Perspective
Avastin Doesn't Blind People, People Blind People

https://doi.org/10.1016/j.ajo.2011.11.023Get rights and content

Purpose

To review the appropriate preparation of bevacizumab for intravitreal injection by compounding pharmacies with specific recommendations designed to prevent microbial contamination.

Design

Perspective.

Methods

A review and discussion of compounding issues with supporting literature, clinical experience, illustrations, and expert opinion.

Results

Closer examination of the events surrounding the recent clusters of infectious endophthalmitis cases occurring after the intravitreal injection of bevacizumab suggest that the vision loss is not the result of the drug or the injection technique, but rather of the compounding procedures used to prepare the syringes containing the bevacizumab. Noncompliance with recognized standards and poor aseptic technique are the most likely causes of these outbreaks. The key to preventing these catastrophic occurrences depends on the implementation of and strict adherence to United States Pharmacopoeia Chapter 797 requirements.

Conclusions

Recommendations arising from a root cause analysis of infectious endophthalmitis outbreaks should focus on the procedures used by pharmacies to compound bevacizumab. Microbial contamination of bevacizumab-containing syringes prepared from the same vial of drug can be avoided by using a single vial of bevacizumab for each eye or by following strict adherence to United States Pharmacopoeia Chapter 797 requirements when compounding a single vial of bevacizumab into multiple syringes.

Section snippets

Compounding and Ophthalmology

Compounding drugs for physicians serves a vital function in medicine. Pharmacists routinely are asked to formulate sterile preparations, especially in ophthalmology, when suitable alternatives simply do not exist from pharmaceutical manufacturers because of incompatibilities of drug strength or composition, route of administration, or the need to eliminate potential allergens. However, there are potential serious pitfalls. In 2001, a well-publicized incident in California involved Serratia

United States Pharmacopeia Standards

Before 2004, pharmacies had a long history of well-intended practice standards aimed at improving quality control when compounding sterile preparations.19, 20, 21 Unfortunately, compliance with these voluntary standards was poor.22, 23, 24 Consisting mostly of best practice recommendations, they were not enforceable by federal regulatory agencies such as the FDA. Limited resources and a variable commitment among states to regulate compounding also contributed to lax adherence with these

United States Pharmacopeia Chapter 797: Intravitreal Bevacizumab-Specific Recommendations

An in-depth review of USP <797> is beyond the scope of this paper. Table 1 provides a breakdown of the major sections in the chapter. In addition to the many compounding requirements detailed in the 61 pages of USP <797>, there are recommendations that have specific relevance to bevacizumab. Bevacizumab comes in a sterile solution 25 mg/mL (i.e., 1.25 mg/0.05 mL), so it does not need to be diluted, reconstituted, or altered in any way. The solution just needs to be transferred aseptically into

Selection of Compounding Pharmacy

One of the easiest steps to take when evaluating a compounding pharmacy is to perform an Internet license search of the pharmacy, the pharmacy manager, and its pharmacists. In some states, information is even available about pharmacy technicians. This will help to identify any disciplinary action or infractions filed against a pharmacy by the state board of pharmacy. A quick search on the FDA's web site also may reveal problems with a particular pharmacy.

Another way to protect yourself and your

Bevacizumab is Innocent

It is wrong to condemn bevacizumab for the recent outbreaks of endophthalmitis and vision loss. Based on the information currently available, these episodes seem to be the result of human error, not a direct result of the drug. By strictly adhering to USP Chapter 797 standards, we can ensure the highest quality product for our patients. When comparing the methods used to prepare a syringe of bevacizumab and a syringe of ranibizumab (Lucentis; Genentech/Roche), it should be apparent that the

Serafin Gonzalez, PharmD, is the Director of Pharmacy Services at Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine, Miami, Florida. He received his doctoral degree in Pharmacy from Nova Southeastern University and worked as a Clinical Pharmacist at Doctors’ Hospital in Coral Gables prior to joining Bascom Palmer in 1999. A specialist in ophthalmic compounding, he was the first to compound bevacizumab for intraocular injection and his protocol is currently used

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  • Cited by (82)

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      Unfortunately, these five cases do not represent the first time bortezomib has been injected in place of bevacizumab. The similarity in the names of the two drugs caused a similar compounding error that blinded six people in Portugal in 2009.9 When a drug is drawn up and repackaged into syringes for injection at a later time, well thought out protocols must be strictly adhered to with careful reading of all vial and syringe labels, especially if similar sounding names exist for multiple drugs.

    • Lessons Learned From Avastin and OCT–The Great, the Good, the Bad, and the Ugly: The LXXV Edward Jackson Memorial Lecture

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      He had been compounding drugs for off-label intravitreal use in ophthalmology for years, and these drugs included antibiotics, steroids, and another Genentech product known as tissue plasminogen activator. After reviewing federal guidelines and Chapter 797 of the US Pharmacopeia (USP), he said that it was legal and safe, as long as strict guidelines were followed.28 My chairman, Carmen Puliafito, approved the compounding of bevacizumab for intravitreal injection and permitted my off-label use intravitreal bevacizumab as salvage therapy only in patients losing vision, only after they had failed routine clinical care—in other words, only after the approved therapies were tried.

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    Serafin Gonzalez, PharmD, is the Director of Pharmacy Services at Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine, Miami, Florida. He received his doctoral degree in Pharmacy from Nova Southeastern University and worked as a Clinical Pharmacist at Doctors’ Hospital in Coral Gables prior to joining Bascom Palmer in 1999. A specialist in ophthalmic compounding, he was the first to compound bevacizumab for intraocular injection and his protocol is currently used worldwide.

    See Accompanying Article on page 204.

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