Documentation

Documentation 1
 What is document?
• Documentation is any communicable material
that is used to describe, explain or instruct
regarding some attributes of an object, system
or procedure, such as its parts, assembly,
installation, maintenance and use.

Documentation 2
Why Documentation is necessary in
pharma industry?

Documentation 3
 Objectives
• Keep track of activities
• Create legal documents
• Provide historical document
• Provide information
• Ensure the quality
• Authorize person responsible
• Comply with regulations

Documentation 4
 Document Characteristics
• Permanent
• Legible
• Accurate
• Prompt
• Clear
• Consistent
• Direct
• Truthful
Documentation 5
 Types of Documentation
(GCP) (GMP)
1. Investigator's Brochure 1. Labels
2. Clinical Study Protocol 2. Specifications and testing
procedures
3. Subject Information and
3. Master formulae and
Informed Consent Form
instructions
4. Analytical reports 4. Batch processing and batch
5. Clinical Study Reports packaging records
6. Case Report/ Form (CRF) 5. Standard Operating
Procedures (SOPs)
6. Record
7. Other documents
Documentation 6
 (GCP): Investigator's Brochure
• Pre-clinical and clinical information related to an
investigational drug
• List of Abbreviations
• Contents
• Summary
• Chemical name / INN / generic / trade name
• Physical, chemical and pharmaceutical
properties and formulation of the medicinal
product.
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 (GCP): Investigator's Brochure
• Non-clinical studies-pharmacological, PK,
metabolic, toxicological
• Clinical studies-PKPD, safety efficacy, history
• Conclusions
• Guidance for the Investigator
• References
(Reviewed annually)

Documentation 8
 (GCP):Clinical Study Protocol
• Introduction (brief description of the problem
and treatment regimen(s))
• Objectives and purposes of the study
• Study duration
• Number of subjects
• Informed Consent
• Opinion of the Ethics Committee
• Subject selection criteria
Documentation 9
 (GCP): Clinical Study Protocol
• Methodology:
– Plan, schedules, visits, procedure, efficacy end
points, treatment cycles
• Safety Reporting
– Adverse events (AEs) Serious adverse events
(SAEs)
– Abnormal laboratory test values
– Abnormal values of other safety parameters
– Withdrawal from the Study
Documentation 10
 (GCP): Clinical Study Protocol
• Clinical laboratory parameters
• Other safety parameters
• Concomitant medications
• Data analysis
• Appendixes

Documentation 11
 (GCP): INFORMED CONSENT
• The purposes of the trial;
• The methods of the trial;
• The study drug(s) and treatment regimens;
• Available alternative treatment(s);
• The potential risks and benefits, and possible
discomforts.

Documentation 12
 (GCP): INFORMED CONSENT
• Types
– A) Interim B) Final
• Full, comprehensive description of the study
• Description of investigational materials, study
design, and presentation & assessment of
results of statistical analysis
• ADR, Patient Entry Form and Patient
Withdrawal Form, Protocol deviation/violation
Report, Study Termination Report etc.
Documentation 13
 (GCP): CASE RECORD FORM (CRF)
• Data collection in accordance with the Study
protocol
• Fulfills regulatory requirement
• Facilitate Effective, comprehensive data
processing and analysis, results reporting
• Promote the safety data sharing between
study team and other depts.

Documentation 14
 (GCP): CASE RECORD FORM (CRF)
• study title and number; • concomitant treatment;
• investigator's name; • adverse events (side
• study subject/patient id effects and intercurrent
(number and initials); diseases);
• inclusion / exclusion • conclusion on subject's
criteria; health;
• demographic data; • Investigator's signature
• detailed description of and date.
dosage regimens of
investigational drug;
Documentation 15
 (GCP): CASE RECORD FORM (CRF)
• Past medical history;
• Results of physical examination;
• Primary and secondary diagnoses;
• Relevant previous treatment;
• Baseline characteristics, results of interim
assessments, evaluation of efficacy endpoints,
laboratory tests, description of study
procedures etc.
Documentation 16
 (GCP): Analytical study Reports
• Identification of the • A Quality Audit Certificate
analytical work by unique • Description of methods and
identification number. materials used
• The clinical trial number. • Statistical methods used
• Identity of the Sponsor. • Presentation of the results
• Identity of the trial facilities • All information and data
and the Investigator to required by the analytical
whom the results are plan
directed. • Location(s) where analytical
• Name of the Analytical any specimens required to
Project Manager. be retained, data and final
• Presentation of the results. analytical report are to be
Documentation stored. 17
GMP-DOCUMENTATION

