Pharma Talk

Your firm failed to conduct adequate manufacturing investigations into out-of-specification (OOS) results obtained by your external laboratory for your (...), an over-the-counter (OTC) drug product. As such, root cause(s) for the OOS results were not determined and no corrective and preventive actions (CAPA) were identified." "your cursory investigation lacked appropriate CAPA" "As a manufacturer, you have a responsibility to fully investigate OOS results and process deviations that may impact product quality." "the procedures for handling deviations and complaints are inadequate. For example, the deviations procedure lacks details for the investigation process". FDA WL

SOPs on Cleaning Validation not followed The FDA criticizes that the cleaning validation for non-dedicated equipment and its maintenance are not sufficient to be used for their intended purpose. This was actually acknowledged by the company's quality assurance personnel. Furthermore, standard operating procedures (SOPs) had not been followed. It was criticized that the company had neither collected nor analysed rinse or swab samples, although this was laid down in the operating procedures. It was also pointed out that equipment was dirty and not well maintained. The FDA concluded that this presented a risk of cross-contamination. The company's response is interesting. They admit to deficiencies in maintenance and sanitary conditions and are recalling all active ingredients that were shipped to the US. They also informed the FDA that they are initiating a "change control" to create a cleaning validation plan and to train personnel on the documentation of cleaning and e...

The FDA has investigated the manufacturing practices of Shantou Kangjie Daily Chemical Industry Co, Ltd (China) and found significant violations of Current Good Manufacturing Practice (CGMP). The FDA concludes that the company's manufacturing processes do not meet the legal requirements, which means that the manufactured products are considered adulterated. The company was therefore placed on the 66-40 import warning list in the USA. 1. Key points of the violations 1.1. Lack of identity verification of raw materials (21 CFR 211.84(d)(1)). The company did not perform systematic identity verification for incoming raw materials used in drug product manufacturing. Of particular concern is that the ethanol used is not tested for methanol impurities, which poses a serious health risk. The FDA requires the company to conduct a comprehensive evaluation of all suppliers and materials and to ensure the identity, strength, quality and purity of all components used. 1.2. Failure to have an ade...

Background During the COVID-19 pandemic, various exemptions were introduced for GDP inspections as well as for the validity and extension of GDP certificates. The aim was to ensure the supply of medicines despite the restrictions caused by the pandemic. In December 2023, the GMP/GDP Inspectors Working Group (IWG) announced that the validity of GDP and GMP certificates that expired at the end of 2023 would be extended until 2024 or until the next on-site inspection, whichever occurred first. No Further General Extension In its latest announcement, the EMA clarifies that a general extension of GDP certificates will no longer be granted in 2025. The following justification is given: "The working group took into account that national competent authorities (NCAs) had resumed regular on-site inspections. It also considered that NCAs are using other methods to gather compliance information, such as distant assessments and inspections that international partners carry out. These methods e...

On the website of the HMA (Heads of Medicines Agencies), under the heading "Variations", you will find the "Guidance Documents" relating to the updated "Variation Regulation" (Commission Delegated Regulation (EU) 2024/1701 of 11 March 2024 amending Regulation (EC) No 1234/2008 as regards the examination of variations to the terms of marketing authorizations for medicinal products for human use). Amongst a large number of other documents, these include the so-called "Best Practice Guides (BPGs) for the Submission and Processing of Variations in the Mutual Recognition Procedure". These consist of 8 chapters, which were last updated in October 2024. Chapters 3 and 6 were revised again in January 2025: Chapter 3: CMDh BPG for the Processing of Type IA Minor Variations (Notifications) in the Mutual Recognition Procedure Updates have been made to subsection 1. Introduction and Annex II. Chapter 6: CMDh BPG for the Processing of (Super-)Grouped Applicat...

In January 2025, the U.S. Food and Drug Administration (FDA) published a draft Guidance for Industry and other interested parties entitled 'Considerations for the Use of Artificial Intelligence to Support Regulatory Decision-Making for Drug and Biological Products'. This draft provides recommendations for 'sponsors' and other interested parties on the use of artificial intelligence (AI) to support regulatory decisions regarding the safety, efficacy or quality of medicinal products. A key element of the draft is the introduction of a risk-based approach to assess the credibility of AI models. This approach is intended to help establish and assess confidence in the performance of an AI model for a specific context of use (COU). The guideline emphasises the importance of a clearly defined context of use for each AI model, as this forms the basis for the evaluation of the model. The risk-based approach comprises seven steps: Step 1: Define the question of interest. Step 2: ...

Failure to record all quality-related activities at the time they are performed. Your quality unit (QU) failed to ensure the integrity of CGMP records. For example, during the inspection, a member of your management stated that two of your operators admitted to falsifying temperature data for a drying oven that was not turned on during the manufacture of a (b)(4) batch, which later failed to meet the residual solvents specification. In addition, an Assistant Manager in Production, an Assistant Manager in Quality Assurance, and a Quality Control Manager admitted to participating in the preparation of a “backdated calculation sheet” that was given to our investigator. Your documentation practices were not indicative of a facility that is in compliance with CGMP. 2. Failure to clean equipment and utensils to prevent contamination or carry-over of a material that would alter the quality of the APIs beyond the official or other established specifications. FDA documented rust-like residues i...

Insufficient monitoring was carried out to ensure that the system was functioning properly and was suitable for production. FDA requirements: Validation of the system, including design, maintenance and continuous monitoring. Implementation of programmes to monitor and record microbiological and chemical parameters. Implementation of a risk assessment plan to evaluate the impact of system failures on the quality of drugs distributed in the US. This will include customer notifications and recalls as appropriate. General measures: The FDA requires the company to submit comprehensive corrective actions and timelines. These include Detailed process validation programmes (PPQ) for active ingredients and finished drug products. Systematic identification and control of process variability. Monitoring and qualification of production facilities and equipment. Risk assessment and preventive measures for products already on the market. In addition, the company is expected to implement measures to ...

Access Letter Here The system was poorly designed, e.g. with ‘blind spots’ and lack of continuous circulation, increasing the risk of biofilm formation. Insufficient monitoring was carried out to ensure that the system was functioning properly and was suitable for production. FDA requirements: Validation of the system, including design, maintenance and continuous monitoring. Implementation of programmes to monitor and record microbiological and chemical parameters. Implementation of a risk assessment plan to evaluate the impact of system failures on the quality of drugs distributed in the US. This will include customer notifications and recalls as appropriate. General measures: The FDA requires the company to submit comprehensive corrective actions and timelines. These include Detailed process validation programmes (PPQ) for active ingredients and finished drug products. Systematic identification and control of process variability. Monitoring and qualification of production facilities ...