Qualified person
1. Each manufacturing site of veterinary medicinal products in the Union shall have at least one qualified person.
2. To comply with the obligation set out under Article 97(6) of Regulation (EU) 2019/6, the qualified person shall, as a minimum, verify the following aspects:
(a)
the source and specifications for the materials used in the manufacture of veterinary medicinal products and the packaging materials comply with the terms of the marketing authorisation;
(b)
the active substances have been manufactured in accordance with good manufacturing practices and distributed in accordance with good distribution practice;
(c)
where applicable, the viral and microbial safety and TSE (transmissible spongiform encephalopathies) status of all materials used the manufacture is compliant with the terms of the marketing authorisation;
(d)
all manufacturing steps, including controls and testing, have been done in accordance with the marketing authorisation and at a manufacturing site authorised therein and in compliance with good manufacturing practice;
(e)
all required in-process controls and checks, including environmental monitoring, have been made and appropriate records exists;
(f)
finished product quality control test data shows compliance with the relevant specifications or, where applicable, the real time release testing programme;
(g)
on-going stability data continues to support certification;
(h)
the impact of any deviation to the manufacturing process or testing has been evaluated and any additional checks and tests are complete;
(i)
the impact of any change to the manufacturing process or testing has been evaluated and any additional checks and tests have been completed;
(j)
audits of manufacturing sites and sites involved in the manufacture or testing of the active substances support the certification of the batch;
(k)
measures related to the implementation of outsourced manufacture or testing, as provided for in the subcontracting arrangements, are in place;
(l)
all investigations on matters that may impact the quality of the batch being certified have been completed to a sufficient degree to support the certification of the batch;
(m)
the self-inspection programme is active.
The qualified person, while being responsible for ensuring that the verifications set out in the first subparagraph are done, may delegate those tasks to appropriately trained personnel or third parties.
3. The qualified person shall have access to any documentation relevant to the steps for which he or she assumes responsibility, including details of the marketing authorisation necessary to assess if the relevant requirements have been complied with and relevant data about the entire manufacturing process of the veterinary medicinal product, including importation activities, if any.
4. Where more than one qualified person is involved in the assessment of one batch of a veterinary medicinal product, the division of responsibilities amongst them, including details on the responsibility for assessment of any deviations, shall be clearly laid down in writing.
5. The qualified person may rely on audits conducted by third parties attesting the compliance with good manufacturing practice in specific manufacturing sites. In such cases, the requirements in Article 43 shall apply. The qualified person shall have access to any documentation that is relevant to the review of the audit outcome.
For the approval of the audit report, the qualified person shall take into consideration the following:
(a)
whether the audit report addresses general requirements of good manufacturing practice, such as the quality management system and production and quality control procedures related to the supplied product, with sufficient level of detail so as to allow a conclusion that the relevant activities covered by the audit comply with the marketing authorisation and good manufacturing practice;
(b)
in the case of outsourced activities, whether there has been verification of the compliance with the marketing authorisation and good manufacturing practice.
Certification and batch release
1. Batches of veterinary medicinal products can only be released for sale or supply to the market after a qualified person certifies – by means of a control report– that each batch of a veterinary medicinal product has been manufactured and tested in accordance with the requirements of the marketing authorisation and good manufacturing practice. Certification can only be performed by the qualified person of a manufacturer described in the marketing authorisation. A model template for batch release certificate is provided in Annex VIII.
2. Reliance by the qualified person on real time release testing or parametric release is only possible if the conditions and requirements laid down in Annex IX are met.
3. Evidence of the certification referred to in paragraph 1 shall be recorded by the qualified person in a register or equivalent document provided for that purpose. That register or equivalent document shall be kept up to date and shall remain at the disposal of the competent authority for one year after the expiry of the batch to which it relates or at least five years after certification of the batch by the qualified person, whichever is longer.
4. The qualified person who performs the certification of the batch of a veterinary medicinal product may assume full responsibility for all stages of manufacture of the batch or may share this responsibility with other qualified persons who have confirmed compliance of specific steps in the manufacture and control of a batch.
If a manufacturing site only undertakes partial manufacturing operations, the qualified person at that site shall, at least, confirm that the operations undertaken at that manufacturing site have been performed in accordance with good manufacturing practice and the terms of the written agreement detailing the operations for which the manufacturing site is responsible. Partial manufacturing shall only occur in a manufacturing site authorised in accordance with the terms of the marketing authorisation. A model template for confirmation of partial manufacturing is provided in Annex VIII.
