DOCUMENTATION

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Documentation

• 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

Evidence

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Types of Documents

• Records/Logs/FormsContemporaneous capture

of data/events• Batch Records (BR’s)• Test Records (TR’s)• Cleaning Log• Training• Sample Submission Form

• Procedures• Standard Operating

Procedures (SOPs)• Facility cleaning• Equipment• Manufacturing• QC• Change Control

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Types of Documents Cont.

• Reports• Deviation• Investigation• Receiving

• Specifications• Facility• Equipment• Raw Materials• Reagents• Process intermediates• Product

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Document Control

Who does it?

Quality Assurance• Issuing• Training• Change Control • Storage

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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

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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

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What is in a SOP?

Header• Organization• Title• Document Number

• Revision Number• Replaces (what revision)• Date in effect (issued)• 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)

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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)

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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

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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)

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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

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Material Specification Sheets

• Raw Material Specification Sheet • Describes the specifications raw material

must meet to be suitable for use in production, e.g., pH 7.00-7.50

• 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

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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”

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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

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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

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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

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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

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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

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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.”

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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!

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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