The "Specifications for the Supply and Management of Drugs Used in Clinical Trials of Biological Products," jointly issued by the China Vaccine Industry Association and the China Standardization Association, was developed and drafted with the participation of Huaren Pharmaceutical Clinvantage. It is a normative standard document in China for the supply and management of drugs used in clinical trials of biological products.

 

 

8. Supply Process Management

8.1. Procurement

8.1.1. The service provider may be entrusted to provide procurement services for the sponsor's drugs, including domestically and internationally marketed drugs, as well as other potentially involved experimental materials.

8.1.2. The entrusted procurement party should provide documents such as the "Approval Notice for Drug Clinical Trials," a summary of the clinical trial protocol, and the filing certificate reported to the municipal-level or above local drug supervision and administration department; if the drug is used for other research, relevant supporting documents and a commitment letter for compliant drug use can be provided, clarifying the purpose, method, and quantity of drug use, and committing that the drug will ultimately be used for research purposes.

8.1.3. For the procurement of drugs approved for marketing abroad, import shall be carried out in accordance with the "Regulations on the Administration of Drug Import" and relevant regulations on the one-time import of research control drugs.

8.1.4. The service provider should ensure that the drug supplier has legal qualifications, and should sign a purchase order and a quality assurance agreement with the supplier, clarifying the special requirements and quality responsibilities of the purchased drugs.

8.1.5. The service provider should establish procurement management procedures, and the procurement process should be recorded.

8.1.6. For vaccines needed in special situations such as vaccine non-clinical research, clinical research, and blood product production, the relevant using units may purchase from the vaccine marketing authorization holder or disease prevention and control institution after reporting to the provincial drug supervision and administration department. The holder, disease prevention and control institution, and relevant using units should strictly manage and keep relevant records to ensure the traceability of vaccine sales and use.

8.2. Packaging Materials

8.2.1. Clinical trial service providers should select qualified packaging material manufacturers, sign procurement agreements and quality agreements, and conduct regular audits.

8.2.2. The service provider should confirm the packaging material design and material requirements with the sponsor, referring to Appendix A if necessary, and retain physical samples for reference.

8.2.3. The service provider should formulate packaging material management procedures, fully and detailedly describing the procedures for receiving, inspecting and/or testing, storing, and handling packaging materials, and execute them according to the procedures.

8.2.4. A quality control procedure should be established to prevent invalid blinding due to differences in the appearance of different batches of packaging materials.

8.2.5. For each batch of different packaging materials received, the acceptance, inspection or testing, approval or rejection status should be recorded and preserved.

8.2.6. The service provider should set up a dedicated area for storing packaging materials, and unauthorized personnel are not allowed to enter.

8.2.7. Excess labels with batch numbers or drug codes should be destroyed; invalid and outdated labels, markings, and other packaging materials should be destroyed.

8.2.8. The storage of returned labels should avoid confusion, and appropriate markings should be affixed.

8.2.9. Samples of packaging materials should be retained according to the sponsor's requirements, and the quantity of retained packaging materials should be sufficient for identification.

8.3. Receiving, Acceptance, and Storage

8.3.1. The service provider should formulate management procedures for receiving and accepting clinical trial drugs and auxiliary drugs, and receive and accept them batch by batch according to the procedures to prevent unqualified products from entering the warehouse.

8.3.2. Upon arrival of the drugs, the receiving personnel should verify whether the transportation method meets the requirements, and verify the drugs according to the accompanying documents and procurement records. Only products with complete and consistent data and meeting transportation requirements can be accepted, referring to Appendix B if necessary.

8.3.3. Acceptance should be counted down to the smallest package with a unique drug code; if the clinical trial design has special requirements, acceptance should be carried out according to the written operating instructions of the sponsor or client.

8.3.4. Qualified products should be stored in a validated warehouse area according to the specified temperature requirements, and managed by a dedicated person. Specially managed drugs should be accepted in a special warehouse or area according to relevant regulations.

8.3.5. Unqualified products should be stored in the unqualified product area, with detailed records of the name, batch number, quantity, and reasons for non-compliance, and reported to the quality control department and relevant personnel. An investigation into the reasons for non-compliance should be conducted, assessing the impact on the trial. Based on the investigation results, a decision should be made on whether to return, destroy, or otherwise dispose of the products, and the decision should be recorded. All relevant records and reports should be archived for audit and inspection.

