Particles in Injections: What about the Patient?

PARTICLES IN INJECTIONS – WHAT ABOUT THE PATIENT?

It is generally recognized that particles in injections may result in serious complications for patients. The potential serious adverse events resulting from the use of a sterile injectable product with particles by the intravenous route include embolic, thrombotic and other vascular events (e.g., phlebitis).

 Complications in connection with the subcutaneous route may include foreign body granuloma, local injection site reactions, and increased immunogenicity (1)

There are therefore official requirements for manufacturers to provide documentation to health authorities concerning particulate matter in injectable products (2)

Many years ago I worked in the sterile department of a public hospital in Norway. In connection with quality control of injections one of my jobs was to count particles in injections with an automatic counter and to identify them microscopically prior to release of each batch.

Particles identified were for example glass, crystals, fibres from filters, or rubber particles from the stoppers. The latter may have been released during the sterilisation process, heating in autoclaves under high temperature and pressure.

I was often present on the wards when patients were given injections after the rubber stoppers on injection vials had been punctured prior to withdrawal of the doses.

For interest, I sometimes counted and identified particles in injections both before and after puncturing the stoppers. There were, as expected, more rubber particles after puncturing and the numbers were higher for thicker needles and several punctures.

Recently I contacted Food and Drug Administration (FDA) and asked if there is a requirement for manufacturers of injections including vaccines to produce documentation concerning particulate matter after puncture of rubber stoppers. The complete reply from FDA is posted below (3).

It is surprising and disconcerning to learn from the answer received :

“TO THE BEST OF MY KNOWLEDGE, THERE IS NO SPECIFIC REQUIREMENT FOR THE MANUFACTURER TO COUNT AND IDENTIFY PARTICLES AFTER VACCINE STOPPERS ARE PUNCTURED”.

If there was a requirement for this, it would undoubtedly result in more awareness from the manufacturers regarding the quality choice of rubber stoppers, an aspect which surely should be considered in connection with patients’ health and safety.

(1) http://www.facebook.com/l/9AQCYRrj3AQDS7EIX9OsMF0Z-LQnrhyHTVUA0JbGok4CjJw/www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm227225.htm

(2)

http://www.facebook.com/l/8AQCyBIwuAQC2WhU88D3cAZNlrJESjyt3trMi8wGce7Nzsw/www.usp.org/pdf/EN/USPNF/PF35(5)_StimArticle-3.pdf

(3) REPLY FROM FDA:

Thank you for your follow-up inquiry. FDA expects purity of all products in single-dose or multi-dose vials.

To the best of my knowledge, there is no specific requirement for the manufacturer to count and identify particles after vaccine stoppers are punctured.

Title 21 of the Code of Federal Regulations (CFR), Part 610.13 ( http://www.facebook.com/l/vAQBo8eL9AQAVC6YkBjr4-OOfoMK16kxINqx02hlj1yTO5A/edocket.access.gpo.gov/cfr_2010/aprqtr/pdf/21cfr610.13.pdf), states, in part, “Products shall be free of extraneous material except that which is unavoidable in the manufacturing process described in the approved biologics license application”. In Title 21 CFR, Part 600.3(r), purity is defined as the “relative freedom from extraneous matter in the finished product, whether or not harmful to the recipient or deleterious to the product”. This regulation can be found at the following web address: http://www.facebook.com/l/LAQA2QmxVAQAK3Ag0YaAhbmHO1HZIM8Sb5rgzU7qi-gx9MA/edocket.access.gpo.gov/cfr_2010/aprqtr/pdf/21cfr600.3.pdf.

We hope this information is helpful.

Food and Drug Administration