Earlier this year, two senior figures at the FDA, Janet Woodcock...

Earlier this year, two senior figures at the FDA, Janet Woodcock (Director of the Center for Drug Evalustion and Research) and Michael Kopcha (Director of the FDA Office of Quality Control), wrote an opinion piece titled Quality: The Often Overlooked Critical Element For Assuring Access To Safe And Effective Drugs.

Woodcock and Kopcha note that quality issues account for 62% of FDA drug recalls. They use propofol as an example of how quality issues can disrupt the supply of important medicines, citing cases of propofol recall due to particulate contamination where the manufacturers responded by ceasing production rather than addressing the underlying issue.

“Subsequently propofol inventories ran out and a drug shortage occurred, impacting an untold number of surgical patients.”

Contaminants that have been found in “sterile” injectables include glass, rubber, plastic, metal, garment fibres and human hair. Although the package insert for propofol says the product should be visually inspected prior to use for particulate matter, propofol’s milky formulation hinders proper inspection.

Particulate contamination is not the only safety issue associated with propofol.

A propofol safety review of Diprivan propofol found that “even though the product contains preservatives, microbial growth is still possible and it is not an antimicrobially preserved product under USP standards. The emulsion is capable of supporting microbial growth in the event of contamination during administration due to the level of soybean oil and egg lecithin or egg yolk phospholipids contained in the product.”

Despite FDA recommendation in the package insert guidelines that strict aseptic technique must always be used during handling, including handwashing prior to use and commencement of administration immediately after the vial or syringe has been opened, instances of microbial growth and infections still occur.

For example, in 2014 the TGA issued a safety alert following reports of patients developing sepsis following administration of 1% propofol injection. A 2016 review of propofol use between 1989 and 2014 found 20 propofol-related infectious disease outbreaks had been reported worldwide, affecting 144 patients and resulting in 10 deaths. The authors speculated that many outbreaks related to propofol are likely undocumented. They observed that the lipophilic nature of propofol formulations strongly supports extrinsic bacterial growth at room temperature and that the propofol formulation is an excellent medium not only for bacterial growth but also for fungal infections.

Finally, although its incidence is rare, anaphylaxis is still a concern when used in patients with allergies to egg or soy. Diprivan’s packaging insert states that it is contraindicated in patients with allergies to eggs, egg products, soybeans or soy products.

This suggests to me that a clear propofol formulation that can be readily visually inspected, and which is free of microbial-growth supporting soybean oil and egg lecithin or egg yolk phospholipids, is relevant in that it addresses an unmet need. If it happens to be cheaper to manufacture than the standard propofol formulation, that's a bonus attraction.



https://www.healthaffairs.org/do/10.1377/hblog20200311.912049/full/

https://www.tga.gov.au/alert/propof...-injection-all-sizes-and-all-batches-update-2

https://pubmed.ncbi.nlm.nih.gov/27192163/

https://www.apsf.org/article/the-propofol-safety-review/

https://diprivan-us.com/