Strategic Planning for Drug Regulatory Science in the United States and Its Enlightenments to China

Chang Yingnan,Gong Jingran,Chang Senhao,Chen Yuwen

(School of Business Administration,Shenyang Pharmaceutical University,Shenyang 110016,China)

Abstract Objective To study the strategic planning of drug regulatory science,the effectiveness and role of policy implementation in the United States so as to gain insights and make suggestions for further improving the strategic planning of drug regulatory science in China.Methods Literature research method and comparative research method were used to compare and analyze the strategic planning of regulatory science in China and the United States.Results and Conclusion Drawing on the US experience,China should set goals based on mission and vision and identify problems,knowledge gaps,and key areas,then concrete measures can be taken to advance regulatory science.

Keywords: the United States;drug;regulatory science;strategic planning

The concept of regulatory science was introduced in the United States in 1991 for the regulation of products in the pharmaceutical field,and since then regulatory science has received much attention[1].In the early 21st century,FDA defined regulatory science as the science of developing new tools,standards,and methods to evaluate the safety,efficacy,quality,and functionality of regulated products[2].The promotion of drug regulatory science is a major strategic choice for regulatory agencies in the world today to achieve modernization of drug regulation.In the process of promoting drug regulatory science,different countries and regions have developed strategic plans and strategies for its implementation,among which the United States has always been in the lead because it has planned the strategic direction of the development of drug regulatory science and strategy implementation from a global perspective.

1 Strategic Planning for Regulatory Science in the United States

1.1 “FDA science and mission at risk” in 2007

The FDA Science Committee’s report in 2007,“FDA Science and Mission at Risk”[3],highlighted the rapid developments in scientific fields such as genomics,systems-based biology,precision medicine(also known as individualized medicine),informatics,and tissue and stem cell-based therapies that have significantly increased the scientific complexity of the challenges.The call is to advance regulatory science in four ways: (1) Focus on scientific organization to better manage new science;(2) Strengthen the scientific base;(3) Increase appropriate modeling;(4)Strengthen the scientific workforce.

1.2 “Advance the Regulatory Science (ARS)” in 2010

Based on the recommendations of the Science Committee,FDA launched the ARS based on the critical path in 2010.It sets a focused agenda and rationalizes the human and financial resources currently available to work with partners to change the way that new products are developed and evaluated,and to inject new creativity into regulation.A four-part strategic framework is also proposed: (1) Leadership,coordination,strategic planning,and transparency to support science and innovation;(2) Support for critical applied research at FDA and collaborative programs;(3) Support for scientific excellence,professional development and learning organizations;and (4) Recruitment and retention of outstanding scientists[4].This strategic framework greatly guides FDA in advancing regulatory science and harnessing its potential to fulfill the FDA’s fundamental mission to promote and protect public health.Supporting these four approaches will develop and advance the field of regulatory science to provide the tools and knowledge needed to deliver on the promise of innovation.

1.3 “Regulatory Science Strategic Plan” in 2011

To enable scientific advances to realize their full potential to improve public health,to play a major role in improving tools for modern product and process development,and to make sound regulatory decisions about the risks and benefits of products that increasingly involve new technologies,FDA developed the “Regulatory Science Strategic Plan” in 2011.

Eight priority areas for regulatory science were identified: (1) Advancing modern toxicology to improve product safety;(2) Promoting innovation in clinical assessment and personalized medical innovations to improve product development and patient outcomes;(3) Supporting new approaches to improve product manufacturing and quality;(4)Ensuring that FDA is prepared to evaluate innovative emerging technologies;(5) Leveraging diverse data through information science to improve health outcomes;(6) Implementing a new preventionfocused new food safety system to protect public health;(7) Promoting the development of medical countermeasures to prevent threats to the United States and global health and safety;(8) Strengthening social and behavioral science to help consumers and professionals make informed decisions about regulated products[5].Apart from the item (6),the other priority areas are related to pharmaceuticals and are areas where FDA needs to take new or enhanced initiatives to engage in regulatory science research.These priority areas address cross-cutting needs and opportunities that often extend to multiple product areas.In these areas,the benefits of regulatory science achievements and the process of their engagement will enhance developmental assessments and health outcomes relevant to multiple products and populations.In 2013,FDA added a ninth strategy:Focus on strengthening the global product safety network,partnerships aimed at improving food safety capacity around the world,implementation of FDA good clinical practice inspections and modest foreign training programs,participation in the World Bank Global Food Safety Facility,and more.

