DOCUMENTATION

Dr. Misari Patel

Assistant Professor
IPNU
• Documentation is essential part of the quality assurance system and as such,
should be related to all aspect of GMP.
• Its aim is to define the specifications for all materials and the method of
manufacture and control, to ensure that all personnel concerned with
manufacture have the information necessary to decide whether or not to release
a batch of a drug for sale, and to provide an audit trail that will permit
investigation of the history of any suspected defective batch.
• The specifications should describe in detail the requirement with which the
products or materials used or obtained during manufacture have to conform.
• They serve as a basis for quality evaluation.
• Documentation provides the route for auditors to assess the over all quality of
operations within a company and the final product.
 TYPES OF DOCUMENT

There are various types of procedures that a GMP facility follows.

I. Quality manual: A global company document that describes, in paragraph form, the
regulations and /or parts of the regulations that the company is required to follow.
II. Policies: Documents that describe in general terms, and not with step-by-step
instructions, how specific GMP aspects (such as security, documentation, health, and
responsibilities) will be implemented.
III. Standard operating procedures (SOPS): Step-by-step instructions for performing
operational tasks or activities.
IV. Batch records: These documents are typically used and completed by the manufacturing
department. Batch records provide step-by-step instructions for production-related
tasks and activities, besides including areas on the batch record itself for documenting
such tasks.
V. Test methods: These documents are typically used and completed by the quality
control (QC) department. Test methods provide step-by-step instructions for
testing supplies, materials, products, and other production-related tasks and
activities, e.g., environmental monitoring of the GMP facility. Test methods
typically contain forms that have to be filled in at the end of the procedure; this
is for documenting the testing and the results of the testing.
VI. Specifications: Documents that list the requirements that a supply, material, or
product must meet before being released for use or sale. The QC department
will compare their test results to specifications to determine if they pass the
test.
VII. Logbooks: Bound collection of forms used to document activities. Typically
logbooks are used for documenting the operation, maintenance, and calibration
of apiece of equipment. Logbooks are also used to record critical activities, e.g.;
monitoring of clean rooms, solution preparation, recording of deviation, change
controls and its corrective action assignment
 BATCH PROPUCTION RECORDS/BATCH
PRODUCTION ANDCONTROL, RECORDS
(BPCR)/BATCH MANUFACTURING RECORD (BMR)

• Definition: Batch manufacturing record is a written document of the batch, prepared

during pharmaceutical manufacturing process. It contains actual data and step by step
process for manufacturing each batch.
• Batch manufacturing record is like a proof that batches were properly made and checked
by quality control personnel.
• Batch production records should be prepared for each intermediate and API/formulation
and should include complete information relating to the production and control of each
batch.
• The batch production record should be checked before issuance to assure that it is the
correct version and a legible accurate reproduction of the appropriate master
production instruction.
• Before any processing begins, a check should be performed and recorded to
ensure that the equipment and workstation are clear of previous products,
documents, or materials not required for the planned process and that the
equipment is clean and suitable for use.
• These records should be numbered with unique batch or identification number
and dated and signed when issued.
• The batch number should be immediately recorded in a logbook or by electronic
data processing system.
• The record should include date of allocation, product identity, and size of batch.
Documentation of completion of each significant step in the batch production
records (batch production and control records) should include:
• Dates and, when appropriate, times.
• Identity of major equipment used (e. g, reactors, driers, mills, etc.)
• Specific identification of each batch, including weights, measures, and batch
numbers of raw materials, intermediates, or by reprocessed materials used during
manufacturing.
• Actual results recorded for critical process parameters.
• Any sampling performed.
• Signatures of the persons performing and directly supervising or checking each
critical step in the operation.
• In-process and laboratory test results.
• Actual yield at appropriate phases or times.
• Description Of packaging and label.
• Representative label (commercial supply).
• Any deviation noted, its evaluation, and investigation conducted (if appropriate) or
reference to that investigation (if stored separately).
• Results of release testing.
• All analytical records relating to the batch, or a reference that will permit their
retrieval.
• A decision for the release or rejection of the batch, with the date and signature of
the person responsible for the decision.
• The production record review.
 MASTER FORMULA RECORD

