Commission Implementing Regulation (EU) 2021/1280 of 2 August 2021 as regards measures on good distribution practice for active substances used as starting materials in veterinary medicinal products in accordance with Regulation (EU) 2019/6 of the European Parliament and of the Council (Text with EEA relevance)
Commission Implementing Regulation (EU) 2021/1280 of 2 August 2021 as regards measures on good distribution practice for active substances used as starting materials in veterinary medicinal products in accordance with Regulation (EU) 2019/6 of the European Parliament and of the Council (Text with EEA relevance)
THE EUROPEAN COMMISSION,
Having regard to the Treaty on the Functioning of the European Union,
Having regard to Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary medicinal products and repealing Directive 2001/82/EC(1), and in particular Article 95(8) thereof,
Whereas:
Article 93(1)(j) of Regulation (EU) 2019/6 requires the holders of a manufacturing authorisation to use as starting materials only active substances which have been manufactured in accordance with good manufacturing practice for active substances and distributed in accordance with good distribution practice for active substances.
Article 95(1) of Regulation (EU) 2019/6 requires importers, manufacturers and distributors of active substances used as starting materials in veterinary medicinal products, that are established in the Union, to comply with good manufacturing practice or good distribution practice, as applicable.
Measures on good distribution practice should ensure the identity, integrity, traceability and quality of active substances used as starting materials in veterinary medicinal products during their movements from the premises where they are manufactured to the manufacturers of veterinary medicinal products by means of various modes of transport and by the use of various storage methods, as well as that those active substances remain within the legal supply chain during storage and transport.
Several international standards and guidelines on good distribution practice exist for active substances for medicinal products for human use(2),(3). At Union level, guidelines on good distribution practice have been adopted only in respect of active substances for medicinal products for human use(4). Corresponding measures in the veterinary domain should take into account the experience gained with the application of the current system under Directive 2001/83/EC of the European Parliament and of the Council(5) in light of the similarities and potential differences between the requirements on good distribution practice for active substances used as starting materials in medicinal products for human use and in veterinary medicinal products.
A significant number of active substances are used as starting materials both in medicinal products for human use and in veterinary medicinal products. Importers, manufacturers and distributors often deal with such active substances. In addition, good distribution practice inspections for both types of medicinal products are often to be performed by the same competent authority experts. Therefore, in order to avoid unnecessary administrative burden on the industry and the competent authorities, it is practical to apply similar measures to the veterinary domain as in the human domain, unless specific needs dictate otherwise.
In order not to affect negatively the availability of veterinary medicinal products in the Union, the good distribution practice requirements for active substances used as starting materials in veterinary medicinal products should not be more stringent than the corresponding ones for those used as starting materials in medicinal products for human use.
The measures on good distribution practice for active substances used as starting materials in veterinary medicinal products laid down in this Regulation should ensure consistency with and complement the implementing measures on good manufacturing practice for veterinary medicinal products and active substances used as starting materials provided for in Article 93(2) of Regulation (EU) 2019/6 and good distribution practice for veterinary medicinal products provided for in Article 99(6) of that Regulation.
Relevant sections of good distribution practice for active substances used as starting materials in veterinary medicinal products should also be adhered to by third-party actors involved in the distribution of active substances used as starting materials in veterinary medicinal products and should be part of their contractual obligations. A consistent approach by all partners in the supply chain is required in order to be successful in the fight against falsified active substances used as starting materials in veterinary medicinal products.
A quality system is required to ensure that the objectives of good distribution practice are achieved and should clearly set out responsibilities, processes and risk management principles in relation to the activities of the persons involved throughout the distribution chain. That quality system should be the responsibility of the organisation’s management, requires their leadership and active participation, and should be supported by personnel commitment.
The correct distribution of active substances used as starting materials in veterinary medicinal products relies significantly on an adequate number of competent personnel to carry out all the tasks for which the importers, manufacturers and distributors of active substances used as starting materials in veterinary medicinal products are responsible. Individual responsibilities should be clearly understood by personnel and be recorded.
The persons distributing active substances used as starting materials in veterinary medicinal products should have suitable and adequate premises, installations and equipment, in order to ensure proper storage and distribution of active substances used as starting materials in veterinary medicinal products.
Good documentation should be an essential part of any quality system. Written documentation should be required in order to prevent errors from oral communication and permit the tracking of relevant operations during the distribution of active substances used as starting materials in veterinary medicinal products. All types of documents should be defined and adhered to.
Procedures should describe all distribution activities that affect the identity, traceability and quality of the active substances used as starting materials in veterinary medicinal products.
