What vaccines, pharmaceuticals, and cosmetics utilize human cell lines (from aborted fetuses)?

Comment by InpharmD Researcher

There do not appear to be many products that directly or clearly utilize human fetal cell lines. We still have pending requests to several pharmaceutical and cosmetic/grooming manufacturers. If they supply any relevant information we will reopen this response on your behalf for updates. We appreciate you using our service. If you or your colleagues are ever in need of specific products assessed for the origin of human cell lines utilized in research or production, it would be our pleasure to research your query and identify possible alternatives. There has been extensive use of human cell lines (such as HEK-293, PER.C6, WI-38, MRC-5) derived from fetal tissue in scientific research. However not all human cell lines are derived from embryos (such as HeLa, HT-1080, CHO). Commonly used human-derived cell lines include those from embryonic, fetal, and cancerous tissue. There are 1,426 embryonic and fetal cell lines per Cellasaurus v.4.0, an online database of animal cell lines by the Swiss Institute of Bioinformatics. Of note, many of these lines have “parent lines'' meaning they were derived from an earlier line instead of a direct human source. It is not possible for a comprehensive list of all health care and grooming items that have utilized human cell lines derived from a fetal source via testing or production as products that have not directly tested these cell lines have likely benefited from research utilizing these lines. Specific regulations on utilizing human cell lines have changed over the decades with increased emphasis on consent and the origin of these cell lines. Various vaccines, medications, and cosmetics are potentially tested or produced with these lines but rarely contain the cells themselves. Vaccines and drugs generally publish pre-clinical studies utilizing cell lines during the FDA approval process. Cosmetic testing is less regulated via the Food, Drug, and Cosmetic Act (FDCA). At this time, there is not a specific FDA labeling requirement to denote human cell line testing derived from embryonic or fetal tissue.

Background

There are 1,426 embryonic and fetal cell lines per Cellasaurus v.4.0, an online database of animal cell lines by the Swiss Institute of Bioinformatics. Commonly used human-derived cell lines include those from embryonic, fetal, and cancerous tissue. Of note, many of these lines have “parent lines'' meaning they were derived from an earlier line instead of a direct human source. It is not possible for a comprehensive list of all health care and grooming items that have utilized human cell lines derived from a fetal source via testing or production as products that have not directly tested these cell lines have likely benefited from research utilizing these lines. [1]

The Congressional Research Service updated in 2019 addressed frequently asked questions regarding human fetal tissue research. Public Health Service Act Section 498A(g) defines “human fetal tissue” as “tissue or cells obtained from a dead human embryo or fetus after a spontaneous or induced abortion, or after a stillbirth.” An embryo is defined as the product of conception (sperm and egg) from implantation until the eighth week of pregnancy, then the product of conception is called a fetus from the ninth week of pregnancy until birth. Using fetal tissue to conduct research in the United States can be dated back to the 1960s, where Hepatitis A, Rubella, Varicella (chickenpox), and Zoster (shingles) were developed from two different cell lines, WI-38 and MRC-5. It was found that cell lines derived from fetal tissues were more helpful in cultivating viruses used in vaccine development than animal cell lines. Additionally, infectious disease and immune system-related studies, including HIV, Hepatitis C virus, Ebola virus, and tuberculosis, also involved fetal tissues. [2]

Use of human fetal tissue is regulated by FDA’s Center for Biologics Evaluation and Research (CBER) as an "HCT/P," which stands for human cells, tissues, and cellular and tissue-based products. FDA regulations define an HCT/P as an article “containing or consisting of human cells and tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient.” HCT/Ps include bone, ligament, skin, dura mater, heart valves, cornea, hematopoietic stem/progenitor cells derived from peripheral and cord blood, and semen or other reproductive tissue. Regulations do not specifically refer to human fetal tissue. [2]

Cosmetics marketed in the United States must comply with labeling requirements of the Federal Food, Drug, and Cosmetic Act (FDCA) and FDA do not require the manufacturers to list all the ingredients including the fetal lines. [3]

HEK-293 is a commonly use cell line, second to only HeLa cells. The source of the cells was a healthy aborted fetus of unknown parenthood. A 2018 review discusses the use of HEK293 cells in the biopharmaceutical industry. Biopharmaceuticals including Xigris (drotrecogin alfa), Eloctate (efmoroctocog alfa), Nuwiq (human-cl rhFVIII), Alprolix (eftrnonacog alfa), and Trulicity (dulaglutide) are produced in HEK293 cells. Additionally, HEK293 cells are used for adenovirus vaccine manufacturing for gene therapy, preventive inoculation, and cancer treatment. The MRKad5HIV-1gag/pol/nef vaccine and VRC-HIVADV014-00-VP vaccines for human immunodeficiency virus (HIV) are produced in HEK293 cells. [4]

