Pharma Talk

corrective action and preventive action (CAPA) according to your procedure until after FDA cited your firm. Bell International Laboratories, USA (February 2024) "Your quality unit (QU) lacked adequate control over your over-the-counter (OTC) drug manufacturing operations and failed to ensure that you had adequate procedures. For example, your QU failed to ensure: - Adequate investigations into non-conformances (21 CFR 211.192). - Adequate investigations into complaints (21 CFR 211.198(a))." "Your response is inadequate because you did not address how you will ensure that investigations contain adequate root cause determinations, corrective action and preventive action (CAPA), and effectiveness checks". Sichuan Deebio Pharmaceutical, China (February 2024) "Your firm's quality unit (QU) failed to (...) extend product quality complaint investigations to other batches or APIs potentially associated with the root cause, failure, or deviation". Cosmetic Spec

The USP has issued a Notice of Intent to Revise General Chapter <621> Chromatography. Based on stakeholder feedback, updates will be made to the sections on System Sensitivity and Peak Symmetry to improve clarity and applicability. The Notice, dated September 25, 2024, states: "Chemical Analysis Expert Committee is canceling the PF 49(6) proposal and will publish an amended proposal in PF 51(2) with a targeted official date of June 1, 2026, to address comments received on the following sections. This upcoming revision will further clarify the use and applicability of the two sections." For  more details  

The significant violations of CGMP regulations for finished products, which are mentioned in the Warning Letter, are listed as follows: "Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a))." "Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b))." "Your firm failed to establish the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e))." Especially, the second observation mentioned in the Warning Letter is related to the lack of Laboratory Data Integrity. It is listed as an example that the firm failed to have "appropriate controls to assure

From 6 February to 15 March 2024, the FDA inspected the pharmaceutical manufacturing facility of Wittman Pharma, Inc. in Brooksville and found violations of Current Good Manufacturing Practices (CGMP) for finished drug products, which led to a number of quality risks for the manufactured products. The subsequent 483 letter from the FDA was inadequately responded to, so that the FDA now published the following Warning Letter. Number of deficiencies In summary, the following deficiencies were listed in the FDA's Warning Letter : 1. Failures in quality control (in accordance with 21 CFR 211.22) Quality assurance/quality control (QU) did not ensure that the products met the required identity, strength, quality and purity standards. Drug batches were released without proper product testing and, for example, in the case of colour-changed tablets, management bypassed QU responsibilities and downgraded deviation classifications to ‘minor’ without adequate investigation to eliminate the nee

In a recent Warning Letter, the FDA has criticised inadequate equipment qualification and deficiencies in process validation. What does the FDA require? The deficiencies at the inspected company also occurred during past FDA inspections in 2014 and 2016. The company responded to the 483 deficiency report by stating that they will validate the processes used to manufacture all future medicinal products. They also said they were discussing internally revisions to calibration and preventive maintenance practices. This was not enough for the FDA, in particular a retrospective assessment of the potential impact was requested. Furthermore, the FDA still expects: Corrective actions to better ensure ongoing management oversight throughout the manufacturing cycle of all medicinal products. A data-driven and science-based programme that identifies causes of process variability and ensures that manufacturing (including packaging) meets appropriate parameters and quality standards. This includes -

When planning new purified water (PW) systems, the question arises as part of the risk analysis or later, when drawing up the qualification and sampling plans as to whether endotoxins should be tested for. According to the specifications of the pharmacopoeias (e.g. USP or Ph.Eur.), endotoxin testing is not required for Purified Water. The endotoxin content is not a test parameter in the valid pharmacopoeia monographs for purified water. However, if purified water is used as feed water for distillation plants and pure steam generators for the production of WFI (water for injection) or pure steam, it may be useful to test for endotoxins as part of the qualification process. This is due to the fact that distillation systems and pure steam generators - depending on the technology and manufacturer - can only achieve a reduction of 3 to 6 log levels of endotoxins. For the validation of the water system, the performance of the purification process must be proven. This applies to all quality p

Swiss medic took new step towards its own database to post GMP/CDP certificate  The Swiss health authority Swissmedic launched the SwissGMDP Database, similar to the European Medicine Agency's (EMA) EudraGMDP database. It lists the GMP and GDP certificates of all companies in Switzerland with a valid establishment licence issued by Swissmedic. The certificates in the SwissGMDP database include all authorised activities, i.e. unlike EudraGMDP, the GDP activities and Switzerland-specific GMP activities of Swiss companies will also be listed in the certificates. All companies, authorities and individuals can easily view a company's GMP/GDP status using the SwissGMDP database. Furthermore, SwissGMDP enables a query of all establishment licence holders with a valid establishment license including their sites and licenced operations and will replace the previous table of establishment licence holders. The SwissGMDP database offers: Public access for all users; Free-of-charge access t

Additional substantive information I. Background The FDA uses the term ‘peptide’ in this notice to refer to alpha-amino acid polymers consisting of 40 or fewer amino acids. Peptides can be isolated from natural sources or produced synthetically or by recombinant expression in a host cell. Peptides isolated from recombinant sources (i.e., genetically modified) prokaryotic or eukaryotic host cells by cell culture/fermentation processes are referred to as recombinant peptides (rPeptides). The FDA describes at this point: HCPs are process-derived impurities from the host cell that copurify with the recombinant peptide of interest and may be present in the final drug product. HCPs are characterised and routinely well controlled during the manufacture of the peptide product. The types and amounts of HCPs in a product depend on many parameters, including differences in the substrate of the expression cells, culture conditions, purification procedure and between different facilities. Therefore

The U.S. Food and Drug Administration (FDA) issued a Warning Letter dated 03 September 2024 to a Canadian over-the-counter (OTC) product manufacturer. The letter follows an inspection conducted in April 2024, discovering multiple violations of Current Good Manufacturing Practices (CGMP). Key Findings Key findings of the FDA include:  Failure to Perform Identity Testing on Components: The company did not adequately perform identity testing for all incoming components used in drug manufacturing. The firm's failure to conduct these tests raises concerns about the potential for contamination or mislabeling of their products. The company also relied on certificates of analysis (COA) from suppliers without verifying the identity of the components themselves, which further compounded the issue. Inadequate Validation of Manufacturing Processes: Another significant issue identified by the FDA was the company's failure to adequately validate its manufacturing processes. The inspection re