KLRI : KOREA LEGISLATION RESEARCH INSTITUTE

Ⅰ. Necessity and Purpose

  1. Necessity of Research

○ The clinical trial sector of medicines and medical supplies has seen a paradigm transition at an unprecedented level as it is now highlighted for its industrial potential as a new growth sector given the growing desire for healthy life among the general public. Likewise, it can significantly increase opportunities for patient treatment by discovering new approaches to the diagnosis, treatment, and prevention of diseases as well as developing new drugs.

○ Clinical trials have clearly increased across the world. In particular, policy efforts have been made aggressively in China, Australia, and European countries to enhance their global competitiveness in clinical trials. On the other hand, the clinical trials in Korea have experienced various problems despite the steady increase in volume, including shift to slow growth trend, necessity of inducing initial clinical trials by multinational pharmaceutical companies, and weakening competitiveness due to increasing cost.

○ Meanwhile, when clinical trials are conducted among healthy people or patients, they cause damages or disadvantages in health or human rights and even distrust or unrest concerning the medications or their research and development when defects are discovered in the stage of their development and marketing after approval. Furthermore, their social and economic impacts are highly significant as they may erode public trust in the overall government system for regulating drugs and medical supplies.

○ In particular, the crucial position of the clinical trials for new drug development has been affirmed anew by the unlimited competition that is intensifying at the global level for the development of vaccines under the pandemic situation involving COVID-19. In-depth research and review are necessary for plans that can enhance the efficiency of clinical trials while securing their safety and effectiveness.

○ The current legal system related to clinical trials of drugs and medical supplies is organized around the Pharmaceutical Affairs Act. Note, however, that various legal problems have been pointed out in the operational processes, including quite a few regulations with insufficient legal grounds or connection of delegation between the superior and subordinate statues and majority of regulations based on administrative rules subordinate to statutory commands.

○ Such problematic situation tends to impede significantly the legal stability and predictability of the parties concerned with clinical trials; it is also widely feared to cause confusion in application or interpretation of provisions on sanctions against violations of statutes or situation wherein the statutes may not be enforced, not to mention fundamentally weaken the driving force for the development of drugs and medical supplies in Korea, which has emerged as a new strong power in the global market of drugs and medical supplies. Therefore, a proactive research on legislative systems should be conducted to prepare systematic improvement plans by reviewing all legislations related to the safety of clinical trials of drugs and medical supplies.

○ Such proactive legislative research should be performed to enhance public reliability in the systems regulating drugs and medical supplies and to resolve legislatively problems in statutes related to their clinical trials while proactively preventing harm or damage to human life and body through the stable operation of the clinical testing system as well as developing good-quality, high value-added drugs and medical supplies through the efficient and effective operation of the clinical testing system.

  2. Purpose of Research

○ The main purpose of this research is to present plans for developing legislations that can induce the development of the advanced biologics sector while effectively securing the safety of clinical trials of drugs and medical supplies based on a comprehensive analysis of the current statutory regulations related to the safety of clinical trials and comparative analysis of legislation trends in key foreign countries.

○ This research aims to present plans for the systematic improvement of pharmaceutics-related statutes regarding the safety of the Korean clinical trials of drugs and medical supplies by especially re-examining and analyzing statutes and administrative rules related to the clinical trials of drugs and medical supplies and deriving implications for the improvement of legal systems through the analysis of the latest legislation trends related to the clinical trials of drugs and medical supplies in the USA, EU, and Japan as the global powers in new drug development leading the harmonization of the international regulations on clinical trials of drugs and medical supplies.

 

Ⅱ. Main Contents

▶ Review of history of key legislations related to clinical trials

○ Provisions related to clinical trials were introduced to the local statutes for the first time in August 2001 when the system for the approval of clinical trial plans was newly stipulated in the Pharmaceutical Affairs Act through its amendment. The amendment aimed at easy entry into clinical trials by significantly simplifying the data to submit for the approval of clinical trials and promotion of capital investment by foreigners and multinational pharmaceutical companies by harmonizing the local systems concerning clinical trials and new drug approval with the international standards while enhancing the level of the local clinical trials by inducing joint clinical trials with multiple countries from the new drug development stage.

○ Since the introduction of systems related to the approval of clinical trial plans in the Pharmaceutical Affairs Act, especially in 2010 and thereafter, the systems for the regulation of drugs and medical supplies for clinical trials have been improved, the requirements were renewed for those who perform clinical trials, and the legal grounds were provided with regard to using drugs and medical supplies for clinical trials with the consent of the subjects when they have serious or life-threatening diseases or in an emergency case. Statutory grounds were provided for the designation and revocation thereof of entities that can conduct clinical trials, bioequivalence tests, non-clinical tests, and quality inspection. The systems were also partially improved in relation to the recording of clinical trials and mandatory subscription to insurance by the clinical trial sponsors.