Regarding vaccinations, two human fetal cell lines are used to produce five COVID-19 vaccines. They include four vaccines that use HEK-293 cells, a cell line derived from the kidney from a fetus aborted in the early 1970s, and one using a PER.C6 cell line from an aborted fetus in 1985. These cell lines, used to produce the AstraZeneca Oxford, Johnson & Johnson, and CanSinoBio adenovirus-vectored vaccines have been propagated for decades and no longer contain remnants of actual fetal tissue. Vaccines for hepatitis A, rubella, and varicella also employ similar cell lines. Recently, the Vatican has indicated that the public health benefits of vaccination outweigh the moral opposition to vaccines from these cell lines.” [5]

References:

1. Swiss Institute of Bioinformatics. Cellosaurus. Version 4.0. https://web.expasy.org/cellosaurus/ Accessed August 27, 2021.

2. Kavya S, Sidath Viranga P, Agata D, et al. Human Fetal Tissue Research: Frequently Asked Questions. https://sgp.fas.org/crs/misc/R44129.pdf. Updated August 8, 2019. Accessed August 25, 2021.

3. Hu J, Han J, Li H, et al. Human Embryonic Kidney 293 Cells: A Vehicle for Biopharmaceutical Manufacturing, Structural Biology, and Electrophysiology. Cells Tissues Organs. 2018;205(1):1-8. doi:10.1159/000485501

4. Food and Drug Administration. Food, Drug, and Cosmetic Act. https://www.fda.gov/regulatory-information/laws-enforced-fda/federal-food-drug-and-cosmetic-act-fdc-act Updated 2018. Accessed August 25th, 2021

5. Hotez P, Batista C, Ergonul O, et al. Correcting COVID-19 vaccine misinformation. EClinicalMedicine. 2021;33:100780.

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What vaccines, pharmaceuticals, and cosmetics utilize human cell lines?

Please see Table 1 for your response.


 

Products Utilizing Human Cell Lines of Embryonic or Fetal Origin for Testing or Production

Origin

Cell Line

Products 

Fetal Lung 

W-38

or 

MRC-5

  • Hepatitis A vaccines (VAQTA/Merck, Havrix/GlaxoSmithKline, and components of Twinrix/GlaxoSmithKline)
  • Rubella vaccine (MERUVAX II/Merck, components of MMR II/Merck, and ProQuad/Merck)
  • Varicella vaccine (Varivax/Merck, and components of ProQuad/Merck)
  • Zoster vaccines (Zostavax/Merck)
  • Adenovirus Type 4 and Type 7 oral vaccine (Barr Labs) 
  • Rabies vaccine (IMOVAX/Sanofi Pasteur)

Embryonic Kidney

 HEK-293
  • Covid-19 Vaccine (Vaxzevria/AstraZeneca [US use pending])
  • Drotrecogin alfa (Xigris/Eli Lilly)
  • Efmoroctocog alfa (Eloctate/Biogen-Idec)
  • Eftrnonacog alfa (Alprolix)/Biogen-Idec)
  • Dulaglutide (Trulicity/Eli Lilly)
  • Human-cl rhFVIII (Nuwiq/Octapharma AG)

Embryonic Retinal 

 Per.C6
  •  Covid-19 Vaccine (J&J/Janssen)



References:

*Not intended to be a comprehensive listing
1. Human Cell Lines. History of Vaccines. https://www.historyofvaccines.org/content/articles/human-cell-strains-vaccine-development Updated June 7, 2021. Accessed August 26, 2021.
2. Olshansky SJ, Hayflick L. The Role of the WI-38 Cell Strain in Saving Lives and Reducing Morbidity. AIMS Public Health. 2017;4(2):127-138. Published 2017 Mar 2. doi:10.3934/publichealth.2017.2.127
3. Hu J, Han J, Li H, et al. Human Embryonic Kidney 293 Cells: A Vehicle for Biopharmaceutical Manufacturing, Structural Biology, and Electrophysiology. Cells Tissues Organs. 2018;205(1):1-8. doi:10.1159/000485501
4. Dumont J, Euwart D, Mei B, Estes S, Kshirsagar R. Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives. Crit Rev Biotechnol. 2016;36(6):1110-1122. doi:10.3109/07388551.2015.1084266
5. Swiech K, Picanço-Castro V, Covas DT. Production of recombinant coagulation factors: Are humans the best host cells?. Bioengineered. 2017;8(5):462-470. doi:10.1080/21655979.2017.1279767
6. Kunert R, Reinhart D. Advances in recombinant antibody manufacturing. Appl Microbiol Biotechnol. 2016;100(8):3451-3461. doi:10.1007/s00253-016-7388-9
7. Genzel Y. Designing cell lines for viral vaccine production: Where do we stand?. Biotechnol J. 2015;10(5):728-740. doi:10.1002/biot.201400388