GOVERNMENT OF MAHARASHTRA

Commissioner
Food and Drugs Administration
(M.S.)
341, Banda-Kurla Complex,
8, ai-AI HZT, Opposite of RBI Buildings,
Bandra (E), Mumbai-400 051
FDA MAHARASHTRA

a - 00 04. Tel:022-26592362-65,
Email: ichq.fda-mah@nic.in &hq10drug@gmail.com
No. NDMAS17 -2021/100 by email Date 08/12/2021

ogl/221
To
All Manufacturers (API & formulations),
Located in Maharashtra.

Subject Detection of Nitrosamine Impurities in Certain DrugS- reg

Refn: 1. Letter of Drugs Controller General (India), CDSCO New Delhi. F. No. 12-
03/19-DC (Safety-007) Dt. 23/09/2019.
2. Letter of Drugs Controller General (India), CDSC New Delhi. F. No. 12-
03/19-DC (Safety-007) Dt. 18/02/2020.
3. WHO information note Ref.
EMP/RHT/Information Note
dated 20 Nov. 2019

Sir/Madam,
This is to inform you that the Drugs Controller General (India), CDSCO New Delhi vide
above referred letter informed that nitrosamine group impurities like N-
nitrosodiethylamine (NDEA), N-nitrosodiisopropylamine (NDIPA), N-
nitrosoethylisopropylamine (NEIPA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA)
etc are detected in Angiotensin ll
Receptor Blocker (ARB) analogue compounds commonly
referred to as the sartans and also detected in ranitidine, pioglitazone etc.

NDMA is classified as probable human carcinogen.

Regulatory Authorities of various
countries have taken precautionary measures/issued advisory in this regard.
WHO has also published information Note dated
20.11.2019. In the said Information
Note' WHO has mentioned the details of nitrosamine
impurity, toxicity, test methods,
regulatory action taken in various countries etc.

As per the note of

WHO, the low levels at which the nitrosamine impurities occur
creates challenges for testing. To assist in the testing of samples the USFDA has published
several test methods that may be considered when
APl or finished formulations.
determining nitrosamine content in the

In the view of above the

Drug Controller General (India) has directed all the
manufacturers to verify their products and take
appropriate measures to ensure patient
safety.

EINew folder 2019Aushadh kharedi

samitiNDMA Letter to mígHQ (1).docx
 Considering the above facts and directions all the manufacturers of above
mentioned drugs (API and formulations) located in Maharashtra are hereby directed as
follows:
A. All API manufacturers shall verify their products and carry out the risk analysis to
ascertain their products are free from these impurities or impurities are within
permissible limit and submit the data of risk analysis and their findings to Licensing
Authority (Joint Commissioner, Drugs) concerned within 3 (three) months.

B. All API manufacturers shall test each batch of their products to ascertain their
products are free from these impurities or impurities are within permissible limit.

C. All formulation manufacturers of these drugs shall ascertain that the raw material
used for manufacturing of these formulations are free from these impurities or
impurities are within permissible limit by testing of initial 3 (three) batches of each
raw material supplier and subsequently by Certificate of Analysis from
manufacturer/supplier and by periodic testing.

D. All formulation manufacturers of these drugs are further directed to test initial 3
(three) batches of each formulation to ascertain that the formulations are free from
these impurities or impurities are within permissible limit and subsequently by
periodic testing.

All the manufactures shall ascertain that their products are free from these
impurities or impurities are within permissible limit and safe for patients. Further it may be
noted that all manufacturers are required to maintain record and make such record
available as and when required as per provisions of the Drugs and Cosmetics Act 1940 and
rules thereunder.

Parimal Singh IAs

Commissioner
Food Drug Administration, M.S.

CC to
1. The Secretary, Medical Education and Drugs Department, Mantralay, Mumbai for
information.
2. All Joint Commissioner (Drugs) and Licensing Authority, FDA, Maharashtra for
necessary action.