Ocb Pharmaceutical S.R.L. — EU GMP NCR (EudraGMDP) Findings

During the inspection, a total of nine (9) deficiencies were identified, one (1) of them were classified as critical and eight (8) as major. The deficiencies identified demonstrate significant weakness in the pharmaceutical quality system implemented at the site and raise serious concerns regarding the reliability of manufacturing, storage, documentation, cross contamination control, traceability and quality assurance oversight activities. The critical deficiency related to the repackaging, relabelling and distribution of bismuth subsalicylate originating from a Chinese manufacturing operating outside the EU GMP framework. The inspection demonstrated that OCB PHARMACEUTICAL, S.R.L. assigned new batch numbers, issued certificates of analysis containing analytical results copied from supplier documentation, removed or replaced original labels and distributed the material to pharmaceutical costumers without adequately preserving the identity of the original manufacturer and the traceability of the supply chain. These practices gave the material the appearance of being associated with OCB PHARMACEUTICAL, S.R.L. manufacturing activities, not complying with GMP Part II requirements concerning the integrity and traceability of the supply chain. Major deficiencies were identified in the effectiveness of the deviation, investigation, CAPA and risk management system; data integrity controls, personnel qualification and training; material management and traceability; contamination and cross-contamination control measures; maintenance and cleaning of facilities and equipment; documentation practices; and quality system governance. The combination of these deficiencies indicates that the quality management system is not capable of consistently ensuring the manufacture, storage and distribution of active substances in compliance with GMP Part II requirements.Particular concerns were identified regarding the design, maintenance, qualification and operation of HVAC systems and differential pressure controls, recurring environmental monitoring excursions, deficiencies in cleaning practices, uncontrolled access between classified and technical areas, inadequate investigation of contamination events and the lack of effective reassessment of cross-contamination risks following multiple significant quality incidents. These deficiencies may have compromised the effectiveness of controls intended to prevent contamination and cross-contamination of active substances manufactured at the site. In addition, deficiencies in governance and management oversight were observed. The inspection findings demonstrate that quality-related decisions were not always supported by adequate quality risk management principles and the quality unit did not exercise sufficient authority to ensure that manufacturing activities were restricted, suspended or adequately controlled when significant quality concerns were identified. Action taken/proposed by the NCA: Recall of batches already released No specific quality defects on concrete batches present in the market were detected, and thus no action/recall is deemed necessary against concrete batches released and placed on the market. Prohibition of supply Suspension of the distribution and sale of any active pharmaceutical ingredient or intermediate that has been manufactured, repackaged or relabelled in the facilities of OCB PHARMACEUTICAL, S.R.L. manufacturing site at the Canovelles. In the event that the competent authorities of the countries deem it necessary, they may use the available stock of these products for their markets upon express request. Suspension or voiding of CEP (action to be taken by EDQM) Suspension of CEP for active substances manufactured in OCB PHARMACEUTICAL, S.R.L. in Canovelles should be considered. The CEP that it has are: - Bismuth subnitrate (R0-CEP 2021-190 Rev.00) Others Action on the Manufacturing Authorisation: Temporary suspension of all manufacturing activities of active pharmaceutical ingredients and / or intermediates performed at the OCB PHARMACEUTICAL, S.R.L. manufacturing site at Canovelles. These measures will be maintained until all the deficiencies observed in the inspection have been corrected and it has been verified through a new inspection. Recommendations/proposed actions: Manufacturers of finished medicinal products using active pharmaceutical ingredients manufactured at the OCB PHARMACEUTICAL, S.R.L. site of Canovelles should not use, release for manufacture, or further process such active substances unless they perform scientifically justified testing, using suitably validated analytical methods and representative sampling plans, to demonstrate that the affected active pharmaceuticals ingredients batches do not contain traces of other bismuth salts at levels that may impact product quality, safety or compliance with the approved specifications. In case of out of specification results are detected, national competent authority (NCA) should be informed by the marketing authorization holder (MAH). This manufacturer should not be authorised in any new/ongoing marketing authorisation or variation applications for these active pharmaceutical ingredients as long as the non-compliance statement is in force. Marketing Authorisation Holders are recommended to evaluate the introduction of alternative qualified sources for active substances currently supplied by OCB PHARMACEUTICAL, S.R.L. in order to mitigate any potential supply impact resulting from the regulatory measures adopted.