Produlab Pharma Production B.V. — EU GMP NCR (EudraGMDP) Findings

A GMP re-inspection of the site was performed on 2, 3 and 4 December 2025. Three critical, two majors and sixteen other deficiencies were identified. The three critical deficiencies were regarding the following: 1. In Unit A (building A), the water quality of the purified water (PW) does not meet the specifications for microbial contamination (<100 CFU/ml) for purified water, which poses risks to animal safety and public health. Purified water may contain microbes in accordance with the requirements of the European Pharmacopoeia, but Produlab Pharma has repeatedly measured exceedances both in the installation and at the point of use (before the filter). This purified water has been used in non-sterile veterinary medicinal products specifically produced in unit A, for cleaning product contact materials for all veterinary medicinal products produced in unit A, and as source water for the WFI (water for injection) installation in unit A. 2. Produlab Pharma manufactures aseptically prepared products in Unit B (building B), where environmental and process monitoring (including personal monitoring) data systematically fail to meet the limits set out in Annex 1 of the EU GMP. This means that the risks of product contamination with microorganisms, particles, and endotoxins/pyrogens are not sufficiently minimized. The quality of the veterinary medicines is insufficiently guaranteed and poses a risk to animal safety and public health. Since the previous inspection, where the same issue was identified, the QPs have released four batches in which contamination was found at the most critical locations near the final filling point of the product (three times at the sedimentation plate next to the filling needle and once on the turntable in the A room). The contamination found on the settle plate in close proximity to the filling needle poses a risk that the product may have become contaminated. No sterilization step takes place after filling. The exceedances were not demonstrably taken into account during release, which therefore did not take place in accordance with Annex 16 EU GMP and the company's own procedure. 3. Dismissing abnormal results found during quality control of veterinary medicines during monitoring, release, and stability testing is standard practice at Produlab Pharma. This poses risks to animal welfare and public health. In doing so, Produlab Pharma is not following its own OOS procedure and is not complying with contractual agreements on reporting OOSs to customers. The cause of the abnormal results is not investigated and/or no action is taken. Action taken/proposed by the NCA: Withdrawal, of current valid GMP certificate No. NL/V 24/0020 The competent authority is not granting a new GMP certificate because of GMP NC which was determined by the Dutch Inspectorate during the inspection in December 2025. This decision has been sent to the company by means of an official decision on the 14th of April 2026. Following this decision, the NCS is issued by the Dutch NCA in EudraGMDP, whereby the current GMP certificate, based on the previous inspection with a compliant result in December 2023, will be withdrawn from EudraGMDP. Recall of batches already released The Dutch Competent Authority (NL) deems not to recall batches of finished products that are produced in Unit A with purified water (PW) and already released and distributed to the market. The risks posed by the non-compliance is deemed to be sufficiently limited by a number of factors, the first of which is the preservatives. Products contain methyl hydroxybenzoate and parahydroxy benzoate, which are bactericidal, or sodium benzoate, which is bacteriostatic. The product containing clindamycin is both bactericidal and bacteriostatic. Furthermore, all concerned products are for oral use, whereby stomach acid acts as an extra chemical barrier. Finally, potential contamination with micro-organisms does not increase during storage of the products concerned, therefore no degradation of the active substance by micro-organisms is expected to occur, making any influence on the efficacy of the veterinary medicinal product highly unlikely. For the batches of aseptic VMPs produced in Unit B, a recall class III on specific batches is issued by the Dutch Competent Authority (NL), based on the provided assessment of PM (process monitoring, including person monitoring) on batch-level. Only batches that are released for the Dutch market and are not deemed critical for the Dutch market are to be recalled. In total, this comes down to 2 batches. For other member states, the recall decision should be made by their respective NCAs, based on criticality of the VMPs and the impact assessment provided by the company. For the batches for which an OOS was reported, the Dutch Competent Authority (NL) issues, at this moment, no recall on the basis of the impact assessments on retested and not-retested batches. The Dutch Competent Authority (NL) agrees with the rationale provided by the company. However, at present, NL is still awaiting the impact assessment for the OOS-results in ongoing stability studies, in which the actions taken or required (market) actions with the relevant MAHs will also be evaluated by Produlab. The company will provide this information to us as soon as possible (deadline April 30th2026 at the latest). Based on this, NL will make a final decision on possible market actions regarding these batches. Others Critical products At this time, NL has identified a list of products that would most likely be critical for the Dutch market and this list is already shared with the company. This list was compiled based on the following principles: - If the market share of the product is <20%, the product is not critical. - If the market share of the product is >20% and <70%, the product could be critical, depending on other factors, such as: o Is the product prescribed / used daily? o How many acceptable* alternatives are available, that are not produced by Produlab? If there are >3, the product is generally not considered critical. - If the market share of the product is >70%, the product is critical. *In some cases, products of other strengths or for other target species may be acceptable. It should be noted that not all necessary information is known by the Dutch authority at this time and therefore the list is subject to change. Each Member State must determine for its own national market which products are critical, as decisions about recall and limiting product release could lead to potential shortages in the market and prevent animals from being treated in time for a specific condition. As NCA, we emphasize that if a product is considered critical for a member state, they may still be released by the QP for that specific market based on a risk-based analysis, even if the manufacturing process did not meet the GMP requirements and the product may pose a potential risk to animal- and public health. The reason is that having no alternative to critical products available, i.e. not treating animal patients, could entail more risk to public and animal health, animal welfare, and animal survival, compared to allowing products for treatment which were produced under the non-compliance findings. After identifying the critical deficiency listed as number 1 above, the Dutch Food and Consumer Product Safety Authority has, in agreement with the Dutch Health and Youth Care Inspectorate, immediately halted the use of PW in Unit A by means of an administrative measure. The manufacture of veterinary medicinal products using microbially contaminated water does not comply with Article 93(1)(j) of Regulation (EU) 2019/6. An administrative measure has already been taken to avert possible danger to animal and public health. This administrative measure means that the use of water from the water-unit in Unit A has been stopped immediately and must remain stopped until sufficient measures have been taken by the company and approved by the Dutch inspectorate. Discontinuation of the use of PW from Unit A applies to both production and cleaning activities involving this water. This administrative measure remains effective currently. It can only be lifted when Produlab has demonstrated, through planning (CAPA plan) and implementing corrective and preventive actions, that the risk of contamination in the water has been eliminated. This must be assessed by the Dutch Inspectorate (IGJ) before the measure imposed by the Dutch Food and Consumer Product Safety Authority can be lifted.