The new gCP showcases a number of new changes In the industry.

With the implementation of the new revision of the Drug Administration Law
at the end of 2019, the State Bureau will introduce supporting regulations, working papers and related guidelines in accordance with the work plan. In the 2019 revision of the Drug Administration Act, a prominent feature is the elimination of the GXP certification system (including GMP/GSP/GCP, etc.), and in order to ensure industry compliance, the official abolition of the GXP certification system, but for some of the many years of use of the specification sedization and improvement is also inevitable choice. The current implementation of the "Drug Clinical Trial Symour", also known as GCP, was issued in 2003, has not been revised for many years, and the development of the industry and the actual operation of the gap, so the revision work is imperative.
large-scale verification of clinical trial projects initiated by the China Drug Administration in July 2015, known in the industry as the "7.22 Incident", and the economic impact and compliance pressures of the 7.22 incident have been affecting the field of drug research and development in China, as well as on all participants in clinical trials (sponsors, CROs, researchers, clinical trial agencies, regulators). The past failures in the management of clinical trials in China revealed by the 7.22 incident are alarming and therefore the need for continued compliance in this area is necessary.
based on the information of the 7.22 incident, combined with the continued boom in China's innovative pharmaceutical field, and China's commitment to gradually adopt the ICH Guidelines after joining the ICH organization in 2017, the State Drug Administration of China has organized a number of revisions to the Code of Quality Management for Drug Clinical Trials. According to the author's repeated search of NMPA official website information, the revision work started in 2015 will be intensive in the 2016-2018 phase. According to the opinions on the other side, the last public request by the State Drug Administration for the revision of the Code of Quality Management for Drug Clinical Trials was released on July 17, 2018.
followed by more than a year of internal compilation of information and repeated discussions, the new version of the Drug Clinical TrialS Code was finally released at the end of April 2020 and will be implemented on July 1, 2020. According to the grasp of industry information, as well as the analysis of this regulatory document, for colleagues analysis as follows:
and 2003 version of the "Drug Clinical Trial Quality Management Code", this version of the drug GCP not only increased in the number of terms, but also the text content increased a lot; This change feature is also shown in this part of the term. The 2020 edition of the drug GCP term entry as many as 40, a lot more than the 2003 version of 19;
Ethics Committee: The 2020 version of the GCP is defined as: a committee composed of medical, pharmaceutical and other background personnel whose duties are to ensure that the rights and safety of the subjects are protected by independently reviewing, agreeing, tracking and reviewing the trial program and related documents, obtaining and recording the methods and materials used by the subjects to obtain and record their informed consent. This new definition emphasizes the diversity of professional backgrounds of the composition of the Committee and the fact that the review of relevant documents is not a one-off, but is followed up as required by the circumstances;
Vulnerable Subjects: This new definition is based on icHE6 (R2) revisions, which refer to a subject whose ability to defend their will and rights is insufficient or lost, who voluntarily participates in a clinical trial, may be improperly affected by the expected benefits of the trial or the refusal to participate in a possible retaliation. These include: students and subordinates of the researchers, employees of the applicant, military personnel, prisoners, patients with no cure for diseases, patients in critical conditions, people in welfare homes, vagrants, minors, and people who are unable to have informed consent. It should be said that the introduction of this weak subject definition was necessary and timely; in 2017, a listed pharmaceutical company used in-house employees to conduct BE trials because there were no similar regulatory restrictions in China at the time.
Computerized System: It should be said that the introduction of this term by The 2020 Edition of GCP is not only an objective requirement for the development of automation technology, but also an inevitable requirement for the strengthening of the management of clinical trial data compliance. Continued strengthening of various types of electronic data specification management is necessary if Chinese bidders are to use clinical trial data from China for global drug listing applications, and it can also be predicted that clinical trial agencies, filers and clinical trial sample analysis laboratories will need to strengthen IT recruitment and electronic data management.
Source Files and Source Data: This version of GCP adds new term source files and source data to clearly define the key documents and core data generated during the implementation of clinical trials. It can be said that the clarity of these two concepts can help all parties involved in clinical trials understand their responsibilities and requirements to ensure that clinical trial data is true and complete.