○ As the representative administrative legislation concerning clinical trials, the Rules on the Safety of Drugs and Medical Supplies were enacted in 2013 when the Korea Food and Drug Safety Agency became responsible for functions related to the safety of drugs through a reshuffle of the government organization at that time. The Rules include provisions concerning the approval procedure of clinical trial plans, details that need to be included in the plans, procedure for applying for approval of therapeutic use of drugs and medical supplies for clinical trials, standards for conducting clinical trials, requirements and procedures for designating clinical trial agencies, and core regulatory provisions related to clinical trials, including the Standards for the Administration of Clinical Trials, reflecting improvements through partial amendments to the Pharmaceutical Affairs Act as the superior statute.

○ A recent noteworthy change in the local legislation related to clinical trials is the enactment of the Advanced Regenerative Medicine Act. Although said Act does not include provisions on direct regulation of the clinical trials of drugs and medical supplies, it still has provisions for securing the quality, safety, and efficacy of advanced biologics and support for their commercialization. In particular, it is highly implicative of the sector related to future clinical trials as a separate act has been enacted for new drugs.

▶ Analysis of key status of legislations concerning clinical trials

○ The Pharmaceutical Affairs Act and the Rules on the Safety of Drugs and Medical Supplies provide direct legal grounds for clinical trials in Korea. The key items of the clinical trials are also regulated by administrative notices such as the Regulations on the Approval of Plans for Clinical Trials of Drugs and Medical Supplies, Regulations on the Designation of Entities Performing Clinical Trials, Standards for the Management of Non-clinical Tests, and Regulations on Fees for the Approval of Drugs and Medical Supplies.

○ The Pharmaceutical Affairs Act is the only act that regulates matters related to clinical trials at the level of acts in the local legislative structure. Embracing the major items related to pharmaceutical affairs, it regulates the clinical trials of drugs and medical supplies through the following provisions under Section 1 (Manufacturing Business of Drugs, etc.), Chapter 5 (Manufacturing, Import, Etc. of Drugs, etc.): Approval, etc. for Protocols of Clinical Trials (Article 34); Designation, etc. of Institutes for 

Clinical Trials, etc. (Article 34-2); Designation, etc. of Non-clinical Trial Institutes (Article 34-3), and Education on Persons Conducting Clinical Trials, etc. (Article 34-4).

○ The Rules on the Safety of Drugs and Medical Supplies set forth delegated matters to be prescribed by the Prime Minister's ordinance and those required for their enforcement as stipulated under the Act and its enforcement decree, including detailed provisions concerning the documents, data, and procedure for applying for approval of clinical trial plans and their modifications, procedure for applying for approval of therapeutic use of drugs and medical supplies for clinical trials, guidelines for the management of clinical trials of drugs and medical supplies, and requirements and procedure for and rules to observe in designating entities performing clinical trials and analyzing specimen for clinical trials, contents, hours, methods, etc. of education on clinical trials.

○ As an administrative notice by the Korea Food and Drug Safety Agency, the Regulations on the Approval of Plans for the Clinical Trials of Drugs and Medical Supplies include detailed provisions concerning the preparation methods, scope, scope of exemption, items excluded from approval, approval procedure, and guidelines for data required for the approval of plans for clinical trials of drugs and medical supplies. In particular, the Regulations define the key terms related to clinical trials and declare the basic principles of a general nature. A critical approach should be applied as to whether it is appropriate for a ministerial notice  or an administrative rule rather than an act setting forth such important items.

○ In addition, detailed administrative procedures and methods related to the clinical trials are regulated by ministerial notices by the Korea Food and Drug Safety Agency such as the Regulations on the Designation of Entities Performing Clinical Trials of Drugs and Medical Supplies, Guidelines for the Management of Non-Clinical Trials, and Regulations on Fees for the Approval of Clinical Trials.

▶ Limitations of systems related to clinical trials under legislative structure and problems of each related issue

○ Under the current legislative structure related to the clinical trials, the Rules on the Safety of Drugs and Medical Supplies—an ordinance by the Prime Minister—perform a role identical to the enforcement decree of other statutes based on the grounds of the Pharmaceutical Affairs Act. The notice by the Korea Food and Drug Safety can be understood to perform the role of enforcement rules in view of the characteristics of the responsible ministry.

○ The Rules on the Safety of Drugs and Medical Supplies and the Regulations on the Approval of Plans for Clinical Trials of Drugs and Medical Supplies provide the majority of detailed regulatory items related to clinical trials. In fact, such regulations include provisions related to regulations on clinical trials under their annex schedules.

