UK-based gene therapy developer Oxford BioMedica voluntarily halted early-phase clinical studies of the three ocular disease therapies - RetinoStat, StarGen and UshStat - in June after detecting ‘very low levels’ of an unidentified impurity.
The impurity turned out to be fragmented DNA derived from foetal bovine serum (FBS) media supplement. Oxford uses the supplement to grow the cells that produce the lentiviral vectors that are key to its LentiVector delivery platform, as spokeswoman Lara Mott explained.
“Our manufacturing process involves culturing a cell line through revival and expansion phases, followed by a production phase. The material is then purified and further processed to drug substance prior to generation of final drug product" she told in-pharmatechnologist.com, adding that “we use foetal bovine serum (FBS) to grow the cell lines – it ensures that the cells can survive. “
Mott also stressed that the fragmented DNA is not contamination, but the result of naturally-occurring biological material in the FBS which she said would usually be broken down during Oxford BioMedica’s manufacturing processes.
Earlier today Oxford announced that both the US Food and Drug Administration (FDA) and France’s ANSM (L'Agence nationale de sécurité du medicament) agreed to allow it to restart patient recruitment.
Mott confirmed this, telling us that: “We have support from FDA and ANSM to continue using the existing clinical material so we have no concerns about the integrity or quality of our products.”
The go ahead is likely to have attracted the attention of Novartis which, in May this year, asked Oxford to use its LentiVector delivery platform to produce clinical trial materials for upcoming leukemia studies.
Restart by the end of the year
Oxford BioMedica said the FBS was supplied by a third-party manufacturer. Mott declined to name the company but did say that: “We may well continue to use the suppliers as this was not a contamination issue.”
She also told us that – with the regulatory approval in place – the firm is now seeking the go ahead from the various ethics committees that oversee the research.
“There is no set timeframe for individual ethics committees to agree the resumption of patient recruitment into the ocular trials, however this is the highest priority for Oxford BioMedica and are working closely with the investigators and ethics committees with the aim to be treating patients as soon as possible – we would hope by year-end.”
Whether Oxford will change its manufacturing processes as a result of the impurity is unclear.
Mott told us that: “As with the manufacture of any biological product, and the development of increasingly sensitive analytical testing methods, new impurities may be detected and the regulatory agencies must be made aware of these.
“In terms of future clinical batches, we will work with FDA and ANSM to define the necessary specifications. For example, it could be that we take steps to remove this particular impurity altogether, or we could set an acceptable specification level for future clinical batches.”
She also said that the firm has just started working to expand its capabilities in serum-free, non-adherent manufacturing techniques as a result of a £7.1m grant it won from the UK Government in September.