DECISION OF COUNCIL OF THE EURASIAN ECONOMIC COMMISSION

of May 20, 2026 No. 67

About modification of Rules of proper production practice of the Eurasian Economic Union

According to articles 30 and 56 of the Agreement on the Eurasian Economic Union of May 29, 2014, Item 14 of the Protocol on application of sanitary, veterinary and sanitary and quarantine phytosanitary measures, emergency phytosanitary measures (appendix No. 12 to the specified Agreement), article 9 of the Agreement on the single principles and rules of drug circulation within the Eurasian Economic Union of December 23, 2014, Items 57 and 82 of appendix No. 1 to the Regulations of work of the Eurasian economic commission approved by the Decision of the Supreme Eurasian economic council of December 23, 2014 No. 98, Council of the Eurasian economic commission DECIDED:

1. Bring in the Rules of proper production practice of the Eurasian Economic Union approved by the Decision of Council of the Eurasian economic commission of November 3, 2016 No. 77 (further – Rules), changes according to appendix.

2. This Decision becomes effective after 180 calendar days from the date of its official publication, except for items 4. 11, 4. 12, 8. 87, 8. 88, 8. 108, 8.124 and 8.136 appendices No. 1 to Rules (taking into account the changes made by this Decision) which become effective after 1095 calendar days from the date of official publication of this Decision.

Members of council of the Eurasian economic commission: From the Republic of Armenia

M. Grigoryan

From the Republic of Belarus

N. Petkevich

From the Republic of Kazakhstan

S. Zhumangarin

From the Kyrgyz Republic

D. Amangeldiyev

From the Russian Federation

A. Overchuk

 

Appendix

to the Decision of Council of the Eurasian economic commission of May 20, 2026 No. 67

The changes made to Rules of proper production practice of the Eurasian Economic Union

Appendix No. 1 to the specified Rules to state in the following edition:

"Appendix No. 1

to Rules of proper production practice of the Eurasian Economic Union (in edition of the Decision of Council of the Eurasian economic commission of May 20, 2026 No. 67)

Requirements to production of sterile medicines

1. Scope of application

Requirements to production of sterile medicines extend to wide range of sterile products (for example, active pharmaceutical substances, excipients, primary packaging materials and dosage forms), packaging formats (from one-dose to multidose), processes (from high-automated to performed manually) and technologies (for example, biotechnology, classical production processes of small molecules, use of the closed systems). This appendix contains general requirements which shall be used during the designing and control of production capacities, the equipment, systems, and also the procedures applied in case of production of sterile products using the principles of risk management to quality (QRM) and to guarantee of protection against contamination of end product by microorganisms, particles and endotoxins (pyrogens).

Risk management to quality is applied to this appendix, except for Items of this appendix where the risks assessment is not applicable. If specific limits, frequencies or the ranges are specified, then they shall be considered as the minimum requirement. They are specified based on regulatory experience in the relation of problems which were determined and exerted impact on safety of patients.

The purpose of this appendix is submission of requirements for production of sterile products. However some principles and requirements (for example, the strategy of control of contamination, design of rooms, classification of net rooms, qualification, validation, monitoring, technological clothes and its use) can be used in case of production of other types of the products which are not sterile (for example, certain liquid dosage forms, creams, ointments and biological intermediate products with low bioloading), but for which important control and decrease in contamination are considered as microorganisms, particles and endotoxins (pyrogens). If the producer makes the choice for benefit of use of the requirements provided in this appendix for unsterile products, it shall document accurately what principles were used, and also to show compliance to these requirements.

2. Principle

2.1. Special requirements which purpose is contamination risk minimization by microorganisms, particles and endotoxins (pyrogens) are imposed to production of sterile products. It is necessary to take the following key areas of production process into account:

i. production capacities, the equipment and process should be designed, qualified and validirovat as appropriate, and also where it is applicable, to perform the continuing verification of production process during lifecycle according to appropriate sections of these rules. Use of appropriate technologies (for example, barrier systems of limited access (RABS), insulators, robotic systems, methods of bystry (alternative) control and systems of continuous monitoring) should be considered for increase in degree of protection of product against impact of external sources of potential contamination by endotoxins (pyrogens), particles and microorganisms (for example, from personnel, materials and the production circle), and also bystry detection of potential contaminants in the production circle and product;

ii. the personnel shall have the corresponding qualification, experience, and also to have the corresponding training and skills of behavior directed to respect for the principles of protection of sterile product during processes of its production, packaging and distribution;

iii. processes and monitoring systems for production of sterile product should be designed, put into operation, to qualify the personnel having the corresponding knowledge concerning processes, engineering project works and microbiology;

iv. raw materials and packaging materials should be subjected to the corresponding control and testing for guarantee that levels of bioloading and endotoxins (pyrogens) are acceptable.

