1. Regulations, Quality Systems and Documentation
Adapted from
Basic Laboratory Methods for Biotechnology by
Lisa Seidman and Cynthia Moore

2. Quality Systems 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 consist of organizational structure, responsibilities, procedures, processes, and resources that together ensure the quality of a product or service

3. Quality in Research Labs
Thought of 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
Quality is strictly enforced 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 and codified in the CFR
Intended to manage all areas of product quality and safety, from pre-production to post-production testing

5. Quality in Regulated Companies
GLPs (Good Laboratory Practices) governing labs involved in nonclinical studies
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

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

7. Quality With Voluntary Standards
Biotech companies making products not regulated by government may choose to comply with voluntary quality standards
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
Only voluntary compliance is expected, not enforced as laws

8. Quality Standards
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
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
All quality systems share a foundation of documentation
GMP regulations and ISO documents are written in very general terms
FDA interprets and enforces GMP requirements in guidance documents called “Guidelines” and “Points to Consider”

10. Documentation The 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

11. 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 an evidence “trail” verifying 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

12. Types of Documents
Documentation types and systems vary depending on the workplace
The regulatory agency or agencies dictates the types of documentation required for each particular industry
Voluntary compliance with standards may dictate additional documenation

13. Types of Documentation
Lab notebooks
SOPs
Forms
Protocols
Reports
Equipment/Instrument logbooks
Instrument printouts/recordings
Electronic documents
Analytical lab documents
Numbering systems
Labels
Chain of custody
Training reports

14. Management of 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
The QA/QC and R&D sections must be involved in change in most instances

15. 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

16. SOPs Standard Operating Procedures
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
Guidelines are established by many federal agencies: FDA, EPA, etc.

17. SOP Guidelines SOP 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

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

30. 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

31. 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

32. 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