5. Where various batches of finished product originate from the same batch of bulk product, certification of the different batches of finished product may be based on the quality control testing of a previously certified batch provided that this is justified based on quality risk management principles. The following elements shall at least be verified by the qualified person:
(a)
the relevant requirements for storage of the bulk product prior to packaging have been complied with;
(b)
the batch of the finished product has been stored and, where applicable, transported under the required conditions;
(c)
the consignment has remained secure and there is no evidence of tampering during storage or transportation;
(d)
the identification of the product has been established;
(e)
the samples tested are representative of all finished product batches derived from the batch of bulk product.
6. Where the qualified person certifies a batch of a veterinary medicinal product in accordance with paragraph 1, he or she shall assign the release status to that batch by means of a formal and unambiguous notification to the manufacturing site releasing the product.
7. Pending the assignment of the release status referred to in paragraph 6, the batch shall remain at the manufacturing site or be shipped under quarantine to another manufacturing site authorised for that purpose. Safeguards to ensure that uncertified batches are not released shall be put in place. Those safeguards may be physical (by using segregation and labelling) or electronic (by using validated computerised systems). When uncertified batches are moved from one authorised manufacturing site to another, the safeguards to prevent premature release shall remain.
Additional considerations for imports of veterinary medicinal products
1. To comply with the obligation set out under Article 97(7) of Regulation (EU) 2019/6, the certification by the qualified person can only occur after a physical importation has taken place. The site of physical importation and the site of the qualified person responsible for the certification/confirmation shall be authorised in accordance with Article 88(1) of Regulation (EU) 2019/6.
2. Sampling of the imported product shall be fully representative of the batch. Samples required for the testing of the imported batch as well as reference and/or retention samples may either be taken after arrival in the Union or at the manufacturing site in the third country in accordance with a documented procedure. Responsibilities in relation to the sampling shall be defined in a written agreement between the manufacturing sites. Any samples taken outside the Union shall be shipped under equivalent transport conditions as the batch that they represent.
3. Where sampling is performed in a third country manufacturing site, the documented procedure referred to in paragraph 2 shall be justified in accordance with quality risk management principles and shall include at least the following elements:
(a)
audits of the manufacturing activities, including sampling, at the third country manufacturing site and evaluation of subsequent transportation steps of both the batch and samples to ensure that the samples are representative of the imported batch;
(b)
a comprehensive analysis supporting the conclusion that samples taken in the third country are representative of the batch after importation, including at least the following:
—
a description of the sampling process;
—
a description of the transport conditions of the sample and the imported batch; any differences shall be justified;
—
comparative analysis of samples taken in the third country and samples taken after importation. In case of discrepancies or out of trends, these shall be documented and investigated;
—
consideration of the time interval between sampling and importation of the batch and generation of data to support appropriate defined limits;
(c)
a random periodic analysis of samples taken after importation shall be performed to justify ongoing reliance on samples taken in a third country;
(d)
the conditions of storage and transport of the finished product and the samples, shall be checked before certifying any batch;
(e)
batch documentation supplied by the third country manufacturing site shall be in a format and language that is understandable for the importer;
(f)
relevant ordering and delivery documentation shall be available for inspection at the manufacturing site responsible for certification;
(g)
where batches are subdivided and partial quantities are imported separately, reconciliation of the quantities shall be verified and documented. Any discrepancy shall be investigated under the responsibility of the qualified person responsible for the certification of the batch;
(h)
the manufacturing site responsible for certification shall ensure that an ongoing stability programme is in place and that reference and retention samples have been taken. The ongoing stability programme may be carried out at the third country manufacturing site.
4. The manufacturing site responsible for certification shall qualify the third country manufacturer and conduct periodic monitoring, including by means of on-site audits, to ensure compliance with good manufacturing practice and the terms of the marketing authorisation.
Repackaging operations
The qualified person of a manufacturing site that is only involved in repackaging operations shall certify that the repackaging has been done in compliance with relevant good manufacturing practice requirements.
Handling of unplanned deviations
Where an unplanned deviation related to the manufacturing process or the analytical control methods has occurred, a qualified person may confirm compliance or certify the batch only if the following conditions are met:
(a)
the specifications for active substances, excipients, packaging materials and finished product are complied with;
(b)
there is an in-depth assessment of the impact of the deviation which supports a conclusion that the occurrence does not have a negative effect on quality, safety or efficacy of the product;
(c)
where appropriate, the need for inclusion of the affected batch/batches in the on-going stability programme has been evaluated.
Source: EUR-Lex (Publications Office of the EU), © European Union, reuse permitted under Commission Decision 2011/833/EU.