The plan offers opportunities for each of the scientific focus areas to use a variety of means to drive a significant new research agenda,from strengthening internal research plan to expanding informal external collaboration and participation in formal consortium models by identifying key scientific challenges and implementation plans for each priority area.Fostering a strong regulatory science culture,improving scientific infrastructure,and promoting and engaging with the regulatory science research agenda set out in the plan is achieved through four potential pathways:(1) Partnerships with government agencies;(2) Staff scientific training and professional development;(3) Direct funding mechanisms;(4) Public-private partnerships[6].

1.4 “Strategy and Implementation Plan for Advancing Regulatory Science for Medical Products” in 2013

In response to the requirements of Section 1 124 of the “FDA Safety and Innovation Act (FDASIA)”[7],FDA developed the “Strategy and Implementation Plan for Advancing Regulatory Science for Medical Products“ in 2013.This can fill current knowledge gaps in drug development to review and address emerging challenges related to the application of advances in biomedical science to improve public health.

FDA advances regulatory science priorities and addresses regulatory science gaps related to drug review through both internal and external regulatory science activities.Internal regulatory science activities include internal research,scientific working groups,and grant programs.Meanwhile,the external regulatory science activities include extensive scientific exchanges and collaborations with partners in government,academia,industry,and nonprofit entities.New regulatory science is adopted through a range of processes and programs: (1) Training and professional development;(2) Integration of new science into the regulatory process;(3) Building infrastructure to enhance the assessment of regulatory submissions and support the adoption of emerging science and technology[8].

1.5 “Strategic Priorities from 2014 to 2018” in 2014(updated every four years)

The strategic priorities and the goals and objectives of the core mission provide a comprehensive framework for understanding how FDA will fulfill its mission and meet the public health challenges of the 21st century.This framework integrates and achieves five cross-cutting strategic priorities: Regulatory science,globalization,safety and quality,smart regulation,and stewardship.Each of these priorities is important and at the same time interrelated and cannot be addressed in isolation.For example,regulatory science is the core of FDA’s work and as such it infiuences and is in turn infiuenced by actions involving other priorities.The cross-cutting nature of this plan will help the FDA achieve the greatest benefit.FDA will implement these strategic priorities through a tiered planning framework.

FDA’s core mission goals are as follows: (1)Strengthen oversight of FDA-regulated products;(2) Improve and safeguard access to FDA-regulated products for health benefits;(3) Promote better understanding of decisions about the use of FDAregulated products;(4) Strengthen organizational excellence and accountability system[9].Specific subgoals for each goal are presented and key strategies are described in detail to help the agency fulfill its public health mission.

1.6 “Advancing Regulatory Science at FDA: Focus Areas of Regulatory Science (FARS)” in 2021

To reflect important changes in the science and technology supporting regulated products,FDA has developed FARS in 2021 to identify and communicate priority areas in regulatory science research capabilities that are critical to supporting FDA’s regulatory and public health missions.

Based on four initiative directions: (1) Public health preparedness and response;(2) Increasing innovation opportunities and competition;(3)Unlocking the power of data;(4) Empowering patients and consumers[10].FDA identified and communicated 23 priority areas where continued targeted investment in regulatory science research is needed to accomplish the regulatory and public health mission.When new science and technology translate into innovative products or help improve the evaluation of existing products,FDA engages the intramural and extramural scientific community to protect and promote public health,invests in regulatory science research to address gaps in scientific understanding,or develops the tools and methods necessary to inform regulatory decision making and policy development.For example,to support decision-making,FDA scientists use an increasingly extensive network of electronic medical records to have near real-time post-market surveillance.Besides,they use real-world data to augment clinical trial data.The capabilities,tools,and resources utilized by FDA centers and offices to conduct research projects related to focus areas can be categorized into: (1) Research management and collaboration;(2) Scientific education,training,and communication;(3) Infrastructure.