Definition: A document or set of documents specifying the starting material with their quantities
and the packaging materials, together with a description of the procedure and precautions
required to produce a specified quantity of a finished product as well as the processing
instructions, including the in-process controls.“
Master production instructions should include:
• The name of the intermediate/AP/ formulation being manufactured and an identifying document
reference code, if applicable
• A complete list of raw materials and intermediates
• An accurate statement of the quantity or ratio of each raw material or intermediate to be used,
including the unit of measure.
• The production location and major production equipment to be used
• Detailed production instructions, including the:
i. Sequences to be followed
ii. Ranges of process parameters to be used
iii. The methods, or reference to the methods, to be used for preparing the critical equipment
(e.g., cleaning, assembling)
iv. Sampling instructions and in-process controls, with their acceptance criteria where
appropriate
v. Time limits for completion of individual processing steps and/or the total process, Where
appropriate
vi. Expected yield ranges at appropriate phases of processing or time
• Where appropriate, special notations and precautions to be followed
• Instructions for storage of the intermediate or API/semi-finished formulations to assure
its suitability for use; instructions should cover the labeling (specimen label sand
packaging materials and special storage conditions with time limits, where appropriate).
• Master Formula Record is also called MFR, Master Production Record. MFR is used as
reference standard for preparing batch manufacturing record (BMR) by manufacturing
units.
• It contains all Information about the manufacturing process for the product.
• There shall be Master Formula records relating to all manufacturing procedures for each
product and batch size to be manufactured.
• These shall be prepared and endorsed by the competent technical staff i.e., head of
production and quality control.
• A Master Formula Record is ether prepared based upon experience qualified staff like
manufacturing chemist or analytical chemist or prepared based upon batch
manufacturing record of a batch size.
MFR includes-
• Product Details : Name, logo and address of the manufacturing company
• Dosage form name. Brand name, Generic name.
• Product code and Label claim of all ingredients
• Product description : Batch size, Pack size and packing style
• Shelf life and Storage conditions
• MFR number and date: Supersede MFR number and date
• Effective batch number
• Authorization by the production and quality assurance head
• Equipment: A list of all required equipment and machines required in the Manufacturing
process with their capacity
• Special instructions: The precautions and special instructions to be followed during the
product manufacturing and packing
• Calculations: Include the calculation steps of all active materials to get the 100% of the
active material.
• Manufacturing Process: All steps in all stages of the manufacturing process are written. All
process steps like shifting, milling, lubricating, granulation, compression and coating are
written in detail including the process time and yield. It also include atmospheric
conditions as temperature, humidity, and storage conditions for every step
• Packing Process: List of all packing materials with their quantity is written. Line clearance,
reconciliation of printed and unprinted packing materials should be included in details
• Yield: Include the theoretical, actual yield and acceptance limit of the batch. Primary

Responsibility is of FD and Production Department and secondary responsibility is of

Quality Assurance Department. Accountability lies with Head-Quality Assurance for
Implementation of SOP.
 SOP

• A Standard Operating Procedure (SOP) is a set of written instructions that document a

