1. DOCUMENTATION

2. Documentation
Evidence
A company is required to have a traceable, written record of all processes and checks.
FDA policy: “If it isn’t written down, it doesn’t exist. If it isn’t written down, it never happened.”
Documentation provides objective evidence
Product made and tested correctly
All personnel followed proper procedures
All Equipment operating correctly

3. Standard Operating Procedures (SOPs) Records/Logs/Forms
Types of Documents
Procedures
Standard Operating Procedures (SOPs)
Facility cleaning
Equipment
Manufacturing QC
Change Control
Records/Logs/Forms
Contemporaneous capture of data/events
Batch Records (BR’s)
Test Records (TR’s)
Cleaning Log
Training
Sample Submission Form
Contemporaneous information includes personnel, equipment used, room, reagents. Log of procedures performed

4. Types of Documents Cont.
Reports
Deviation
Investigation
Receiving
Specifications
Facility
Equipment
Raw Materials
Reagents
Process intermediates
Product

5. Document Control Quality Assurance Who does it? Issuing Training
Change Control
Storage

6. Document Numbering System
Used to control documents
In place for SOPs, Production & Specification documents, part & lot numbers for components, raw materials, intermediates, final products, equipment
Should be logical, traceable, unique
Controlled SOP written to describe the numbering system & personnel responsible for administering it

7. Standard Operating Procedures
Primary documents of Process Control
Typically followed for
Equipment use, cleaning & maintenance
Department responsibilities
The first SOP written should be a procedure for writing SOP’s, which should include
Format & contents of procedures to be written
Responsibility for writing, numbering, approving, distributing, controlling, revising, and archiving SOP’s

8. What is in a SOP? Purpose and Scope: Definitions/Principle
Header
Revision Number
Organization
Replaces (what revision)
Title
Date in effect (issued)
Document Number
Page x of y
Purpose and Scope:
What it is about and who it applies to
Definitions/Principle
Definitions of technical terms
Why the SOP is done, why it is important, and how it works
Responsibilities
Technician (following procedure)
Supervisor (training, reviewing, compliance)
Manager (reviewing & compliance)
QA (Audits & Archives)

9. SOP Content Cont. Material/Equipment/Reagents Identity of material
Concentration, pH
Sterile?
Specific vendor or supplier
Can substitutions be made? With or without approval?
References
Other SOPs
Forms
Literature
Manuals (Equipment)

10. SOP Content Cont. Procedure
Step by step, reasonably detailed
Use specific numbers only if required; otherwise use ranges
Write in active voice
“Wash the tray” instead of the “tray is washed”
Include what to record and where to record it
Include what to do if something doesn’t work
If a form is to be submitted, say to whom or to where
Procedures should reflect what IS DONE, not how it SHOULD BE DONE
In FDA’s view, it is much worse to not follow a great written procedure, than to follow a procedure that could be improved
Examples of what to do if something does not work… “Contact supervisor immediately”
“Do not use”
Writing and SOP: Have person who does the job, write down what he does and how he does it
Have supervisor review this document, and discuss with “doer” any questions
“Assigned” writer then reviews and discusses procedure with above personnel

11. Equipment Cleaning & Use Log (21 CFR 211.182)
Written record of major equipment cleaning, maintenance & use
Must show
Date
Time
Product
Lot number of each batch
Persons doing the cleaning or maintenance date & sign (or initial)

12. Receiving Report
Documents raw materials entering facility
Raw materials are assigned a receiving number, which is recorded on the report
Receiving report and Certificate of Analysis (COA) given to QA
QA notifies QC to sample material and begin testing if necessary

13. Material Specification Sheets
Raw Material Specification Sheet
Describes the specifications raw material must meet to be suitable for use in production, e.g., pH
Actually tested by QC to confirm meets spec.
Final Product Specification Sheet
Describes the attributes the final product must meet to be released by QA, e.g., purity > 90%
Tested by QC to confirm

14. Batch/Test Records
Directs operators on how to make or test the product
Accompanies product/test as it is made/performed. Must be followed exactly
Contains blank spaces that are filled in as each task is performed, then signed by operator
Critical steps are witnessed & signed
A controlled copy is issued by QA each time a new batch of the product is made
Data is recorded on them in “real time”

15. Batch/Test Record Essential Components
Title or Subject
Lot or Batch # (unique, identifying number)
Page Number on every page, (“1 of 6”)
Hazard Communication
Warns operator of hazards associated w/procedure & required safety precautions

16. Batch/Test Record Components Cont.
Procedure
Details what operator will do in chronological order
Includes monitoring specifications so operator will know if process is proceeding properly
Blanks to collect raw data
Materials and equipment listed & Lot #’s/ID’s recorded
Signatures to identify operators
Label Information
Specific instructions for labeling in-process samples and final product
Storage
Total number of containers
Conditions

17. Laboratory Notebooks
Primary form of documentation where research is performed (Process/Assay Development)
Legal Document – Can be used to establish patent claim, assign credit for discovery, document honesty & integrity of data for publication
Can be subpoenaed in litigations & examined by the FDA or other regulatory organizations
Are the property of the company

18. Maintaining a Lab Notebook
Chronological order
Sign and date the bottom of every page
Bound Notebook
No spiral or loose leaf books
Pages must never be removed/torn out
Identification
Label book w/your name, company name & assigned book #, starting & ending dates covered in the book
All entries in ink
Cross out errors with a single line; never erase or try to obscure. Initial error and date, with explanation

19. Maintaining a Lab Notebook Cont.
Enter observations & data directly
Not onto paper towel or loose paper
Record calculations as performed
Inserting photos/print-outs/raw data…
Glue to page, then initial & date spanning insert and notebook page. Tape sides
Do not leave blank areas
Draw a diagonal line through blank spaces, initial and date line
Witness signature and date at the bottom of each page
Fill in the Table of Contents

20. Can Not Stress Enough:
Documentation proves that a company has done what it said.
A company is required to have a traceable, written record of all processes and checks.
“If it isn’t written down, it doesn’t exist. If it isn’t written down, it never happened.”

21. cGMP Popcorn Exercise
Goal: Make a batch of cGMP popcorn within a specified time-frame (1 hour) Objective: Understand the complexity of a cGMP process & gain appreciation of teamwork and cooperation of all departments How it mirrors industry: You will be frustrated at times and you will be rushed. However, you will feel a sense of accomplishment once you make the batch!

22. Teams
Material Control: 2 People
Quality Control: 2 People who like to test material
Quality Assurance: 2 People with an eye for written details
Production: 4 People who like to work