Regulatory requirements in the good manufacturing practice production of an epithelial cell graft for ocular surface reconstruction.

In the past decade, stem cell therapy has been increasingly employed for the treatment of various diseases. Subsequently, there has been a great interest in the manufacture of stem cells under good manufacturing practice, which is required by law for their use in humans. The cells for sight Stem Cell Therapy Research Unit, based at UCL Institute of Ophthalmology, delivers somatic cell-based and tissue-engineered therapies to patients suffering from blinding eye diseases at Moorfields Eye Hospital (London, UK). The following article is based on our experience in the conception, design, construction, validation and manufacturing within a good manufacturing practice manufacturing facility based in the UK. As such the regulations can be extrapolated to the 28 members stated within the EU. However, the principles may have a broad relevance outside the EU.

Validation of alternative methods of preparing 99mTc-MAG3.

Parameters in the preparation of 99mTc-mertiatide (99mTc-MAG3) were investigated to determine the importance of total activity, activity concentration, boiling time, and delay before boiling for the radiochemical purity (RCP) and stability of the product. Satisfactory RCP results (>90%) were obtained over a range of concentrations including a dilute preparation for paediatric use. RCP was not affected by the time between the addition of pertechnetate and boiling, but low RCP (<60%) resulted when the kit was boiled for less than 10 min.

Simplified method for determining the radiochemical purity of 99mTc-MAG3.

UNLABELLED: 99mTc-Mercaptoacetyltriglycine is used for dynamic renal imaging, and the summary of product characteristics (SPC) for the European formulation specifies a shelf life of 1 or 4 h, depending on the reconstitution volume of the kit. To minimize the time required to test the radiochemical purity, a simplified quality control method was developed. METHODS: To satisfy the recommendations of the International Commission on Harmonisation, results obtained with the methods described in the European and American SPCs were compared with those obtained with the simplified method. Further validation of the new method was performed by comparison with the standard 2-strip thin-layer chromatographic method as well as tests for linearity and limits of detection and quantification. RESULTS: The simplified method provided results comparable to those provided by the registered SPC methods but was more rapid to perform and used smaller volumes of solvents. CONCLUSION: The simplified method is a reasonable alternative to the registered SPC methods.

Stem cell therapy delivery: treading the regulatory tightrope.

The concept of stem cell therapy has engaged the attention of the public and scientists alike. Intensive research effort is focused upon understanding the biology and therapeutic potential of embryonic and adult stem cells, with the eventual goal of treating such pathologies as Parkinson's disease, diabetes, neurological injury and degenerations and cancer. Ex vivo expansion and transplantation of limbal epithelial stem cells to the corneas to treat blinding ocular surface disease was one of the first stem cell therapies to successfully reach the clinic. However, limbal epithelial stem cell research and therapy delivery has remained largely within the noncommercial academic clinician-scientist environment from which it was originally pioneered. In our experience, gaining regulatory approval has been as great a hurdle as surmounting the scientific challenges of stem cell therapy. Based upon our model of delivering 'accredited' limbal epithelial stem cell therapy to patients in compliance with Good Manufacturing Practice and the new European Union Tissues and Cells Directive, we address the key regulatory questions. This may help colleagues who are developing innovative academic research-driven stem cell therapies regarding donor consent, raw materials, quality assurance, laboratory specification, indemnity and funding.