routine or repetitive activity which is followed by employees in an organization.
• The development and use of SOPs are an integral part of a successful quality system.
• It provides information to perform a job properly, and consistently in order to achieve
pre-determined specification and quality end result.
BENEFITS OF SOP
1. To ensure that processes continue uninterrupted and are completed on a Described
schedule. Ensure against process shut-downs caused by equipment failure or other
facility damage.
2. To ensure that no failures occur in manufacturing and other processes that would
harm anyone in the surrounding community.
3. To ensure that approved procedures are followed in compliance with company and
Government regulations. Well-written SOPs help ensure that government regulations
are satisfied. They also demonstrate a company good-faith intention to operate
properly.
4. To serve as a training document for teaching users about the process for which the
SOP was written. Thorough SOPs are used as the basis for providing standardized
Training for employees who are new to a particular job and for those who need
retraining.
5. To serve as a checklist for co-workers who observe job performance to reinforce
proper performance. When the proper procedures are outlined in a good SOP, any co-
worker can coach another to help improve work skills.
6. To serve as a checklist for auditors. Auditing job performance is a process similar to
Observation mentioned in the previous item only it usually involves record keeping.
SOPs should serve as a strong basis when detailed audit checklists are developed.
7. To serve as an historical record of the how, why and when of steps in an existing
process so thee is a factual basis for revising those steps when a process or equipment
are changed. As people move from job to job within and between companies,
unwritten knowledge and skills disappear from the workplace. Properly maintained
written SOPs can chronicle the best knowledge that can serve new workers when
older ones move on
8. To serve as an explanation of steps in a process so they can be reviewed in accident
investigations.A good SOP gives you a basis from which to being investigating accidents
FORMAT OF TECHNICAL SOP
In general, technical SOPs will consist of five elements:
• Title page
• Table of Contents
• Procedures
• Quality Assurance/Quality Control
• References
1. Title Page.
2. Table of Contents
3. Procedures - The following are topics that may be appropriate for inclusion in technical
SOPS. Not all will apply to every procedure or work process being detailed.
a. Scope end Applicability (describing the purpose of the process or procedure and any
organization or regulatory requirements, as well as any limits to the use of the
procedure),
b. Summary of Method (briefly summarizing the procedure),
c. Definitions (identifying any acronyms, abbreviations, or specialized terms used),
Health & Safety Warnings (indicating operations that could result in personal injury
or loss of life and explaining what will happen if the procedure is not followed or is
followed incorrectly; listed here and at the critical steps in the procedure
d. Cautions (indicating activities that could result in equipment damage, degradation of
sample, or possible invalidation of results; listed here and at the critical steps in the
procedures
e. Interferences (describing any component of the process that may interfere with the
accuracy of the final product),
f. Personnel Qualifications/Responsibilities (denoting the minimal experience the user
should have to complete the task satisfactorily, and citing any applicable requirements,
like certification or "inherently governmental function"),
g. Equipment and Supplies (listing and specifying, where necessary, equipment, materials,
reagents, chemical standards, and biological specimens
h. Procedure (identifying all pertinent steps, in order, and the materials needed to
accomplish the procedure such as:
• Instrument or Method Calibration and Standardization
• Sample Collection
• Sample Handling and Preservation
• Sample Preparation and Analysis (such as extraction, digestion, analysis, identification, and
counting procedures)
• Troubleshooting
• Data Acquisition, Calculations & Data Reduction Requirements (such as listing any
mathematical steps to be followed)
• Computer Hardware & Software (used to store field sampling records, manipulate analytical
results, and/or report data)
• Data and Records Management (e.g., identifying any calculations to be performed, forms to be
used, reports to be written, and data and record storage information).
4. Quality Control and Quality Assurance Section- QC activities are designed to allow
self verification of the quality and consistency of the work. Describe the preparation of
appropriate QC procedures (self-checks, such as calibrations, recounting,
reidentification) and QC material (such as blanks; replicates; splits; spikes; and
performance evaluation samples) that are required to demonstrate successful
performance of the method. Specific criteria for each should be included. Describe the
frequency of required calibration and QC checks and discuss the rationale for
decisions. Describe the limits/criteria for QC data/results and actions required when
QC data exceed QC limits or appear in the warning zone. Describe the procedures
for reporting QC data and results.
5. Reference Section - Documents or procedures that interface with the SOP should be
fully referenced (including version), such as related SOPs, published literature, or
methods manuals.
 QUALITY AUDIT

• A systematic and independent examination to determine quality activities and related

