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Kerrigan L.,10801 University Blvd | Nims R.W.,RMC Pharmaceutical Solutions Inc.
Regenerative Medicine | Year: 2011

Authentication of human tissues, cell lines and primary cell cultures (including stem cell preparations) used as therapeutic modalities is often performed using phenotyping and technologies capable of assessing identity to the species level (e.g., isoenzyme analysis and/or karyotyping). This authentication paradigm alone cannot provide assurance that the correct human cell preparation is administered, so careful labeling and tracking of cells from the donor, during manufacture and as part of the final product are also employed. Precise, accurate identification of human cells to the individual donor level could, however, significantly reduce the risks of exposing human subjects to misidentified cells. The availability of a standardized method for achieving this will provide a way to improve the safety profile of human cell-based products by providing assurance that a given lot of cells originated from the intended donor and were not inadvertently mixed or replaced with cells from other donors. In support of this goal, an international team of scientists has prepared a consensus standard on authentication of human cells using short tandem repeat profiling. Associated with the standard itself will be the establishment and maintenance of a public database of short tandem repeat profiles for commonly used cell lines. © 2011 Future Medicine Ltd.

Nims R.W.,RMC Pharmaceutical Solutions Inc. | Gauvin G.,Amgen Inc. | Plavsic M.,Genzyme
Biologicals | Year: 2011

Animal-derived materials such as animal sera represent a low, but finite, risk for introduction of an adventitious agent (virus or mollicute) into a biological bulk harvest during upstream manufacturing processes involving mammalian cell substrates. Viral and mollicute (Mycoplasma sp. and Acholeplasma sp.) contamination events have been relatively rare, but many of those that have been reported have been attributed to use of infected animal sera in growth media during cell expansion. The risk of introduction of viruses and mollicutes may be mitigated by elimination of the use of animal sera and implementation instead of chemically defined or serum- and animal-derived material-free cell culture media. When use of animal sera is unavoidable, however, mitigation of the risk of introducing an adventitious contaminant may involve treatment of the sera to inactivate potential contaminants. Gamma irradiation is one of the most widely employed methods for viral and mollicute inactivation in animal sera. In this article, we review the inactivation results reported for viral and mollicute inactivation in frozen serum. Studies performed to assess the impact of gamma irradiation on serum quality and performance are also discussed. The available data indicate that inactivation of mollicutes in serum is essentially complete at the gamma radiation doses normally employed (25-40 kGy), while the efficacy and kinetics for viral inactivation in serum by gamma irradiation appear to be dependent in part upon the size of the target virus. © 2011 The International Alliance for Biological Standardization.

Lebrec H.,Amgen | Narayanan P.,Amgen | Nims R.,Amgen | Nims R.,RMC Pharmaceutical Solutions Inc.
Journal of Applied Toxicology | Year: 2010

Biopharmaceuticals represent significant advances in therapeutic approaches for unmet medical needs, and increasingly, traditional pharmaceutical firms have been incorporating biotechnology capabilities into their product portfolios. There are some differences in the overall safety testing paradigms for small molecules and biopharmaceuticals, this safety testing including both quality and toxicology aspects. These differences are associated with both the manufacturing processes involved and the molecules themselves. For example, for biopharmaceuticals, living cells represent the factories for synthesizing complex molecular entities. As a result of this, safety testing for this class of drugs includes adventitious agent testing (e.g. viral, mycoplasma, transmissible spongiform encephalopathy agents) not normally needed for small molecules. Also, strategies for nonclinical toxicology testing of biopharmaceuticals differ from the paradigms used for small molecules and often need to be defined on a case-by-case basis, primarily taking into consideration species cross-reactivity attributes of the molecule of interest. Certain studies required for small molecules are not applicable to most biopharmaceuticals (i.e. genotoxicity testing, testing for interactions with the hERG channel). This manuscript provides an overviewof both the quality and nonclinical toxicology testing for these mammalian-cell-derived products, two elements pivotal to the overall nonclinical assessment of the safety of these biopharmaceutical products. Copyright © 2010 John Wiley & Sons, Ltd.

Nims R.W.,RMC Pharmaceutical Solutions Inc. | Meyers E.,Amgen
BioPharm International | Year: 2010

The United States Pharmacopeia has recently published chapter <63> Mycoplasma Tests. Biopharmaceutical companies conducting mycoplasma testing as a lot release assay for unprocessed bulk material will need to comply with this new regulation once it becomes effective later this year. In this article, we compare the language of USP <63> to that of the existing regulation (European Pharmacopoeia chapter 2.6.7 Mycoplasmas) and guidance (1993 Points to Consider in the Characterization of Cell Lines used to Produce Biologics).

Nims R.W.,RMC Pharmaceutical Solutions Inc. | Sykes G.,10801 University Blvd | Cottrill K.,10801 University Blvd | Ikonomi P.,10801 University Blvd
In Vitro Cellular and Developmental Biology - Animal | Year: 2010

The role of cell authentication in biomedical science has received considerable attention, especially within the past decade. This quality control attribute is now beginning to be given the emphasis it deserves by granting agencies and by scientific journals. Short tandem repeat (STR) profiling, one of a few DNA profiling technologies now available, is being proposed for routine identification (authentication) of human cell lines, stem cells, and tissues. The advantage of this technique over methods such as isoenzyme analysis, karyotyping, human leukocyte antigen typing, etc., is that STR profiling can establish identity to the individual level, provided that the appropriate number and types of loci are evaluated. To best employ this technology, a standardized protocol and a data-driven, quality-controlled, and publically searchable database will be necessary. This public STR database (currently under development) will enable investigators to rapidly authenticate human-based cultures to the individual from whom the cells were sourced. Use of similar approaches for non-human animal cells will require developing other suitable loci sets. While implementing STR analysis on a more routine basis should significantly reduce the frequency of cell misidentification, additional technologies may be needed as part of an overall authentication paradigm. For instance, isoenzyme analysis, PCR-based DNA amplification, and sequence-based barcoding methods enable rapid confirmation of a cell line's species of origin while screening against cross-contaminations, especially when the cells present are not recognized by the species-specific STR method. Karyotyping may also be needed as a supporting tool during establishment of an STR database. Finally, good cell culture practices must always remain a major component of any effort to reduce the frequency of cell misidentification. © 2010 The Author(s).

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