In the European Pharmacopoeia (Ph. Eur.), the monograph 2153 defines excipient-free pellets for homeopathic preparations as solid preparations made from sucrose, lactose, or other suitable excipients. 

These excipient-free pellets form the basis for the well-known globules. The Ph. Eur. distinguishes between two different types of globules:

• Impregnated homeopathic pellets (Globules – Granula homoeopathica imbuta) Ph. Eur. Monograph 2079
• Coated homeopathic pellets (Globuli velati – Granula homoeopathica velata) Ph. Eur. Monograph 2786

The impregnated homeopathic pellets are the excipient-free variant, which are impregnated with one or more liquid homeopathic preparations.

In contrast, the excipient-free pellets in coated homeopathic globules are coated with a sucrose syrup in which the homeopathic preparations are contained (dissolved). Independently, other triturations (for example, mineral active substances triturated with milk sugar) can also be incorporated.

Both groups are common in that they are intended for sublingual or oral use. Even though the water activity of the two product groups is likely to be very low (low water content, high sugar content), the Ph. Eur. requires a microbiological quality control for globules. The acceptance criteria are identical for the excipient-free pellets and both variants of globules.

The following acceptance criteria are required in the respective monographs:

• Total aerobic microbial count (according to Ph. Eur. 2.6.12): 102 CFU/g
• Total yeast and mold count: (according to Ph. Eur. 2.6.12): 101 CFU/g
• Pseudomonas aeruginosa (according to Ph. Eur. 2.6.13): Absent
• Staphylococcus aureus (according to Ph. Eur. 2.6.13): Absent

In order to comply with the Ph. Eur. requirements, globules also require microbiological testing. As a microbiological laboratory specializing in the testing of pharmaceuticals, the BAV Institute can gladly assist you with this.

In the European Pharmacopoeia (Ph.Eur.), the monograph 2153 defines excipient pellets for homeopathic preparations as solid preparations made from sucrose, lactose, or other suitable excipients.

These excipient pellets form the basis for the well-known globules. The Ph. Eur distinguishes between two different types of globules:

• Impregnated homeopathic pellets (Globuli – Granula homoeopathica imbuta) Ph.Eur. Monograph 2079
• Coated homeopathic pellets (Globuli velati – Granula homoeopathica velata) Ph.Eur. Monograph 2786

Impregnated homeopathic pellets are excipient variants impregnated with one or more liquid homeopathic preparations.

In contrast, the excipient pellets for coated homeopathic pellets are covered with a sucrose syrup in which the homeopathic preparations are contained (dissolved). Independently, other triturations (for example, mineral-effective substances with lactose powdered) can also be incorporated.

Both groups are intended for sublingual or oral use. Even though the water activity of both product groups is likely to be very low (low water content, high sugar content), the Ph.Eur. provides for a microbiological purity test for globules. The acceptance criteria are identical for the excipient pellets as well as for the two variants of globules.

The following acceptance criteria are required in the respective monographs.

• Total aerobic microbial count (according to Ph.Eur. 2.6.12): 102 CFU/g
• Total yeast and mold count (according to Ph.Eur. 2.6.12): 101 CFU/g
• Pseudomonas aeruginosa (according to Ph.Eur. 2.6.13): Absent
• Staphylococcus aureus (according to Ph.Eur. 2.6.13): Absent

Therefore, to comply with the Ph.Eur. requirements, globules also need a microbiological test. As a microbiological laboratory specialized in the testing of pharmaceuticals, the BAV Institute would be pleased to support you.

Lecture "Statutory Reporting Obligations for Microbiological Self-Inspections"

A technical guideline (EURL Lm TECHNICAL GUIDANCE DOCUMENT for conducting shelf-life studies on Listeria monocytogenes in ready-to-eat foods) was published by the EU Commission, which describes the procedure for conducting challenge tests with Listeria monocytogenes.

Some important aspects of it:

• The conditions during the shelf life must be considered (including foreseeable changes compared to the information on the packaging, such as refrigerator temperatures in households).
• A mixture of at least 2 strains of Listeria monocytogenes should be used for contamination. Not only laboratory strains should be used, but also strains isolated from similar foods or even from the respective food company.
• The food should be contaminated at the beginning of the challenge test with a germ concentration of about 100 CFU/g.
• DIN EN ISO 20976-1:2019-09 (https://www.beuth.de/de/norm/din-en-iso-20976-1/297296778)

These tests provide a statement about whether Listeria monocytogenes can multiply in the food. This statement is very important for manufacturers of ready-to-eat, perishable foods for two reasons:

1. As part of their duty of care, every food business operator must ensure that their products do not pose a health risk until the end of shelf life. Because Listeria monocytogenes is widely distributed in the environment, contamination with these bacteria cannot be completely ruled out in the production of many foods. It is therefore important to know whether Listeria monocytogenes can multiply in these foods during their shelf life. If the growth of Listeria monocytogenes is favored, the hygiene and safety levels during production must be even higher.
2. The Regulation (EC) 2073/2005 on microbiological criteria requires in Annex I, Chapter 1 that certain food safety criteria for Listeria monocytogenes are met. Ready-to-eat foods that favor the multiplication of Listeria monocytogenes must not show Listeria monocytogenes presence in 5 samples of a batch, each 25g, at the production level (Criterion 1.2 in Chapter 1 of Annex I). If this is not complied with or this food safety criterion is exceeded, and the ready-to-eat food is already on the market, a public recall is threatened.

However, if ready-to-eat food does NOT favor the multiplication of Listeria monocytogenes, it is sufficient according to this regulation that the food safety criterion of 100 CFU/g is not exceeded in 5 sub-samples of the batch at the production level.

For ready-to-eat foods with a pH value of ≤ 4.4 or an aw value of ≤ 0.92, the food safety criterion of 100 CFU/g applies directly at the production level. The same applies if the ready-to-eat products have a pH of ≤ 5.0 and an aw of ≤ 0.94 or have a shelf life of less than 5 days. This is noted in the footnotes of Chapter 1 of Annex I of Regulation (EC) 2073/2005, as it is assumed in these cases that Listeria monocytogenes does not grow under these conditions, or the food safety criterion of 100 CFU/g for Listeria monocytogenes in ready-to-eat foods at the trading level is not exceeded.

The food business operator must provide this proof of the growth potential of Listeria monocytogenes in ready-to-eat foods to the authority. Otherwise, in case of doubt, the authority must assume that the stricter criteria for Listeria monocytogenes ("not detectable in 25g in each of 5 sub-samples of the batch") must be complied with for the products.

To provide this proof to the authority, contamination or challenge tests are required for many perishable foods unless the ready-to-eat food meets the above-mentioned chemical-physical properties or has a shelf life of less than 5 days.

In these tests, the food product is contaminated with specific bacteria. In this case, it is conducted with various strains of Listeria monocytogenes. Subsequently, the product is stored over its shelf life under real conditions and regularly tested for these bacteria.