results comply with the planned arrangements and whether these arrangements are
implemented effectively and are suitable to achieve objectives
• Quality audit are typically performed at defined intervals. Any failure in their proper
implementation may be published publicly and may lead to revocation of quality
certification
• TYPES OF AUDIT:
I. A first is an audit performed by an organization on itself i.e. an internal audit
II. A Second party audit performed by one organization on its own behalf on another
usually on a supplier by a customer
III. A third party audit is an audit by an independent organization other than the
customer on a supplier
PHASES OF AUDIT:
• Phase-01 Preparation: this phase precedes the actual review meeting it is the
responsibility of the chairman and presenter to organize the quality review and notify all
that invited
• Phase-02 The review meeting: the central phase of quality review process is the review
meeting itself during the review meeting the emphasis should be on error detection, in
line with the criteria, and only limited discussion of corrective action should occur
• Phase-03 The follow-up: following the quality review meeting there should be a follow up
period during which the error identification at the review that were committed to
follow-up action list are rectified and signed
OBJECTIVES OF QUALITY AUDIT:
Pharmaceutical manufacturer audit as an effective mechanism to verily comply with GMP
regulation.The general objectives of quality audit are as follows:
• To determine conformity or non conformity of the quality system elements with
specified requirements
• To determine the effectiveness of the implemented system in meeting specific quality
objectives
• To afford an opportunity to improve the quality system
• To provide managers with information
• Internal Audit (Self Inspection): Conducted within the premises to monitor the
implementation and respect of GMP. This is also done to have prior information
about the flaws in the system and taking necessary corrective and preventive
measures.
• Observations of internal team must be well documented
• Written instructions by company for internal audit, questionnaire
1. Personnel 2. Premises including personnel facilities
3. Maintenance of buildings & equipments
4. Storage of starting materials & finished products
5. Equipment 6. Production & in process controls
7. Q.C. 8. Documentation 9. Sanitation & HYGIENE
10. Validation & revalidation programmes 11. Recall procedure
12. Calibration of instruments 13. Complaints Mgt
14. Labeling control
15. Results of previous self inspections & corrective measures taken