○ The inherent limitations of legislations related to the clinical trials in Korea are largely attributable to the deficiency of the superior statute—the Pharmaceutical Affairs Act—itself, which includes very limited regulations on the procedure for the approval of plans for clinical trials and designation of entities performing clinical trials.

○ The clinical trials take only a very meager position in the current Pharmaceutical Affairs Law due to such legislative limitations despite its policy-level importance as it is related to the safe administration of the clinical trials. Thus, matters directly related to the rights or duties of the people are provided under administrative rules or notices through inclusive delegation.

○ In reviewing the individual issues of the systems related to the clinical trials, first of all, it can be pointed out that the terms related to the clinical trials are provided in a somewhat jumbled manner without uniform or consistent establishment in the legislature structure based on their scientific or medical specialization. Consistent and rational regulation is required for the terms under the statutes to enhance the efficacy of the policy implementation even for the high-level specialization held by the relevant sector.

○ There is apparently room for violating the principles of statutory reservation or clarity based on the rule of law as clear statutory provisions are insufficient for basic issues such as the requirements and procedural provisions for the approval of plans for clinical trials. Thus, such minimum statutory provisions concerning the requirements, standards, and procedures for approval of plans for clinical trials should be provided under a statute for the efficient development of the relevant sector as well as safe administration of clinical trials.

○ As one of the individual issues related to the clinical trial systems, it can be pointed out that the regulation under the superior statute concerning the Clinical Trial Review Committee is insufficient. The Pharmaceutical Affairs Act does not have any clear provisions on the regulation of the Committee that performs core roles in the safe management of clinical trials of drugs and medical supplies. Legislative reshuffle is required as only fractional provisions are set forth under an annex table of the Prime Minister's ordinance to which the regulation is delegated.

○ The current legislative system has adopted a method of providing overall regulation on the system of the clinical trial subject's consent under an administrative legislation rather than a statute. The issue related to the consent by the subjects is one that should be reserved for a statute in a clinical trial and which is closely related to the restriction of basic human rights under the Constitution. Yet, it is simply provided as an item that needs to be followed under various procedures related to clinical trials. This passive method under the current legislative system leaves a lot to be desired.

○ Although the researcher clinical trial is different from the general clinical trial outsourced to outside parties, the current regulations—especially the Regulations on the Approval of Plans for Clinical Trials of Drugs and Medical Supplies—have provisions on the approval of plans for researcher clinical trials among the provisions concerning the clinical trials, making it ambiguous as to whether to apply the other provisions to the researcher clinical trials or to exclude them. Such ambiguity is feared to cause confusion in applying or interpreting the law.

▶ Overseas legislation trends concerning clinical trials and their analysis

○ The European Union evaluates, administers, and supervises all issues related to drugs and medical supplies by appointing EMA (European Medicines Agency) as the exclusive entity responsible for the regulation of clinical trials inclusively. In particular, it has reorganized the legal structure related to clinical trials, upgrading the legal binding force over the member states including the enactment of its Clinical Trial Regulations (CTR) to embrace the detailed guidelines under a statute. 

   The efficiency of the regulation has been enhanced by introducing a risk-based approach while defining a timeline from the application for clinical trials to their completion.

   In particular, it has continued efforts for enhancing the transparency of clinical trials by disclosing all data-related clinical trials, providing easy search functions, and publishing abstracts for laymen while enhancing the operational efficiency and reliability of the data related to clinical trials by operating a database where all data are inclusively stored while setting up a single digital path to the clinical trials.

○ The US Food and Drug Administration (FDA) has the right to regulate the entry of drugs and medical supplies. The Federal Food, Drug, and Cosmetic Act (FD&C Act), Public Health Service Act (PHS), and provisions concerning food and drugs under US Title 21 deal with overall issues related to clinical trials. It has actively pursued the improvement of legislations for accelerating the development of drugs and medical supplies by enacting the 21st Century Cures Act ("Cures Act") in 2016 to promote regenerative medicine in the bio industry.

○ Japan regulates issues related to clinical trials through the Ministry of Health, Labor, and Welfare and Pharmaceutical and Medical Device Agency (PMDA). The country enacted statutes on the support for regenerative medicine and safety regulation in 2013 and the Act on Clinical Research in 2018. In so doing, Japan is evaluated to have introduced and operated the statutory regulation on clinical trials, escaping the level of the existing autonomous compliance with ethical guidelines by individual researchers. In May 2020, the PDMA enacted and operated the guidelines for immediate documentary survey of appropriateness and physical survey of GCP sites due to the outbreak of new coronavirus infections (新型コロナウイルス感染症の発生に伴. う当面の適合性書面調査及び GCP 実地調査の実施要領に関する取扱いについて), reflecting the situation of limiting the physical survey of the sponsors and medical institutions performing clinical trials due to the COVID-19 outbreak.

