Pharma Talk

There is relatively little information on FDA requirements for equipment qualification. You can find guidance in the FDA Guidance for Industry General Principles and Practices: Process Validation on 'DQ', 'IQ' and 'OQ'. However, the terms 'DQ', 'IQ' and 'OQ' are not mentioned there. A footnote refers to the ASTM standard E2500. But what does the implementation look like in practice in companies? A current Warning Letter gives some clues.  What is it about? An over-the-counter (OTC) drug manufacturer is criticised under 21 CFR 211.113 for finding germs in water monitoring. This water was used to manufacture OTC drugs and to clean the equipment. Among other things, the FDA criticised the inadequate qualification of the water system. It refers to installation and functional qualifications carried out by the manufacturer in 2019, whereby data collection was only completed three years later. However, the data was not analysed. Subsequently, th...

 FDA warning letters, the FDA sometimes advises the employment of a consultant in order to remedy the deficiencies addressed. But what are the requirements regarding such consultants from a GMP perspective? The FDA's CGMP guidelines provide instructions on this in 21 CFR 211.34: "Consultants advising on the manufacture, processing, packing, or holding of drug products shall have sufficient education, training, and experience, or any combination thereof, to advise on the subject for which they are retained. Records shall be maintained stating the name, address, and qualifications of any consultants and the type of service they provide." Fortunately, the EU GMP Guideline Part I includes almost the same requirements in chapters 2.23 and 2.24: Consultants should have adaquate education, training and experience, or any combination thereof, to advise on the subject, for which they are retained. Records should be maintained stating the name, adress, qualification, and type of se...

The ICH Secretariat announced the publication of the updated Q9(R1) Annex 1- Q8/Q9/Q10 Questions & Answers (R5) related to ICH Q9(R1) Quality Risk Management (QRM). The ICH Assembly approved the updated Annex on 30 October 2024. The Q&As have been updated by removing outdated text and rephrasing the Q&As considered in view of the implementation of ICH Q8, Q9 and Q10, with minor additions to address minor content gaps in the document. Furthermore, minor edits have been made to improve the readability of the document. Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the ICH Q8(R2), Q9 and Q10 Guidelines have resulted in the need for some clarification. The Questions and Answers developed by the Quality Implementation Working Group (IWG) are intended to facilitate the implementation of the Guidelines, by clarifying key issues. Besides the core topics Pharmaceutical Development, Quality Risk Management, Pharmace...

The topic of "risk" appears 16 times in FDA's Process Validation Guidance. Annex 15 to the EU GMP Guidance clearly states: "As part of a quality risk management system, decisions on the scope and extent of qualification and validation should be based on a justified and documented risk assessment of the facilities, equipment, utilities and processes." In their guidance, the FDA also recommends a risk-based approach to determining critical parameters. But how should inadequately validated processes be handled in retrospect? The FDA comments on this in a recent Warning Letter. The FDA criticized Outin Futures Corp. for failing to validate the homogeneity of the API in an intermediate for its over-the-counter (OTC) drugs. Deficiencies in the cleaning validation were also criticized. In response, Outin sent a validation protocol to the FDA to demonstrate the homogeneity of the active ingredient. A validation protocol for cleaning validation was also included in the r...

The European Shortages Monitoring Platform (ESMP) has gone live with a core set of functionalities. Using this first version of the ESMP, marketing authorisation holders (MAHs) can now submit data to routinely report shortages of centrally authorised medicines. This marks the start of a transition period that will end on 2 February 2025, when the use of the platform becomes mandatory. Marketing authorisation holders can now use the platform to report shortages of centrally authorised human medicines. The launch of the functionality for routinely reporting shortages will be followed by the release of the second version of the ESMP in February 2025 with the full scope of functionalities for MAHs and national competent authorities (NCAs). By then MAHs and NCAs will also be able to submit data on the supply, demand and availability of centrally and nationally authorised medicines during crises and preparedness actions led by EMA's Executive Steering Group on Shortages and Safety of Med...

The trend in the pharmaceutical industry is also moving towards cloud computing. Financial but also organizational advantages speak for the cloud. At the same time, however, potential dangers and regulatory restrictions should also be taken into account. Nine experts from the pharmaceutical industry and regulatory authorities answer a comprehensive catalog of questions from the following GxP-relevant topics: Basics of Cloud Computing Technology Regulations and Expectations of Inspectors Customer-Supplier-Relationship Requirements for Cloud Service Providers (CSP) Requirements for Supplier Evaluation and Supplier Audits Requirements for Qualification / Validation The following question is one of a series of questions that we will publish in further GMP News articles on this site in the coming weeks If quality-related services are outsourced by the pharmaceutical company to third parties, the contractors must be assessed for their competence and suitability; this assessment must be avail...

In October 2024, the IPEC (International Pharmaceutical Excipients Council Europe (IPEC Europe) asbl) announced on its website the new version 3 of its GDP guide  'Good Distribution Practices Guide for Pharmaceutical Excipients' . The document is currently only available in the IPEC member area. The updated guide is to be published after a period of three months (probably at the beginning of 2025). It can be assumed that this will be available as usual under the 'Resources' section in the 'Guidelines' area of the IPEC website. You can currently view a summary and table of contents of the revised guide. The table of contents of the new version is as follows: 1 INTRODUCTION    1.1 Purpose    1.2 Scope     1.3 Principles Adopted 2 PHARMACEUTICAL GRADE EXCIPIENTS 3 GOOD DISTRIBUTION ACTIVIES FOR PHARMACEUTICAL EXCIPIENTS Table 1 Matrix of Applicability Table 2 Applicability for Supply Chain Activities     1. Quality Management ...

Torn batch production records were found in plastic bags on the rooftop. These included missing batch production records, which allegedly could not be found during an FDA inspection. Furthermore, duplicate, incomplete batch records with the same batch numbers and issuance dates as the batch records presented during the inspection were found among the torn records. Batch records were "retrospectively prepared" in order to present them to the inspectors. Unfortunately, it happens again and again that pharmaceutical companies do not archive their documentation but discard it, a violation of basic GMP requirements. Occasionally this is discovered during inspections. The number of unreported cases is certainly higher. Now Unexo Lifesciences, an Indian manufacturer, has been caught by the FDA. Access here US FDA WL

On 29 October 2024, the U.S. Food and Drug Administration (FDA) has published a Warning Letter dated 21 October 2024. The document goes back to an inspection performed earlier this year at a manufacturer of over-the-counter (OTC) topical drug products in North Carolina. The Warning Letter summarizes a couple of significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals Condition of the Laboratory The initial observation already says a lot about the condition of the buildings and facilities, especially the laboratory. The authority writes: "Our investigator observed pest activity in your raw material storage area, and evidence of water leaks and missing ceiling tiles in your drug manufacturing area. In addition, our investigator observed that your quality control (QC) laboratory was used by employees for meal preparation, dishwashing, and storage of soiled employee garments." This misuse of the laboratory environment poses a h...