In the past few weeks, the PRC National Medical Product Administration ("NMPA") has released several pieces of regulations or drafting rules with respect to the administration and supervision of drugs and medical devices. It comes to our notice that these rules put further emphasis on the quality management requirements regarding different aspects in the lifecycles of drugs and medical devices, which may shed light on the NMPA's regulatory focus in the near future. This article aims to provide brief but practical introductions to these upcoming regulations or drafting rules.
Drugs
Appendix of Clinical Trial Drugs on the Good Manufacturing Practice of Drugs
On May 27, 2022, the NMPA released the Appendix of Clinical Trial Drugs on the Good Manufacturing Practice of Drugs ("GMP Appendix"), which will come into effect on July 1, 2022. The GMP Appendix will apply to (i) the preparation of drugs used in clinical trials, including experimental drugs and placebos, and (ii) the changes in packaging and labeling in marketed drugs if they are used as control drugs and experimental drugs. It is further emphasized in this GMP Appendix that the preparation and quality control of clinical trial drugs shall still comply with the relevant principles and requirements of the GMP of Drugs.
Taking into consideration the special characteristic of clinical trial drugs, especially the immature manufacturing process, inadequate research on the drugs' nature, potential side effect, and toxicity, as well as the higher risks of being mixed up or contaminated, the GMP Appendix has provided specific quality requirements for the preparation of clinical trial drugs, including but not limited to:
- the appointment of responsible personnel for drug release, who shall especially have at least one-year experience in quality management of drugs, in addition to other qualification requirements;
- the requirement for a study on the comparability of drug quality between different sites if the drug used for clinical trials is prepared in different sites, which is regarded as implicit permission for multiple-site preparation; and
- further detailed requirements on packaging and labeling, especially the required items on the labels, and measures to avoid mislabeling.
Implementation Regulations for the Drug Administration Law (Draft for Public Comments)
On May 9, 2022, the NMPA released the Implementation Regulations for the Drug Administration Law (Draft for Public Comments) ("Draft Regulation"). The collection of public comments ended on June 9, 2022, but the timeline for the finalized version has not been specified yet. Compared to the current version, which is effective from March 2, 2019, the Draft Regulation further highlights the following with respect to quality management:
- In accordance with the Drug Administration Law effected from December 1, 2019, in addition to the market authorization holder ("MAH"), all other parties participating in drug-related activities, including the IND applicants, medical institutions, and manufacturers shall establish quality management systems respectively;
- Institutions can only conduct non-clinical safety assessments and research on drugs after certification of Good Laboratory Practice, obtaining a certificate valid for five years; and
- In terms of innovative drugs, drugs in urgent clinical needs, and other drugs, the manufacturing process can be divided into different stages with the approval of the NMPA, but the MAH shall establish a consistent quality guaranteeing system to cover the whole process and all manufacturing sites.
Medical Devices
Guidelines for the Verification of Quality Management System in Medical Device Registration (Draft Amendment for Public Comments)
On May 23, 2022, the NMPA released the Guidelines for the Verification of Quality Management System in Medical Device Registration (Draft Amendment for Public Comments) ("Draft Guideline"), aiming to amend the current version effected from March 10, 2020. The collection of public comments ended on June 27, 2022.
Compared to the current version, the Draft Guideline provides further detailed updates in sections including institution and personnel, factory, facilities and equipment, documentation management, and the design and development process of different types of medical devices. More importantly, the Draft Guideline adds several articles for contract R&D as well as contract manufacturing of medical devices, which appear to impose more requirements on the registration applicants. This is in line with the multiple regulations and guidelines regarding contract manufacturing of medical devices released earlier this year.
The Draft Guideline also provides a checklist of on-site verification items, which may be helpful in the registration applicant's self-verification if necessary.