Documentation 18
 Inclusions Of Documentation !!!
• Revised schedule M has the following elements which
are related to documentation:-----
– Records
– Labels
– Specifications And Testing Procedures
– Master Formulae
– Packaging Instructions
– Batch Production and Control records (BPCR) / Batch
Manufacturing Records
– Batch Packaging Records (BPR)
– Standard Operating Procedures (SOPs)
Documentation 19
RECORDS

Documentation 20
 Records to be maintained
• Receipt and issue records of raw materials and containers
• Log book of assigning batch number
• Analysis record (Generally by Q.C. department)
• Finished product distribution records
• Major critical equipment cleaning, maintenance, calibration,
validation records
• House keeping, maintenance, cleaning and sanitization records
• Personnel matters including qualification, training etcetera
• Environmental monitoring
• Complaints
• Recalls
• Returns Documentation 21
 LABELS

• Introduction
• Label of finished product
• Label of reference standard

Documentation 22
 Introduction
• In pharma industry, Labels are used for identification
and/or status of container, equipment and premises.
• Labels should be unambiguous and in format approved
by the company.
• Sometimes colored labels are used to indicate status.
For Example, colored labels for starting materials
according to their status:
Quarantine - Yellow
Approved - Green
Rejected - Red
Documentation 23
 Label of finished product
• Name of product • Batch number
• Ingredients • Expiry date
• Storage condition
• Net Content

• Information
about manufacturing company (Lice.
No. and Address)

Documentation 24
Label of reference standard
• Name of material • Batch number
• Potency • Shelf-life
• Date of preparation • Storage condition

Documentation 25
 SPECIFICATIONS AND TESTING
PROCEDURES

• Introduction
• Specifications for Raw Materials
• Specifications for Finished Product
• Specifications for Packaging Materials
• Testing Procedures

Documentation 26
 Introduction
• It is a list of detailed requirements with which product/material
used or procedure followed during manufacture need to conform.
• They serve as basis for quality evaluation.
• Specifications should be available for :
• Raw Materials
• Finished Products
• Packaging Materials

• First twos can be referred from their individual monographs from

pharmacopoeia.
• If standard data is not available in pharmacopoeia, then manufacturer can write
specification himself.
• Specifications for packaging materials such as plastic or glass containers and
closers etcetera, are not given by any monograph. However certain
requirements have been laid down for them in appendix-11 of I.P.
Documentation 27
 Specifications for Raw Materials
• Generic and chemical name of material
• Trade name or product code established by manufacturer
• Description
• Name of pharmacopoeia or any other recognized book of
standards in which monograph appears or INN
(International Non-proprietary Name).
• Approved supplier
• Frequency of testing of stored material
• Special precautions to be taken during storage including
safety aspects
• Date of Issue of specifications
Documentation 28
 Specifications for Finished Product
• Generic name of product
• Trade name
• Dosage form and Strength
– Description (Color, State, Dimension, Taste)
– Physical properties
– ( Weight/Volume (with limit), pH, Viscosity, Density, Hardness,
– Friability, Disintegration time, Dissolution Time, etc.
– Name of Pharmacopoeia as a reference
– Date of Expiry
– Precautions during storage including safety aspects
– Date of issue of specification Documentation 29
 Specifications for Packaging Materials
• Below mentioned Indian standards may referred, while
preparing specifications for packaging materials:

Number of IS Specification for

IS 7803 Plastic Containers
IS 3692 Rubber Closures
IS 1776 Folding Box Board
IS 2771 Corrugated Box
IS 3101 Collapsible Tubes
IS 7852 Eye Ointment Tubes
IS 10133 Glass Bottles
IS 8970 Paper Aluminum Foil
IS 8393 Pilfer Proof Closures
IS 1984 Glass Vials

