Commission Implementing Regulation (EU) 2025/2091 of 17 October 2025 laying down good manufacturing practice for veterinary medicinal products in accordance with Regulation (EU) 2019/6 of the European Parliament and of the Council

CHAPTER I

GENERAL PROVISIONS

Article 1

Subject matter and scope

Additional requirements and specific adaptations to the requirements laid down in this Regulation are set out in Annex III for the following veterinary medicinal products:

(a) herbal veterinary medicinal products;

(b) veterinary medicinal products intended for incorporation into medicated feeding stuffs;

(c) ectoparasitic veterinary medicinal products for external application;

(d) liquids creams and ointments;

(e) medicinal gases;

(f) pressurised metered dose aerosol products for inhalation.

Article 2

Definitions

For the purposes of this Regulation, the following definitions shall apply:

(1) ‘pharmaceutical quality system’ means the total sum of the measures implemented as part of the manufacturing process to ensure that medicinal products are of the quality required for their intended use;

(2) ‘quality risk management’ means a systematic process, applied both proactively and retrospectively, for the assessment, control, communication and review of risks to the quality of the veterinary medicinal product across the product’s lifecycle;

(3) ‘manufacturing site’ means a site that is engaged in any of the activities for which a manufacturing authorisation is required in accordance with Article 88(1) of Regulation (EU) 2019/6;

(4) ‘batch’ means a defined quantity of materials or product that undergo the same process(es) so that it can be expected to be homogeneous. For the control of the finished product, a batch of a veterinary medicinal product comprises all the units of a pharmaceutical form which are made from the same initial mass of materials and have undergone a single series of manufacturing operations or a single sterilisation operation or, in the case of a continuous production process, all the units manufactured in a given period of time. In the case of continuous manufacturing, a batch corresponds to a defined fraction of the production, characterised by its intended homogeneity;

(5) ‘bulk product’ means any product which has completed all processing stages up to, but not including, final packaging;

(6) ‘intermediate product’ means a partly processed material which must undergo further manufacturing steps before it becomes a bulk product;

(7) ‘finished product’ means a veterinary medicinal product that has undergone all the stages of production, including packaging in its final container;

(8) ‘packaging’ means all operations, including filling (with the exception of sterile filling) and labelling, which a bulk product has to undergo in order to become a finished product;

(9) ‘packaging material’ means any material employed in the packaging of a veterinary medicinal product, excluding any outer packaging used for transportation or shipment. Packaging material can relate to immediate packaging or outer packaging;

(10) ‘in-process controls’ means the checks performed during production in order to monitor and, if necessary, adjust the process to ensure that the product conforms to the required specifications. Environmental monitoring and equipment controls are part of in-process controls;

(11) ‘qualification’ means the process of demonstrating that entities, premises, equipment, utilities, systems or materials are suitable for the intended task and can deliver the expected outcomes;

(12) ‘validation’ means the process of demonstrating that a method or process is suitable for its intended use;

(13) ‘reference sample’ means a sample of a batch of materials used in the manufacture of a veterinary medicinal product or finished product which is stored for the purpose of being analysed should the need arise during the shelf life of the batch concerned;

(14) ‘retention sample’ means a sample of a fully packaged unit from a batch of finished product which is stored for identification purposes;

(15) ‘reprocessing’ means the treatment of all or part of a batch of product of an unacceptable quality from a defined stage of production so that its quality may be rendered acceptable by one or more additional operations;

(16) ‘area’ means a space. A specific set of rooms within a building associated with the manufacture of one or more products that has a common air handling unit is considered as a single area;

(17) ‘clean area’ means an area designed, maintained, and controlled to prevent particle and microbiological contamination;

(18) ‘contained area’ means an area that is designed (including air handling and filtration), maintained and controlled so as to prevent contamination of the external environment by biological or other agents;

(19) ‘segregated area’ means an area within a manufacturing site that has separate storage, separate production suite with separate HVAC (heat, ventilation and air conditioning), dedicated equipment reserved solely for the production of one type of product with a specific risk profile and restrictions on the movement of personnel and equipment;

(20) ‘airlock’ means an enclosed space with interlocked doors, constructed to maintain air pressure control between adjoining rooms (generally with different air cleanliness standards). The intent of an airlock is to preclude ingress of particle matter and microorganism contamination from a lesser controlled area. A pass-through hatch has the same meaning as ‘airlock’ but is typically of a smaller size;

(21) ‘closed system’ means a system designed and operated so as to avoid exposure of the product or material to the room environment. Materials may be introduced to a closed system, but the addition must be done in such a way so as to avoid exposure of the product to the room environment (e.g. by means of sterile connectors or fusion systems). A closed system may need to be opened (e.g. to install a filter or make a connection) but it is returned to a closed state through a sanitisation or sterilisation step prior to process use;

