Labeling Standards for Biosimilar Products.

In 2010 Congress established a regulatory pathway for the approval of biosimilar products in the United States. FDA has embarked on developing the implementation framework for this pathway which includes creating guidance to assist biosimilar manufacturers in the development of these products. However, to date, the guidances have focused primarily on the technical standards that manufacturers should consider in order to successfully achieve product registration. As labeling is critical to the safe and effective use of medicinal products, as well as being essential to the content of subsequent promotional material, FDA should consider providing labeling standards that ensure that health care providers have the information needed to make informed decisions regarding the use of these important products.

Recommendations regarding technical standards for follow-on biologics: comparability, similarity, interchangeability.

BACKGROUND: Policy makers around the world are currently considering the creation of a regulatory pathway for follow-on biologics (FOB), which will have to account for the substantial technical challenges associated with FOB development. These challenges will likely involve more complexity than comparability assessments of process changes made by the same manufacturer. The history of industry-regulator comparability discussions helps explain why the same degree of testing and flexibility now applied to change-control within a manufacturer's own process, at this time, cannot be extrapolated to the observed and possibly unknown differences between two manufacturing processes that are independently developed by different (non-collaborating) parties. OBJECTIVES: This commentary provides recommendations on the technical aspects that should be considered in the creation of an approval pathway for FOB products. CONCLUSIONS: In the authors' view, analytical methodology in its current state cannot alone provide full assurance that the FOB is sufficiently similar to the innovator product. Moreover, the FOB manufacturer will not have access to the extensive knowledge accumulated by the innovator manufacturer from early development through marketing. Thus, extensive clinical evaluation will likely be necessary to provide assurance that the FOB is safe and efficacious. If such testing demonstrates the FOB is safe and efficacious per existing regulatory standards, the product should receive marketing approval as a 'similar' product. Since 'similarity' is a fundamentally different determination than establishing interchangeability between the two products, an interchangeability determination must be based on additional testing and market experience to ensure patient safety. Post-marketing surveillance of the FOB should be conducted to ensure that the approved molecule has similar clinical safety and efficacy as the innovator product, prior to any consideration of interchangeability.

Infectious disease risk factors of corneal graft donors.

OBJECTIVE: To determine how donor health status affects the risk of infection after corneal transplant. METHODS: An adverse reaction surveillance registry was used to conduct a matched case-control study among transplanted donor corneas from January 1, 1994, to December 31, 2003. Cases comprised 162 reports of endophthalmitis after penetrating keratoplasty including 121 with microbial recovery, of which 59 had concordant donor and recipient microbial isolates. Two controls were matched to each case by surgery date. Conditional logistic regression estimated adjusted odds ratios with 95% confidence intervals according to the premortem status of decedent donors. RESULTS: Postkeratoplasty endophthalmitis was associated with recent hospitalization (odds ratio, 2.84; 95% confidence interval, 1.61-4.98) and fatal cancer (odds ratio, 2.46; 95% confidence interval, 1.53-3.97) among donors. Endophthalmitis appeared more likely with tissues transplanted longer than 5 days after donation (odds ratio, 1.55; 95% confidence interval, 1.02-2.35). The prevalence of concordant microbial isolates from donors and recipients was greater among fungal endophthalmitis than among bacterial endophthalmitis (P < .001). CONCLUSIONS: Corneal grafts with eye tissue obtained from donors dying in the hospital or with cancer may have an increased risk of postsurgical endophthalmitis, possibly due to donor-to-host microbial transmission. Together with donor screening and processing, improvements in microbiological control may reduce infection associated with corneal transplant.