New FDA Guidance on Residual Solvents

On 24 November 2009, the FDA published the Guidance for Industry "Residual Solvents in Drug Products Marketed in the United States".

The backdrop for this topical FDA Guidance is the new USP Chapter <467> Residual Solvents, which came into force on 1 July 2008, which replaced the former Chapter <467> Organic Volatile Impurities.

On this subject, the FDA now makes the following recommendations:

1. On medicinal products that are listed in the pharmacopoeia and for which a marketing authorisation (NDA or ANDA) has been granted:

The General Chapter <467> requires that residual solvents in finished products be tested. Instead, the active pharmaceutical ingredients and excipients used can be tested for residual solvents. In this guideline, the FDA clarifies that the finished product does not have to be tested for residual solvents if the limits for residual solvents in all starting materials used are not exceeded.

Besides, the FDA will accept test methods other than the methods mentioned in <467> provided that these methods have been described in sufficient detail, validated and will be verified during routine operation.

Furthermore, the FDA points out that changes to test methods can be submitted via the Annual Report.

For NDAs and ANDAs already submitted to the FDA, amendments regarding the implementation of Chapter <467> can still be handed in. However, this should be done as soon as possible!

2. For finished drug products that are listed in the pharmacopoeia and for which no NDA or ANDA marketing authorisation exists:

Here, too, the regulations of General Chapter <467> apply and here, too, other analytical test methods can be used under the conditions described above.

3. On NDA or ANDA finished products not described in the pharmacopoeia:

The General Chapter <467> does not apply to these cases. Here, the relevant regulations are those of the ICH Guideline Q3C Impurities: Residual Solvents.

The complete document can be found here:

Dr Günter Brendelberger
On behalf of the European Compliance Academy (ECA)

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