A figure to understand the latest drug packaging material change sixteen documents, at the end of the original document!
The main content of the change of pharmaceutical packaging materials is reflected in the "Measures for the Supervision and Administration of Drug Production" and "Measures for the Administration of Drug Registration" implemented by The General Office of the State Council and the State Drug Administration in 2020, and the three relevant equipment change
In 2017, The General Office of the State Council "Opinions on Deepening the Reform of the Review and Approval System to Encourage Innovation of Pharmaceutical Medical Devices", the NMPA announcement on July 16, 2019 on further improving the relevant matters of drug related review and approval and supervision, and the NMPA on July 01, 2020 The Measures for the Supervision and Administration of Drug Production and the Measures for the Administration of Drug Registration shall be implemented. In 2021, the State Food and Drug Administration successively promulgated (trial) "Technical Guidelines for Pharmaceutical Alteration Research of Listed Chemical Drugs", (trial) "Technical Guidelines for Pharmaceutical Alteration Research of Listed Chinese Medicine", (trial) "Technical Guidelines for Pharmaceutical Alteration Research of Listed Biological Products", According to incomplete statistics, nine provincial drug administration departments have successively issued further interpretations of the regulations on the change of pharmaceutical packaging materials.
The main contents of the changes in pharmaceutical packaging materials are reflected in the "Measures for the Supervision and Administration of Drug Production" and "Measures for the Administration of Drug Registration" implemented by The General Office of the State Council and the State Drug Administration in 2020, and the three relevant technical guidelines for pharmaceutical change research of marketed drugs (biological products, chemicals and Chinese medicine) implemented in 2021 In the preparation of the change of regulatory documents, and the interpretation of the regulations of the nine provincial drug regulatory departments on the change of drug equipment, as a drug listing holder how to understand these fifteen documents, I hope that through this article can give the applicant some understanding, in order to be able to say more clearly, China State Consulting in the following split form to give a brief introduction:
(a) The General Office of the State Council promulgated the relevant laws and regulations on the change of pharmaceutical packaging materials
Implement related examination and approval of drugs and pharmaceutical raw materials and packaging materials. Apis, pharmaceutical excipients and packaging materials are reviewed and approved at the same time when the drug registration application is approved, the API approval number is no longer issued, and the API, pharmaceutical excipients and packaging materials approved by the associated review and approval and their quality standards are publicized on the designated platform for relevant enterprises to choose. The holder of a pharmaceutical marketing authorization is responsible for the quality of the raw materials, pharmaceutical excipients and packaging materials selected for the production of the pharmaceutical preparations.
Article 33 Manufacturers of raw materials, excipients, packaging materials and containers that come into direct contact with drugs that have been approved or approved through associated review and approval shall comply with the quality control norms formulated by the State Drug Administration and the relevant requirements for associated review and approval.
Ensure the continuous compliance of the quality assurance system, accept the quality audit of the drug marketing authorization holder, and accept the supervision and inspection or extended inspection of the drug regulatory department.
Manufacturers of excipients that have been reviewed for relevance, packaging materials and containers that come into direct contact with drugs, and other units and individuals engaged in drug-related production activities shall bear corresponding responsibilities according to law.
Article 14 The State Drug Administration shall establish a related review and approval system for chemical raw materials, excipients and packaging materials and containers that come into direct contact with drugs. In the approval of drug preparations, the chemical raw materials are reviewed and approved, and relevant excipients,
Packaging materials and containers in direct contact with pharmaceutical products are reviewed together. The Drug Evaluation Center establishes a registration platform for chemical raw materials, excipients and packaging materials and containers that come into direct contact with drugs, and publicizes relevant registration information.
for the relevant applicant or holder to choose, and in the relevant drug preparation registration application review associated review.
Section 3 Associated Review Approval
Article 41 When evaluating the application for registration of a drug preparation, the drug evaluation Center shall conduct related evaluation of the chemical raw materials, excipients and packaging materials and containers that come into direct contact with the drug preparation.
Article 43 When evaluating the application for registration of a drug preparation, the drug evaluation Center conducts related evaluation of the chemical raw materials, auxiliary materials and packaging materials and containers that are in direct contact with the drug preparation, and needs additional information, In accordance with the supplementary data procedure, the applicant for pharmaceutical preparations or the registration enterprise of chemical raw materials, excipients and packaging materials and containers that come into direct contact with drugs can propose extended inspection of chemical raw materials, excipients and packaging materials and containers that come into direct contact with drugs based on risk.
Article 44 Chemical raw materials, excipients and packaging materials and containers in direct contact with drugs have passed the associated review or have passed the separate review and approval, the drug evaluation center will update the registration status mark on the registration platform for chemical raw materials, excipients and packaging materials and containers in direct contact with drugs, and publicize relevant information to the society. Among them, the chemical API approval notice and the approved production process, quality standards and labels are issued at the same time, and the registration number is indicated in the chemical API approval notice; If no approval is granted, a notice of no approval shall be issued to chemical raw materials.
Failed to pass the associated review and approval, the registration status of chemical raw materials, excipients and packaging materials and container products in direct contact with drugs remains unchanged, and the application for related drug preparations is not approved.