○ A fierce global competition unfolds around the clinical trials for the development of medicine for treating COVID-19. In particular, it is understood that many countries encourage the development of new vaccines and therapeutic agents through exploratory research and clinical trials by individual researchers. In this connection, no active attempts have been made yet for reshuffling the legal regulation system related to the clinical trials in major foreign countries.

○ Effectively addressing the COVID-19 pandemic—which is assessed to be a global disaster rather than a problem in individual countries—urgently requires promptly deploying and supplementing the local legal and institutional foundation for the stable and efficient operation of clinical trials, which serve as the gateway to the early success in the development of vaccines and therapeutic agents. Furthermore, we should lead the global standards for norms related to the clinical trials.

▶ Plans for improvement of legislations related to the safe clinical trials of drugs and medical supplies

○ The points listed below may be presented as measures for improving related legislations to ensure efficiently the safety of the clinical trials of drugs and medical supplies. First, the necessity of active response to the development of the latest science and technology like AI and ICT and socio-environmental changes; Second, the realization of basic human rights under the Constitution for improving clinical trial systems focusing on patients and researchers; Third, the pursuit of harmony between the global standard norms and local legislations related to clinical trials; Fourth, the compliance with legislative principles, including prohibition of inclusively delegated legislation and securing of predictability; Fifth, the securing of safe clinical trials through rational proactive and follow-up regulations; and Sixth, the consideration of other statutes and current practical conditions related to the clinical trials of drugs and medical supplies.

○ As a detailed plan to improve the legislative system related to clinical trials, the amendment or supplementation of the Pharmaceutical Affairs Act may be considered as it provides the general statutory grounds for the regulation of clinical trials. This improvement approach has significant merit as it can resolve the problem of delegated legislation under the legal structure related to clinical trials while acknowledging the current legal structure based on the Pharmaceutical Affairs Act and can minimize confusion under the existing working-level administrative conditions while achieving the effects of improving legislative systems without causing heavy burden for the improvement of legislations.

○ Nonetheless, the following may be pointed out as the limitations of this improvement approach: 

It would be difficult to regulate effectively the sector of clinical trials of drugs and medical supplies, which is expected to require quite a few regulations due to changes in the times like COVID-19 with partial amendments to the Act; 

In fact, it is limited to inserting major provisions of administrative legislations related to clinical trials anew into the Act in view of its structure of inclusively embracing overall items related to pharmaceutical affairs; and 

The problem of complexity will persist as many provisions will remain scattered in different administrative regulations such as Prime Minister's ordinances and ministerial notices even if some of them are inserted into the superior statute.

○ In order to resolve the problems of the current legislative structure related to clinical trials, enacting a separate act on clinical trials (tentative name: " Act on Clinical Trials of Drugs and Medical Supplies") can be considered. This approach will offer the following merits: 

It will effectively support the promotion of various policies to correspond to the quantitative and qualitative growth of the sector of clinical trials;

It will address more systematically the demand for new regulations emerging along with changes in the times like COVID-19;

It will have a significantly greater effect of improving the legislative system than the proposed partial amendment to the Pharmaceutical Affairs Act; and

It will resolve legislative problems related to clinical trials due to the concentration on administrative legislations.

○ The Act on the Clinical Trials of Drugs and Medical Supplies (tentative name) will consist of the following:

A chapter on the definition of core terms related to clinical trials, general provisions consisting of the responsibilities of the government, and development of basic plans for deploying integrated administrative governance;

A chapter on the safe management of clinical trials consisting of the total life-cycle management processes, including the development, implementation, suspension, completion, and follow-up management of plans for clinical trials;

A chapter that provides the grounds for the establishment of the central clinical trial review committee and institution-based clinical trial review committee;

A chapter on the protection of clinical trial subjects, including a system for securing their consent; and

A chapter on non-clinical tests and researcher clinical trials.

Most of all, it would be viable to focus on the resolution of the problem of excessive delegated legislation that appears in the current legislation structure.

 

Ⅲ. Expected effects

○ Ensuring the safe use of effective drugs and medical supplies while generating various conditions wherein the people may participate in safe clinical trials with confidence is expected to contribute to the enhancement of people's health and welfare by deploying the legislative or institutional foundation for securing the safety of clinical trials effectively.

○ These research data related to the legislation of clinical trials will be utilized sufficiently as data for basic research and legislation in future research on legislation related to clinical trials by pursuing the grounds and alternative solutions to the legal problems that arise in the sector of clinical trials based on the comparative analysis of local legislation related to clinical trials and legal systems of major foreign countries.