It is my understanding that CLTX did take this issue very seriously and that they are well prepared for PIII trials.
Miljenko
Gene Therapy Quality Testing Should Be Similar to Testing for Drugs, Advisory Committee Says
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WASHINGTON (Reuters Health) Apr 05 -Manufacturers of gene transfer therapies should be required to conduct essentially the same quality testing as is done by drug makers, including tests for sterility and potency, an advisory panel told the US Food and Drug Administration (FDA) on Thursday.
With the potential for large-scale production of therapeutic gene vectors raising a host of new questions, the FDA's Center for Biologics Evaluation and Research (CBER) asked the Biological Response Modifiers Advisory Committee for input on a number of testing and manufacturing issues.
CBER is working to formulate policies so that it will be prepared when the gene vector technology, which is still under development, is ready to be introduced to the marketplace.
"Regulations from 10 years ago are no longer adequate," Dr. Joyce Frey-Vasconcells, of CBER's Division of Cellular and Gene Therapies, told the panel.
Frey-Vasconcells emphasized the need to identify particular areas of gene therapy testing that need improved "training and outreach" in order to "move products to market, increase public confidence...and ensure proper reporting and oversight."
"Right now, we are policing ourselves," noted advisory committee chair Dr. Daniel Salomon of The Scripps Research Institute, which is based in La Jolla, California.
The panel agreed that the same battery of quality control tests required for drugs should be demanded for the DNA plasmids in gene vector products. These tests measure sterility, potency and concentration and detect the presence of residual toxic reagents and endotoxins.
The panel recommended, however, that identity testing should be more closely tailored to the complexities of gene transfer products. For example, most panelists felt that intermediate plasmids should be fully sequenced before processing, but do not need subsequent lot-to-lot sequencing as long as sponsors can show that the plasmid used to make the vector is stable and not likely to mutate.
Panelists also suggested that companies could demonstrate a plasmid's potency, or its ability to transfect a cell, via lot-to-lot cellular assays. However, the committee would not endorse CBER's proposal to ban the use of so-called "single expression cassette" cell packaging lines used to make vectors.
CBER is concerned that the cell packaging lines can produce a large number of replication-competent retroviruses (RCRs), which are able to regain their viral properties once inside a cell and so pose a serious risk to gene therapy recipients.
"Before you drive a stake in the heart of [the single expression cassette] packaging line," more data is needed on factors such the particular vector used with the cell line and other possible causes of cross-infection, argued panelist Dr. Richard Mulligan of Harvard Medical School.
CBER also sought advice from the panel on potential conflicts of interest in gene therapy research.
Dr. Jay Siegel, director of CBER's Office of Therapeutic Research and Review, noted that academic institutions could hire an outside contract research organization or form a monitoring arm from within to oversee the studies.
"We're seeing a growing number of institutions building clinical oversight programs," Siegel noted. He stressed that the recent death of a teenager in a gene therapy trial at the University of Pennsylvania "clearly indicates" that the issue of oversight "needs to be dealt with."
On the other hand, a recent random survey by CBER of 30 of 211 approved and active gene therapy trials suggests that things are getting better.
Study investigators are doing a "fairly decent job" of following study protocols, noted Joseph Salewski, of CBER's Division of Inspections and Surveillance.
Violations identified in gene therapy trials are similar to those found in other kinds of clinical research, Salewski noted, including failure to follow protocol, incorrect dosing and problems with patient enrollment and informed consent. "This is basically what we find in our normal course of business," he said. |
