Attachment No. 18 (19)
to the Rules of Good Manufacturing Practice
Содержимое (Table of Contents)
- 1 CONTROL AND RETENTION SAMPLES
- 1.1 I. SCOPE OF APPLICATION (1)
- 1.2 II. PRINCIPLE (2)
- 1.3 III. STORAGE PERIOD (3)
- 1.4 IV. QUANTITY OF CONTROL AND RETENTION SAMPLES (4)
- 1.5 V. STORAGE CONDITIONS (5)
- 1.6 VI. AGREEMENTS (6)
- 1.7 VII. CONTROL SAMPLES. GENERAL PROVISIONS (7)
- 1.8 VIII. RETENTION SAMPLES. GENERAL PROVISIONS (8)
- 1.9 IX. CONTROL AND RETENTION SAMPLES OF PRODUCTS IMPORTED (SOLD) BY SEVERAL ORGANIZATIONS SELLING MEDICINES IN BULK (9)
- 1.10 X. CONTROL AND RETENTION SAMPLES IN CASE OF LIQUIDATION OF THE MANUFACTURER (10)
1. (1.1) This Attachment sets requirements to collection and storage of control samples of starting raw materials, packing materials or finished products and retention samples of finished products.
2. (1.2) Special requirements to medicines intended for clinical studies are specified in Attachment No. 13 to these Rules.
3. (1.3) This Attachment shall also apply to works with retention samples of medicines sold (imported) by several organization selling medicines in bulk.
4. (2.1) Samples shall be stored for two purposes: firstly, to ensure the availability of a sample for analytical studies, and secondly, to ensure the availability of a sample of completely finished products. According to these two purposes samples may be divided into two categories:
control sample: a sample taken from a batch of starting raw materials, packing materials or finished products that is stored for analysis during the expiration period of the batch if it is necessary. It is necessary to take and store samples of critical intermediate stages (e.g. stages after which analytical studies shall take place or release permits shall be issued) and samples of intermediate products supplied outside the control area of the manufacturer, if the stability of the samples allows it;
retention sample: a sample in the final packaging taken from a batch of finished products which is stored for identity confirmation. For example, during the period of storage of the batch it may be necessary to examine the sample or packaging, marking, directions for use, or get the information on the batch number and the expiration date. In exceptional cases the said requirements may be observed without storing sample copies, in particular, if small batches are packed for different markets or in case of manufacture of very expensive medicines.
5. In most cases control and retention samples of finished goods are identical and are items of products in the final packaging. In such cases control and retention samples may be considered substitutes.
6. (2.2) The manufacturer, importer or the enterprise where a permit for the release of a batch is issued (as indicated in Items 20 — 25 hereof) shall store control and (or) retention samples of each batch of finished products, and the manufacturer shall store control samples of each batch of starting raw materials (see the exceptions in Item 10 hereof) and (or) intermediate products. It is necessary to store control samples of each batch of primary packing materials and printed materials at each production site where packaging operations are performed. It is allowed to include printed materials in control and (or) retention samples of finished products.
7. (2.3) Control and (or) retention samples shall characterize a batch of finished products or starting raw materials and materials, shall form an attachment to the batch dossier and may be assessed, in particular, in case of claims to the quality of the medicine, checking of the observance of requirements set during the state registration, examination of marks and packages or in case of an inspection performed by the authorized federal executive body.
8. (2.4) It is necessary to keep records to ensure tracing of the samples. The records shall be available for authorized federal executive bodies.
9. (3.1) Control and retention samples of each batch of finished products shall be stored during at least the expiration period of the batch and one year after this period has expired. A control sample shall be packed in its primary packaging. If the primary packaging is very big, the control samples may be packed in a package made of the same materials as the primary packaging in which the medicine is released. Relevant guidelines with regard to imported medicines for veterinary application, except immunobiological medicines, are given in Items 5 — 6 of Attachment No. 4 to these Rules.
10. (3.2) Samples of starting raw materials (except solvents, gases or water intended for manufacturing purposes) shall be stored for at least two years after the release of the medicine, unless a longer period is specified in relevant regulatory legal acts of the Russian Federation. The said period may be reduced, if the specifications indicate a shorter period of stability of the raw materials. Packing materials shall be stored within the expiration period of corresponding finished products.
11. (4.1) The quantity of control samples shall be sufficient to conduct complete analytical monitoring of a batch of products for at least two times pursuant to the requirements set during the state registration. If necessary, sealed packages shall be used for each type of analytical monitoring. Any exceptions to this requirement shall be well-grounded and approved by the authorized federal executive body.
12. (4.2) If regulatory legal acts of the Russian Federation set requirements to the quantity of control and retention samples, these requirements shall be met.
13. (4.3) Control samples shall be representative for the batch of starting raw materials, intermediate or finished products from which they have been taken. Additional samples may be taken to monitor the most critical stages of the process (in particular, the beginning and completion of the process). If the packaging process for a batch is conducted in the course of two or more separate packaging operations, at least one retention sample shall be taken after each of these operations. Any exceptions to this requirement shall be well-grounded and approved by the corresponding authorized federal executive body.
14. (4.4) It is necessary to ensure that within one year after the shelf life of the last manufactured batch has expired all required analytical materials and equipment are available or easily accessible in order to conduct all tests indicated in the specifications.
