Questions and answers on Full declaration HMV4

A statement must be included in the medicinal product information texts even where sodium content <1mmol (23 mg) (see the corresponding entry in Annex 3a TPLRO). Therefore, since any content of sodium necessitates the inclusion of a warning, sodium is always considered to be an excipient of particular interest during oral or parenteral administration, regardless of the quantity, i.e. the threshold for sodium is effectively zero.

Hence the need for the quantitative declaration in the Information for healthcare professionals and the qualitative declaration on the packaging materials.

In such cases either the maximum content should be declared, or the sodium content stated as a range.

Example of declaration as maximum content:

According to Ph.Eur., croscarmellose sodium has a substitution grade of up to 0.85 (i.e. on average it contains a maximum of 0.85 O-carboxymethyl groups per glucose unit). If all O-carboxymethyl groups of the polymer are present as sodium salt, then – based on the resulting molecular formula, e.g. C₇₇₀H₁₀₈₅O₆₇₀Na₈₅ calculated for 100 monomer units, of which 85 are simply substituted [C₈H₁₁O₇Na] and 15 are unsubstituted [C₆H₁₀O₅]), – a maximum sodium content of approximately 9% results.

Example of declaration as a range:
According to Ph.Eur., carboxymethyl starch sodium (type A) contains 2.8-4.2% sodium.

Alternatively, if sodium hydroxide is used only in very small quantities to adjust the pH value of liquid pharmaceutical forms, the quantitative information on sodium content may be omitted and the additional information “(for pH adjustment)” included instead.

The exact sodium-containing excipients should preferably be stated individually. If several excipients containing sodium are included in the medicinal product, a blanket statement is possible (e.g. "contains sodium compounds").

No, the full active substance declaration, e.g. "xy as xy sodium" is sufficient in this case.

In this case, there are several correct options for the declaration on the folding cartons:

One variant would be similar to the suggested option, "Fragrance (contains allergen 1, allergen 2 and allergen 3)". Alternatively, only the allergens contained in the product can simply be listed under the composition, or a sentence can be added at the end of the composition, e.g. "contains a fragrance with allergen 1, allergen 2 and allergen 3."

The warnings in Annex 3 a TPLRO apply to the use of the corresponding substances as excipients. If sodium, potassium, glucose or soya bean oil are included as active substances and if corresponding entries are already included in the Information for healthcare professionals, then this is usually sufficient.

Yes, this is possible.

In these cases the statements should be included on the packaging, in accordance with sections 1.1 and 1.4 of Annex 3 of the TPLRO.

Co-marketing medicinal products are a special case here, i.e. the modifications under the revised TPLRO are not linked to renewal. As soon as the modifications under the revised TPLRO have been implemented for the basic product, the corresponding changes must be implemented by means of a type IA / IB variation (the application type A.101 should be used for this purpose).

Inclusion in ongoing procedures according to the old legislation is not possible as a rule. An exception may be made only for new applications, in which case the following should be observed:

• The integration of the new requirements according to the revised TPLRO can lead to an additional loop if corrections are required or questions arise (i.e. risk of a delayed official decision on first authorisation).
• For the additional work required for integrating the new requirements according to the revised TPLRO, a fee is charged when the new medicinal product is authorised.
• The applicant is solely responsible for submitting the application. Swissmedic does not refer to this option either in the "List of Questions" or in the Preliminary decision of approval.

No.

No, a general declaration as “printing ink” is sufficient, as there is no direct contact with the skin, and usually no relevant penetration through the plaster material.

No, as in this case the capsule shell forms part of the packaging material and is not administered.

Since 1 July 2020, the revised Annex 3a of the Therapeutic Products Licensing Requirements Ordinance (TPLRO, SR 812.212.22) has applied. This means that, as of this date, the requirements for pharmaceutical excipients of particular interest must be complied with and any applications for variations (also in connection with the full declaration) must be submitted to Swissmedic in accordance with Arts. 21-24 of the Therapeutic Products Ordinance (TPO; SR 812.212.21) in conjunction with TPLRO Art. 22a ff. 
In the case of authorised medicinal products for which adjustments in line with the TPLRO revision as of 1.1.2019 have not yet fallen due, therefore, the revised Annex 3a TPLRO must be taken into account for the future submission of variation A.109. In the case of medicinal products for which variation A.109 has already been completed, an A.100 variation must be submitted where necessary so that the requirements of the Annex revision of 1.7.2020 are implemented. In these cases, there is no transitional period. The procedure outlined here also applies to subsequent revisions of Annex 3a TPLRO.