Quality & Compliance In FDA-regulated Industries Good Documentation Practices

Quality & Compliance

In FDA-regulated Industries

Good Documentation Practices

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Good Documentation Practice

• What are they?

• Standards by which documents are created and maintained.

• Not codified by FDA, but are considered cGMP.

• While not law:

• Authorities will inspect against these guidelines and cGMP expectations.

• Make observations if not in place.

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• Why are they needed?

• To standardize the documentation practicesthroughout the industry.

• To increase and assure the accuracy, quality and integrity of data, documentsand records.

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• Who needs to implement them?

• EVERYONE! Cleaning LogsTraining

Records

• ALL POSITIONS!

Correspondence

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• What are the standards?• Creation of New Documents

• Review and Approval of Documents

• Completion of Documents - Data Entry

• Reproduction of Documents - Copying

• Maintenance of Documents

• Modification of Documents - Change

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Good Documentation Practice• What are the standards?• Creation of New Documents:• Contemporaneous (Timely)

• Typed (Not Handwritten)

• Checked for Accuracy (Error-free)

• Formatted for Trend Evaluation

• Adequate space for data entries

• For SOPs, include:• Process Flow Diagram

• RACI Matrix (Responsible, Accountable, Consulted, Informed)

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Good Documentation Practice• Process Flow Diagram –

Example

Phase 6 - CAPA Effectiveness Check

Note: The Process Flow Diagram above has been simplified to focus on the Quality Event Investigation activities that involve Company's IRB.

An Event occurs.

Quality Event Investigation commences.

For Critical and Major Quality Events, QA alerts IRB Chairperson or delegate

that an IRB Meeting is necessary.

No

QA dispositions Product / Material.

CAPA(s) are implemented. PPCN(s) are implemented.

CAPA Owner and Team execute the CAPA Effectiveness Check.

CAPA Owner and QA close Effectiveness Check CAPA in QETS.

QA closes PPCN(s) in QETS.

Investigation Team identifies corrective and preventive measures as a path forward.

Lead Investigator revises QIIR to address IRB's input.

No

Lead Investigator drafts QIIR .

IRB Chairperson convenes an IRB Meeting to review the Quality Event and QIIR, including

a presentation by the Lead Investigator.

Does QIIRmeet IRB's

established criteria?

Yes

QA and IRB approve QIIR and the corrective and preventive

measure(s) for release.

Investigation Team formalizes corrective and preventive measure(s) into CAPA(s) / PPCN(s) by

initiating CAPA / PPCN QETS records.

Investigation Team identifies root cause(s).

Compliance periodically reviews and reports the results of CAPA Effectiveness Checks to the IRB.

If QA determines that a CAPA Effectiveness Check is necessary, then CAPA Owner opens an Effectiveness Check CAPA.

QA initially classifies Quality Event as Critical, Major or Minor.

QA approves CAPA(s) / PPCN(s).

For Minor Quality Events, QA periodically provides the IRB with a summary / update.

IRB Chairperson or delegate updates IRB Meeting Log and prepares IRB Meeting Minutes.

IRB Chairperson or delegate saves IRB Meeting Log and IRB Meeting

Minutes to I:\\Shared\IRB Folder.

If any preliminary Quality Event-relatedinformation is available, the IRB

Chairperson or delegate distributes it to the IRB for review prior to the IRB

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Good Documentation Practice• RACI Matrix - Example

IRB Chairperson & Co-chair

IRBMembers & Delegates

Quality Assurance

(QA)

Primary Responsible

Group (PRG) - Event Owner

Lead Investigator

Investigation Team

Members

QUALITY EVENT INVESTIGATION PROCESS PHASES AND STEPS (SOP #14-001-216)Based on information detai led in the Bas ic Event Profi le Form, class i fy Qual i ty Event initial ly as Critical , Major or Minor. I I A R C IAlert IRB Chairperson or delegate that an IRB Meeting is necessary (for Critical and Major Qual i ty Events only). I A I IProvide draft investigation reports and other materia ls in support of their presentation to the IRB prior to schedul ing a meeting. R I C C A RCommunicate investigation status and fi ndings to Investigation Review Board (IRB) (for Critical and Major Events only) and management. I I R R A RReview QIIR, including corrective and preventive measure(s ). A R R R RMeet establ ished IRB cri teria under Phase 5. C C R C A RApprove QIIR and the corrective and preventive measure(s) for release. R R A R R I

SPECIFICSchedule IRB Meetings (Standard and Emergency), as needed. A I R I I IDistribute related materia ls and information to the IRB. R I C C AReview the dis tributed related materia ls and information in preparation for the IRB Meeting. A R R R A RAppoint an IRB Delegate from their department i f IRB Member cannot attend an IRB Meeting. R A R R RLead IRB Meeting. A RAttend IRB Meeting. A R R R R RProvide overs ight to investigations for internal and external manufacturing operations. A R R R R IEngage in the review of investigations and provide input towards ensuring a l ignment of the investigation with Regulatory, Compl iance and Qual i ty expectations.