8.3.6. The quantity, source, packaging, storage temperature, and expiration date of in-stock drugs should be checked and recorded regularly, with particular attention paid to products with special storage requirements and short expiration dates. For drugs with problems such as unidentifiable packaging, non-compliant storage temperature, or expiration, measures such as isolation storage and warning signs should be taken, and communication should be made with the sponsor for evaluation and disposal.

8.3.7. Service providers should use an inventory management system to automatically track and control the expiration dates of drugs, taking measures such as near-expiration warnings and automatic locking of expired drugs to prevent expired drugs from leaving the warehouse; for near-expiration or expired clinical trial drugs and auxiliary drugs, communication should be made with the sponsor for evaluation and disposal.

8.4. Packaging and Labeling

8.4.1. The service provider should establish standard procedures for packaging and labeling, and perform packaging and labeling operations according to the procedures.

8.4.2. The sponsor should provide or confirm the packaging and labeling plan, and changes to the plan should be recorded.

8.4.3. Packaging and labeling operations should be separated from other drug operations using physical or spatial isolation to avoid mixing and cross-contamination.

8.4.4. The sponsor should ensure that packaging and labeling are carried out in a GMP-compliant environment, and that complete batch packaging records are available.

8.4.5 Orders for packaging and/or labeling a certain quantity of products should be given to the service provider by the sponsor or on behalf of the sponsor. The order should be in the form of a document (or electronic document/system order, etc.), clear and unambiguous. The order should be formally approved, indicating the product quality standards, and if necessary, the clinical protocol, with reference to Appendix C.

8.4.6 Unlabeled drug packaging containers awaiting subsequent labeling operations should be labeled to avoid mislabeling of individual containers, batches, or parts of batches.

8.4.7 Before packaging and labeling, a pre-operation clearance should be conducted to ensure that all drugs from previous operations have been removed, and that all packaging materials unsuitable for subsequent operations have been removed. The inspection results should be recorded in the batch packaging record.

8.4.8 Before packaging and labeling, the suitability and correctness of the packaging materials should be checked and recorded in the batch packaging record.

8.4.9 Investigational medicinal products are generally packaged individually for each subject in the clinical trial. The number of units to be packaged, including the number of samples for testing and retention samples, should be specified before packaging begins. To ensure the correct number of each product at each processing stage, necessary packaging material balance calculations should be made, and deviations from the packaging material balance should be explained or investigated.

8.4.10 The packaging of investigational medicinal products should prevent and avoid deterioration, contamination, damage, and confusion during storage and transportation; any opening or alteration of the packaging should be identifiable.

8.4.11 Packaging and labeling should be carried out within a reasonable temperature-controlled range according to the storage conditions of the investigational medicinal products and ancillary medicinal products. If packaging and labeling are carried out outside the storage conditions, an assessment should be made based on the clinical trial protocol requirements and drug stability data to ensure that the drug quality is not affected. The assessment process and basis should be documented.

8.4.12 Test drugs and control drugs are generally not packaged simultaneously on the same packaging line. If simultaneous packaging on the same packaging line is required for clinical trial purposes, appropriate operating procedures and equipment should be in place, and relevant personnel should be trained to avoid confusion and errors.

8.4.13 If the expiry date needs to be changed, an additional label should be affixed to the investigational medicinal product, indicating the new expiry date and covering the original expiry date. The additional label should not cover the original batch number or drug code.

8.4.14 For blinded trials, when control drugs are repackaged using different packaging materials, the expiry date of the repackaged control drugs should not exceed the expiry date of the original product. If the expiry dates of the investigational medicinal products and control drugs are inconsistent in a blinded trial, the expiry date should be based on the earlier expiry date.

8.4.15 According to the blinding requirements of the clinical trial protocol, the similarity of the appearance and other characteristics of the packaging of the investigational medicinal products should be checked and recorded to ensure the effectiveness of blinding.

8.4.16 For manual labeling, a 100% visual inspection is carried out during or after the final operation to check for correct labeling. This inspection must be carried out by one person and independently verified by a second person. The verifier should check the drug code, batch number, expiry date, and other key information against the label template provided by the sponsor, and record the verification results.

8.4.17 After packaging and labeling, the drugs should be inspected in the final process to ensure that the labels on the containers and packaging within the batch are correct.

8.4.18 After the final process, representative packaging unit samples should be taken for visual inspection of label correctness, and the inspection results should be recorded in the batch packaging record or control record.

8.4.19 The release officer should review the batch packaging record and only release the relevant products after approval.

To be continued......