The FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) released briefing documents in advance of its Wednesday meeting to discuss the use of cell lines derived from human tumors for vaccine manufacture.

The Center for Biological Evaluation and Research (CBER) has consulted with VRBPAC a number of times since 1998 in order to shape policy for new types of cell substrates being used for viral vaccine production.

The current meeting will respond to requests by manufacturers to add new cell lines to the repertoire of substrates approved for vaccine manufacture, because the current list has been found to be inadequate for the growth of newer-generation products.

Cell lines historically used for vaccine manufacture include human diploid cell lines from fetal lung tissue for rubella, polio, hepatitis A, rabies and varicella; diploid monkey cells for rotavirus and rabies; and kidney cells from African green monkey (Vero) for polio.

Tumorigenic cell lines came into use following consideration of the risks and benefits by the VRBPAC in 1998. PER.C6, an immortalized human fetal retinal cell, was the first tumorigenic cell line used in the production of a vaccine. It was used to produce a replication-defective adenovirus-vectored HIV-1 vaccine.

That cell line was considered safe because it was producing replication-defective virus and because the mechanism of immortalization was known, creating comfort around the use of those cells.

Other tumorigenic cell lines have been approved on a case-by-case basis. Such cells may be the only substrate possible for propagating certain vaccine viruses. The current meeting is a continuation of discussions of scientific considerations of the use of the new cell lines and risks that may be associated with them.

The proposed new cell lines are a CEM leukemia T-cell line, an A549 lung adenocarcinoma cell line and a HeLa cervical carcinoma cell line.

CBER has asked that those cell lines be considered as representative of the class of tumor-derived cell lines in order to solicit recommendations that would be applicable to others, both human and nonhuman, proposed for manufacture in the future.

The CEM T-cell line is derived from a patient with leukemia, and is suitable for HIV-1 strains using co-receptor CXCR4. The A549 cell line is from a person with adenocarcinoma of the lung, and is amenable to growth of replication-competent adenoviruses for some investigational vaccines.

The HeLa cell line is derived from cervical carcinoma. HeLa has been used broadly for research purposes and is permissive to the growth of many human viruses, including adeno-associated virus (AAV) for gene therapy applications and for vaccines.

Concerns – and potential hazards – involved with the use of tumorigenic cell lines include the possible presence of residual live cells that could cause tumor growth, residual DNA from the cell substrate, and contamination with adventitious agents, such as viruses that contribute to the tumorigenic phenotype.

Guidelines for testing cell substrates for tumorigenic potential are detailed in the 2010 document, "Guidance for Industry for Characterization and Qualification of Cell Substrates and Other Biological Starting Materials Used in the Production of Viral Vaccines for the Prevention and Treatment of Infectious Diseases."

In other news from Washington:

• FDA scientists from CBER adapted a limiting dilution assay for the purpose of monitoring the number of mesenchymal stem cells (MSCs) able to differentiate into fat-producing cells from specific populations. The technique could also be used to identify which MSCs may become cartilage- or bone-producing cells. The scientists also measured gene expression linked to differentiation into fat-producing cells identifying possible biomarkers for those cells. The work is published in Tissue Engineering, ahead of print.

• National Institutes of Health researchers discovered a mutation that increases production of red blood cells in tumors that may clarify the formation of the blood supply that sustains tumor growth. The discovery was made by analyzing tissue from rare endocrine tumors, and it could have relevance for treating cancers with excessive production of red blood cells. The study was published in The New England Journal of Medicine.

• Provisions of the Leahy-Smith America Invents Act of 2011 went into effect Sept. 16, that will streamline the patent application process and introduce new procedures. Those provisions and rules include new administrative trial provisions offering alternatives to district court litigation for challenging an issued patent, a supplemental examination provision for submission of additional information related to a patent, an inventor's oath that allows assignee filing of a patent and more. Other provisions of AIA will go into effect on March 16, 2013, such as shifting to a first-inventor-to-file system. (See BioWorld Today, Sept. 9, 2011.)

• The Office of Management and Budget (OMB) issued its sequestration report, as required by the Budget Control Act of 2011, showing that an 8.2 percent cut scheduled to take effect Jan. 2, 2013, would cut $318 million from the FDA's budget, including $112 million in user fees. The NIH will lose more than $2.4 billion. (See BioWorld Today, July 30, 2012, and Sept. 17, 2012.)