A R R R I IServe as a forum for cross-functional department communication regarding investigational activities and trends . A R R R I IDiscuss s ignifi cant i ssues that may affect investigations. A R R R R RReview any open IRB action i tems from previous meetings . A R R R ITake meeting notes and then prepare minutes of the IRB Meeting. A RPlace IRB Meeting Minutes in IRB Shared Folder on Company's I:\\ Drive for access ibi l i ty by IRB Members et a l . A RMaintain electronic entries in the IRB Meeting Log. A RAct as the owner of the IRB Shared Folder on Company's I:\\ Drive, and ensure that a l l IRB members have read/write access to that folder. A RMaintain IRB Member - Delegate Telephone Number Matrix. A RPeriodica l ly present Qual i ty Event / QIIR / PPCN / CAPA Status Updates to IRB. I I A IPrepare IRB Metrics for presentation to other Company Groups/Committees/Boards . A R R I I IReview investigation trends and recommend actions to the MOC. A R R IPeriodica l ly present Qual i ty Event / QIIR / PPCN / CAPA Status Updates to Lead Investigators and Investigation Team Members . A R R I I IProvide ongoing review of tra ining activities for and qual ifi cations of Lead Investigators . A R R C C I

GENERALEnsure a l ignment of this SOP with appl icable Regulatory Guidance Documents . A C REnsure a l ignment of this SOP with appl icable Industry Standards and Practices . A C REnsure a l ignment of this SOP with appl icable Company Pol icies and Procedures . A C R CImplement and mainta in Good Documentation Practices . A R R R R RTraining specifi c to this SOP. A C R I I I

Participating Parties (R = Responsible; A = Accountable; C = Consulted; I = Informed)

ResponsibleThose who do the work to achieve the task. There is typica l ly one role with a participation type of respons ible, a l though others can be delegated to ass is t in the work required.

RACI DEFINITIONS

AccountableThe one ultimately answerable for the correct and thorough completion of the del iverable or task, and the one who delegates work to those Respons ible. In other words , an Accountable must s ign off (approve) on work that a Respons ible provides . There must be only one Accountable specifi ed for each task or del iverable.ConsultedThose whose opinions are sought, typica l ly subject matter experts ; and with whom there is two-way communication.InformedThose who are kept up-to-date on progress , often only on completion of the task or del iverable; and with whom there i s just one-way communication.

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Good Documentation Practice• What are the standards?• Review and Approval of Documents• Reviewed by appropriate and authorized personnel

• Approved by appropriate and authorized personnel

• Signed

• Dated

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Good Documentation Practice• What are the standards?• Completion of Documents - Data Entry – The Dos)• Make entries in permanent/indelible Ink (NOT RED)• Make entries Concise, Accurate and Legible• Enter data in English (unless otherwise directed)• For Critical Entries, have a second authorized person

independently verify activity/entry• Number the pages to be added:• Actual Page # followed by Total Page #

• Follow company’s format for Date and Time:• Format cannot have numerous different meanings

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Good Documentation Practice• What are the standards?• Completion of Documents - Data Entry – The Dos)• Follow company’s format for Initials and Signatures• Signatures and initials are serve as an employee’s

confirmation that the activity performed was per the appropriate SOP or Work Instruction.• Signatures and initials have

company-specific, legal, and/or ethical ramifications.

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Good Documentation Practice• What are the standards?• Completion of Documents - Data Entry – The Dos)• For incorrect data entries:• Use a single line-out• Leave original date/entry legible

• Sign or initial• Date• At the time that the correction is made

• Include justification of the correction• Concise and Accurate

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Good Documentation Practice• What are the standards?• Completion of Documents – Data Entry – The Don’ts• Make entries on the reverse side of the document• Unless a note is written on the front page

• Leave spaces blank• If unused, cross-out or enter "N/A" (or similar text)

• Use pencils!• Entries must be in indelible ink

• Use ditto marks (‘’)• Use continuation lines• Use signature stamps

Good Documentation Practice• What are the standards?• Completion of Documents – Data Entry – The Don’ts• Obliterate data / entries - original data / entries must

remain legible• Overwrite data / entries – scribble / marker

• Use Corrective Solutions (e.g., Wite-out®)

• Use Corrective Tape

• Omit data• Falsify data

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Good Documentation Practice• What are the standards?• Completion of Documents – Data Entry – The Don’ts• Back date• Use current date and include an explanation of the

delay• Destroy or remove pages – obscures data that were

present• To invalidate a page,

use a single line cross-out, then initial and date it.

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Good Documentation Practice• What are the standards?• Completion of Documents – Data Entry – The Don’ts• Transcribe Data – obscures original data• Data Transcription may prove helpful if original is of

poor quality writing or is physically damaged

• If used, should be clearly marked as a transcription and the original retained.

• Use Scrap Paper or Post-it® Notesto record raw data• Temporary, non-official record

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Good Documentation Practice• What are the standards?• Completion of Documents – Data Entry – The Don’ts• Use asterisks (*) where there is insufficient space

for a fully notated hand change• Use a number near the correction, and record the same

number along with a notation where this is sufficient space.• Reduces the risk that an additional change made by

another person will not use the same mark.• Sign / initial for another person• Can sign of behalf of the other person, but must identify

this along with an explanation.

