Record Keeping and Notebooks BT 201 Biotechnology Techniques I

Quality Systems Many laboratories are concerned with quality Biotechnology industries are concerned with product quality Clinical labs are concerned with quality of test results and instrument performance Research labs are concerned with quality of knowledge Quality systems help ensure product quality Organizational structure, responsibilities, procedures, processes, and resources that together ensure the quality of a product or service

Quality in Research Labs Thought of more as “doing good science” Consistent, thoughtful, and effective methods Keeping honest and thorough records Verifying all results and employing “good laboratory practices” Scientists submit results of work to journals to be subjected to peer review

Quality in Regulated Companies Strict enforcement of quality in industry cGMPs (current Good Manufacturing Practices) are used in drug and related medical product producing companies Covers everyone from makers of medical products to people who distribute, package, sell or use the items GMPs are formalized into regulations Requirements that government-sanctioned agencies impose on an industry and companies within that industry

Regulations Objective and focus on safety, efficacy, honesty Don’t cover subjective areas of quality Imposed by the government acting on behalf of the consumer Laws that are enforced by the government Industries are required to comply

Quality in Regulated Companies GLPs (Good Laboratory Practices) governing labs that use animals to test drug safety EPA uses GLPs governing agrochemical product testing CLIA ’88 (The Clinical Laboratory Improvement Amendments of 1988) is a system of regulations intended to ensure quality of results generated by labs performing tests on human specimens Helps ensure trust in quality of medical test results

Quality With Voluntary Standards Biotech companies making products not regulated by government may choose to comply with voluntary quality standards Enzymes and other molecular biology reagents used in research labs fall into this category Standard is a concept, method, or way of doing things that is established by some authority, by custom, or by general agreement Established by various organizations, agencies, and other entities Not law, not government enforced, compliance voluntary

Quality Standards Some standards are subjective Some standards are objective Some standards are broad in scope intended to ensure quality of final products ISO (International Organization for Standardization) 9000 is a series of quality standards Many companies follow ISO 9000 standards to improve product quality, make processes cost-effective, increase profitability, demonstrate quality manufacturing to potential customers Can be applied to any company that makes a product or even one that provides a service Companies develop and follow their own quality plan with ISO 9000 Formalized and documented in quality manual Hires certified auditor to evaluate their status If they are in compliance and all parts of quality program exist, they will be ISO certified ISO Guide 25 focuses on lab specific issues, similar to ISO 9000

Quality Documents GMP regulations and ISO documents written in very general terms To be applicable across a broad range of labs, organizations, and companies Do not give specifics about implementation of quality system or plan FDA interprets and enforces GMP requirements in guidance documents called “Guidelines” and “Points to Consider” Not law, these are intended to help companies apply GMP principles to their own situation

Common Elements of Quality Systems Quality systems have elements in common Documentation consists of written records that guide activities and substantiate and prove what occurred Documentation is a cornerstone of good quality systems Written procedures ensure consistency Written records show who did what, and when, provides accountability Common sayings about documentation and record keeping “If it isn’t written down, it wasn’t done” “Do what you say and say what you do” Resources are another common quality element All labs need resources, regardless of type Skilled personnel are one of most important Employer’s responsibility to ensure all employees have necessary education and training for adequate and appropriate performance under all circumstances Records show qualifications, track training, education, acquisition of new skills Employees are responsible for accuracy and completeness of their own work and accountability for their actions Following instructions, documentation of work, observation of problems and appropriate reporting, understanding impact and consequences of their actions, and undergoing continuoustraining Facilities, equipment, instruments, and raw materials are resources necessary for production Facilities must be sufficiently equipped for all activities occurring within, be appropriately sized, maintain necessary environment

Management of Change One of the most important and difficult aspects of quality systems in a manufacturing environment is managing change Changes must be reviewed, evaluated, and approved before and after they are made Require detailed assessment and evaluation Some changes must be approved by proper regulatory agency for regulated companies Change must be controlled and done in a procedural manner

Management of Change Each lab, facility, or organization should have a procedure for change Non-research environments usually have SOP outlining change process Change should always be justified In a manufacturing facility, proposed changes should be evaluated and pre-approved by R&D A technical review of the proposed change should be performed to assess its value, and to address risks associated with the change In a regulated company the QC/QA unit must review the change to see if it requires approval by regulatory agencies If necessary, the change should be evaluated for financial implications After the change is made its effects should be investigated and documented

Documentation Defined most simply as a system of records Essential to any quality system Adequate documentation must be maintained to satisfy requirements of regulatory agencies and laws along with voluntary standards that a facility chooses to comply with Important in all settings, from manufacturing to research to clinical