(22) ‘cross-contamination’ means the contamination of a material or a product with another material or product;

(23) ‘isolator’ means an enclosure capable of being subject to reproducible interior bio-decontamination, with an internal work zone meeting grade A conditions that provides uncompromised, continuous isolation of its interior from the external environment (e.g. surrounding cleanroom air and personnel). There are two major types of isolators: (a) closed isolator systems, which exclude external contamination of the isolator’s interior by accomplishing material transfer via aseptic connection to auxiliary equipment, rather than use of openings to the surrounding environment. Closed systems remain sealed throughout operations; (b) open isolator systems, which are designed to allow for the continuous or semi-continuous ingress or egress of materials during operations through one or more openings. Openings are engineered (e.g. using continuous overpressure) to exclude the entry of external contaminant into the isolator;

(24) ‘campaign manufacture’ means the manufacture of a series of batches of the same product in sequence in a given period of time followed by strict adherence to preestablished control measures before transfer to another product. Use of the same equipment for distinct products is possible in campaign manufacture provided that appropriate control measures are applied;

(25) ‘aseptic processing/manufacturing’ means processing or manufacturing activities performed under conditions which prevent contamination;

(26) ‘quarantine’ means the isolation – physically or by other effective means – of materials, intermediate, bulk or finished products whilst awaiting a decision on their release or refusal;

(27) ‘reconciliation’ means a comparison, having due regard for normal variation, between the amount of product or materials theoretically and actually produced or used;

(28) ‘bracketing’ means an approach such that only the extremes of certain predetermined factors are tested or validated. The design assumes that validation of any intermediate levels is covered by the tests or validation of the extremes;

(29) ‘matrix’ means an approach where a subset of the total number of possible samples for all factor combinations is tested at a specified time point and another subset of samples is tested for all factor combinations at a subsequent time point. The results of each subset of samples is assumed to be representative for all samples at a given time point;

(30) ‘signed’ means the record of the individual who performed a particular action or review. This record can be initials, a full handwritten signature, a personal seal, or an advanced electronic signature as defined in Article 3(11) of Regulation (EU) No 910/2014 of the European Parliament and of the Council (¹).

Article 3

Role of the marketing authorisation holder regarding good manufacturing practice

CHAPTER II

PHARMACEUTICAL QUALITY SYSTEM

Article 4

Implementation of a pharmaceutical quality system

Article 5

Requirements of the pharmaceutical quality system

The design of the pharmaceutical quality system shall be based on the following risk management principles:

(a) the evaluation of the risks to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the user and the safety of the animals treated;

(b) the level of effort, formality and documentation of the quality risk management process is commensurate with the level of risk.

The pharmaceutical quality system shall ensure that:

(a) there is an adequate number of personnel with the necessary qualifications and adequate training and there is clear allocation of responsibilities, including managerial responsibilities;

(b) the premises and equipment are suitable for the intended use and they are appropriately maintained;

(c) there is an adequate documentation system that ensures that appropriate specifications are laid down for materials used in the manufacture of the veterinary medicinal product, intermediate product, bulk product and finished product, that the production and quality control procedures are clearly defined, and that appropriate records are kept;

(d) arrangements are put in place for the selection and monitoring of suppliers;

(e) the manufacturing process is systematically reviewed to ensure that it is capable of consistently delivering a product of the required quality in compliance with the relevant specifications and the terms of the marketing authorisation;

(f) appropriate controls on intermediate products and any other in-process controls and validations are carried out;

(g) veterinary medicinal products are not sold or supplied before a qualified person has certified that each production batch has been produced and controlled in accordance with the requirements of the marketing authorisation and in compliance with good manufacturing practice;

(h) the results of product and process monitoring are taken into account in the context of batch release and in the investigation of deviations;

(i) quality defects, deviations and other problems or unusual events that may have an impact on the quality of the veterinary medicinal product are identified as soon as possible, the causes investigated, and appropriate corrective and/or preventive measures are taken. The effectiveness of such measures shall be monitored and assessed;

(j) arrangements are put in place for the prospective evaluation of planned changes and their approval prior to the implementation thereof taking into account applicable regulatory requirements, as well as for the evaluation of changes implemented (change control);

(k) processes are implemented to ensure adequate management of outsourced activities;

(l) knowledge related to the product and the manufacturing thereof is duly managed throughout the life-cycle of the veterinary medicinal product and in particular in the context of the transfer of activities and the implementation of changes to the manufacturing process or control procedures;

(m) there is a process of self-inspection and/or quality audit which regularly appraises the effectiveness of the pharmaceutical quality system.