2. Basic considerations; (V) Change of auxiliary materials and packaging materials
This guideline covers changes in excipients and packaging materials after the marketing of biological products and changes in suppliers of excipients and packaging materials. For changes in the production process of excipients and packaging materials, changes in quality standards, etc., which may have an impact on their quality and thus on biological products, The registrant of excipients and packaging materials and the holder of biological products shall conduct change research and change management in accordance with the Announcement of the State Food and Drug Administration on Matters Related to the Further Improvement of Drug Related Review, Approval and Supervision (No. 56 of 2019).
Five, biological products common change categories and technical requirements
(a) stock solution (3.2.S)
F, direct contact materials and containers in production
Changes: Changes in disposable liquid storage bags, packaging materials, containers and filters
Reference category: Medium; Technical requirements: 1-7
Reference category: Small; Technical requirements: 1,3,8; Prerequisite: ①
Prerequisite:
① Disposable liquid storage bags, packaging materials and containers, and filter membranes before and after the change are equivalent (including transport stability studies, etc.). Changes do not increase the risk of extractable/extractives. The sterilization process of packaging materials, containers and filter membranes remained unchanged.
Technical requirements:
1. Explain the content and basis of the change.
2, if relevant, update the quality standards for direct contact pharmaceutical packaging materials and containers (including analytical methods), state the basis of the standards, and make a comparison of the changed standards or verification methods.
3, if applicable, specify updated packaging materials and containers (e.g. appearance, construction, etc.). Proof of suitability of packaging materials and containers (e.g. extract/extract inspection).
4, if involved, transport stability studies should be carried out. Provide comparative data of production process control and batch release verification before and after the change. If so, a quality study of the expansion of the primary solution is required to demonstrate that changes in the direct contact material and container have no effect on the intermediate product or the primary solution.
5, if involved, changes in direct contact with disposable liquid storage bags, containers, filters, etc., should be subject to compatibility studies and risk assessments.
6, unless special requirements, use at least three batches of packaging containers to be changed to conduct stability studies, provide the results of commercial production scale stock solution and preparation (if it has an impact on the preparation) at least 3 months before and after the change under accelerated and/or degraded conditions (or until substandard). Provide stability study data under real time/real conditions for at least 3-6 months after the change of commercial production scale stock solution, or until it fails. A comparable study of accelerated and/or forced degradation of the stock solution and the formulation before and after the change (if it has an impact on the formulation) and stability under real-time/real-world conditions. The data before the change may be the result of historical stability tests.
7. Develop stability study plan. Continue to conduct long-term stability studies to confirm the storage time of the stock solution (or intermediate). Commitment to report on non-conformities arising from long-term stability studies.
· Document 5: Implementation of the "Technical Guidelines for Pharmaceutical Modification Research of Marketed Chemical Drugs" on February 10, 2010
Chapter 9 (Changes to Packaging Materials and Containers P37-41)
(a) Minor changes
1. Changes
Such changes include, but are not limited to, the following:
(1) Change the packing size of the API and single-dose packaging preparations, such as the number of grams per bag, the number of capsules per plate, the number of injections per box, etc.
(2) Changes in the material and/or type of packaging materials and containers for apis and non-sterile solid preparations not specified in these Guidelines. The modified packaging materials and containers have been used in marketed pharmaceutical products with the same route of administration and have the same or better applicable properties.
(3) Changes in the supplier, size and/or shape of packaging materials and containers not specified in this Guideline.
2, research validation work:
(1) Explain the reason for the change of packaging materials and containers, and describe the changed packaging materials and containers in detail. List the quality standards for packaging materials and containers after the change.
(2) Comparative study on the related characteristics of packaging materials and containers before and after the change.
(3) The modified batch of samples shall be tested in accordance with the quality standards.
(4) Investigate the long-term stability of the first batch of samples after the change and report the long-term stability test data of this batch of samples in the annual report.
1. Changes
(1) Change the packaging volume of the multi-dose packaging preparation, such as the number of tablets per bottle, the number of grams per bottle, the number of milliliters per bottle, etc.
(2) Change the material and/or type of packaging materials and containers for liquid/semi-solid formulations (other than inhaled formulations, injectable formulations, ophthalmic formulations), sterile and/or liquid apis. For example, the oral liquid medicinal polypropylene bottle is changed to the oral liquid medicinal polyester bottle, etc.
(3) Change the material and/or type of the packaging materials and containers of non-sterile solid preparations in the following circumstances: for example, change between blister packaging, bottling, bag, etc., change of double aluminum blister to aluminum-plastic blister, etc.
(4) Change the supplier, size, and/or shape of the packaging material and container for the injection.
(1) Explain the reason for the change in packaging materials and containers, and describe the changed packaging materials and containers in detail. List the quality standards for packaging materials and containers after the change.
(2) Comparative study on related characteristics of packaging materials and containers before and after the change, and carry out packaging materials
.
(3) The compatibility of packaging materials should be studied as appropriate. For the change of seals should also carry out packaging sealing research.
Consultation
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