The House appropriations report for FDA takes a two-pronged approach to advising the agency how to exercise its oversight of compounding: take care with particular products to make sure patients are protected, but step back in other areas to make sure traditional compounding can be maintained.

Roche/Genentech Inc.’s degenerative eye disease treatment Lucentis (ranibizumab) could benefit from the Congressional instructions on a guidance that covers repackaging biological products outside a BLA. If finalized as envisioned by the House committee, FDA's guidance would likely discourage repurposing of the company’s Avastin (bevacizumab)‎ for ophthalmic uses.

Like Lucentis, Avastin is a vascular endothelial growth factor-directed antibody, but unlike Lucentis it's approved for a variety of cancers and formulated in larger-volume vials designed for IV infusion. Lucentis is approved for wet age-related macular degeneration, macular edema following retinal vein occlusion, and diabetic macular edema and comes in a "single-use glass vial designed to provide 0.05 mL for intravitreal injections," labeling notes.

But they're pharmaceutical cousins, and many physicians feel Avastin is as good if not better for ophthalmic uses. It certainly is much cheaper when administered in the low volumes needed for eye treatment – hence, the desire to repackage Avastin.

Finalizing the guidance without major changes probably means that Avastin repackaging would essentially cease, according to the American Society of Retina Specialists and the American Academy of Ophthalmology.

"While the draft guidance recognizes the importance of repackaged products to ophthalmology, it includes some restrictions that would, in effect, eliminate the ability of an ophthalmologist to use bevacizumab. … Proposed 'beyond use dates' (BUDs) would make it extremely difficult for ophthalmologists to order and store bevacizumab for office use," the physician groups state in a briefing paper.

FDA's draft guidance was issued in February; comments were due in May and 355 have been received.

The House appropriations report wants FDA to act post-haste. "The Committee urges the FDA to finalize the guidance without delay … and continues to emphasize the need for close FDA inspection and supervision of large-scale compounding and repackaging of sterile injectable drugs and biological products, particularly products that are administered into areas of the human body where there is tempered immunity, such as the eye or spinal column, to ensure that they are processed in keeping with current good manufacturing practice for sterile products, in particular 21 CFR 200.50 regarding ophthalmic preparations."

But even if the guidance puts a halt to Avastin repackaging, Lucentis still has to contend with a recent head-to-head study that found it less effective than rival Eylea (Regeneron Pharmaceuticals Inc.'s aflibercept) in patients with more advanced diabetic macular edema Also see "Eylea, Avastin Both Get A Boost From NIH Comparative Study In DME" - Pink Sheet, 19 February, 2015..

The lawmakers' instructions regarding the repackaging guidance are just some of the specific policy-shaping recommendations contained in the report. Most notably, representatives lay out the criteria for how the agency should finalize the generic labeling rule ([A#14150623004]).

In other product-focused compounding recommendations, the report, which was issued by the House Agriculture/FDA Appropriations Subcommittee to accompany fiscal year 2016 appropriations for agencies under its jurisdiction, states "the Committee is concerned that the FDA has not yet approved a list of Active Pharmaceutical Ingredients (APIs) for use by compounding pharmacists pursuant to the Drug Quality and Security Act" (DSQA) of 2013 that was passed in response to the deaths from tainted epidural steroid injections from the New England Compounding Center.

Appropriators ask FDA to provide a report within 90 days after the bill is signed detailing when the agency will complete its API review. So far, the agency's policy-making efforts seem to have focused mostly on the "do-not-compound" list ([A#00150302003]).

Don't Overreach On Office Use

While the repackaging guidance and API list may circumscribe compounder activity in some ways, the appropriations report also asks FDA to step back from oversight in certain areas.

"The Committee is concerned that since the passage of … [DQSA], the FDA has interpreted provisions of Section 503A of the FDCA in a manner inconsistent with its legislative intent and with the agency's own previous provisions."

"Office-use" compounding – sending drugs to a doctor in anticipation of, rather than after receipt of, a prescription "is authorized in the vast majority of states and was intended to be allowable under DQSA," the report states.

FDA is now saying that office-use is not permissible, which the committee finds distressing because the agency had in fact been working on a draft compliance policy guide explaining how office-use compounding could be undertaken.

"Therefore, the Committee directs the FDA to issue a guidance document" within 90 days of the enactment of the appropriation law that would outline how to conduct office-use compounding.

Distribution ≠ Dispensing

The committee also is "very concerned" about the draft memorandum of understanding (MOU) that FDA has proposed, which appropriators fear may have "a deleterious effect on small pharmacies."

In DQSA, "Congress only allowed the FDA to regulate 'distribution.' But the MOU appears to exceed the authority granted in the statute by redefining 'distribution' in a manner that includes dispensing – something unprecedented," the report notes.

"The committee expects that, when a final MOU is proposed as a model agreement for states to consider, that distribution and dispensing are treated as the different and separate activities that they actually are," the report states.

Roche's Lucentis Could Get Boost From House Compounding Directives To FDA

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