Article 6

Product quality reviews

Product quality reviews shall be conducted and documented annually for each veterinary medicinal product, taking into account previous reviews, and shall include at least a review of the following elements:

(a) materials used in the manufacturing process, especially those from new sources;

(b) the supply chain traceability of active substances;

(c) critical in-process controls and finished product results;

(d) all batches that failed to meet established specification(s) and the investigation thereof;

(e) significant deviations or non-conformances, the investigation thereof, and the effectiveness of resultant corrective and preventive actions taken;

(f) changes carried out to the manufacturing process or analytical methods;

(g) variations to the terms of the marketing authorisation affecting quality that have been submitted, granted or refused, as well as a review of post-marketing obligations affecting quality, including those relevant for veterinary medicinal products intended only for export;

(h) the results of the stability monitoring programme and any adverse trends;

(i) quality-related returns, complaints and recalls and the investigations performed at the time;

(j) adequacy of any other previous product, process or equipment corrective actions;

(k) the qualification status of relevant equipment and utilities, such as HVAC, water or compressed gases;

(l) any contractual arrangements for outsourced activities to ensure that they are up to date.

Article 7

Self-inspection

Article 8

Management review

There shall be a periodic review of the operation of the pharmaceutical quality system with the involvement of senior management to identify opportunities for the improvement of the veterinary medicinal products, the manufacturing process and of the system itself.

CHAPTER III

PERSONNEL

Article 9

General requirements for personnel

Article 10

Training

Article 11

Hygiene

CHAPTER IV

PREMISES AND EQUIPMENT

Article 12

General requirements for premises

Article 13

Production areas

Article 14

Quality control areas

Article 15

Storage areas

Article 16

Ancillary areas

Article 17

Temperature and environmental controls

Article 18

Equipment

Article 19

Qualification of premises and equipment

CHAPTER V

DOCUMENTATION

Article 20

Documentation system

Article 21

Specifications and instructions

The specifications for the materials used in the production of veterinary medicinal products and for the finished product, as well as the manufacturing instructions shall be adequate to ensure compliance with the terms of the marketing authorisation and the required level of quality. In particular, the following shall be duly documented:

(a) specifications for active substances and other substances used in the manufacture of the veterinary medicinal product and for immediate packaging materials, including the following: — a description of the active substances or other substances used, including any relevant information required to avoid risk of error (e.g. use of internal codes), and identification of the approved supplier(s). Where relevant, reference to a pharmacopeial monograph shall be provided; — the quality and quantitative requirements as well as acceptance criteria, as appropriate; — instructions for sampling and testing, as appropriate; — storage conditions and, where applicable, any special handling precautions; — the maximum period of storage;

(b) specifications for intermediate products and bulk products, including release criteria and the maximum period of storage, shall be set out for critical stages and when those products are purchased or dispatched;

(c) specifications for finished products, in particular: — the name or identification of the product and, where applicable, the reference code; — a description of the pharmaceutical form and packaging; — instructions for sampling and testing; — the qualitative and quantitative requirements with acceptance limits; — storage conditions and, where applicable, any special handling precautions; — the shelf-life;

(d) manufacturing instructions (including a description of the principal equipment to be used) and in-process controls, including the following: — the name of the product, with a product reference code relating to its specification; — a description of the pharmaceutical form, strength of the product and batch size; — a list of all materials to be used and the relevant amounts of each; — an indication of the expected final yield with the acceptable limits and, where applicable, of relevant intermediate yields; — an indication of the location where the relevant step should take place and the principal equipment to be used; — an indication of or reference to the methods to be used for preparing the critical equipment (e.g. cleaning, assembling, calibrating, sterilising); — detailed stepwise instructions to be followed (e.g. verification that equipment and workstation is clear of previous products, checks on materials, pre-treatments, sequence for adding materials, critical process parameters such as time, temperature, etc.); — instructions for any in-process controls, together with their limits; — where necessary, the requirements for bulk storage of the products, including the container, labelling and, where applicable, special storage conditions; — any special precautions to be observed;

(e) packaging instructions for each veterinary medicinal product and pack size, including: — the name of the product as well as the batch number of the bulk product and finished product; — a description of its pharmaceutical form, and strength where applicable; — the pack size expressed in terms of the number, weight or volume of the product in the final container; — a complete list of all the packaging materials required, including quantities, sizes and types, with the code or reference number relating to the specification of each packaging material; — relevant instructions with an indication of the equipment to be used, and relevant precautions, including the need for a careful examination of the area and equipment in order to ascertain the line clearance before operations begin; — details of in-process controls with instructions for sampling and acceptance limits.

Article 22

Records

Adequate records shall be kept to enable the entire history of a batch to be traced. As a minimum, the following shall be documented: