Challenges of Running a GMP Facility for Regenerative Medicine in a Public Hospital

Viganò, Mariele; Giordano, Rosaria; Lazzari, Lorenza

doi:10.2217/rme-2017-0051

Cited by 26 publications

(18 citation statements)

References 24 publications

(22 reference statements)

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“…GMP-qualified labs are not practically available for such an experiment, as there is currently insufficient GMP capacity [26], and they have very high-associated costs [11]. The use of a non-GMP setting in development facilities should provide sufficient sensitivity to detect failure.…”

Section: Cell Linesmentioning

confidence: 99%

“…The nature of 'unexpected deviations' and how they are dealt with highlights the requirement for a quality system that will change with time, which emphasises the importance of change management protocols across sites. Consideration of candidate corrective and preventative actions for the low-level contamination explored the following: (i) the delivery of the product to the patient with antibiotics (recently discussed at Phacilitate [24]) is under the guidance of the treating physician; however, this may pose the risk of litigation as has recently occurred in the USA [11] following a regulatory recall [22]. This approach also does not address viral contamination.…”

Section: Anticipated and Unexpected Outcomesmentioning

confidence: 99%

“…This publication consequently reports on the results of an experiment to measure and record deviations (both anticipated and unanticipated) when the mature manufacturing protocol of a pluripotent stem cell-derived therapeutic is transferred across multiple development sites. The paper begins with a presentation of the materials and methods used, the key results of the culture process followed by a description of the [11,12]. For alternatives see [2].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Distributed automated manufacturing of pluripotent stem cell products

Shariatzadeh

Chandra

Wilson

et al. 2019

Int J Adv Manuf Technol

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Establishing how to effectively manufacture cell therapies is an industry-level problem. Decentralised manufacturing is of increasing importance, and its challenges are recognised by healthcare regulators with deviations and comparability issues receiving specific attention from them. This paper is the first to report the deviations and other risks encountered when implementing the expansion of human pluripotent stem cells (hPSCs) in an automated three international site-decentralised manufacturing setting. An experimental demonstrator project expanded a human embryonal carcinoma cell line (2102Ep) at three development sites in France, Germany and the UK using the CompacT SelecT (Sartorius Stedim, Royston, UK) automated cell culture platform. Anticipated variations between sites spanned material input, features of the process itself and production system details including different quality management systems and personnel. Where possible, these were pre-addressed by implementing strategies including standardisation, cell bank mycoplasma testing and specific engineering and process improvements. However, despite such measures, unexpected deviations occurred between sites including software incompatibility and machine/process errors together with uncharacteristic contaminations. Many only became apparent during process proving or during the process run. Further, parameters including growth rate and viability discrepancies could only be determined post-run, preventing 'live' corrective measures. The work confirms the critical nature of approaches usually taken in Good Manufacturing Practice (GMP) manufacturing settings and especially emphasises the requirement for monitoring steps to be included within the production system. Real-time process monitoring coupled with carefully structured quality systems is essential for multiple site working including clarity of decision-making roles. Additionally, an over-reliance upon post-process visual microscopic comparisons has major limitations; it is difficult for non-experts to detect deleterious culture changes and such detection is slow.

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Section: Cell Linesmentioning

confidence: 99%

Section: Anticipated and Unexpected Outcomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distributed automated manufacturing of pluripotent stem cell products

Shariatzadeh

Chandra

Wilson

et al. 2019

Int J Adv Manuf Technol

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“…europa.eu/en/medicines/human/EPAR/chondrocelect) [12] . [29] . 因此监管部门对此类产品评价主要基于风险认知和临床医疗实践积累的研究结果, 结合实际具体分析的审评原则 [15,30,31] .…”

Section: 有5×10unclassified

Research progress and regulatory perspectives for stem cell-based regenerative medicine products

Lü¹,

Liu²,

Luo³

2018

Sci. Sin.-Vitae

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Advances in stem cell therapy have led to the surge of regenerative medicine products for treating severe diseases worldwide in the recent years. Stem cells are capable of self-renewal and differentiation, and regenerative medicine products are remarkably complex and varied in their manufacturing processes including methods for cell culture, induction of differentiation and engraftment. The outcomes of the clinical trials of stem cell products also bear uncertainty partly due to the disparities among patients. Therefore it is challenging for the drug administrative agencies to regulate stem cell products. In this article, we review the research progress of the licensed stem cell-based products in the USA, Europe and Japan, along with the regulations and guidance documents of FDA, EMA and PMDA. We also summarize the considerations in evaluating the Chemistry, Manufacture and Control section of stem cell product applications. We hope our effort would contribute to the establishment of science-based regulatory policy in China, and provide the insights for the development and evaluation of regenerative medicine products. regenerative medicine products, stem cell, mesenchymal stem cell, embryonic stem cell, induced pluripotent stem cell, cell therapy, drug evaluation

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“…The special report by Viganò et al offers an insight into the establishment of a good manufacturing practice facility for manufacturing Advanced Therapy Medicinal Products in a public hospital in Milan [8]. This work highlights the rigor, complexity and challenges associated with the regulated clinical translation of Advanced Therapy Medicinal Products in Europe, but also highlights some of the advantages of situating good manufacturing practice facilities in public hospitals.…”

mentioning

confidence: 99%