2.2. Process management, it is necessary to exercise of the equipment, production capacities and productive activity according to the principles risk managements for quality for the purpose of ensuring advance identification, scientific assessment and control of potential risks for quality. In case of application of alternative approaches, such approaches shall have the corresponding reasons, be followed by risks assessment and actions for decrease in risks, and also to answer the purpose of this appendix.

Priorities of risk management system for quality, first of all, shall include the corresponding designing of production capacities, the equipment and processes with the subsequent implementation of accurately developed procedures, and also application of monitoring systems as element of demonstration of the fact that project decisions and procedures were realized properly and continue to work according to expectations. Carrying out only monitoring or testing is not sufficient for ensuring sterility.

2.3. The strategy of control of contamination (CCS) should be applied on the production site to determination of critical points of control and efficiency evaluation of the performed control actions (project, procedural, technical and organizational), and also the actions of monitoring performed for risk management for quality and safety of medicines. The combined strategy of control of contamination shall promote creation of steady guarantee of prevention of contamination. The strategy of control of contamination (CCS) shall be analyzed actively and be updated in case of need, and also promote permanent improvement of production methods and control. Its efficiency shall be considered within the periodic overview from management. In case of availability of control systems and their relevant management, replacement of such systems can not be necessary, however they shall be mentioned in the strategy of control of contamination, and all connected interactions between systems shall be clear.

2.4. The control of contamination and measure performed for contamination risk minimization by microorganisms, endotoxins (pyrogens) and particles include number of the interconnected actions and measures which, as a rule, are estimated, controlled and exposed to monitoring in individual procedure, however their overall effectiveness should be considered in total.

2.5. Development of strategy of control of contamination requires availability of detailed technical knowledge, and also knowledge concerning processes. Potential sources of contamination are connected with products of microbiological and cellular disintegration (for example, pyrogens, endotoxins), and also with particles (for example, splinters of glass and other visible and invisible particles).

The elements requiring consideration within the strategy of control of contamination shall include the following (but not limited to):

i. designing of the production site and processes, including documentation connected with it;

ii. rooms and equipment;

iii. personnel;

iv. engineering systems;

v. control of initial materials (including actions of interoperational control);

vi. containers and materials of packing for product;

vii. approval of suppliers (for example, key components, sterilization of components and one-time systems, critical services);

viii. management of the activities transferred for accomplishment to other person (for example, services in sterilization within the agreement), and also availability (transfer) of critical information between the parties;

ix. risk management concerning process;

x. validation of production process;

xi. validation of processes of sterilization;

xii. preventive maintenance – maintenance of the equipment, engineering systems and rooms (routine and unplanned maintenance) at the level of the standards providing lack of additional risks of contamination;

xiii. cleaning and disinfection;

xiv. monitoring systems, including assessment of possibility of implementation of the evidence-based alternative methods optimizing process of detection of contamination of the circle;

xv. prevention mechanisms, including the analysis of trends, the detailed investigations, the determination of the root reason adjusting and preventing actions (SARA) and need of use of complex tools for conducting investigation;

xvi. permanent improvement on the basis of information obtained concerning above-mentioned subitems.

2.6. The strategy of control of contamination (CCS) shall include all aspects of control with implementation of permanent and their periodic analysis, with the subsequent modification of the pharmaceutical quality system if necessary. Changes of the available systems shall be exposed to assessment regarding influence on the strategy of control of contamination before their implementation.

2.7. The producer shall undertake all necessary measures and precautions for ensuring sterility of the products made with use of its capacities. It is not allowed to prove sterility or other indicators of product quality only due to finishing processing or results of quality control of finished goods.

3. Pharmaceutical quality system

3.1. Production of sterile products is complex activities which require implementation of special events regarding control and taking measures for quality assurance of the made products. Respectively, the pharmaceutical quality system (PQS) of the producer shall provide special requirements for production of sterile products and guarantee effective control of all transactions, promoting risk minimization of contamination of sterile products microorganisms, particles and endotoxins (pyrogens). In addition to requirements for the pharmaceutical quality system, in detail certain in Chapter 1 of part I of these rules, the pharmaceutical quality system for production of sterile products shall guarantee also that:

i. effective risk management system is implemented to all areas of product lifecycle for the purpose of minimization of microbic contamination and quality assurance of the made sterile products;

ii. the producer has sufficient expert knowledge concerning the made products, the used equipment, technical and production methods exerting impact on product quality;

iii. the analysis of actual basic reasons concerning procedural, technological failures and failures of the equipment is carried out in such a way which allows to identify and understand correctly risks for product and to realize the corresponding adjusting and warning actions (SARA);

iv. risk management is used in case of development and maintenance of strategy of control of contamination for identification, assessment, decrease (elimination) (when applicable) and contamination risk control. Risk management shall be drawn up documentary and include reasons for decisions which are made on decrease in risk degree and acceptance of residual risk;