Documentation FDA says “if it isn’t written down, it isn’t done” Any documentation that is missing will prohibit the sale of that batch of product Documents associated with products must be completed, stored securely, and protected Research must be appropriately documented to be credible Documentation protects personnel in the event of future questions regarding procedure, quality, safety, equipment functionality regardless of facility

Functions of Documentation To record what the individual has done and observed To establish ownership for patent purposes To tell workers how to perform particular tasks To establish specifications by which to evaluate a process or product To demonstrate that a procedure was performed correctly To record operating parameters of a lab instrument or manufacturing vessel To demonstrate and evidence “trail” that a product meets its requirements To ensure traceability: the ability to trace the history, applications, and location of a product and to trace the components of a product To establish a contract between a company and consumers To establish a contract between a company and regulatory agencies

Types of Documents Documentation types and systems vary depending on the workplace Research labs primarily use lab notebooks SOPs that describe how to perform specific tasks are used in production facilities Some documents may be used in both research and production facilities

Types of Documentation Lab notebooks: chronological log of everything that an individual does in a lab SOPs detail how to complete a specific task and how to document that the task was done correctly Forms contain blanks that are filled out by an operator to record information Typically associated with SOPs or other documents Protocols are similar to SOPs except usually apply where hypotheses are being tested or procedure is going to be performed only one time Reports are documents generated during protocol execution Equipment/Instrument logbooks keep track of maintenance, calibration, and problems for a given instrument or piece of equipment Recordings from instruments Electronic documents Analytical lab documents that record information regarding sample testing Numbering systems like lot number assignments to keep tract of materials, equipment, or products Labels attached to solutions, products, or items to identify them Chain of custody forms used to trace movement of a sample throughout a facility and to keep samples and test results from being confused with one another Training reports document that individual employees were properly trained to perform particular tasks

Production Facility Specific Documents Batch records are collections of documents associated with a particular batch of a product Regulatory submissions are forms filled out and sent to regulatory agencies to inform them of what a company is planning and /or to ask permission to test or sell a product Release of final product record is filled out when a product has been approved for sale

Laboratory Notebooks Assigned to individuals and are a chronological log of everything that individual does and observes in the laboratory Should be complete enough you or another person could exactly repeat your work based on information in the notebook Most widely used form of documentation in laboratories Most important in a research lab

Typical Notebook Format Inside front of the notebook should have an ID number for the notebook, the person to whom it is assigned, date of assignment, the project, company and any other identifying information Table of contents on the first page Including page numbers and descriptions with sufficient detail to allow easy searching of the notebook’s contents A page number on every page in consecutive order A thorough listing of the results of any literature search and experimental information from colleagues for each project Dates, titles, and descriptions Begin each day’s record with date, title, and description of objectives for the day Draw diagonal lines across unused parts of the previous day’s page Dates and signatures on each page In some labs a witness must read, sign, and date each page, along with the person doing the work The scientist and witness should verify that there are no blank spaces, all tables are complete, and that the page is complete Corrections made later should be signed and dated by scientist and the witness The rationale for each activity performed Relevant equations or calculations Complete descriptions of all instrumentation (including models and serial numbers), chemicals used (including manufacturers, catalog and lot numbers, expiration dates) supplies used (with a complete description) samples assayed (including complete descriptions and sample identification numbers), standards or reference materials used, etc. Procedural details If an SOP or protocol is followed it should be referenced in a manner so that it can be identified Any deviations or justification should be noted If procedure is from print source, like book or journal, etc. the complete reference for the procedure should be cited and procedural details may need to be recorded as well Data Take many forms Instrument print-outs may be affixed with a permanent adhesive Print-outs should be titled and dated so they can be replaced in the notebook, if necessary If not affixed to notebook, they should be checked, titled, signed, dated, filed, and referenced clearly in the notebook Observations may include chanegs in pH, temperature, instrument operational paramaters A brief summary of the work completed A conclusion and brief interpretation of data collecetd may be needed For example, if investigation ifs pursued based on preliminary results Avoid negative or extraneous comments

Notebook Guidelines Use only a bound notebook Number every page consecutively prior to using the notebook Never rip out a page Make all entries in ink (preferably black) Use legible, clear, complete writing Enter all observations and data immediately and directly into the notebook Cross out errors with a single line, initial and date Never attempt to erase or cover completely, do not scribble over or use correction fluid Note all problems; never try to hide or ignore mistakes Be honest and objective, don’t editorialize Cross out blank lines or blank pages with diagonal lines to avoid changes being added later Always include detailed information about reagents, instruments, samples, materials, and equipment used Be able to account for and trace all materials used Store your notebook in a secure location