STEPS OF INTERNAL QUALITY AUDIT

1. Constitution of Internal audit team: Team members from out side or inside the
company constituted by Mgt. , Expert should be experienced, familiar of GLP concept
2. Frequency of Audit: At least once a year, stated in procedure
3. Audit Report: At completion of process, report of results, evaluation, conclusions of
inspection along with the corrective measures
4. Follow up action: Company should evaluate internal audit & recommend corrective
measures to be followed timely for effective results
Exteral Audit: Conducted for the suppliers or any outsourcing operations carried out
by the pharmaceutical industry. The contract giver (Industry) is responsible to access
the competence of the Contract acceptor (supplier or any other outsource operations
department) as per the GMP guidelines.
Done to evaluate the ability of suppliers (raw material, packaging materials etc.) to
conform GLP std. Pharmaceutical company may conduct audits of their suppliers –
External audits
STEPS
1. Notification: To alert the company, Date & time of audit. List of documents auditors
wants to review can be provided
2. Planning: The auditor identify key areas of risk & areas of concern to be evaluated
during audit
3. Opening Meeting: Meeting b/w auditors & staff of company under audit. Process of
audit is described. Company under audit – explains auditors about schedule of
employees, areas of concern of audit
STEPS
4. Start of Audit procedure: After opening meeting, final audit plan is prepared.
Company employees are notified of audit sch. & procedure starts
5. Communication: Audit team should be in touch with company’s audit team for
clarifications on procedures, for access to company docs.
6. Draft audit report: After completion of audit, draft report is prepared. It contains
outcomes of audit, list of concerns. Then submitted to company Mgt. for review &
suggestions if any
7. Mgt response: Final audit report is prepared and submitted to company Mgt. The
Mgt is requested for there agree/ disagree with report, any corrective measures,
problems etc. & expected date of addressal of problems or compliance.
STEPS
8. Final Meeting: Between auditors & company officials/ Mgt. to close loose
ends, discuss Mgt. response & scope of audit
9. Report distribution: Distribution of final audit report to concerned officials
inside & outside audit area
10. Feedback: Audited company implements recommended changes & auditors
review, test quality, adherence effects of implemented changes.
• It is mandatory that there should be a well written procedure for conducting an audit
whether it is an internal or external audit.
Important points in Quality Audit
• Frequency of Audit: The procedure how frequency of audit must be defined and as
per that frequency must be set and followed accordingly.
• Responsibilities: The audit team must be defined that who will be responsible for
conducting and reviewing the audit reports. The people in the audit team must be well
equipped with the operations and procedures that are being audited.
• Documentation: It is important to document each and every audit conducted as it not
only helps from regulatory perspective but also act as reference document to have a
insight of flaws previously faced.
 CONDUCTING AUDIT:
• The audit team must abide rules and regulations specific to the operations carried
out at the premises. Ex: if the audit is conducted in aseptic section it is mandatory
to put the safety clothing as per cGMP that is must for everyone who so ever enter
that portion.
• The audit must be done by communicating by the audit team with the personnel
working and all the findings must be documented. But it is also important to
explain the observations that make it more realistic rather than just noting it down
and explaining later on.
• The audit team must be flexible. The procedure to meet the requirements of cGMP
could be different in different industries hence the auditor must focus on the results
and then decide about the observations.
• The conclusions obtained must be prepared, documented and finally completed as a
audit report.
 QUALITY REVIEW & QUALITY DOCUMENTATION
• Quality Review is the last stage in QC procedure, before the dispatch of product
• It ensures that the finished product released for sale, all the relevant records
(production and control records) are cross checked i.e. reviewed.
• Thorough investigation of any batch not conforming to standards
• Other batches of same product with specific failure needs to be investigated
• Written record of investigation, conclusion of investigation, follow up (remedial
measures) must be kept
Objective of Product Quality Review:
• To evaluate compliance status of manufacture & identify areas of
improvements
• It should involve personnel from QC unit, production, engineering,
maintenance, Purchase etc.
 QUALITY REVIEW & QUALITY DOCUMENTATION
Review of following should be done periodically & documented:
• Starting materials/ packaging material used, sources, supply chain
• Critical in process controls & finished product test
• Failed batches with results of investigation
• Significant deviations, investigations, preventive measures taken
• Changes done in process & analytical methods
• Sales authorization submitted, granted, rejected for third party (Exports) dossiers
• Stability monitoring results, adverse trends
• All quality related returns, complaints, recalls, investigation made
• Previous product, process or equipment corrective measures
• Post marketing commitments, new marketing authorizations etc
• Qualifying status of equipments, utilities used: HVAC
 QUALITY DOCUMENT (GDP GOOD DOCUMENT
PRACTICES)
• Document is any written statement or proof of any activity in pharmaceuticals.
Documentations are to define the manufacturers system of information & control, to
minimize the risk of misinterpretation & errors inherent in oral or casually written
communication, to provide unambiguous procedures to be followed to provide
confirmation of performance, to allow calculations to be checked & to allow tracing of
batch history
• Good documentation is a systematic procedure of preparation, checking, verifying,
issuing, storing and reviewing of any documents.
• Prevent errors of various activities in pharma
• Purpose of Documentations
• Defines specifications and procedures for all materials and methods of manufacture
and control
• Ensures all personnel know what to do and when to do it
• Ensure that authorized persons have all information necessary for release of product
• Ensures documented evidence, traceability, provide records and audit trail for
investigation
• Ensures availability of data for validation, review and statistical analysis.
 QUALITY DOCUMENT (GDP GOOD DOCUMENT
PRACTICES)
• Classification of Documentation
• organization & Personnel.
• For Buildings & facilities
• For Equipments.
• For Handling of R.M.& P.M.
• For Production & process control.
• For Packaging & Labeling control.
• For Holding & Distribution
• For Laboratory Control.
• For Records & Reports.
• For Return & Salvaged finished products.
 QUALITY DOCUMENT (GDP GOOD DOCUMENT
PRACTICES)
• Preparation, issues and uses of Documents
Documents should be carefully and logically specify to prevent wrong uses. All
necessary information’s are written unambiguously. Each document includes:
1. Company name
2. Purpose and title of documents
3. Identification No and revision No.
4. Date of authorization
5. Date of review
6. Signature of prepared by, checked and authorized by.
7. Distribution list
8. Page no.
9. Reason for revision should be documented.
10. Abbreviation and reference
HEIRARCHY OF QUALITY DOCUMENTATION SYSTEM

Outlines company’s Goal, mission, vision

Quality
Manual

Define the quality objectives

POLICY

Describes what should be done, by whom,,

PROCEDURE how, when, where

Working Description of activities

instruction
Quality documentation system
Records
 QUALITY MANUAL
• It is guiding document, approved by upper management, outlines companies goals,
vision and mission,
• Describes the scope of QMS: what to be included in Quality system
• Explains each & every requirement of ISO 9001
It should include:
• Title & table of contents
• Scope of QMS
• Exclusions from ISO 9001
• Version information & approval
• Quality policy & objectives
• QMS description
• Business process model of organization
• Definition of responsibilities for all personnel for all personnels
• References to relevant documents
• Relevant appendices
 QUALITY MANUAL-QUALITY POLICY

Purpose of QUALITY MANUAL:

