MAINTENANCE OF CGMP CELL BANKS PRESENTER: K. RAJENDRA 09-02-2013
TABLE OF CONTENT• Design, Develop & Deliver• cGMP Definition• Cell Banking• Characterization of Cell Banks • Tests for Identity • Tests for Purity • Tests for stability• Documentation of Cell Banks and Validation• Cell Bank Storage• Documentation of stored material
DESIGN, DEVELOP & DELIVER Global CMC Support Consultancy Regulatory IGN or Training DES In-House Strategic Issues Clinical logistics LO P EVEProcess design Cell Line Development& Development Process Development D Analytical Development VER Cell Banking Cell Bank Storage DELIcGMP Manufacture Mammalian Cell Culture Microbial Fermentation Viral Production
CURRENT GOOD MANUFACTURING PRACTICES (CGMP) DEFINITION“A set of current, scientifically sound methods, practicesor principles that are implemented and documentedduring product development and production to ensureconsistent manufacturer of safe, pure and potentproducts”. FDA - Guidance for Industry: cGMP for Phase 1 Investigational Drugs.
CELL BANKING (ICH Q5D / EMEA)Cell bank – A cell bank is a collection of appropriatecontainers, whose contents are of uniform composition,stored under defined conditions. Each containersrepresents an aliquot of a single pool of cells.MCB (Master Cell Bank) – An aliquot of a single pool ofcells prepared from the selected clone under definedconditions. The MCB is used to derive working cell banks.WCB (Working Cell Bank) – The Working Cell Bank isprepared from aliquots of a homogenous suspension ofcells obtained from culturing the MCB under definedculture conditions.
CELL BANKING SYSTEM (ICH Q5D / EMEA)The cell bank system consists of two tiers:1.Master Cell Bank (MCB – Single tiered).2.Working Cell Bank (WCB – Two tiered) orManufacturer’s Working Cell Bank (MWCB).A newly prepared WCB should be appropriatelyqualified by characterization and testing.
CELL BANKING PROCEDURES (ICH Q5D / EMEA)Manufacturers may prepare their own cell banks ormay obtain from external sources.Manufacturers should describe the type of bankingsystem used along with size of cell bank, container andclosure system, cryopreservation and storage methods.Manufacturers should describe the procedures used toavoid microbial contamination and cross-contamination by other cell types present in thelaboratory.Labelling system which can withstand the process ofpreservation, storage, and recovery from storage
CHARACTERIZATION OF CELL BANKS (ICH Q5D / EMEA) Testing objectives of cell line --Confirm identity --Confirm purity --Confirm Suitability or Stability Quality assurance established from master bank to end-of-production/post production cells (EPC/PPC). The manufacturer may choose to characterise the WCB instead of the MCB, if justified.
TESTS FOR IDENTITY (ICH Q5D / EMEA) Phenotypic or Genotypic Generally performed on MCB limited to WCB. For human or animal cells Morphological, Isoenzyme analysis Banding cytogenetics or species – specific antisera. For microbial cells Phage typing.
TESTS FOR PURITY (ICH Q5D / EMEA) Free from adventitious microbial agents and cellular contaminants. Generally performed on MCB & WCB. Tests for presence of Bacteria & fungi*. (1% of total No. but not less that two containers 1) Tests for presence of Mycoplasma*. In Vitro assay In Vivo assay Sterility testing. Viability testing.
TESTS FOR STABILITY (ICH Q5D / EMEA) Two concerns for cell bank stability tests. Consistent production of the intended product. Retention of production capacity during storage. Generally performed on MCB & WCB. Tests for Copy number determination DNA & RNA Sequencing Restriction map analysis Retention of selectable markers Retention of recombinant construct
DOCUMENTATION OF CELL BANKS & VALIDATION Accession No. New Culture Master Cell Bank Passage records Cell Bank Ref. No Validation data Working Cell BankQC & Validation Ref. Cell Stocks at Extended Passage (e.g. every 10 to 20 passage) Cell Line Data File
CELL BANK STORAGEThe cell bank storage should be:Long term storage. (e.g., liquid nitrogen, ultra-low temperaturefreezer) (or)Vapor phase (as compared to the liquid phase).Cell stability under the freezing and storage conditionsshould be validated using cell recovery or viability data.Storage of MCB & WCB should be in two or morelocations.
DOCUMENTATION OF STORED MATERIALTraceability through Reference Numbers on LaboratoryRecords.Reference No Accession Cell Bank Cell Q.C. Media Batch Sterilization Day Book Ampoules Banking Records Preparation Record Records RecordAccession No. + + +Cell Bank No. + + +Q.C. Ref. No. + +Media BatchRef. No. + + +SterilizationReference + +
REFERENCES ICH- Q5D, Derivation and characterisation of cell substrates used for production of biotechnological / biological products, July 1997. FDA Guidance for Industry - Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications, Feb’ 2010. Glyn Stacey - Fundamental Issues for Cell Line Banks in Biotechnology and Regulatory Affairs Cell Biology, NIBSC, South Mimms, UK 2004. EMEA 2006: CPMH/ICH/294/95, Note for guidance on quality of biotechnological products: derivation and characterisation of cell substrates used for production of biotechnological/biological products
“GOOD SEEDS GIVES YOU SWEET FRUITS” “THANK YOU” K. Rajendra