to the Rules of Good Manufacturing Practice
I. PRINCIPLE (1)
1. (1.1) The parameter-based release is a product release system ensuring that the products have the required quality on the basis of the information collected during the manufacturing process and on the basis of compliance with particular requirements of these Rules with regard to the parameter-based release.
2. (1.2) The parameter-based release shall meet the basic requirements of these Rules, including corresponding Attachments hereto and requirements specified therein.
II. PARAMETER-BASED RELEASE (2)
3. (2.1) A comprehensive set of parameter examinations and control in the manufacturing process may ensure a greater guarantee of compliance of finished products with the specifications as compared to tests of finished products.
4. (2.2) A parameter-based release may be permitted for certain special parameters as an alternative to the traditional tests of finished products. A parameter-based release shall be permitted or rejected and a parameter-based release permit shall be revoked by cooperating officials of authorized federal executive bodies whose competence covers the assessment of products in case of registration and inspections of the observance of these Rules.
III. PARAMETER-BASED RELEASE OF STERILE PRODUCTS (3)
5. (3.1) Items 5 — 21 hereof set requirements to a parameter-based release of finished products without testing for sterility. It may be allowed to omit sterility tests, if it is successfully confirmed that the previously set conditions have been achieved during the sterilization process validation.
6. (3.2) Sterility tests enable detection of only significant violations in the sterility management system.
7. (3.3) A parameter-based release shall be permitted only if the parameters of the sterilization process of a batch of products can guarantee that the validated sterilization process ensures the sterility of the products.
8. (3.4) A parameter-based release shall be permitted only for medicines subject to terminal sterilization in the primary packaging.
9. (3.5) It is possible to select for a parameter-based release sterilization methods that pursuant to the requirements of the State Pharmacopoeia of the Russian Federation use steam, dry heat and ionizing radiation.
10. (3.6) A parameter-based release shall not be permitted for the manufacture of entirely new medicines, as satisfactory results of sterility tests within a particular period of time are a part of acceptance criteria. In some cases the data of sterility tests already collected for other medicines may be deemed sufficient for the new medicine where only slight changes have been made in terms of sterility management.
11. (3.7) It is necessary to analyse the risks of the sterility management system in order to assess the risks of releasing non-sterile products.
12. (3.8) The previous work experience of the manufacturer of medicines shall evidence that its manufacturing process meets the requirements of these Rules.
13. (3.9) Assessing the compliance of the manufacturing process with the requirements of these Rules it is necessary to take into account the detected cases of violations of the product sterility, as well as results of sterility tests of this medicine with regard to medicines sterilized by the same or a similar method.
14. (3.10) The processing and sterilization area shall be supervised by a qualified engineer with experience of sterility management and a qualified microbiologist.
15. (3.11) The development and primary validation of the product shall ensure that the products will have the same quality if all corresponding conditions are observed.
16. (3.12) The change management system shall include their analysis by the staff managing sterility.
17. (3.13) it is necessary to organize a system of microbial contamination control of the medicine before sterilization.
18. (3.14) It is required to prevent any confusion of products that have been sterilized and products that have not been sterilized by means of physical separation of products or use of validated electronic systems.
19. (3.15) Sterilization records shall be checked for compliance with the requirements of specifications with the help of at least two independent control systems. This checking may be made by two employees or an employee and a validated computer-aided system.
20. (3.16) Before releasing each batch of products it is also necessary to check the following:
if all scheduled maintenance works and current tests of the applied sterilizer have been performed and conducted;
if all repairs and changes have been approved by the engineer and the microbiologist who are responsible for the sterilization process;
if the applied devices have been calibrated (tested);
if the validity period of validation of the sterilizer for this batch has not expired.
21. (3.17) If a permit for the parameter-based release of a batch of products is issued, the decisions to release or reject the batch of products shall be based on the requirements approved by the instructions in terms of a parameter-based release. If these requirements are not observed, a parameter-based release shall not be permitted even in case of a successful sterility test.
22. For purposes of this Attachment the following basic terms shall have the following meaning:
parameter-based release: a product release system ensuring that the products have the required quality on the basis of the information collected during the manufacturing process and in accordance with particular rules of the organization of manufacture and quality control of medicines related to a parameter-based release;
sterility management system: a set of measures ensuring the sterility of the products. For medicines subject to terminal sterilization this set of measures shall include:
а) (a) the development of the medicine;
b) (b) registration and, if possible, control of microbiological properties of starting raw materials and technological auxiliary facilities (e.g. gases and lubricants);
c) (c) contamination control in the manufacturing process to prevent introduction of microorganisms into the products and their growth generally achieved by means of cleaning and sanitary treatment of the surfaces contracting the products, to prevent contamination from the air by working in clean rooms, limiting the manufacturing process in time and, when appropriate, using filtration stages;
d) (d) prevention of confusion of production flows of sterilized and unsterilized products;
e) (e) constant achievement of the quality of products;
f) (f) the sterilization process;
g) (g) the quality system as a whole, including the sterility management system, namely: the management of changes, staff training, instructions approved by the manufacturer, control at the release of products, scheduled maintenance, failure analysis, prevention of human-caused errors, validation and calibration (testing).