v. the top management should exercise effective supervision of control condition on production and for product lifecycle. Results of risk management shall be exposed to the regular analysis within the continuing quality management, in case of modification in case of vital issues, and also in case of periodic reviews of product quality;

vi. the processes connected with final processing, storage and transportation of sterile products shall not threaten sterile product. The aspects requiring consideration include integrity of system of packaging (packing), risks of contamination and prevention of degradation by means of ensuring storage of products in constantly supported storage conditions and the treatment of them according to requirements of the registration file;

vii. persons responsible for certification and release of sterile products shall have the corresponding information access about production and quality, and also to have the corresponding knowledge and experience in the relation of production of sterile products and their critical indicators of quality. It is necessary for possibility of carrying out assessment by such persons of whether sterile products were made according to the registered specifications within the approved process and whether they have the established quality.

3.2. All discrepancies (for example, variations when testing for sterility, variations when monitoring the production circle or variation from the established procedures) shall be investigated before certification and release of series. During the investigation it is necessary to determine potential influence on process and product quality, and also availability of potential influence on other processes or series. The reason of inclusion (exception) of product or series to the area (from area) investigations shall be accurately proved and documented.

4. Rooms

4.1. Production of sterile products shall be performed in the respective net rooms, the personnel entrance to which shall be performed through the rooms of disguise acting as air locks for transition of personnel. For material transfer and the equipment air locks shall be used. Net rooms and rooms for disguise shall be supported according to the existing requirements for purity, be supplied with air which passed through the filters having the corresponding efficiency. Actions for control and monitoring shall be evidence-based and give opportunity of effective assessment of conditions of the production circle in net rooms, air locks and transfer windows.

4.2. Different transactions on preparation of components, preparation of product and its filling shall be carried out with implementation of the adequate technical and organizational measures on separation of transactions in the net room and on production sites for the purpose of prevention of possibility of pereputyvaniye and contamination.

4.3. Barrier systems of limited access (RABS) or insulators are the most preferable to providing necessary conditions and minimization of the microbic contamination connected with the direct interventions performed by the person in critical zone. Their use shall be considered within the strategy of control of contamination. Any alternative approaches to use of barrier systems of limited access or insulators shall be proved.

4.4. There are 4 classes of net rooms (zones) for production of sterile products:

class A: critical zone for implementation of transactions of the increased risk (for example, the line of aseptic process, filling zone, the reservoir for loading of traffic jams, open primary package or accomplishment of aseptic connections by means of ensuring protection by means of primary air). Usually such conditions are provided with the localized protection by air flow (for example, with use of workstations with the unidirectional flow of air in barrier systems of limited access (RABS) or insulators). Maintenance of the unidirectional air flow shall be shown and be exposed to qualification in all zone of class A. Direct interventions (for example, without protection by means of barrier technology or glove port) in class A zone from operators shall be minimized by means of the corresponding designing of rooms, the equipment, development of processes and procedures;

class B: the production circle which is directly surrounding the class A zone intended for aseptic preparation and filling (if the insulator is not used). Pressure differences shall be exposed to permanent monitoring. In case of use of insulator technology use of net rooms of lower class, than class B can be considered (according to Item 4.20 of this appendix);

classes C and D: the net rooms intended for implementation of less critical production stages of the products filled aseptically or for use as the background circle for insulators. Also they can be used for preparation (filling) of the products which are exposed to finishing sterilization (transactions of finishing sterilization are described in the Section 8 of this appendix).

4.5. In net rooms and critical zones all surfaces which are affected by the production circle shall be smooth, impervious and unimpaired to minimize allocation or accumulating of particles or microorganisms.

4.6. For decrease in possibility of accumulating of dust and simplification of process of cleaning the cleared deepenings which are not allowing to carry out effective cleaning therefore use of ledges, shelves, cases and the equipment shall be minimized shall not be difficult. Doors shall be designed so that to prevent emergence of not cleared niches. For this reason use of sliding doors can be undesirable.

4.7. The materials used in net rooms (both in case of room construction, and for the objects used indoors), shall be chosen so that to minimize possibility of formation of particles, and also to allow reuse of the cleaning, disinfecting and sporotsidny means (in case of their use).

4.8. Ceilings shall be designed and pressurized so that to prevent possibility of contamination from space over them.

4.9. Use of sinks and drainages is forbidden in zones of classes A and B. In other net rooms air gaps between the equipment or sink and drainages shall be organized. Drainages in floors of net rooms of lower class shall be equipped with the traps or hydrolocks developed for prevention of possibility of the return flow. They shall be exposed to regular cleaning, disinfection and servicing.

4.10. Transfer of the equipment and materials to net rooms and critical zones or from them is one of the most significant potential sources of contamination. Any actions capable to threaten class of purity of net rooms or critical zone shall be exposed to assessment and if they cannot be eliminated, it is necessary to realize the relevant control activities.

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