Production Records and DocumentationProduction Records and Documentation

Joanna Stanson, M.S.Joanna Stanson, M.S.Senior Specialist for Cellular Products Senior Specialist for Cellular Products

LaboratoryLaboratory

Cellular Product LaboratoryCellular Product LaboratoryUniversity of Pittsburgh Cancer InstituteUniversity of Pittsburgh Cancer InstituteUniversity of Pittsburgh Medical CenterUniversity of Pittsburgh Medical Center

Document CreationDocument CreationWhat to documentWhat to document

●● Documentation is the electronic or written record of Documentation is the electronic or written record of all information regarding methods, conduct, and/or all information regarding methods, conduct, and/or results of laboratory work; the factors affecting results of laboratory work; the factors affecting laboratory work; and the regular or corrective actions laboratory work; and the regular or corrective actions taken.taken.

●● Document what we do, how we do it, the expected Document what we do, how we do it, the expected result, the actual result, what went wrong, what was result, the actual result, what went wrong, what was done about what went wrong, what was changed, how done about what went wrong, what was changed, how we know the change was effective, and so on.we know the change was effective, and so on.

DocumentationDocumentation

●● Documents generated by a laboratory include, but are Documents generated by a laboratory include, but are not limited to, the following:not limited to, the following:●● Results of all work performed, all instrument readings, all Results of all work performed, all instrument readings, all

reagents/supplies used, all calculations and assay results on reagents/supplies used, all calculations and assay results on worksheets and assay records, and all data summaries worksheets and assay records, and all data summaries

●● Quality control records for assays and instrumentationQuality control records for assays and instrumentation●● Instrument printouts or computer generated reportsInstrument printouts or computer generated reports●● Reagent record sheets and reagent inventory logsReagent record sheets and reagent inventory logs●● Log books, requisitions and shipping formsLog books, requisitions and shipping forms●● Freezer inventory recordsFreezer inventory records●● Laboratory reports from reference laboratories, such as Laboratory reports from reference laboratories, such as

hematology and microbiologyhematology and microbiology

General Points to ConsiderGeneral Points to Consider

●● Documents must be versionDocuments must be version--controlled, with traceability of all controlled, with traceability of all changeschanges

Demonstrate which version is approved and in use●● Review and approval cycles need to be wellReview and approval cycles need to be well--managed.managed.

Version control, date of approval●● Information must be easy to retrieveInformation must be easy to retrieve

The information recorded should be available within certain time period●● There should be few opportunities for human errorThere should be few opportunities for human error

Simple checklist Yes/No is always helpfulless likely to make a mistake if the document is formatted to make it easy to read:

•• what information is required• the required format of the information • where information is missing

● Everything must comply with the current regulations.Everything must comply with the current regulations.

Documentation of the Production Documentation of the Production Process Process

●● Process recorded on the daily worksheetProcess recorded on the daily worksheet● All steps of the production are sequentially documented

●● A complete record of all raw dataA complete record of all raw data

● A record of all calculations performed in connection with the test, including units of measure, conversion factors, and equivalency factors

●● Required Signatures:Required Signatures:● The initials or signature of the person who performs each test and the date

(s) the tests were performed;

● The initials or signature of a second person verifying for accuracy, completeness, and compliance with established standards

● The initials or signature of a person (supervisor/QA) reviewing the document

Test ResultsTest Results

●● Time and date of the assay/test performed.Time and date of the assay/test performed.●● Identity of the person performing the assayIdentity of the person performing the assay●● A statement of the test results verifying the quality: recovery,A statement of the test results verifying the quality: recovery,

viability, purityviability, purity and sterility of the productand sterility of the product●● Statement defining acceptable range and normal control if Statement defining acceptable range and normal control if

applicable applicable ●● Statement defining the method used for testingStatement defining the method used for testing

● e.g.. Viability determined by manual counts● Mycoplasma test by PCR

●● Signature of the person responsible for the release of the test Signature of the person responsible for the release of the test resultsresults

DocumentationDocumentation required for Production (Test) Process

●● Standard Operating Procedures (SOPs)Standard Operating Procedures (SOPs)● SOP for writing and management of the documents

●● Production (Test) procedure validationProduction (Test) procedure validation●● Batch records and worksheets designBatch records and worksheets design

● Preparing the daily worksheetsTitle, version number, facility address Location of the document

●● Synchronization of worksheets with work flowSynchronization of worksheets with work flow:• accurate • permanent• legible • dated • detailed enough to provide product historyenough to provide product history

●● Test resultsTest results●● Biological Product Deviation ReportsBiological Product Deviation Reports●● Other documentation Other documentation

● Training Records identify person performing work

CPL Worksheet CPL Worksheet

Cellular Products Laboratory (CPL)

● The CPL handles somatic cells from leukapheresis or smaller volumes of body fluids and human tissues for processing to single cell suspensions

● The recovered cells are variously manipulated: purified, activated, cultured, etc.

● Most of the products are for autologous use

Documentation as performed in CPL

● All cellular products manufacture in CPL, the cGMP facility are based on INDs ● All important manufacture steps are specified in the SOPs and

on the worksheet● All documents are linked by the UID Number

● Production equipment description and specified on worksheets

● Safety testing, product review and release records are part of the patient specific folder

● All records are entered into the computer database

Production Batch RecordsProduction Batch Records

●● Batch records should include documentation that each significantBatch records should include documentation that each significant step in the step in the production of the batch was accomplished including: dates, and wproduction of the batch was accomplished including: dates, and where here appropriate, times;appropriate, times;

●● Specific identification of each batch, including materials used Specific identification of each batch, including materials used during during manufacturing, reagent record.manufacturing, reagent record.

