T90 13648-13655 Sentence denotes Funding
T91 13656-13694 Sentence denotes No funding was received for this work.
T92 13696-13716 Sentence denotes Conflict of Interest
T93 13717-14196 Sentence denotes All authors are employed by multinational biopharmaceutical companies, as indicated in their affiliations: J.S. (Pfizer), P.H. (Pfizer), L.A. (Merck), D.A. (Astra Zeneca), S.B. (Bristol‐Myers Squibb), P.B. (Bayer), H.F. (Glaxo Smith Kline), C.G. (Eli Lilly and Company), M.G. (Astra Zeneca), M.H. (Bristol‐Myers Squibb), R.K. (Novartis), S.M. (Merck), L.O. (Janssen), E.R. (Sanofi), K.R. (AbbVie), A.S.R. (Sanofi), M.T. (Amgen), R.T. (AbbVie), K.V.B. (Janssen), and M.W. (Bayer).
T94 14197-14334 Sentence denotes As an Associate Editor of Clinical Pharmacology and Therapeutics, P.H. was not involved in the review or decision process for this paper.