| Biosimilar | Postmarketing Requirements and Commitments |
|---|---|
| Zarxio [filgrastim-sndz] |
Commitment: (Due May 2016) Enhance the control strategy of … by development, validation, and implementation of an analytical method to assess … concentration for release or in-process testing of drug product. (Due May 2020) Implementation of analytical test for release to assess … concentration in the drug product. (Due May 2016) Confirm stability of drug product in 5% glucose at concentrations ranging from 5 mcg/mL to 15 mcg/mL of in the presence of 2 mg/mL human serum albumin, in glass bottles, polyvinyl chloride and polyolefin IV bags, and polypropylene syringes. Testing will include potency and subvisible particles. (Due May 2018) To readjust the … bioburden limit of … for the … drug substance based on process capability from 10 batches of product. (Due August 2017) Establish bioburden and endotoxin action limits for … after data from more than 10 batches are available and provide the limits in an annual report. (Due May 2016) Conduct studies to support the worst-case hold times … at scale from a microbiology perspective. (Due May 2016) To update the stability program for prefilled syringe drug product to include syringe force measurements, glide force, and functional testing of the needle safety device. The update to the stability program will include establishment of appropriate specifications and verification activities for these attributes. |
| Inflectra [infliximab-dyyb] | None |
| Erelzi [etanercept-szzs] |
Requirement: (Due December 2019) Develop a presentation that can be used to accurately administer to pediatric patients who weigh less than 63 kg. Commitment: (Due December 2017) Adequately assess levels of hydrophobic variants, including wrongly bridged disulfide bond variants. For TNF-α neutralization, etanercept-szzs and U.S.-etanercept did not meet statistical criteria for equivalence; the average mean potency of etanercept-szzs was higher than for U.S.-etanercept. It seemed that U.S.-etanercept had wrongly bridged disulfide bonds (a hydrophobic variant) but that these bonds would refold in vivo. Additional data in an in vitro system using mild redox conditions that mimic the in vivo environment showed this was the case—a reduction of levels of wrongly bridged disulfide bonds and restoration of potency. (Due September 2017) Repeat microbial retention study using a more suitable surrogate solution. (Due October 2019) Measure break loose, glide force (BLGF) for prefilled syringes. (Due October 2017) Confirm injection depth (needle length exposed for injection), audible feedback (occurrence of second click), and visual feedback (plunger fills the window and stops moving). (Due September 2016) Transport validation to assess mechanical stress on the new folding box. |
| Amjevita [adalimumab-atto] |
Requirement: Assessment for treatment of: (Due December 2020) Pediatric UC (aged 5-17 years). (Due September 2021) Pediatric CD (aged 6-17 years). (Due September 2021) JIA in 2 to <4 years. (Due September 2021) Develop a presentation that can be used to accurately administer Amjevita to pediatric patients who weigh < 15 kg. Commitment: (Due July 2017) Perform a drug product shipping study using the approved commercial shipping lane to evaluate the impact of shipment on product quality. (Due December 2016) Perform supplemental method validation and introduce a nonreduced CE-SDS test into the integrated control strategy for drug substance manufacture. Submit the analytical procedure, validation report, proposed acceptance criterion, and data used to set the acceptance criteria that will be provided in a CBE-0 supplement. |
| Renflexis [infliximab-abda] |
Commitment: (Due January 2018) Implement a test for FcγRIIa binding affinity into the drug substance release specification. (Due January 2018) Implement the reducing CE-SDS purity test into the drug substance and drug product release specification. (Due March 2018) Re-evaluate and establish final in-process … limits. … In addition, provide the qualification test data for the … samples. (Due October 2019) Re-evaluate and establish final endotoxin limits for the … sucrose, pH 6.2 solution, and … polysorbate 80 solution. (Due November 2017) Repeat the container closure integrity test validation for the SB2 drug product using a positive control with a defect size of no more than … microns. (Due December 2017) Qualify an in-process … method and establish an in-process … limit for the … of the SB2 drug product manufacturing process. (Due December 2017) Conduct endotoxin, bioburden, and sterility test method qualification study using 1 additional batch of SB2 drug product manufactured according to the commercial drug product manufacturing processes. (Due November 2017) Conduct the … determination study of the … with 2 additional lots of SB2 drug product. |
Note: The ellipses represent items that were blacked out in the FDA documents.
CBE-0= changes being effected; CD = Crohn’s disease; CE-SDS = capillary electrophoresis-sodium dodecyl sulfate; Fc γ RIIa = low affinity immunoglobulin gamma Fc region receptor II-a; FDA = U.S. Food and Drug Administration; IV = intravenous; JIA = juvenile idiopathic arthritis; SB2 = Samsung’s proposed infliximab biosimilar; TNF-α = tumor necrosis factor-α; UC = ulcerative colitis.