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Good Documentation Practice• What are the standards?• Reproduction of Documents – Copying• Clear and Legible

• No Errors are introduced

• Copy must remain identical to the original

• Watermarks are sometimes used to identify original document from copies.

DRAFT

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• What are the standards?• Maintenance of Documents• Periodically Reviewed to Keep Current

• Securely Retained

• Change Control Program

• Controlled Availability for Appropriate Duration

• Electronic Document Management Systems (EDMS) must be Validated

• Electronic Records are Backed-up and Archived

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• What are the standards?• Modification of Documents – Change• Handwritten modifications – signed/ dated• Altered text is not to be obscured• Justification for alteration must be noted• Controls to prevent use of superseded documents• Versions can only be modified by authorized personnel• Access to electronic versions must be controlled by

password or other means• A history (audit trail) must be maintained of changes

and deletions to electronic versions

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• Data

• Significant Figures: All non-zero digits are significant, all zeros to the left of a nonzero digit are not significant, and a decimal point has no bearing on what numbers are significant.

• The number of significant figures in the final result is determined by the significant figures of the original numbers.

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• Data• Significant Figures: (Continued)

• Examples:• 67 mg - All digits are significant - no “0”s.

• 0.067 g – Two digits are significant – “6” and “7”. The “0”s are not significant - only hold decimal place.

• 0.0670 g – Three digits are significant - “6”, “7” and the far right “0” which identifies the limit that the substance was weighed to (0.0001 g).

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Good Documentation Practice• Data• Significant Figures:• Examples: (Continued)• 670 mg - Two digits are significant – “6” and “7”;

however, the “0” may or may not be significant.• The “0” may hold the decimal place in which case

it is not significant.• The “0” may identify the limit that the substance

was weighed to (1 mg).• Resolutions:- Record value as 0.67 g or 0.670 g- Use scientific notation.

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Good Documentation Practice• Data• Significant Figures: (Continued)• Using Significant Figures for Calculations• Addition and Subtraction: Final value has only as

many figures to the right of the decimal as there are in the number having the least number of figures to the right of the decimal.• Example: 111.1+ 22.22- 3.333 136.653 136.6

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• Data• Significant Figures:• Using Significant Figures for Calculations (Continued)• Multiplication and Division: Final value only has

many figures as in the value with the least number of figures.• Example: 11.1x 0.022222 0.2466642 0.246

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• Data• Significant Figures:• Using Significant Figures for Calculations (Continued)• Scientific Notation: All values expressed as 10# with

one significant figure to the left of the decimal point.• Examples:1.0000 x 102

2.02020 x 102

1.23 x 10-2

2.02020 x 10-1

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• Data (Continued)

• Rounding-off: Process by which one reduces the number of figures in a value.

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Good Documentation Practice• Data• Rounding-off: (Continued)• Focus on the digit to the right of the last place in

the limit expression. • If this digit is < 5, it is eliminated and the preceding

digit is unchanged.• If the digit is > 5, it is eliminated and the preceding

digit is increased by one.• If this digit = 5, the 5 is eliminated and the preceding

digit is increased by one.• For calculations, do not round values until final

result is calculated.

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• Data (Continued)

• Truncation: Reduces the number of figures in a value by deleting the unnecessary figures.

• No other change is made to the remaining number.

• Unlike Rounding-off, only the last several digits in a numerical string are dropped.

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• Data• Truncation: (Continued)• Consider the significance of digits to the final

result.• Do not truncate values until the final result is

calculated.• Example:Values not truncated prior to calculation:

456.789 x 0.1234 = 56.36Values truncated prior to calculation:

456 x 0.1 = 45.6

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CONFIDENTIALITY• What’s the Big Deal?• Company’s Code of Ethics• Adopted by companies to enable employees to:• Understand difference between 'right' and 'wrong'

• Apply understanding to their business decisions.

• Implies documents at three (3) levels:• Codes of Business Ethics

• Codes of Conduct for Employees

• Codes of Professional Practice

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CONFIDENTIALITY• What’s the Big Deal?• Codes of Professional Practice (Continued)

• Honesty• Integrity• Transparency• Accountability• Confidentiality• Objectivity• Respectfulness• Obedience to the Law

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CONFIDENTIALITY• What’s the Big Deal?• Codes of Professional Practice (Continued)

• Confidentiality - "confidential information"• Trade Secret:• A formula, practice, process, design, instrument,

pattern or compilation of information• Not generally known or reasonably ascertainable• Require reasonable measures to protect the

information• Enables a company to obtain an economic

advantage over competitors

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CONFIDENTIALITY• What’s the Big Deal?• Trade Secret (Continued)• Impact:• Intellectual Property:• Copyright• Patent• Trademark

• Time To Market• Competitive Advantage• MONEY!

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Summary• GDPs are considered cGMP.• All employees must follow GDPs.• Original data and entries must not be

obliterated; must remain legible.• Follow the GDP Dos and Don’ts.• Always use the current date.• Know what you are signing/initialing.• Follow company policies/SOPs on significant

figures, rounding-off and truncating values.• Protect your company’s trade

secrets by maintain confidentiality.

END

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