Opinions on Strengthening the Hierarchical Supervision of Medical Device Manufacturing and Distribution (Draft for Public Comments)
On June 1, 2022, the NMPA released the Opinions on Strengthening the Hierarchical Supervision of Medical Device Manufacturing and Distribution (Draft for Public Comments) ("Draft Opinion"), which aims to replace the Provisions on the Classificational and Hierarchical Supervision and Administration of Medical Device Manufacturers (effected from September 30, 2014) and the Provisions on the Classificational and Hierarchical Supervision and Administration of Medical Device Distributors (effected from August 17, 2015) (together, "Current Provisions"). The collection of public comments ended on June 19, 2022.
According to the Draft Opinion, the operation situation of the quality management system is one of the most important factors for the classification of medical device manufacturing and distribution enterprises. To catch up with the regulatory updates regarding the medical device registrant regime, compared to the Current Provisions, the Draft Opinion has put its emphasis on the supervision of medical device registrants, especially the registrants and contractors in the contract manufacturing scenario, by explicitly providing that (i) the classification level of registrants in the contract manufacturing scenario may be raised as appropriate; and (ii) the all-item inspection of registrants would include the inspection of contractors.
All-item inspections refer to the inspections of all applicable items on registrants in accordance with the GMP and its appendixes. The Draft Opinion indicates that for registrants classified as Level 4 (i.e., manufacturers of products on the Catalog of Key Regulated Varieties issued by the NMPA, registrants/contractors with worse operation situation of the quality management system, or seriously bad credit records), the all-item inspection could be conducted at least once a year, while for Level 3 registrants, the all-item inspection could be conducted at least once every two years.
Appendix of Third-Party Logistics Quality Management on the Good Supply Practice of Medical Devices (Draft for Public Comments)
On June 10, 2022, the NMPA released the Appendix of Third-Party Logistics Quality Management on the Good Supply Practice of Medical Devices (Draft for Public Comments) ("Draft GSP Appendix"). In view of the rapid developments of third-party logistics services, as well as the different practices and regulations set forth in local provinces and cities, the Draft Appendix aims to provide consistent guidelines for third-party logistics of medical devices in practice. The collection of public comments ended on June 20, 2022. Compared to the general medical device GSP, the Draft GSP Appendix provides more specific and tailored quality management requirements for third-party logistics enterprises, with emphasis imposed on the computer information management system and the qualifications of managing personnel of the computer system.
According to the Draft GSP Appendix, third-party logistics of medical devices refers to enterprises providing transportation or storage services for medical device registrants, record-filers, and distributors. As a general requirement, such enterprises shall (i) be equipped with the basic conditions and management capabilities to engage in modern logistics storage and transportation business; (ii) have the interface to synchronize electronic data in real-time with the entrusting party, NMPA and its local counterparts; (iii) be equipped with a computer information platform based on the unique identification of medical devices to realize the traceability of the whole process of medical device transportation and storage; and (iv) establish and operate a quality management system covering the entire process of transportation and storage services, so as to ensure the quality, safety and traceability of medical devices during the contract storage and transportation.
Additionally, the Draft GSP Appendix echoes the GSP and other regulations that medical device registrants, record-filers, and distributors, as entrusting parties, should bear the responsibilities of quality management, including but not limited to reviewing the qualifications of suppliers and buyers and monitoring adverse events. Whereas, the third-party logistics enterprises are responsible for the specific operation and play a rather assisting role.
It is worth noting that according to the Draft GSP Appendix, the entrusting parties and third-party logistics enterprises are allowed to further entrust competent and qualified logistic partners to transport medical devices, with written agreements specifying the quality-related responsibilities and requirements. In such a scenario, it is required to assess the abilities of the logistic partners on a regular basis.
Conclusion
In reviewing the abovementioned updates and other regulatory documents throughout these years, it indicates that the NMPA is paying more and more effort into regulations and guidelines in relation to the "quality management system", for both drugs and medical devices. Given this regulatory concern, it is suggested to keep monitoring the regulatory progress and get well-prepared with respect to the quality management system. We will also keep a close eye in this regard and provide our clients with the most practical insights.
Authored by Lu Zhou, Carol Shao and Olivia Xie.