2 Implementation achievements and impacts of regulatory science policy in the United States

2.1 Implementation achievements of the policy

To advance the science of medical product development and evaluation,FDA research has developed new computational methods such as toxicology models for preclinical drug evaluation and made them available to the product development community.Computational modelling and simulation methods and tools to evaluate medical devices include virtual populations,multimodal imaging -detailed anatomical models of the human head and neck,new experimental methods and tools for preclinical evaluation of medical products.Researchers are developing assessment methods to support generic drug and biosimilar development and protein therapeutics.In vitromethods and tools have been developed to help understand the properties of drugs,biologics,including vaccines.Tools needed to evaluate medical devices are being developed as well.Animal models for medical product evaluation have been improved for clinical evaluation of medical products.Some pathways are well designed to facilitate biomarker development and adoption of qualified new biomarkers to guide therapeutic decisions and predict disease progression.Clinical pharmacology studies are made to support drug development,helping to identify dosing and design elements.New methods such as antibiotics and minimality methods have been developed to make clinical trials more effective.At the same time,3D printing facilities have been created.Automated methods have been developed to predict key properties of human stem cell preparations,such as the ability to contribute to bone growth.Lastly,product quality standards in key areas have been developed.

2.2 Positive impacts of the policy

It is clear that the implementation of regulatory science in the United States has had a positive impact on promoting public health and driving innovation in regulatory decision-making.FDA has used regulatory science to improve the efficiency and predictability of the research and development process,while enhancing the capacity of regulatory authorities to ensure that the safety of new products is safeguarded and medicines are safe and effective for public use.When it comes to new areas such as regenerative medicine,gene therapy and digital health,traditional regulatory approaches and technology levels are challenged,leading to a comprehensive approach to modern regulation and the continuous development of new methods,tools,and standards,which in turn drive innovation in regulatory decision-making.

3 Strategic advances in regulatory science in the United States

As to international collaboration,FDA has sponsored an annual international conference since 2011 -“The Global Summit on Regulatory Science(GSRS)”[11],to discuss innovative technologies and partnerships to facilitate the translation of basic science into regulatory applications worldwide.The FDA’s National Center for Toxicology Research(NCTR) collaborates with the European Food Safety Authority,the Joint FAO/WHO Expert Committee on Food Additives,and the International Agency for Research on Cancer to promote international standards in regulatory science.As to domestic collaboration,FDA cooperates with institutions of higher learning through the Centers of Excellence in Regulatory Science and Innovation (CERSI) program and has set up four centers of excellence in regulatory science and innovation together with University of Maryland,University of California,San Francisco,Stanford,Johns Hopkins University,and Yale Mayo Clinic to conduct frontier research in regulatory science and support the construction of regulatory science curriculum system[12].

In addition to offering relevant majors and courses at universities,FDA also promotes the development of regulatory science by offering and organizing regular courses,regulatory science seminars,academic exchange activities,relevant competitions and other training for personnel at institutions and departments such as the Center for Drug Evaluation and Research,the University of Regulatory Affairs Office,the Centre of Excellence in Regulatory Science and Innovation,and NCTR.

The Office of Regulatory Science and Innovation within FDA supports high-quality collaborative scientific activities to address important public health and regulatory questions about FDA-regulated products,including their assessment,quality,safety,and effectiveness.It also supports core scientific capabilities and infrastructure and promotes the development and use of innovative technologies in product development and evaluation.Besides,it addresses scientific and public health priorities by supporting high-quality,peer-reviewed scientific research programs within and outside of FDA.FDA seeks advice from stakeholders and external consultants to help define,review,and meet FDA’s scientific needs and priorities.

FDA builds data platforms through collaborative programs that help assess the benefits and risks of drugs throughout their life cycle.In 1997,FDA partnered with National Institutes of Health (NIH)to develop the US ClinicalTrials.gov to provide access to clinical trial information for patients,health care professionals and the community at large,to provide clinical trial registration services to medical researchers and institutions,and to share progress reports on all clinical trials worldwide via the Internet.in 2008,FDA and Department of Health and Human Services (HHS) worked together on a long-term project to build and implement a national electronic drug safety monitoring system -the Sentinel Initials,which complements the already established system for tracking adverse event reports related to the use of regulated products[13].

4 Enlightenment to China

In April 2019,the National Medical Products Administration (NMPA) launched the “Action Plan on Drug Regulatory Science” to fully open China’s drug regulatory science research.Regulatory science is an emerging frontier discipline.To promote pharmaceutical regulatory science research,China should strengthen international collaboration,fully draw on international experience to achieve its leapfrog development.

