Materials

The Use of PVC for Critical Medical Applications

Dr. CSB Nair, Director, Research & Development, TERUMO PENPOL Ltd, Trivandrum, Kerala State

The Requirements of Non-Toxic PVC Compounds for Medical Applications

Compliance with Standards

PVC compounds intended for medical applications should comply with the specifications laid down in the National Pharmacopoeia of the country where it is manufactured and also the Pharmacopoeial requirements of the countries where it is marked as given below:

Country/Region Compliance

These standards require that the PVC material should comply with stringent physical, chemical and non toxicity requirements. To meet these criteria, utmost care has to be exercised in the selection of raw materials used. All additives used must be of high purity to meet the specific end use requirements. The US FDA has an approved list of additives for use in food and drug applications. The European Pharmacopoeia has specified additives to be used for blood bag applications.

In addition, low toxicity of PVC materials are required to be assured by conducting a series of suitable biological tests.

Pharmaceutical Requirements for Medical Grade PVC Materials

The requirements for medical grade PVC in Pharmacopoeias are discussed below:

The European Pharmacopoeia

The European Pharmacopoeia is quite comprehensive. It has defined the plasticisers, stabilisers, lubricants and other additives to be used for making non toxic PVC to be used for blood bags and for intravenous fluids. Compliance requirements for PVC materials, extracts prepared therefrom, physical, physico-chemical and biological tests to be done on container material are clearly specified. Sub section 3.1 has laid down requirements for containers and tubings respectively as follows:

Sub section 3.1.1 :

Materials based on plasticised poly vinyl chloride for containers for human blood and blood components and for aqueous solutions for intravenous infusion.

Sub section 3.1.2 :

Materials based on plasticised poly vinyl chloride for tubing used in sets for the transfusion of blood and blood components.

Containers for blood and blood components are discussed under four sub sections viz.

3.2.3 Sterile plastic containers for human blood and blood components.

3.2.4 Empty sterile containers of plasticized poly vinyl chloride for human blood and blood components.

3.2.5 Sterile containers of plasticized poly vinyl chloride for human blood containing an anticoagulant solution.

3.2.6 Sets for the transfusion of blood and blood components.

The only biological test required to be done is Abnormal toxicity which is systemic injection test using normal saline extract of the PVC material and mice as test animals.

The British Pharmacopoeia

The specifications of European Pharmacopoeia for plastic containers are incorporated in edited form in Appendices XIXE and XIFF of the British Pharmacopoeia. The Appendices provide guidance for users of plastic containers and the statements made therein are not mandatory.

Appendix XIXF relates to containers for blood and blood components and is discussed under three sub sections as in the European Pharmacopoeia.

The United States Pharmacopoeia

The US Pharmacopoeia requires that plastic materials for medical applications should in addition to tests on plastic material and on extracts prepared therefrom under specified conditions, also meet the requirements of three in vitro biological tests on the material or extracts prepared therefrom.

These tests are designed to assess the biological reactivity (cellular degeneration and mal formation) of mammalian fibro plast cell cultures in contact with the test material. The in vitro tests are :

1. Agar diffusion test

2. Direct contact test

3. Elution test

Materials that meet the requirements of the in vitro tests are not required to undergo further testing. Materials that do not pass the in vitro tests are not suitable for containers for drug products.

The USP has classified plastics into six plastic classes based on responses to three in vivo biological tests (Table-2).

• Systemic injection test

• Intracutaneous test

• Implantation test

These three tests are applied to materials or medical devices if there is a need for classification of plastics based on in vivo biological reactivity testing.

The systemic injection test and the intracutaneous test are used for elastomeric material especially where biological reactivity tests in vitro have indicated significant biological reactivity. These two tests in addition to implantation test are applied for plastics and other polymers used for fabricating containers and accessories thereto for parenterals, and for use in medical devices, implants and other systems.

The Indian Pharmacopoeia

Physical, chemical and biological tests are described for plastic containers in which pharmaceutical preparations are dispensed.

Physical and chemical tests comprise tests on containers and container material to assess permeability, toxicity and heavy metal content.

Physico chemical tests are done on water extracts of the plastic material as described earlier under USP requirements.

Recommended biological tests are:

Systemic injection test on mice and intracutaneous test on albino rabbits using the four extracts given below:

1. Sodium chloride injection

2. 5% solution of ethanol in sodium chloride injection

3. Polyethylene glycol 400 and

4. Vegetable oil

Standards for Polyvinyl Chloride Containers for Collection and Storage of Blood and Blood Components

International Standard ISO - 3826

This is a comprehensive standard and covers all aspects of the design and testing of containers of plasticised PVC comprising physical, physico chemical and biological test protocols, requirements and testing of labels, cannulae and packaging.

Non toxicity of the PVC material is of utmost importance and assessments are to be based on the basis of a series of suitable tests as described below :

1. Pyrogenicity

2. Haemolysis test

3. Systemic injection test

4. Intracutaneous test

5. Cytotoxicity and

6. Sensitation test

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