Clinvantage, a subsidiary of Huaren Pharmaceutical, participated in the development and drafting of the "Specifications for the Supply and Management of Drugs Used in Clinical Trials of Biological Products," jointly released by the China Vaccine Industry Association and the China Standardization Association. This document is a normative standard for the supply and management of drugs used in clinical trials of biological products in China.

 

 

8.5 Release and Shipment

8.5.1 Before shipment, it should be confirmed that the investigational medicinal product has been approved for release.

8.5.2 The shipment of investigational medicinal products should be carried out according to the sponsor's shipping instructions and specific requirements.

8.5.3 The service provider should select a suitable mode of transportation based on the packaging, quality attributes, and storage requirements of the investigational medicinal product and ancillary medicinal products. Appropriate measures should be taken to prevent deterioration, damage, contamination, or temperature control failure, and confirmation should be obtained that the medicinal products have been delivered to the designated clinical trial site.

8.5.4 The shipment of investigational medicinal products and ancillary medicinal products should include at least the certificate of conformity for the batch of medicinal products, a packing list, and a receipt confirmation form. If a thermometer is included with the shipment, a thermometer calibration report should also be included.

8.5.5 When receiving the medicinal products, the clinical trial site should verify the relevant documents and inspect the appearance of the medicinal products, the integrity of the packaging, the historical temperature conditions, etc. Only after inspection and confirmation by the recipient's signature can the medicinal products be accepted.

8.5.6 Investigational medicinal products should generally not be transferred directly from one clinical trial site to another. If absolutely necessary, the sponsor and the clinical trial sites involved in the transfer should develop comprehensive quality assessment and operating procedures, which should only be implemented after thorough evaluation and approval by the sponsor.

8.5.7 If a public safety event affects the regular on-site visits of subjects, the distribution method of investigational medicinal products can be adjusted to ensure subject safety and trial integrity. Adjustments should consider whether the medicinal products are suitable for storage and management at the subject's home, stability during transportation, safe storage measures for the medicinal products, and management of inventory and treatment compliance assessment. Any changes should be managed through records or subject diaries.

8.5.8 If a public safety event affects the regular on-site visits of subjects, for investigational medicinal products that can be self-administered, alternative safe delivery methods can be used to deliver the medicinal products directly to the subject's home without increasing safety risks, reducing the need to visit the clinical trial site. Before making changes to the protocol, the adjustment of the distribution method should be recorded in a protocol deviation record.

8.6 Return and Destruction

8.6.1 Investigational medicinal products and ancillary medicinal products may need to be returned due to the completion of the clinical trial, expiration of the medicinal products, changes to the clinical trial site, or adjustments to the clinical trial protocol. The sponsor should establish a return management system and a destruction system for investigational medicinal products and ancillary medicinal products. All destruction processes for investigational medicinal products and ancillary medicinal products should be documented, with accurate counting throughout the process.

8.6.2 In addition to unused investigational medicinal products and ancillary medicinal products, opened and used remaining medicinal products and packaging materials should also be systematically returned, counted, and destroyed.

8.6.3 Before the investigational medicinal products and ancillary medicinal products and packaging materials leave the clinical trial site, the drug management personnel responsible for the return at the clinical trial site should complete on-site confirmation of the quantity, type, minimum counting unit, storage conditions, etc., complete the balance calculation at the clinical trial site level, return them to the designated location, and pay attention to maintaining blinding during the return process.

8.6.4 The service provider should establish corresponding operating procedures, clarifying the return process and requirements for investigational medicinal products and ancillary medicinal products and packaging materials. Returns should be recorded. Returned investigational medicinal products and ancillary medicinal products and packaging materials should be clearly labeled and stored in a controlled, dedicated area.

8.6.5 Returned investigational medicinal products and ancillary medicinal products are generally not to be reused in clinical trials. If necessary, the sponsor should thoroughly evaluate the quality of the returned investigational medicinal products and ancillary medicinal products. Evidence must demonstrate that the quality of the returned medicinal products has not been affected, and they may only be reused after processing according to the corresponding operating procedures.

8.6.6 The sponsor is responsible for the destruction of investigational medicinal products and ancillary medicinal products, or destruction may be carried out by the clinical trial site or service provider after authorization by the sponsor; written authorization is required if authorization is given for destruction.

