A draft of Ph. Eur. chapter 3.1.13. Plastic additives has been published for comment in Pharmeuropa 29.2. The chapter has been revised following the identification of di(2-ethylhexyl)phthalate as a substance of very high concern (SvHC) according to the criteria of Article 57 of regulation (EC) 1907/2006 (REACH). Di(2-ethylhexyl)phthalate is currently used as a plasticiser in most poly(vinyl chloride) (PVC) materials and containers for pharmaceutical use. In this context, the European Pharmacopoeia proposes to include descriptions of the following four additional plasticisers in order to provide manufacturers with alternatives to di(2-ethylhexyl)phthalate (plastic additive 01) whenever possible:

• cyclohexane 1,2-dicarboxylic acid, diisononyl ester (plastic additive 24);  
• butyryl tri-n-hexyl citrate (plastic additive 25);  
• tris(2-ethylhexyl) trimellitate (plastic additive 26);  
• bis(2-ethylhexyl) terephthalate (plastic additive 27).

Furthermore the sections "Definition and General requirements" have been added to provide additional information regarding the quality of plastic additives to be used for materials and containers for pharmaceutical use. To avoid duplicating reference numbers for each substance, it is proposed to delete the plastic material registration numbers (PM RN) from the list of additives.

The changes proposed in this general chapter are to be considered in conjunction with the proposed changes in the following general chapters, which are also published in Pharmeuropa 29.2:

• 3.1.1.1. Materials based on plasticised poly(vinyl chloride) for   containers for human blood and blood components;  
• 3.1.1.2. Materials based on plasticised poly(vinyl chloride) for tubing   used in sets for the transfusion of blood and blood components;  
• 3.1.14. Materials based on plasticised poly(vinyl chloride) for containers   for aqueous solutions for intravenous infusion;  
• 3.2.4. Empty sterile containers of plasticised poly(vinyl chloride) for   human blood and blood components;  
• 3.2.5. Sterile containers of plasticised poly(vinyl chloride) for human   blood containing anticoagulant solution.

Additional proposed changes to 3.1.1.1, 3.1.1.2, 3.1.14, 3.2.4, and 3.2.5 are:

• Production: in order to better reflect the composition of materials in   containers available on the market, the limit for di(2-ethylhexyl)phthalate   (plastic additive 01) has been increased to 45 per cent and the four mentioned   additional plasticisers are proposed (maximum 45 per cent respectively) for   inclusion in the above-named chapters (with exemption of 3.1.14, see below). A   paragraph has also been added to explain that the selection of the composition   of the materials and additives must be suitable for the intended use.  
• Identification B of plastic additive 01/ Extractable   di(2-ethylhexyl)phthalate: absorption spectrophotometry has been replaced by a   cross-reference to the test for plastic additives 01, 24, 25, 26 and 27 by GC   coupled with mass spectrometry.  
• Test for plastic additive 01: TLC has been replaced by GC coupled with   mass spectrometry, which is also applicable to the four additional   plasticisers (plastic additives 24, 25, 26 and 27). Readers are invited   to comment on the proposed limits for the plasticisers for use in containers   in the scope of the general chapters.

3.1.14: The four plasticisers have not been included in this chapter due to the lack of information regarding the use of these plasticisers in containers for aqueous solutions for intravenous infusion. In order to consider the addition of these additional plasticisers in the future, authorities and manufacturers are invited to send information on plasticisers other than di(2-ethylhexyl)phthalate with regard to the typical amount used, suitable specifications and analytical procedures for testing additives, and complete information on relevant authorised medicinal products or certified medical devices.

The deadline for comment is June 30, 2017. Following your registration on the Pharmeuropa website you will have access to the complete drafts of the Ph. Eur. general chapters covering PVC materials and containers for pharmaceutical use.

Courtesy: ECA