14/15 December 2021
With Regulation (EU) 2019/6 on veterinary medicinal products, which will apply from 28 January 2022, the European Union has revised the veterinary medicinal products legislation.
Already since August 2021, the "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" has been in force.
The Regulation was published in the Official Journal of the European Union on 3 August 2021.
The Implementing Regulation is strongly based on the GDP of APIs for human use Guidelines (Guidelines of 19 March 2015 on principles of Good Distribution Practice of active substances for medicinal products for human use - 2015/C 95/01). In some cases, paragraphs are even taken over literally. Accordingly, the requirements are quite detailed.
Recital 5 of the new Regulation states: "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."
The following is an overview of the most important provisions of the new Regulation.
Article 1 defines the subject matter and the scope. The new Commission Implementing Regulation (EU) 2021/1280 lays down the measures on good distribution practice for active substances used as starting materials in veterinary medicinal products.
The Regulation applies to
Intermediates are explicitly excluded from the Regulation.
Article 2 provides definitions relevant for the purpose of the Regulation.
A quality system is required to ensure that the objectives of good distribution practice are achieved.
According to Article 3, importers, distributors and manufacturers covered by the Regulation shall develop and maintain a quality system which shall take into account the size, structure and complexity of the activities.
Article 4 sets out detailed requirements for the quality system. Among other things, the following must be ensured:
Implementation of a change management system
According to Article 5, a person responsible for the quality system must be appointed at each location where distribution activities are performed. This person shall have defined authority and responsibility for ensuring that a quality system is implemented and maintained as well as be personally responsible for fulfilling their obligations. The persons responsible for the quality system may delegate their tasks but not their responsibilities.
According to Article 6, the responsibilities of all personnel involved in the distribution of active substances used as starting materials in veterinary medicinal products shall be specified in writing.
As per Article 7, personnel shall receive initial and continuing training relevant to their role, based on procedures and in accordance with a written training programme.
Appropriate clothing must be worn at work in accordance with Article 8 and hygiene standards must be maintained.
Article 9 of the Implementing Regulation describes requirements for premises and equipment. This includes, among other aspects:
According to Article 10, premises shall be suitably secured to prevent unauthorised access.
Good documentation is an essential part of any quality system.
Article 11 describes the general requirements for documentation. All documentation must be easily accessible or retrievable, written in a language understandable to staff and clearly and unambiguously formulated. Any change to the documentation must be signed and dated, with the original version still recognisable despite the change, and the reason for the change should be noted.
Article 12 states that procedures shall describe, for example, receipt and verification of supplies, storage, cleaning or the planning of recalls. According to the definition in Article 2 of the Regulation, "procedures" means "a documented description of the operations to be carried out, the precautions to be taken and the measures to be implemented which are directly or indirectly related to the distribution of active substances used as starting materials for veterinary medicinal products".
Article 13 sets out in detail what records must be created and how long they must be kept.
Chapter VI contains requirements for the verification of eligibility and approval of suppliers in Article 14 and a list of points to be checked at receipt of active substances in Article 15.
Article 16 deals with storage. Active substances shall be stored under the conditions specified by the manufacturer, i.e. where necessary at controlled temperature or humidity and in such a way that contamination or mix-up cannot occur. The records shall be reviewed regularly by the person responsible for the quality system.
For outsourced activities, Article 17 requires ensuring that the contract acceptor knows and follows the appropriate storage and transport conditions. A written contract between the contract giver and contract acceptor should clearly specify the duties of each party. This will avoid misunderstandings that could affect the quality of the active substances.
A supply of the active substances may only be made within the Union to distributors, manufacturers, dispensing pharmacies or to persons permitted by national law, in accordance with Article 18.
Article 19 deals with the transfer of information. All relevant information and incidents are to be passed on, both in the direction of the customers, the manufacturers and to the authorities.
According to Article 20, all complaints received about the quality of an active substance shall be documented and evaluated. Records of complaints shall be retained in order to evaluate trends, product related frequencies, and severity, with a view to taking additional, and if appropriate, immediate corrective action.
According to Article 21, returned active substances shall be identified as such and segregated. Article 21 also specifies the conditions for returns to saleable stock.
In the event of a necessary recall, a procedure shall be established in advance in accordance with Article 22. The person responsible for the quality system shall be involved in the recall procedure.
According to Article 23, self-inspections must be carried out at regular intervals according to a defined plan, these must be documented and, if necessary, CAPAs must be defined. In order to involve management in the process, the reports on the self-inspections shall be presented to the management.
ticle 24 concludes that the Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union and shall be binding in its entirety and shall be directly applicable in all Member States.