8.6.7 If the clinical trial site or service provider is required to destroy the medicinal products, a certificate of destruction should be provided to the sponsor.

8.6.8 Complete records should be kept for all destructions, including at least the reason for destruction, time of destruction, batch numbers and/or drug codes involved, actual quantity destroyed, person responsible for destruction, and supervisor. Destruction records should be kept by the sponsor.

8.6.9 The sponsor or authorized service provider is responsible for confirming the balance of the issuance, use, return, and remaining inventory of investigational medicinal products and ancillary medicinal products. Destruction or other compliant handling of unused and returned investigational medicinal products and ancillary medicinal products may only occur after investigation of any imbalances, satisfactory explanation, and acceptance of the calculated results.

8.6.10 The destruction process should comply with relevant regulations on environmental protection, biosafety, and drug management.

8.6.11 After the termination of a clinical trial, remaining unused and unexpired investigational medicinal products and ancillary medicinal products, as well as those returned from the clinical trial site and accepted into inventory, may be used in another clinical trial or other pharmaceutical and non-clinical research after standardized unblinding, repackaging, and relabeling activities.

9 Blinding Management

9.1 The preparation of the subject randomization table and drug coding table in clinical trials, and the processes of receiving, accepting, storing, packaging and labeling, distributing, returning, and destroying investigational medicinal products should be carried out by a third-party company independent of the subject party (subjects and their designated personnel) and the investigator party (sponsor and its commissioned institutions, clinical trial sites, other third-party institutions, etc.) commissioned by the sponsor.

9.2 The entrusted blinding management parties should develop standard operating procedures to ensure that investigational medicinal products maintain blinding throughout blinded clinical trials, and should not send documents, emails, or other information containing unblinding information to the investigator party or disclose it to the subject party.

9.3 The design of packaging and labeling should ensure blinding in blinded trials.

9.4 When designing a blinding management plan, the characteristics of biological products, such as temperature sensitivity and differences in preparation processes, should be considered to avoid adverse effects on blinding management.

9.5 The sponsor is responsible for developing a contingency plan for blinding management. In the event of an accidental unblinding incident, detailed records of the time, cause, process, assessment conclusions, and relevant personnel involved in the accidental unblinding incident should be kept in accordance with the contingency plan, and a written report should be submitted to the principal investigator, monitor, and ethics committee within 24 hours of the incident.

9.6 The service provider should establish relevant procedures for unblinding management.

10. Sample Management

10.1 The sponsor or service provider should establish standard operating procedures for the management of retained samples of investigational medicinal products, ancillary medicinal products, and packaging materials.

10.2 The quantity of retained samples of packaging materials should be sufficient to meet the needs of identification.

10.3 The retention time for packaging materials should be no shorter than the retention time for the corresponding investigational medicinal products and ancillary medicinal products; packaging materials in direct contact with the drug (such as infusion bottles), if the finished product has been retained, may not need to be retained separately.

10.4 Samples of each batch of investigational medicinal products should be retained. The packaging form of the retained samples should be the same as the packaging form of the investigational medicinal products. The quantity of retained samples should generally be sufficient to ensure that two full inspections can be completed according to the relevant quality standards, and at least one minimum package of finished product should be retained.

10.5 If the packaging of the investigational medicinal product is changed, samples should be retained according to the packaging form before and after the change, with at least one minimum package of finished product retained for each packaging form.

10.6 The quantity of retained samples of marketed control medicinal products and ancillary medicinal products can be determined based on risk principles. The quantity of retained samples should meet the needs of possible quality investigations, and at least one minimum package of finished product should be retained.

10.7 Retained samples should include blinded investigational medicinal products, and at least one complete package of investigational drug and control drug (including placebo) should be retained for verification of product information if necessary.

10.8 The retention period for investigational medicinal products should be in accordance with the following requirements, or the longer time specified by the sponsor:

a) Two years after the approval of the marketing authorization application or two years after the termination of the clinical trial;

b) Two years after the expiry date of the investigational medicinal product.

10.9 Finished product samples of investigational medicinal products and ancillary medicinal products for bioequivalence trials should be retained in conjunction with the clinical trial protocol; drugs suspected of having quality problems or all drugs of that batch should be immediately isolated and controlled, and the sponsor should be promptly informed.

To be continued......