Editorial: Avastin, Genentech, and Particulate Matter

One of the positions of Genentech is that Avastin does not meet the particulate matter standards for ophthalmics. However, if you review the USP, you see that this is not true. Let's look at the following:

1. The only official monograph for an "ophthalmic injection" is Carbachol Intraocular Solution, and it contains no specific monograph requirement for particulate testing.
2. USP Chapter <1151> Pharmaceutical Dosage Forms describes ophthalmic solutions as "sterile solutions, essentially free from foreign particles, suitably compounded and packaged for instillation into the eye." (Comment: Instillation is topically applied drops, etc., not injections. This is important in the next paragraph.)
3. USP Chapter <789> Particulate Matter in Ophthalmic Solutions uses the terminology "ophthalmic solutions" so this chapter seems to apply to topically applied solutions. However, in the third paragraph, it states the following: "Light obscuration and microscopic procedures for the determination of particulate matter in ophthalmic solutions are identical to those for injections; therefore, where appropriate, Particulate Matter in Injections <788> is cross-referenced."

So, if Avastin meets the Particulate Matter in Injections <788> requirements, there should be no problem, as the USP does not specifically mention particulate requirements for ophthalmic injections, as they should be covered under USP Chapter <788> regarding injections.

The testing methods include the "Light Obscuration Particle Count Test" and the "Microscopic Particle Count Test" in both chapters. The chapter on injections is more detailed.

Does "repackaging/compounding" of the Avastin make the product noncompliant? I don't think so, as there is not an additional standard than what the injection already meets for particulate matter. Drawing into a sterile syringe for ophthalmic use is the same procedure used in its routine mode of administration, so there should not be a concern of picking up additional particulates from the sterile syringe regardless of whether Avastin or Lucentis is injected.

In summary, it appears that Avastin Injection should meet compendial standards for particulate matter for injections, and even ophthalmic solutions, if the latter applied.


Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief

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"Stop and smell the roses"!
As we enter this Thanksgiving season, we should pause and be thankful for what we have. Traveling all over the world (in fact, I'll be in Portugal Sunday through Wednesday of next week speaking at a hospital pharmacy meeting), I have become even more appreciative of what we have here in the United States. The Pilgrims were astutely aware of the blessings this country offers and we can follow their example.