Bachem’s Post

❗ ❗ ❗ #RegulatoryWatch: #impurities #nitrosaminedrugsubstancerelatedimpurities #NDSRIs #EDQM #Swissmedic #OMCL First OMCL analytical procedures for determination of nitrosamine drug substance-related impurities (NDSRIs) and intermediate-related contaminants published The General European OMCL Network initiated the development of procedures for detecting N-nitrosamine contaminants in 2018. These procedures have been made available to the public on EDQM website. Subsequently, upon receiving reports of NDSRI contamination in medicinal products, the OMCLs started working on creating internal procedures to detect these impurities. As a result of their efforts, six additional procedures have been published on the EDQM website. In one particular case involving sitagliptin tablets and sitagliptin/metformin tablets, the contaminant originates from an active pharmaceutical ingredient intermediate. The two laboratories responsible for developing these six procedures were the German OMCL at the Landesamt für Gesundheit und Lebensmittelsicherheit in Bavaria and the OMCL at Swissmedic. The molecules are: ✅ 7-Nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (NTTP) in sitagliptin and sitagliptin/metformin tablets; ✅ N-nitroso ramipril in ramipril tablets; N-nitroso fluoxetine in fluoxetine tablets; ✅ N-nitroso sertraline in sertraline preparations; ✅ N-nitroso duloxetine in duloxetine preparations; and ✅ N-nitroso hydrochlorothiazide in various preparations. PS: analytical techniques used to detect these contaminants are GC-MS/MS in the case of NTTP and LC-MS/MS in the other five cases. 📍 Below the link to the EDQM webpage https://lnkd.in/ePfZwnHt

📘 The #updated IPEC Federation Position Paper on " The Role of Excipients in Determining N-#Nitrosamine Risks for Drug Products " is now available. 💬 The #positionpaper describes #IPEC 's position on the role of excipients when conducting nitrosamine risk assessments for drug products. 🔁 This revision highlights the key messages associated with #excipients and how they feature in the ongoing debates on the #nitrosamines topic and has been updated to reflect current perspectives. 📌 Read the Position paper: https://lnkd.in/eZNFsX6K

For today's #ProductFocus, we're looking at our Benzalkonium Chloride #ReferenceStandard. Benzalkonium Chlorides (BACs) are a mixture of alkylbenzylammonium chloride. The mode of action of BACs involves the perturbation and disruption of the membrane bilayers by the alkyl chains and disruption of charge distribution of the membrane by the charged nitrogen. As such they are strong antimicrobial preservatives for many consumer products and have a very broad application spectrum. Explore now: https://okt.to/VOUEX4 #pharma #ScienceForASaferWorld

Last month, the FDA released a new guidance on the “Control of Nitrosamine Impurities in Human Drugs”, updating their 2021 recommendations. The guidance covers: 🔬 Root Causes of Nitrosamine Formation – including small molecule nitrosamines and nitrosamine drug substance-related impurities (NDSRIs) 📊 Control & Mitigation Recommendations – for both APIs and drug products ✔️ Acceptable Intake Limits – with guidance on testing, risk assessment timelines, and necessary regulatory submissions Ready to stay ahead of evolving regulations? Solvias provides rapid nitrosamine screening and development/validation of control methods for small nitrosamines, NDSRIs, and any other genotoxic impurities with unparalleled sensitivity and selectivity. We utilize well-established GC/MS/MS and LC/MS/MS methods which showcase exceptional accuracy, consistently delivering outstanding performance within the low parts-per-billion thresholds mandated by regulatory authorities. Contact us at info@solvias.com to learn more

In August 2023, the #FDA released its guidance on nitrosamine contamination, Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs). This guidance set a November 1, 2023, deadline for risk assessment updates and an August 1, 2025, deadline for all drug manufacturers and market authorization holders to comply fully with the NDSRI limits set. With 30% of approved APIs susceptible to nitrosamine formation, drug makers now are on the clock to correct issues that may arise with current commercial products. Issues with in-development APIs must be addressed before filing. Adare Pharma Solutions' work directly informs a customer’s response to the requirement for a control strategy that keeps the product within the acceptance limits.

𝗖𝗼𝗻𝘁𝗿𝗼𝗹 𝗼𝗳 𝗡𝗶𝘁𝗿𝗼𝘀𝗮𝗺𝗶𝗻𝗲 𝗜𝗺𝗽𝘂𝗿𝗶𝘁𝗶𝗲𝘀 𝗶𝗻 𝗛𝘂𝗺𝗮𝗻 𝗗𝗿𝘂𝗴𝘀 𝗚𝘂𝗶𝗱𝗮𝗻𝗰𝗲 𝗳𝗼𝗿 𝗜𝗻𝗱𝘂𝘀𝘁𝗿𝘆 The second revision of this guidance by FDA is out! Important note in the Preface: "Comments may be submitted at any time for Agency consideration. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to https://lnkd.in/ePsUPEmU. All comments should be identified with the docket number FDA-2020-D-1530 and complete title of the guidance in the request." #nitrosamine #nitrite #pharmaceuticals

Nitrosamines are carcinogenic impurities: generally categorised as small molecule nitrosamines, which can be found in any drug product, or Nitrosamine Drug Substance Related Impurities (NDSRIs) related to specific Active pharmaceutical ingredients (API's)   Discovery of N-Nitrosamines in a drug product can seriously undermine patient trust in a medication, as well as causing product recalls and global drug shortages. LGCs range of Nitrosamine Reference Materials can support your laboratory testing supporting our goal, Science for a safer world. #nitrosamines #referencematerials #laboratory #drugdevelopment #drugdiscovery

#nitrosamines ... Are you attending the upcoming "Updates on Approaches to Acceptable Intakes of Nitrosamine Drug Substance Related Impurities (NDSRIs) and Bioequivalence Assessment for Reformulated Drug Products" workshop co-host by FDA and the Center for Research on Complex Generics (CRCG)?? #nitrosaminas #nitrosamine #nitrosammine #nitrosaminne All the information at the Nitrosamines Exchange: https://lnkd.in/eddB68PC

What is the Regulatory Certainty Strategy for Biosimilars? #biosimilars #drugproducts #marketingauthorization #biotechnologicalmedicines #cofepris #regulatorycertainty https://lnkd.in/eXHd6tJT 

🚨 A publication by Constantine et al. (2024) evaluates log D/pH-specific log Kow and bioconcentration factor (BCF) data for 64 active pharmaceutical ingredients (APIs). The goals were to test, 1) the validity of the current European Medicines Agency (EMA) conservative trigger of log Kow ≥ 3 for conducting, in Phase II of environmental risk assessments (ERA), a bioconcentration study in fish (OECD TG305) and 2) whether testing two dose levels plus a control (involving the use of 200 fish), as per guideline, was always necessary to determine appropriate hazard classification and labelling. 👉 Based on their findings, the authors propose to increase the EMA Phase II BCF testing trigger to log Kow ≥4. The results also indicated a strong correlation between the lipid normalized log-transformed BCF values obtained at low- and high-test concentrations. Overall, this suggests that conducting the study at one dose level is sufficiently conclusive, reducing the number of fish used in the studies and aligning with the 3R principles (refinement, reduction, and replacement). Link: https://lnkd.in/deyNvy8i #EMA #ERA #3Rs #NAMs #BCF #OECD_305