Documentation 30
 Testing Procedures
• These are nothing but the procedures for testing
raw materials, intermediated and finished
products.
• These procedures are basically based on
Pharmaceutics and Analytical techniques.
• While preparing these procedures Various
pharmacopoeia (like IP, BP, JP, EP, USP etc) and
other recognized books of standards like drug and
cosmetics rules, USNF, other authoritative books on
analysis of drugs. Documentation 31
 Format For Standard Testing Procedure
Name : Pages:
Code No. : Shelf Life :
Status : Effective Date :
STP No. : Review Period :
Prepared By Checked By Approved By
Signature
Date

Documentation 32
 MASTER FORMULAE

• Definition

• Preparation of Mater Formulae

• Description
• Sample of Master Formulae

Documentation 33
 Definition
• Master formulae also can be said and written as
‘Master Formula Record’, ‘Manufacturing Formula’,
‘Master Production and Control Record’ (MPCR)
etcetera.
• It is defined as -
“An approved master document that describes the full
process of manufacturing for the batch of specific product.”
• It includes all the materials used in any batch
manufacturing and step by step process of
manufacturing.

Documentation 34
 Preparation of Mater Formulae
• Master formulae can be prepared by competent
technical staff.
• It should be reviewed by the heads of
production, quality control department and
research & development.

Documentation 35
 Description
• Name and Strength of the product with dosage form
• MFR No.
• A complete list of all ingredients with their quantity
• Description of Containers, Closures and Packaging materials to
be used
• Description of all Vessels and Equipments used in the process
• Processing and Packaging Instructions
• IPQCs to be exercised during processing and packaging
• Precautions to be taken during manufacture and storage of
semi-finished product including any special storage conditions
• Reference

Documentation 36
Sample Of Master Formulae

Documentation 37
BATCH PRODUCTION AND CONTROL RECORD
(BPCR)
OR
BATCH MANUFACTURING RECORD

Documentation 38
 Definition
• Batch Processing Record can also be said as
Batch Manufacturing Record (BPCR) .
• It is defined as –
“The Batch Manufacturing Record (BPCR) is the
necessary quality and GMP documentation for
tracing the complete cycle of manufacture of a
batch or lot.”

Documentation 39
 Notes about BPCR
• BPCRs are required to be maintained for each
batch of the product manufactured.
• These should be based on Master Formulae
records.
• Methods of preparation of BPCR should be such
that ‘trasncription errors’ do not occur.
• Before any process begins, a check should be
made to ensure that all work stations are clear
of previous products, materials and documents.
This check should be recorded
Documentation 40
 Contents of BPCR
• The name and batch number of the product
• Dates and times of commencement, of significant intermediate
stages and of completion of production
• Identification (initials) of the operator(s) who performed each
significant step of the process and, where appropriate, the name of
any person who checked these operations
• Quantities of each starting material actually weighed
• A record of the in-process controls and the initials of the person(s)
carrying them
• The product yield obtained at different and pertinent stages of
manufacture
• Notes on special problems including details, with signed
authorization for any deviation from the Manufacturing Formula and
Processing Instructions
Documentation 41
• Approval by the person responsible for the processing operations.
 Basic Difference B/W MPCR and BPCR
• MPCR is the type of master document,
means with the help of MPCR only, the
BPCR is prepared…
• BPCR is unique batch wise, means all
batches have their individual BPCR.
• Moreover BPCR contains ‘Date and Time’,
that when the batch was processed.

Documentation 42
 BATCH PACKAGING RECORD

• Introduction

• Contents of BPR

Documentation 43
 Introduction
• In fact, BPR is a part of BPCR.
• These records are based on packaging
instructions.
• One important operation that should be
carried out before packaging operation is
line purging (clearance).