• Communicate mgt’s expectations for quality to the organization
• Organizations conformity with ISO 9001 requirements
• Measure for compliance to Mgt’s expectations for Internal audits: ISO Registrar audits,
customer audits
QUALITY POLICY:
• It is declaration by the organization
• It defines the quality objectives to which the organization strives.
• Should provide outline for creating, stating, measuring the performance of quality objectives
• Ex: To provide products & services meeting the expectations of customers. Actively pursue
ever improving quality by various programs so to enable the employees to do the wok
correctly for the first time and ever
 QUALITY MANUAL- QUALITY PROCEDURES
It can be described by text, tables, flowcharts to make them effective
• Elements of quality procedures:
1. Title: Identifies procedure
2. Purpose: Explain why this procedure
3. Scope: what expects will be covered in procedure & what will not
4. Responsibilities of all persons, functions to be the part
5. Records as a result of activities done as per procedure
6. Document control: Identification of changes, date of review, approval & version
of document should be included in procedure
7. Description of activities: This relates all other elements of procedures, describes
what to be done, by whom, how, when & where. Its most imp. Inputs & outputs
of activities must be explained
8. Appendices to be included if required
 QUALITY MANUAL- WORK INSTRUCTIONS
It covers following
1. Manner in which work will be done
2. Equipment & tools that will be used
3. Environment or location associated with the work
4. Material handling requirements
5. Safety alerts for all employees
6. Cross reference to any other required process or instructions
7. Critical process & Product parameters to be monitored including
instructions of monitoring
8. Equipment maintenance procedures
9. Methods for verifying that product meets specs
10. Other non product related criteria for the final product
 QUALITY MANUAL- RECORDS
• It is final tier of Quality Documentation system. All data, information's,
records, forms etc are achieved. Quality records management shows that
quality system has been executed.
• It describes how the quality of end product was verified to meet the specs,
meeting the customers satisfaction and needs.
• SOURCES QUALITY RECORDS
• Non conformance investigations
• CAPA’s (Corrective & preventive action)
• AUDIT RESULTS
• SUPPLIER DOCUMENTATION
• CALIBRATION RESULTS
• MAINTENANCE RECORDS
 REPORTS & DOCUMENTS
• They are used through out manufacturing process, and in supporting process
(QA/QC). It must meet Good Documentation Process. Various records/ reports are
(some)
• Batch Record Form * Bill of materials
• Specifications * Policies
• Protocols * SOP’s
• Work instructions * Checklist
• Forms/ Log sheets * Certificate of analysis
• Technical transfer reports * Technical agreements
• Technical reports * Test methods
• Training assessments * Worksheets, logbooks, etc
• Validation docs * Quality manual
• Audit plans * Manufact./ pack. Instructions
• Quality system docs * Deviation reports etc
 DISTRIBUTION RECORDS
• Good distribution practices (GDP) : Proper storage & distribution of drug products
minimizes risk of its quality
• These are written data of distribution of drug products from Mfg. to distributors
• Records of distribution retained, accessible to trace history if req.
• Helps in recall of product when in need
• Distribution Records contain information on wholesalers, direct costumers
• SOP’s of warehousing & distribution of products to be adopted
• Periodic audit of warehouse & distribution centers
• Before dispatch of a batch, ensure about the testing, approval, & release by QC,
• Random inspection on consignments to ensure correctness of goods must be done
• Maintain Distribution registers having details about distribution: Name, strength, dosage
form description, consignees name & address, date & quantity shipped, lot number of
drug product. Maintain inventory card also to find the position of stock.
 DISTRIBUTION RECORDS

FORMAT OF INVENTORY CARD

M/S Name & address of company

Name of Poduct
Receipt No Date of issue
Transfer No.
Quantity Received
Quantity Issued Invoice No.
Batch No.
Address of distributor
Balance Sign of issuing person
 DISTRIBUTION RECORDS
• Checklist of distribution records
1.Whether pre dispatch inspections are carried out before release
Y/N
2.Whether periodic audit of distribution centre are carried out to
access warehousing practices Y/N
3.Whether distribution records are part of batch record. If not
how batch wise distribution record up to retail levels are
maintained Yes/N
4.Whether instruction for warehousing & stocking of products
like Low volume parentrals (LVP’s), heat sensitive etc. are
available in store Yes/N
5.Whether Good distribution practices followed Y/N