4.1 Determining goals based on mission and vision

Based on the information obtained from the US regulatory science strategic plan,FDA identifies main goals to promote the smooth implementation of regulatory science.These goals help create a clear vision and enable alignment with staff and external stakeholders.For each goal,guiding principles or subgoals are articulated,presenting specific opportunities for development and the key actions needed to achieve the goal and measure progress and impact.The strategy repeatedly emphasizes the public mission of FDA,which shows its importance in the strategic planning of regulatory science.

The process of developing China’s strategy begins with a clear understanding of the inherent mission of drug regulatory science,based on which sub-goals in different areas are set in the context of drug development,and the goal of protecting and promoting public health can be achieved.Drug regulatory authorities promote public health by accelerating innovation to make medicines more effective,safer and affordable.They also help the public to access accurate and scientific information.As a result,they can remain true to the mission in the face of emerging challenges.

4.2 Identifying scientific barriers and knowledge gaps

Pharmaceutical regulatory science is applied to future decision making,which means it uses a limited number of known methods to make decisions about the future.Products and technologies need to be continuously updated to identify existing knowledge gaps and translate them into priorities,which can lay a good foundation for advancing regulatory science.Through internal analysis,external assessment and a recommendation process,we can fully understand what knowledge gaps remain and what challenges our pharmacovigilance sector have between fulfilling its responsibilities and the application of emerging science and technology to policy making.Effective measures must be taken to address these issues and apply the knowledge to improve regulatory standards,methods,tools,and capabilities if we are to address the expected impact on public health and pharmaceutical research and development.

4.3 Identifying key areas and proposing specific opportunities

Based on the current situation of drug regulation in China and drawing on the experience of the United States,we can identify key areas for drug regulation by closely focusing on safety,efficacy and industrialization of drugs.Based on the key areas,we can apply the latest cutting-edge technologies to address pressing issues that are currently unresolved in the field of drug regulation,and propose specific opportunities to set the direction for further development of drug regulatory science.

4.4 Taking concrete measures to advance medical regulatory science

4.4.1 Cooperation

Firstly,we should take the NMPA as the main body to promote the implementation of key drug regulatory work.Local drug regulatory authorities at all levels must refine and implement the regulatory responsibilities of each link and strengthen departmental synergy.Enterprises should fulfil their responsibilities and the supervision of products can be carried out at source.Besides,the government can conduct strategic cooperation with a number of universities and scientific research institutions with high international influence and a certain research experience in the field of drug regulation,jointly building national scientific research bases to have systematically basic theoretical research,promote discipline construction,cultivate leading talents,and accelerate the research and application of new tools for regulation.

4.4.2 Talent cultivation

Talent is the foundation for scientific research,so it is necessary to increase the training of talents constantly to provide support for regulatory research and scientific regulatory implementation.There are multiple channels to enrich the strength of regulatory personnel,for example,we can strengthen the team of drug regulators and increase the introduction of highlevel professional and technical personnel.Efforts are made to attract and retain new scientific and regulatory personnel and to improve post-marketing safety monitoring.In addition,regular training should be provided for regulatory personnel to continuously improve their regulatory capacity and supervision.

4.4.3 Infrastructure

We should establish a multi-participant regulatory agency platform by building a complete regulatory framework in the full life-cycle safety surveillance of medicines.Besides,we should improve the regulatory framework and strategic design in response to changes in the environment.Meanwhile,a scientific and policy infrastructure should be set up to support the increasing use of real-world evidence for regulatory decision-making.Lastly,we should improve the efficiency of drug reviews through technologysupported workflows that standardize access to and use of scientific data for future regulatory decisions.

4.4.4 Organizational structure

At present,drug regulatory science in China is still in its infancy and the relevant organizational structure is not well developed.For example,China should have established a regulatory science strategy office to carry out internal and external work and provide guiding principles for the development and implementation of drug regulatory science strategies.There is an urgent need for a systematic regulatory organizational structure for regulatory science strategic planning to provide a strategic vision and leadership for regulatory science program and to support the setting of scientific priorities.

4.5 In conjunction with the system

In advancing the regulatory process,China needs to continuously improve the system of drug regulation in line with China’s development of economy.The government should further refine law enforcement processes and requirements and strengthen enforcement supervision.Besides,some regulations and implementation evaluation mechanisms should be made,and they must be revised and supplemented in a timely manner.From China’s actual conditions,a more complete action plan for the development of drug regulatory science can be developed based on new tools,standards and methods,which will create a drug regulatory science with Chinese characteristics.