●● Worksheets prepared and completed as production proceeds (in reWorksheets prepared and completed as production proceeds (in real time)al time)● Worksheets, test documents, testing results are assembled in a batch specific file and are

retained in a subjects folders● Folders are placed and maintained in a secure location

●● Identity of major equipment used;Identity of major equipment used;●● Signatures of the persons performing and checking each significaSignatures of the persons performing and checking each significant step in the nt step in the

operation or directly supervising production; operation or directly supervising production; ●● Information on any deviation that occurs and investigations conInformation on any deviation that occurs and investigations conducted or ducted or

reference to that investigation if stored separately;reference to that investigation if stored separately;●● Results of release testing.Results of release testing.

● These records should include complete information relating to the production and control of each batch, checked for accuracy, dated, and signed.

UPCI-IMCPL CPLHCC, Suite 1.27, Pittsburgh, PA 15213

Ph: (412) 624-0080PRODUCT RELEASE FORM

CPL Batch #: ___________________________________ Protocol #: _____________________Patient Name: ______________________________ Vaccine #: ____________________Sample Received: ___________________________ Date/Time Sample Rec’d: _________Release Form Completed by: _________________ Date: _________________________

Final Results: Date:

IL-12 by ELISA / Luminex (pending)Potency (IL-12 production with J558)

>70%CD86+

>70%HLA-DR+

Pending;No Growth 14-15 daysSterility (last wash and cells)

No Growth 14-15 daysSterility (2-3 day prior)

<5EU/kg of body weight/doseEndotoxin

NegativeMycoplasma

No polys or organismsGram stain

>70%Purity (%)

>70%Viability (%)

# of Cells Infused

InitialsReported resultProtocol Acceptance Criteria Test

Product Release Date: ___________________Comments: __________________________________________________________________________________________________

I certify that this product has met the release criteria as per the IND filed for the above listed Protocol and the product is acceptable to be released for its intended use____________________________________________________________________________________________________________Product Review by: Date:

_________________________________________________________________________________________________________________________ Lab Director/Designee Review/Release Date:

:Faxed to Coordinator/Date: ______________________

Additional RecordsAdditional Recordsrelated to the batch recordrelated to the batch record

●● COA records COA records ●● Equipment logEquipment log●● Labeling logLabeling log●● Packaging logPackaging log●● Records of test sent to reference labsRecords of test sent to reference labs●● VendorsVendors●● PersonnelPersonnel●● Record of inspectionsRecord of inspections●● Records maintained and well organized and readily Records maintained and well organized and readily

available for reviewavailable for review●● Backup of electronic recordsBackup of electronic records

Other RecordsOther Records

●● Production personnel training recordsProduction personnel training records●● Specific SOPs training recordsSpecific SOPs training records●● Competency assessment Competency assessment

●● Documentation of participation in training Documentation of participation in training eventsevents●● Training course/lectures.Training course/lectures.●● WebinarsWebinars//AudioconferencesAudioconferences●● SeminarsSeminars

Policy for the Maintenance of Laboratory Policy for the Maintenance of Laboratory RecordsRecords

●● Records may be electronic, hard copy or copies Records may be electronic, hard copy or copies ●● Written procedures describing retention time for records, Written procedures describing retention time for records,

handling of all records in the laboratoryhandling of all records in the laboratory●● This policy should meet the regulations and standards This policy should meet the regulations and standards

established by state, federal, and accreditation agencies as welestablished by state, federal, and accreditation agencies as well l as the needs of clients. Therefore, retention times for recordsas the needs of clients. Therefore, retention times for recordsand materials shall be reviewed on a case by case basis for the and materials shall be reviewed on a case by case basis for the studies and clinical trials in which laboratory participate.studies and clinical trials in which laboratory participate.

●● Records are considered confidential and shall be stored Records are considered confidential and shall be stored on site in a secure location with access restricted to on site in a secure location with access restricted to authorized personnel only or in an approved off site authorized personnel only or in an approved off site storage facilitystorage facility

Ref: 42CFR493.1105 Standard: Retention requirements. Ref: 42CFR493.1105 Standard: Retention requirements. 21CFR58.195 Retention of Records21CFR58.195 Retention of Records

●● All records are assembled into a file which is unique for each All records are assembled into a file which is unique for each product product

●● Traceability to primary records of the facility are maintainedTraceability to primary records of the facility are maintained●● Safety assays performed, all documentation linked by unique ID Safety assays performed, all documentation linked by unique ID

numbernumber●● Records of the environmental monitoring: particle counts, Records of the environmental monitoring: particle counts,

viable count, humidity, temperature recorded are part of the viable count, humidity, temperature recorded are part of the recordrecord

●● Reagents and prepared reagents are product specific and Reagents and prepared reagents are product specific and traceable to the original manufacture recordtraceable to the original manufacture record

●● QC results: viability, sterility, QC results: viability, sterility, mycoplasmamycoplasma, Endotoxin tests and , Endotoxin tests and phenotypic characterization records are part of the patient phenotypic characterization records are part of the patient specific folder. specific folder.

Production Records in CPLProduction Records in CPL

Thank you Thank you

PittsburghPittsburgh