As mentioned in Article 9 of the 2020 GCP, the quality management system for clinical trials should cover the entire process of clinical trials, with a focus on the protection of subjects, reliability of test results, and compliance with relevant laws and regulations. This edition of the GCP continues to place the protection of the safety of the subjects in a prominent position, and through the following requirements:
the independent right of the subject to participate in and withdraw from clinical trials must be respected, for example, the 2020 edition of GCP Article 18 mentions that subjects can withdraw from clinical trials without a reason.
the researchers should abide by the ethical principles of the Helsinki Declaration when implementing informed consent. For example, Article 23 of the 2020 GCP states that researchers must not use coercion, inducement, and other improper means to influence subjects to participate in or continue clinical trials.
the subjects due to intellectual, physical disability and other reasons, can not personally fulfill the right to informed consent, this version of the GCP fully consider all kinds of special circumstances, and in the overall framework perspective designed the relevant provisions to ensure the rights and interests of the subjects. For example, it is required that oral and written materials provided to subjects, such as informed consent, should be in easy-to-understand language and expression, so that the subject simply or their guardians and witnesses can easily understand. If the subject or his or her guardian lacks reading ability, a fair witness should witness the entire informed consent process.
the 2003 version of the GCP, which contains six articles on ethics committees, and the 2020 version of the GCP, which deals with ethics committees, is integrated into four articles, but the content has expanded many times. The documents reviewed by the
's Ethics Committee include, at a minimum, a revised version of the pilot scheme and the test scheme, an informed consent form and its updates, the method and information for the recruitment of the subject, other written information provided to the subject, a researcher's manual, an existing security information, a document containing the subject's compensation information, a document containing the qualification of the researcher, and other documents required by the Ethics Committee to perform its duties. It was also mentioned that, in order to protect the rights and interests of the subjects, the Ethics Committee was required to focus on examining whether the subjects had been forced, induced and other improper influence to participate in clinical trials.
in addition to the review before a clinical trial is launched, the Ethics Committee needs to keep an eye on the risks during the clinical trial. For example, the 2020 edition of the GCP mentions: clinical trial implementation to eliminate the deviation or modification of the trial program for urgent harm to the subject, increase the risk of the subject or significantly affect the change in clinical trial implementation, all suspicious and unanticipated serious adverse reactions, may adversely affect the safety of the subject or the implementation of clinical trials new information.
in order to give full play to the role of the Ethics Committee, the 2020 edition of the GCP states that the Ethics Committee has the right to suspend and terminate clinical trials that are not carried out in accordance with the relevant requirements, or that subjects experience unintended serious damage.
in order to urge the Ethics Committee to perform its duties actively, the 2020 Edition gCP requires the Ethics Committee to conduct regular reviews of ongoing clinical trials at least once a year. It also requires records to be kept for five years after the end of the clinical trial.
bidders should be the biggest beneficiaries of clinical trialimplementation. In order to urge the applicant to actively fulfill its compliance responsibilities, rather than just considering benefits and violating the GCP, the 2020 Edition of the GCP mentions that the applicant must take the protection of the rights and safety of the subjects and the authenticity and reliability of clinical trial results as a basic consideration for clinical trials. At the same time, the applicant is required to establish a quality management system for clinical trials.
For the applicants, a sound quality management system is required, which should cover the entire process of clinical trials, including the design, implementation, recording, evaluation, results report and documentation of clinical trials. Quality management includes effective pilot design, methods and processes for collecting data, and information gathering necessary for decision-making in clinical trials.
the applicant is required to implement effective quality management for clinical trials based on the results of the risk assessment. Among other things, QRM should identify risks that affect key links and data in clinical trials. The risk should be considered at two levels: system levels, such as facility equipment, standard operating procedures, computerized systems, personnel, suppliers, and clinical trials such as experimental drugs, trial design, data collection and recording, and informed consent processes.
if the applicant entrusts part or all of the work and tasks of the clinical trial management task to the contract research organization (CRO) for its own resources or other reasons, and the applicant is still the ultimate person responsible for the quality and reliability of clinical trial data, the applicant shall supervise the work undertaken by the contract research organization. The contract research organization shall implement quality assurance and quality control. This means that the bidder must be effectively managed in the process of selecting, evaluating, auditing and supervising the CRO organization, without being left to the point.
the impact of the new crown pneumonia outbreak since late 2019 on ongoing clinical trials is expected to put many bidders to work hard to meet compliance requirements.
