New FDA Requirements for the Development of Herbal Medicinal Products

The previous FDA guideline for herbal medicinal products from 2004 is supposed to be replaced by a new version. In August 2015, the FDA has presented the draft of the revised guideline. Find out more about the FDA Guideline Botanical Drug Development.,Z-RAM_n.html

In August 2015, the FDA has published a draft of the guideline “Botanical Drug Development”. This guideline addresses issues arising from the particular nature of herbal medicinal products. After its finalization it is supposed to replace the previous guideline from June 2004.

The general approach in the development of herbal medicinal products remained unchanged since 2004. But due to the better understanding of herbal medicinal products and the experience gained during the review of the approval documents for herbals (NDAs/New Drug Applications and INDs/Investigational New Drug Applications), specific recommendations could be adjusted. Still, new sections will be supplemented to better address the late development phase.

The draft guideline also covers the following topics:

  • General, regulatory requirements
  • INDs for phase 1-3 clinical trials
  • NDAs for herbal medicinal products

For further information please see the full FDA document ‘Botanical Drug Development’.

Genotoxic impurities: the new ICH M7 addendum to calculation of compound-specific acceptable intakes

Genotoxic impurities: the new ICH M7 addendum to calculation of compound-specific acceptable intakes

The draft for a guideline ICH M7(R1) published recently supplements the ICH-M7 guideline published last year. Read more about the calculation of compound-specific acceptable intakes of genotoxic impurities.

The final document of the ICH-Guideline M7 was published in June 2014. It describes the procedure for evaluating the genotoxic potential of impurities in medicinal products (see also our news Final ICH M7 Guideline on Genotoxic Impurities published dated 23 July 2014).

An important approach to the risk characterisation of impurities is the TTC concept (TTC = threshold of toxicological concern). According to this approach the exposure to a mutagenic impurity having the concentration of 1.5 µg per adult person per day is considered to be associated with a negligible risk. It can be used as default evaluation approach to most pharmaceuticals for long-term treatment (> 10 years) and where no carcinogenicity data are available (classes 2 and 3). According to ICH M7 the TTC concept should not be used where sufficient carcinogenicity data exist. Instead the data should be used to calculate or derive compound-specific acceptable intakes.

Now the ICH published an addendum to Guideline M7 with the title “Application of the principles of the ICH M7 Guideline to calculation of compound-specific acceptable intakes” (“Addendum to ICH M7”; short name “M7(R1)”).

This addendum describes the basis for calculating the acceptable intakes for 15 substances in total that are common and widespread in pharmaceutical manufacturing. These substances are known to have mutagenic/carcinogenic potential (ICH M7(R1) contains comprehensive references on the toxicology of these substances). The calculations of the AI (acceptable intake) or PDE (permitted daily exposure) values are partly based on a linear extrapolation from the TD50 values as well as on toxicological data on the non-linear dose-response curve of the relevant substances.

ICH M7(R1) has the status of a draft consensus guideline (step 2 document). The draft guideline was published on the EMA “Scientific Guidelines” site as step 2b document on 4 August 2015 for consultation (deadline for comments: 3 February 2016)