The drugmaker asked the FDA to extend the nitrosamine risk assessment period

Some pharmaceutical companies want the U.S. FDA to delay its nitrosamine risk assessment deadline (March 1, 2021) and ask for more time to evaluate new and approved products.
for a variety of reasons.
, for example, Perrigo said that the internal testing site was affected by a home order caused by the new Crown (COVID-19) pandemic, limiting the site's ability to conduct testing and risk assessment.
addition, these assessments may encounter "serious compliance challenges" due to the lack of the necessary equipment to detect and quantify nitrosamine impurity limits.
" comments are feedback to the FDA's guidelines for the immediate entry into force of the Human Drug Control of Nitrosamine Impurities in Central Asia.
guidelines recommend that drugmakers assess the risk of nitrosamine impurities associated with all chemical synthesis APIs and all approved and marketed drugs containing these APIs or other nitrosamine sources by March 1, 2021.
perrigo and Pfizer have recently submitted feedback on the guidelines to the FDA.
urged the FDA to meet a deadline with the European Union.
, the European Union regulator, announced in August that it had extended the deadline for risk assessment of nitrosamine-related chemicals from October 1, 2020 to March 31, 2021 due to the COVID-19 pandemic.
said, "It is important to coordinate dates in different regulatory jurisdictions, so we ask the FDA to accept the current EXTENDed risk assessment time limit in the European Union."
"Perrigo said the current deadline was "unsoable".
Perrigo noted that a large number of risk assessments were required and could not be completed by that deadline.
these assessments cover "thousands of inventory units (SKUs) that approve or sell products in the United States and contain hundreds of unique materials, all of which require nitrosamine risk information and assessment."
complicated by the challenges posed by the "1990s" pandemic and the inability to speed up detection.
Perrigo noted that other regulators, such as EMA, Health Canada and Israel Health, had extended the risk assessment due to implementation challenges.
urged the FDA to extend the risk assessment deadline until September 2021.
the scope of the assessment, the two drugmakers also want the FDA to clarify whether the scope of the test includes only seven nitrosamines.
, the FDA identified seven nitrosamine impurities that could theoretically be present in drugs: NDMA, NDEA, NMBA, NIPEA, NDIPA, NDBA, and NMPA.
guidelines further indicate that five types have been detected in APIs or medicines: NDMA, NDEA, NMBA, NIPEA, and NMPA.
said the guidelines "provide a list of seven nitrosamines that can be interpreted as falling within the scope of assessment."
please clarify whether only the seven nitrosamines listed are under the scope of assessment.
" Perrigo wants the FDA to clarify more clearly what impurities need to be studied.
Perrigo is concerned that the list of seven nitrosamines could be mistaken by FDA reviewers for review lists or limit the assessment of other nitrosamine risks.
FDA should make it clear that the specific nitrosamines identified are based on specific risk factors and that the list of seven nitrosamines is not entire and does not exclude other nitrosamines.
" lack of laboratory equipment, and at a recent GRx-Biosims web conference hosted by AAM, Martin Ehlert, Apotex's vice president of research and development, acknowledged the challenge of completing risk assessments by the current deadline.
Ehlert said many AAM members have "hundreds of approved products that are difficult to obtain by March 1."
one of the challenges, he says, is getting risk assessment information from suppliers of accessories.
API vendors traditionally provide information about nitrosamine risks, accessories manufacturers are unable to do so.
drugmakers often have to use "good default assumptions" when calculating nitrosamine risk for inactive ingredients.
another challenge, says Ehlert, is finding the necessary analytical equipment to detect nitrosamine impurities.
, for example, FDA guidelines state that NDEA levels of nitrosamines per day must not exceed 26.5 ng/day.
In order to accurately detect impurities within this specification, chromatography separation is required, combined with well-used high-resolution, high-sensitivity mass spectrometers, such as orbitrap mass spectrometers," he said.
are unusual in the lab for many industry members, and even if they do, the number is very limited.
" Ehlert further noted that nitrosamines are "ubiquitous" compounds that are common in the environment, especially in raw materials, but do not pose a safety hazard most of the time.
pointed out that 25% of all pharmaceutical ingredients have mid-amines or schoamines that form nitrosamines , and in most cases these compounds are very low in the drug .
"The more you see, the more nitrosamines you'll find."
"s Lin-Pepper