Documentation 44
 Contents of BPR
• Name, Batch number and Qty. of bulk finished product to be
packed
• Theoretical and Actual Yield and Reconciliation
• The date and time of the packaging operation
• The name of responsible person and his initials
• Details of packaging instructions like equipments and
packaging lines used
• Qty. along with identification of different printed packaging
materials issued, used, destroyed and/or returned to store
and reconciliation
• In any case of problems, if any deviation made, written
authorization for the sameDocumentation 45
 SITE MASTER FILE

• Introduction

• Inclusions of Site Master File

Documentation 46
 Introduction
• Site Master File is a document, which
gives a complete information regarding a
site of pharmaceutical plant.
• This document generally should not be
very massive, like running into more than
100 pages.
• M.H.R.A. has given certain guidelines for
length of the format for it.

Documentation 47
 Inclusions OF SMF
• The Information about -
– Company
– Personnel
– Premises and Equipment
– Documentation
– Production
– Quality Control
– Contract manufacture and analysis
– Distribution, Complaints and Product Recalls
– Regulatory inspections and self-inspections
– Details of Annual Product Review
– Change Control System
– Technical Quality Agreement for Contract Manufacturing
Documentation 48
(Technical Agreement, Quality Agreement)
 Calibration Records
Calibration:-
The act of checking or adjusting (by comparison with a standard) the
accuracy of a measuring instrument.
Why?
 To confirm suitability of the equipment and proper operation of
the apparatus.
When?
 Before using new test equipment
 After relocation or major maintenance
 Calibration Records
The procedure must include the following details:
• Name of instrument
• Date of calibration
• reference standard used
• Other reagents or tool used
• Deviation
• Name & sign of person who calibrated
 Distribution Record
• It is a written data related to distribution of drug products from
the manufacturer to the distributors.
• These records should be maintained in such a way that complete
up to date and progressively recorded data of all batches of drug
products are easily available.
• Every distributor is also obliged to maintain a complete and
accurate record of further distribution

Why??

• An inventory card may be maintained to find out stock position

quickly.
• A distribution register may be maintained for detailed information
about distribution of each batch of drug product.
 Batch Packaging Records
• Batch Packaging Record should be kept for each batch or part
batch processed. It should be based on the relevant parts of the
Packaging Instructions and the method of preparation of such
• Records should be designed to avoid transcription errors.
• The record should carry the batch number and the quantity of
bulk product to be packed, as well as the batch number and the
planned quantity of finished product that will be obtained.
• Before any packaging operation begins, there should be recorded
checks that the equipment and work station are clear of previous
products, documents or materials not required for the planned
packaging operations, and that equipment is clean and suitable
for use.
 Batch Packaging Record
• The name of the product;
• The date(s) and times of the packaging operations;
• The name of the responsible person carrying out the packaging operation;
• The initials of the operators of the different significant steps;
• Records of checks for identity and conformity with the packaging instructions
including the results of in-process controls;
• Details of the packaging operations carried out, including references to equipment
and the packaging lines used;
• Whenever possible, samples of printed packaging materials used, including
specimens of the batch coding, expiry dating and any additional overprinting;
• Notes on any special problems or unusual events including details, with signed
authorisation for any deviation from the Manufacturing Formula and Processing
• Instructions
• The quantities and reference number or identification of all printed packaging
materials and bulk product issued, used, destroyed or returned to stock and the
quantities of obtained product, in order to provide for an adequate reconciliation.
 Retention of Record
• Record should be kept in such a way that activities concerning the production
and QC of API are traceable.
• Record should be retained for at least one year after the expiry of the finished
product or for a specified period if there is no expiry date.
Life cycle of record have three stages:
• Stage 1: Active Use- the record is currently in use and/or is referred to
frequently
• Stage 2: Semi Active use- The record is not in current use but still referred to on
occasion
• Records in stage 1 & 2 are retained and stored for as long as they are useful to
the organization, whether that be for six months or ten years. Very few records,
if any are actually in semi active use after ten years. Records no longer in use are
in the final stage of life cycle that is stage 3.
• Stage 3: Disposition- The record is no longer use. It is rarely or never needed for
reference. It is no longer needed for legal or financial purposes.
• Most record in stage 3 are destroyed or discarded
IF DOCUMENTED IT IS DONE

Documentation 55