Introduction Proposed changes Comment
The China Food and Drug Administration (CFDA) recently proposed the most comprehensive revisions of the pharmaceutical good clinical practices (GCPs) in 13 years, which are open for public comment until January 31 2017.
The revisions have rewritten the articles of the existing pharmaceutical GCPs. However, the sweeping changes are not especially innovative, as most of the concepts and principles have already been addressed in the International Conference on Harmonisation (ICH) GCPs.
Overall, the revisions establish:
- general principles for conducting clinical studies in China;
- guidance on the roles and responsibilities of ethics committees, investigators and sponsors; and
- requirements for protocol and investigator brochures.
Regulation of handling and retention of biological specimens Under the revisions, sponsors are prohibited from conducting testing on biological specimens that is unrelated to the study protocol approved by the relevant ethics committee. Further, the revisions require sponsors to seek written consent from subjects regarding the continuous storage and possible use in future research of leftover biological specimens after the completion of a trial. The consent form must specify issues such as:
- the retention period;
- the data confidentiality requirements; and
- the circumstances under which the data and specimens can be shared with other investigators.
Extension of insurance coverage to institutions Unlike the existing GCPs, the revisions require sponsors to insure or indemnify investigators and institutions against all claims – except those arising from malpractice.
Individuals permitted to serve as sponsors or contract research organisations In response to the marketing authorisation holder pilot programme promulgated by the State Council in June 2016, the revisions allow individuals to act as sponsors and contract research organisations.
Requirement and quantity of retention samples Under the revisions, reserve samples of study drugs must be retained at the study site for bioequivalence and bioavailability testing for no less than two years after marketing approval is obtained. The investigator will randomly select the reserve samples from the supply sent by the sponsor and should retain enough to allow for five rounds of quality standard testing.
Process of seeking informed consent from subjects Under the revisions, the ethics committee must pre-approve any new information that may affect subjects' willingness to participate in a study. The revisions prohibit agreements (oral and written) that:
- ask subjects to waive their legal rights; or
- may release the investigator, the institution or the sponsor or its agents from liability.
Notification requirement of unblinding results The revisions propose that, for any double-blinding studies, sponsors must provide the investigator and all study participants with the treatment allocation status after unblinding.
Data retention requirement While the current GCPs impose different data retention requirements on investigators (eg, five years after the study ends) and sponsors (eg, five years after obtaining marketing approval), the revisions impose similar obligations on both: data must be retained for two years after marketing approval or five years after the study ends.
Requirement to specify direct access to source records The revisions require that, under a protocol or clinical trial agreement (CTA), the investigator and institution must give the monitors and auditors direct access to the source data and source documents relating to a clinical trial. This change may help to clarify the industry's concern regarding who can access subjects' medical records to verify the authenticity of study data, especially for the clinical trial data inspection campaign.
Clarify contractual arrangements regarding CTAs The revisions clearly stipulate that a CTA must be structured as a three-party agreement between the sponsor, the investigator and the institution. Each party must sign the CTA in its own capacity. Further, for multi-centre trials, the revisions specify that the sponsor must sign the CTA with all participating investigators and the relevant institutions.
Impose regular review requirement for investigator brochures The requirement regarding the investigator's brochure in the existing GCPs is simple and general, whereas the revisions incorporate the same detailed regulatory requirement provided in the ICH GCPs. In particular, under the revisions, sponsors must establish a written procedure regarding amendments to a brochure, noting that it must undergo an annual review and revision. Further, the revisions include several new provisions setting out the brochures':
- purpose;
- general considerations; and
- contents.
Changes reflected in latest ICH GCPs The latest version of the ICH GCPs (E6 (R2)) was adopted by the ICH on November 9 2016. Accordingly, the revisions include a number of the new changes reflected in the E6 (R2), such as the notions of certified copies and validation of computerised systems, as well as the sections regarding, among other things:
- quality management;
- risk management;
- oversight of contract research organisations; and
- risk-based monitoring.
To some extent, this reflects the CFDA's willingness to establish a regulatory framework that is in line with international standards.
The revisions would standardise the conduct and strengthen the management of pharmaceutical studies in China. It remains unclear whether and when these changes will be adopted. Pharmaceutical companies are advised to monitor the progress of the revisions closely and submit their comments by January 31 2017.
For further information on this topic please contact Katherine Wang at Ropes & Gray LLP by telephone (+86 21 6157 5200) or email (k[email protected]). The Ropes & Gray LLP website can be accessed at www.ropesgray.com.
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