1. Record Keeping and Notebooks
BT 201
Biotechnology Techniques I

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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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