Nitrosamines Published Limits -reference

Limits of Nitrosamines
42

Thanks Sir…

Guidances (Drugs) | FDA

I went through above path, where i found as below

image
image1013×273 22.6 KB

Above published document is 2020.

Is there recent updated guidance’s 2022, available in website?

thanks
Nilesh

43

Hello
EMA updated their list of nitrosamines

EMA/409815/2020 Rev.10

One new N-nitrosamine was added

image
10. Limit based on a class specific threshold of theoretical concern (TTC) of 18 ng/day.

1 Like
44

Hi, @Naiffer_Host.
I checked your AI table. Please confirm the red color figure in the following table.

image
image875×1008 40.6 KB

I found the original TD50 of NMPEA, N-nitroso-piperidine, and NTHP in LCDB. Those are considered the extrapolation from TD50. And please add the N-nitrosodabigatran that @Rafa mentioned.

1 Like
45

@Nilesh The original FDA guide is the one you found in the website. FDA just published an update in the website (see below) but did not update the official guide.

https://www.fda.gov/drugs/drug-safety-and-availability/updates-possible-mitigation-strategies-reduce-risk-nitrosamine-drug-substance-related-impurities

46

Updated. Thanks @Rafa

47

Updated. Thanks @Yosukemino

48

Thanks Naiffer Sir…
Noted all the things as per your provided links…

49

Hi Rafa…

Thanks you very much sharing this information, so far i gone through revision 9, in that N-Nitroso Dabigatran not there…
They might have used default option 18ng/day as per LCDB, correct me if I am wrong…

1 Like
50

@ Yosukemino
Thanks for technical inputs & information…

@ Naiffer sir…
Could you please share this complied AI Limit in PDF format, instead image one?

Complied AI Limit in PDF format will cover all Nitrosamine AI limit with respect to all Regulatory agency (FDA, EMA, ANVISA, Health Canada, NPMA & other Agency)
You have already covered all Nitrosamine AI limit, except N-nitrosodabigatran.

Thanks
Nilesh

51

New NDSRI included in TGA. @Naiffer_Host
Date: 20 July 2022.

N -nitroso-tamsulosin AI 18.0 ng.day.
Nitrosamine impurities in medicines - Information for sponsors and manufacturers | Therapeutic Goods Administration (TGA)

1 Like
52

@Sarada.jena
Thanks for sharing this information…
It’s really great to update/share the Nitrosamine limit…

1 Like
53

@Naiffer_Host @Yosukemino @Sarada.jena @AmandaGuiraldelli

Dear Team,
What is the Default class specific TTC for nitrosamine, as per Health Canada & ANVISA guidance’s?

However, as per USFDA is 26.5ng/day and EMA & TGA is 18.0ng/day

Thanks
Nilesh

1 Like
54

Hi, @Nilesh.

You can find the links to the guidelines in the following post. HC and ANVISA allow 18.0ng/day to use. And details in those guidelines are helpful to understand their policies.

55

@Yosukemino
Great…
Thanks for providing all useful references…

1 Like
56

@Yosukemino @Naiffer_Host @Sarada.jena @AmandaGuiraldelli @jxl

I am just sharing one more reference, China NMPA CDE published a guidance on May 08, 2020 in continuation with above references

https://www.cde.org.cn/main/news/viewInfoCommon/776b663787ec5a60ac744071c3714d5a

Note: China NMPA CDE published a guidance is shared by @jxl . Thanks to him.

57

Hi, @Nilesh.

Thank you for sharing the information. I share the translated document by Google. It does not include a class-specific limit.

化学药物中亚硝胺类杂质研究技术指导原则（试行）(2).pdf (135.9 KB)

58

Thanks @Yosukemino
Yes, It does not include a class-specific limit.

59

No, it does not. ICH M7 is referenced to calculate the limit.

60

@Naiffer_Host Please add N-nitroso-tamsulosin to the table

1 Like