[DOI] [PubMed] [Google Scholar] Karplus M
The following are the Top Ten most frequently cited adverse observations from FDA: Top Ten All affect Sterility Assurance and are cited greater than 60% of the time in inspections: Inadequate facilities designs and controls, inadequate smoke studies Inadequate or lack of environmental monitoring of facility and people Inadequate laboratory procedures and controls (definition of a batch, sampling and testing controls) Lack of Standard Operating Procedures to prevent microbial contamination Inadequate deviation/variance controls and lack of adequate investigation Stability program nonexistent or does not support beyond use dating Validation of final sterilization (filter or terminal), media fill design Inadequate cleaning and disinfecting programs Batch release (most done at risk or with no testing for sterility, potency, identity, and pyrogens) Control of equipment (preventive maintenance and calibration program inadequate or nonexistent) The top ten are now followed by: Lack of validated analytical methods for stability and potency testing, lack of analytical methods for determining impurities and extraneous peaks in chromatography, personnel qualifications, training and skill maintenance, no segregation of beta lactams for other preparations, ineffective quality unit, labeling matters, personnel not trained in GMPS, change control, incoming supplies acquisition and approval, inadequate raw material controls, inadequate separation of operations, record keeping, and inadequate SOPs for operations, Why is the Industry struggling to meet FDA requirements and expectations
Consistent with the diverse AR +/- BCL-2 +/- cell subtypes observed in patient CRPC, the 4 xenograft CRPC models manifested variegated cellular subpopulations: the LNCaP (1 and 2) CRPC predominantly AR + BCL-2 + , LAPC9-CRPC AR - BCL-2 + , LAPC4-CRPC AR cyto BCL-2 + and VCaP-CRPC predominantly AR cyto BCL-2 - phenotype, respectively
The heat capacities, entropies and free energies of ten compounds containing oxygen or nitrogen
doi: 10.1083/jcb.200809125 52 HttemannMLeeIGrossmanLIDoanJWSandersonTH
In disease states like aging or fibrosis, changes in ECM composition, such as increased cross-linking and fragmentation of collagen, and the mechanics (increased stiffness) that the fibroblast encounters disrupt these crucial feedback loops, leading to impaired fibroblast function