Records of all significant activities or events should be made and kept to ensure the traceability of the origin and destination of active substances used as starting materials in veterinary medicinal products, as well as the identification of all suppliers of, or those supplied with, such active substances.
The quality system should fully describe all key operations in appropriate documentation.
Complaints, returns, and recalls should be recorded and handled carefully in accordance with established procedures. Records should be made available to the competent authorities. An assessment of returned active substances used as starting materials in veterinary medicinal products should be performed before any approval for resale.
Any activity covered by good distribution practice for active substances used as starting materials in veterinary medicinal products that is outsourced should be correctly defined and agreed in order to avoid misunderstandings that could affect the integrity of such substances. A written contract between the contract giver and the contract acceptor should clearly establish the duties of each party.
Regular self-inspections are necessary to monitor the implementation of and compliance with good distribution practice for active substances used as starting materials for veterinary medicinal products.
The measures provided for in this Regulation are in accordance with the opinion of the Standing Committee on Veterinary Medicinal Products referred to in Article 145 of Regulation (EU) 2019/6,
HAS ADOPTED THIS REGULATION:
CHAPTER I GENERAL PROVISIONS
Article 1 Subject matter and scope
This Regulation lays down the measures on good distribution practice for active substances used as starting materials in veterinary medicinal products.
This Regulation shall apply to importers and distributors of active substances used as starting materials in veterinary medicinal products, and to manufacturers who distribute active substances, which they manufactured, used as starting materials in veterinary medicinal products.
This Regulation shall not apply to intermediates of active substances used in veterinary medicinal products.
Article 2 Definitions
For the purposes of this Regulation, the following definitions shall apply:
‘good distribution practice for active substances used as starting materials in veterinary medicinal products’ means the part of the quality assurance throughout the supply chain which ensures that the quality of active substances used as starting materials in veterinary medicinal products is maintained throughout all stages of the supply chain from the site of their manufacturer to the manufacturers of veterinary medicinal products;
‘quality system’ means the sum of all aspects of a system that implements quality policy and ensures that quality objectives are met;
‘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 an active substance used as a starting material in veterinary medicinal products across the substance’s lifecycle;
‘procuring’ means obtaining, acquiring or purchasing active substances used as starting materials in veterinary medicinal products from manufacturers, importers or other distributors;
‘holding’ means storing active substances used as starting materials in veterinary medicinal products;
‘supplying’ means all activities of providing, selling or donating active substances used as starting materials in veterinary medicinal products to distributors, pharmacists, manufacturers of veterinary medicinal products, or other persons in accordance with national law;
‘deviation’ means departure from approved documentation or an established standard;
‘procedure’ means a documented description of the operations to be performed, the precautions to be taken and measures to be applied directly or indirectly related to the distribution of active substances used as starting materials in veterinary medicinal products;
‘distribution of active substances used as starting materials in veterinary medicinal products’ means all activities consisting of procuring, importing, holding, supplying or exporting of active substances used as starting materials in veterinary medicinal products;
‘documentation’ means written procedures, instructions, contracts, records and data, in paper or in electronic form;
‘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(6);
‘expiry date’ means the date placed on the container or labels of an active substance used as a starting material in veterinary medicinal products designating the time during which that active substance is expected to remain within established shelf life specifications if stored under defined conditions, and after which it should not be used;
‘batch’ means a defined quantity of starting material, packaging material or product processed in a single process or series of processes, so that it is expected to be homogeneous;
‘retest date’ means the date when an active substance used as a starting material in veterinary medicinal products should be re-examined to ensure that it is still suitable for use;
‘transport’ means moving active substances used as starting materials in veterinary medicinal products between two locations without storing them for unjustified periods of time;
‘batch number’ means a distinctive combination of numbers or letters that uniquely identifies a batch;
‘contamination’ means the undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or active substance during production, sampling, packaging or repackaging, storage or transport;
‘calibration’ means the set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system, or values represented by a material measure, and the corresponding known values of a reference standard;
‘quarantined’ means the status of materials isolated physically or by other effective means pending a decision on approval or rejection;
‘qualification’ means the action of proving that any equipment works correctly and actually leads to the expected results;
‘validation’ means a documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria;
‘falsified active substance used as a starting material in veterinary medicinal products’ means any active substance used as a starting material in veterinary medicinal products with a false representation of any of the following:
its identity, including its packaging and labelling, its name or its components as regards any of the ingredients and the strength of those ingredients;
its source, including its manufacturer, its country of manufacturing, its country of origin; or
its history, including the records and documents relating to the distribution channels used.