Considerations for Notebooks Write it down! If you did it, record it Procedures can be pasted into notebooks if it is the first time they are used, referenced after that Keep it as neat as possible Be clear and concise; no need for unnecessary writing Include all appropriate materials/sections

SOPs Detail how to complete a task; what all is involved Preliminary work must be done before writing an SOP, like listing important characteristics of final product What considerations contribute to quality should be evaluated and described It should be determined if particular brands or grades of materials should be used in a procedure

SOP Guidelines SOPs must be reviewed and accepted before use The writer has to sign it and accept responsibility for it A second individual knowledgeable about the work also approves and signs In companies a QA employee also signs it SOPs may require changes Old SOPs must be destroyed or made unavailable when changes are made except for historical copies Changes may need to go through several levels for acceptance Each revision needs a date and revision number

SOP Components Title Author Statement of purpose ID number and date Revision number, date of revision Statement of scope describing when procedure is relevant Who is qualified to follow the procedure, statement of responsibility Materials required, including manufacturers and identifying information Calculations required, may need an example Steps in the process References to other documents, as required How to document performance and references to forms

Potential SOP Problems SOP says what to do, not how to do it Procedure written by someone inexperienced SOP is too detailed or not detailed enough Procedure not written in correct order SOP not updated as needed Right SOP can’t be found or older version is used

Forms Often used in conjunction with SOP and filled in as procedure is followed Blanks must be filled in as employee goes along, requiring them to monitor their process Serves as a reminder to record necessary information Some key steps may need to be signed

Protocols Some industries used the term to describe a procedure that tells an operator how to perform a task or an experiment that is intended to answer a question or test a hypothesis May also be used to describe a procedure that may only be used one time Protocols typically lead to an answer, SOPs give procedural directions

Protocol Components The hypothesis or question the study is designed to answer Description of the study Protocol may reference SOPs Plan for conducting the study Information about sample collection, processing, and identification Methods needed to test the hypothesis Testing schedule How study results and conclusions will be reported Criteria to be used to reach conclusions

Reports Document that describes the results of an executed protocol What was done, by whom, why, data obtained, conclusions drawn Written in narrative format Scientific research published in journals Private company investigation reports may not be published but are required to be available for inspection

Logbooks and Instrument Recordings Logbooks are chronological records about status and maintenance of equipment or instruments Instruments may generate automatic result printouts Considered to be raw data May be affixed to notebooks or filed Some instruments continuously monitor themselves and record parameters as they operate Must be thoroughly identified and be signed and dated by technician

Electronic Documentation Used to control and monitor instruments Recording and analysis of data Storage of protocols and SOPs Printouts, disks, other media may be generated by computers Appropriate security and validity of electronic documentation must be established for it to be of value

Analytical Lab Documents Analytical labs measure properties of a sample Environmental labs, clinical labs, reference labs Documentation must be provided concerning methodology used and sample identification

Necessary Analytical Lab Information Assay method information Test purpose Test limits Test method origin Validation information Suitability of test Sample information ID number Collection method and details Storage location and conditions Disposition information Assay information Sample tested Test date Who performed test Reagents and materials used Method used for test Raw data collected Calculations for results Reported conclusions based on the test

Identification Numbers and Labels ID numbers used to uniquely identify items Raw materials, documents, equipment, parts, product batches, chemicals, solutions, lab samples Tells what it is and which one in the set it is Labels identify equipment, materials, products, other items Have various types of information

Label Components Preparation date Person responsible ID number Lot number Identity, composition, or name of the item Safety information Name of company or institution Storage and stability information

Chain of Custody Provides a paper trail for samples Used to organize information about samples Each sample has a unique ID number Records show sample source, collector, transporter, condition upon receipt, date of receipt, sample processing and testing methods and personnel, storage information, disposition Every move along the process must be logged

Training Reports Keep track of individuals who have been trained in a facility Shoe what training has been completed Dates of training Purpose of training Demonstrates who is competent to perform job

Production Facility Specific Documents Batch records Accompany a particular batch or product, directing the process by which a product is to be made, raw materials required, SOPs to follow Stays with product as it is made Includes blanks to be filled in as procedures are performed Must be complete, readable, correct

Batch Record Components Product identification Document identification Company name Dates of manufacturing Step by step account of processing and testing to be done Monitoring specifications Raw data to be collected and blanks to record it in Materials and equipment to be used Required signatures

Regulatory Submissions & Release of Final Product Records Regulatory submissions are completed to meet the requirements of an outside regulatory agency Ask for permission, report activity Release documents are completed to show when a product has been manufactured and tested Certifies the product, shows specifications, established the documentation has been reviewed and approved, state the product is ready to be sold

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