15. (5.1) Control samples of finished products and pharmaceutical substances shall be stored in accordance with the requirements of regulatory legal acts of the Russian Federation.
16. (5.2) The storage conditions shall meet the requirements set during the state registration of the medicine (e.g. storage at low temperatures, if necessary).
17. (6.1) If the entity in whose name the Marketing Authorization has been issued is not the legal entity responsible for the release of a batch of products in the Russian Federation, the obligation to take and store control and retention samples shall be determined in the agreement between the parties pursuant to Items 237 — 255 of these Rules. It also concerns cases when any activities of manufacture or release of a batch of products are conducted at the production site which does not belong to the manufacturer responsible for the batch of products circulating in the Russian Federation. The procedure for taking and storing control and retention samples for each production site engaged in the manufacture shall be described in the agreement between the manufacturers possessing these production sites.
18. (6.2) The authorized person issuing a permit for the release of a batch of the medicine shall ensure that all relevant control and retention samples are available within a reasonable period of time. If necessary, all requirements to such availability shall be indicated in the agreement.
19. (6.3) If several production sites engaged for the manufacture of finished products belong to different manufacturers, agreements between these manufacturers shall be the key condition to meet the requirements set for sampling and the place of storage of control and retention samples.
20. (7.1) Control samples shall be intended for analysis and shall be easily accessible for laboratories having validated methods of such analysis. Samples of starting raw materials used in the manufacture of medicines in the Russian Federation and samples of finished products shall be stored at the production site where finished medicines are manufactured.
21. (7.2) The procedure for handling control samples of finished medicines manufactured in other countries:
а) (7.2.1) if there is a signed mutual recognition agreement between the Russian Federation and the corresponding state, control samples may be taken and stored at the production site where the products are manufactured. It shall be indicated in the agreement (pursuant to Items 17 — 19 hereof) between the importer in the Russian Federation and the manufacturer located outside its territory;
b) (7.2.2) if there is no signed mutual recognition agreement between the Russian Federation and the corresponding state, control samples of finished products shall be taken and stored at the production site located in the Russian Federation. Samples shall be taken pursuant to the agreement(s) between all parties concerned. It is recommended to store samples in a place where delivered products are checked;
c) (7.2.3) control samples of starting raw materials and packing materials shall be stored in a place where they are used to manufacture finished medicines.
22. (8.1) Retention samples shall represent a batch of finished products in the form in which they are sold in the Russian Federation and may be used for control to confirm their compliance with requirements set during the state registration and other requirements set by regulatory legal acts of the Russian Federation. It is recommended to store retention samples at the site where the authorized person who has issued the permit for the release of products works.
23. (8.2) Pursuant to Item 22 hereof, if there is an effective mutual recognition agreement and control samples are stored by the manufacturer located outside the territory of the Russian Federation (Sub-item ‘а’ of Item 21 hereof), individual retention samples shall be stored in the Russian Federation.
24. (8.3) Retention samples shall be stored at the production site that belongs to the manufacturer having a license for the manufacture of medicines and shall be available for the authorized federal executive body.
25. (8.4) If more than one manufacturer in the Russian Federation take part in the sequence ‘delivery — packaging process — control — release of a batch’, the responsibility for taking and storing retention samples shall be determined in the agreement(s) between all participants.
IX. CONTROL AND RETENTION SAMPLES OF PRODUCTS IMPORTED (SOLD) BY SEVERAL ORGANIZATIONS SELLING MEDICINES IN BULK (9)
26. (9.1) If the secondary packaging of the medicine is not opened, it is necessary to store only used packing materials, as the risk of confusion of products is insignificant or null.
27. (9.2) If the secondary packaging is opened, for example, to replace the carton or directions for use, it is necessary to take one retention samples for each operation of the packaging process, as there is a risk of confusion of the products in the packaging process. It is required to develop a procedure to quickly determine the party guilty of the confusion (the manufacturer or the organization selling medicines in bulk), as the volume of recalled products depends on this fact.
28. (10.1) After the manufacturer has been liquidated and the license for the manufacture of medicines has been terminated (due to revocation or expiry of the validity period), a great number of batches of medicines manufactured by this manufacturer whose shelf life has not expired may remain in the market. With regard to batches remaining in the market the manufacturer shall sign contracts for the provision of control and retention samples (including corresponding documents in terms of these Rules) for storage in a specially dedicated place. The manufacturer shall submit to the authorized federal executive body evidence that it has taken sufficient measures for storage, and samples, if necessary, are easily accessible for assessment and analysis.
29. (10.2) If the manufacturer cannot take the above measures, the obligations to perform the required actions may be entrusted to another manufacturer. The entity in whose name the Marketing Authorization has been issued shall be responsible for this transfer of functions and provision of all required information to the authorized federal executive body. The entity in whose name the Marketing Authorization has been issued shall agree with the authorized federal executive body the adequacy of the measures for storage of control and retention samples.
30. (10.3) These requirements shall also apply to cases of liquidation of a manufacturer located outside the territory of the Russian Federation. In this case the importer shall be responsible for signing the above storage contracts and having them approved by the authorized federal executive body