A review of fetal cell lines used during drug development: Focus on COVID-19 vaccines, transplant medications, and biologics.

PURPOSE: The recent coronavirus disease 2019 (COVID-19) pandemic and vaccine mandates have increased the number of patient questions related to how fetal cell lines are used during drug development and final manufacturing. This article describes our literature search and review of COVID-19 vaccines, transplant medications, and biologics whose development included use of fetal cell lines. SUMMARY: A detailed literature search was conducted to identify the common fetal cell lines used in COVID-19 vaccine development; the two most prevalent fetal cell lines identified were HEK-293 and PER.C6. Subsequent literatures searches were conducted to identify transplant medications and biologics whose development included use of the HEK-293 or PER.C6 cell lines. For the COVID-19 vaccines, only the viral vector vaccine by Janssen was found to contain proteins produced by PER.C6 in the final preparation administered to patients, and Novavax is the only vaccine for which fetal cell lines were not directly involved in any portion of drug development. For transplant medications, many medications were studied in fetal cell lines in postmarketing studies after Food and Drug Administration approval; however, none of these medications contained fetal cells or would expose a patient to a fetal cell line. Many new biologics and cellular therapies for genetic diseases and malignancies have been directly developed from HEK-293 fetal cells or contain proteins produced directly from fetal cell lines. CONCLUSION: There were very few drugs reviewed that were found to contain HEK-293 or PER.C6 fetal cells or proteins derived directly from fetal cell lines; however, use of fetal cell lines in biologics and gene therapies will continue to increase. Healthcare providers should be mindful of patients' beliefs while also correcting common misconceptions about how these fetal cell lines are used throughout drug development and manufacturing.

Multicenter, randomized, phase II trial of CI-1033, an irreversible pan-ERBB inhibitor, for previously treated advanced non small-cell lung cancer.

PURPOSE: To evaluate the efficacy of the pan-ERBB inhibitor, CI-1033, in platinum-refractory or recurrent advanced-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This open-label, randomized phase II trial evaluated CI-1033 in patients with advanced-stage NSCLC who experienced treatment failure after or were refractory to platinum-based chemotherapy. Three oral CI-1033 doses were evaluated in 21-day dosing cycles: 50 mg daily for 21 consecutive days, 150 mg daily for 21 consecutive days, and 450 mg daily for 14 consecutive days followed by 7 days of no treatment. The primary efficacy end point was the 1-year survival rate. RESULTS: One hundred sixty-six patients were randomly assigned to treatment. Baseline patient demographics were well balanced. The most common drug-related adverse events were rash and diarrhea. The 450-mg arm (14 days on/7 days off) was closed early due to an excessive rate of adverse events. The 1-year survival rates were 29%, 26%, and 29%, respectively, in the three arms. The response rates were 2%, 2%, and 4%, and stable disease was confirmed in 16%, 23%, and 18% of patients, respectively, in the three study arms. Exploratory analyses demonstrated a prolonged survival in patients who developed a rash and in those with baseline tumor ERBB-2 expression. CONCLUSION: CI-1033 had modest activity in unselected NSCLC patients but did not meet its primary end point. Future studies should focus on identifying methods of patient selection.