Although the biggest beneficiary is the bidder for clinical implementation purposes. But in terms of participation in clinical trials, the researchers were the most involved party. In terms of Chinese reality, the broad-definition researchers include medical personnel and clinical trial institutions involved in clinical trial studies, while the researchers in the 2020 edition of the GCP are narrowly defined as researchers. The background to this different concept is that American medical personnel are mostly independent subjects, they only borrow medical facilities to practice, and medical institutions have no affiliation. The reality in China is that medical personnel are all full-time employees of medical institutions, and medical institutions are an overall stakeholder.
in order to ensure the quality of clinical trials, the 2020 Edition of the GCP requires that the researcher sligible to practice in clinical trial institutions, the expertise, training experience and ability required for clinical trials, and the ability to provide up-to-date work resumes and relevant qualification documents as required by the applicant, the ethics committee and the drug regulatory authority. Second, the researchers are familiar with the pilot program, the researcher's manual, and the information on the experimental drug. Furthermore, researchers should be familiar with and comply with this specification and the laws and regulations related to clinical trials.
In order to effectively implement clinical trials, the 2020 version of the GCP requires: First, the researchers have the ability to enroll a sufficient number of subjects within the time frame agreed upon by the clinical trial. Second, the researchers had enough time to implement and complete the clinical trial within the agreed time frame. Furthermore, the researcher has the right to control the person involved in the clinical trial during the clinical trial, and has the authority to use the medical facilities required for the clinical trial to conduct the clinical trial correctly and safely.
to ensure the safety of subjects, researchers need to have the expertise to deal with professional issues. For example, the 2020 edition of GCP he mentioned that researchers are responsible for all medical decision-making related to clinical trials for clinicians or authorized clinicians. During clinical trials and follow-up, researchers and clinical trial institutions should ensure that subjects are treated properly for adverse events associated with the trial, including clinically significant laboratory abnormalities.
the 7.22 incident, which began in 2015, and although the centralized verification process has been completed, its impact remains to this day. According to the summary report issued by CFDI on July 21, 2017, during the centralized verification period, the distribution of defects found was included in the following figure:for effective supervision, the role of the 2020 GCP for the drug regulatory department is described as follows:
the drug regulatory department may, according to the work needs, the drug regulatory department can conduct audit and inspection of the relevant documents, facilities, records and other aspects of clinical trials, inspection can be in the test site, the applicant or the contract research organization location.
, the Drug Administration may request the Ethics Committee to provide its standard operating procedures and a list of ethics review committees, depending on the needs of the work.
, the drug regulatory department may request the researcher to provide an up-to-date job resume and relevant qualification documents, depending on the job needs. According to the
, according to the needs of the work, the researchers and clinical trial institutions shall be subject to the inspection and inspection organized by the applicant, as well as the inspection by the drug supervision and administration department.
if the researcher needs to revise the clinical trial plan, they need to report to the drug regulatory department in a timely manner.
, without violating the principles of confidentiality and relevant regulations, inspectors from the Drug Administration may consult the subject's original medical records to verify the process and data of the clinical trial.
predictably, in the second half of 2020, the FDA will focus on the normative nature of clinical trial data affected by the outbreak of new coronary pneumonia.
the implementation of clinical trials, a lot of documents and data are bound to be generated;
In view of the increasingly wide-ranging application of computerized systems, the 2020 Edition of the GCP stipulates that the method of data modification of computerized systems used in clinical trials should be specified in advance, the modification process should be completely recorded, the original data (such as the retention of electronic data audit tracks, data tracks and editing tracks) should be retained; If data conversion occurs during data processing, ensure that the converted data is consistent with the original data and that the visibility of the data conversion process is consistent.
the 2020 Edition of GCP provides detailed and detailed regulations on the recruitment of subjects' informed consent, clinical trial programs, researchers' manuals and other important documents.