Ph. Eur. chapter 2.8.13: What is changing in pesticide testing for herbal drugs

After a “Request for Revision” for chapter 2.8.13 “Pesticide residues” of the Ph. Eur. was submitted to the EDQM in 2023, the revision has now been provisionally completed and the draft is available for comment in Pharmeuropa. The list of substances has been updated on a data basis, ubiquitous substances are given their own limits for the first time, and the calculation of limits for preparations is becoming more flexible. Entry into force is expected in mid-2027 at the earliest, making now the right time to rethink your own testing strategy.

Why this revision is relevant

Chapter 2.8.13 is the central basis for the pesticide testing of herbal drugs and preparations of herbal drugs in the European Pharmacopoeia. Anyone who manufactures or places on the market herbal medicinal products, extracts or other preparations works with the requirements of this chapter every day: when defining the scope of testing, the limits, and when evaluating analytical results.

The current version (01/2022:20813) remains binding until the revised text is finally adopted. Entry into force of the monograph amendment is expected from mid-2027 at the earliest.

The key changes

Updated Table 2.8.13-1: Substance list based on current residue data

Table 2.8.13-1 has been reassessed on the basis of current residue data. Pesticides that are no longer detected in practice, or only rarely, have been removed; substances that regularly occur in current investigations have been newly added. Highly toxic, persistent substances remain included regardless of their detection status. The limits are based on the 90th percentile of the evaluated residue data.

A notable addition in the draft text: the substance list is expressly intended only as an example of frequently found substances. On a risk basis, the scope of testing can also be reduced.

New Table 2.8.13-2: Dedicated limits for ubiquitous substances

Some substances do not enter a drug through crop protection measures but now occur ubiquitously in soil, air and water. Until now, these so-called ubiquitous or multiple-source substances were assessed as pesticides under Regulation (EC) 396/2005. In practice, this regularly led to an unsatisfactory result: exceedances of limits were reported even though no pesticides had been used.

With the new Table 2.8.13-2, these substances are given their own limits that take their ubiquitous occurrence into account.

ADI concept for preparations: more flexible, but more documentation-intensive

Until now, the calculation of limits for preparations of herbal drugs was tied to the drug-extract ratio (DER). In future, the calculation via the Acceptable Daily Intake (ADI) can be applied independently of the DER. Flowcharts have been added to the chapter for guidance.

Risk assessment: three situations in which it becomes mandatory

A formal risk assessment will in future be required in the following cases:

when reducing the scope of testing compared to Table 2.8.13-1
for non-oral use of the drug or preparation
when no valid ADI is available or the ADI concept is not applicable, for example for CMR substances

What to do now

The revision gives manufacturers more scope in designing their testing strategy. However, this scope does not come without a trade-off: anyone who reduces the scope of testing, applies the ADI concept flexibly or uses a risk assessment needs an analytically and documentarily sound basis.

It makes sense to review the following points already now:

Comparison of the previous scope of testing with the updated Table 2.8.13-1: which substances are newly added, which are dropped?
Checking whether relevant drugs or preparations are affected by ubiquitous substances in accordance with Table 2.8.13-2
Assessment of the limit calculation for preparations with regard to the new ADI option
Adaptation of internal risk assessment processes if a reduction of the testing scope is intended

The chapter will enter into force in mid to late 2027 at the earliest. Anyone who waits until then risks having to implement changes under time pressure.

Conclusion

The revision of chapter 2.8.13 addresses real weaknesses in the previous rules: an outdated substance list, a systematically unsatisfactory treatment of ubiquitous substances and a rigid limit calculation for preparations. The new rules give manufacturers more room for manoeuvre, but in return require more personal responsibility in documentation. Anyone who knows the changes and adapts their testing strategy in good time is well positioned.

How is PhytoLab responding to the revision?

PhytoLab offers a comprehensive analytical package that lets you align your testing strategy with the coming regulatory requirements already today.

With the established Phytrace P2 package as well as various GMP-certified single and group methods, PhytoLab already covers a large part of the substances that will be required in future. In addition, a supplementary screening method is available with which those substances not yet included in the Phytrace P2 package can also be captured. Owing to the tight time frame, this analysis is currently not yet carried out under GMP conditions. At the latest when the revision enters into force, the method will be integrated into the GMP-certified Phytrace P2 package.

Drugs, extracts and tinctures from the medicinal product sector can thus be comprehensively tested in accordance with the requirements of Ph. Eur. 2.8.13 (both the current and the revised version), the USP and the ChP.

The following overview shows the methods required to cover the substances from the revised substance list (Tables 2.8.13-1 and 2.8.13-2):

On request, we will work with you to develop an individual, risk-based testing strategy and support you in your risk analysis with our data base.

Questions about pesticide analysis or about preparing for the revision?

Write to us at sales@phytolab.com. We will help you bring your testing strategy up to date.