B PHARMA 6TH SEM
PHRAMACEUTICAL QUALITY ASSURANCE
Pharmaceutical documentation
Need of documentation
Objectives of documents
Scope
Documentation lifecycle
Types of documents
Characteristic of document
Documentation review
Documents model
Standard operating procedures (sop’s)
Master formula record
Batch formula record
Quality audit plan and reports
Specification and test procedures
2. CONTENTS
2
1. Introduction
2. Need of documentation
3. Objectives of documents
4. Scope
5. Documentation lifecycle
6. Types of documents
7. Characteristic of document
8. Documentation review
9. Documents model
10. Standard operating procedures (sop’s)
11. Master formula record
12. Batch formula record
13. Quality audit plan and reports
14. Specification and test procedures
4. INTRODUCTION
4
Documentation is the cornerstone of any company’s quality management
system and is an essential GMP requirement.
It is critical that anyone dealing with GMP documents and documentation
systems understand the regulatory requirements and adopts best practice.
It defines a system of information and control so that risks inherent in
misinterpretation and/or error in oral communication are minimized.
5. NEED OF DOCUMENTATION
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Mandatory asper regulatoryguidelines
Keep track of activities
Evidence toface legal issues
Maintains ahistorical record
6. OBJECTIVES OF DOCUMENTS
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To define the specifications and procedures for all materials and method of
manufacture and control.
To ensure that all personal concern with manufacture know what to do and
when to do it.
To ensure that authorized persons have all the information necessary to decide
whether or not to realize a batch of a drug for sale.
To ensure the existence of documented evidence, trace ability, and to
provide records and an audit trail that will permit investigation.
It ensures the availability of the data needed for validation, review and
statistical analysis.
7. SCOPE
Good documentation encompasses practically all the aspect of
pharmaceutical production:
Building And Premises: Installation, Validation , Cleaning And Maintenance
Personnel: Training, Hygiene Etc
Equipment: Installation , Calibration , Validation , Maintenance , Cleaning
Materials: Specification, Testing, Ware-housing, Use, Rejection/Disposal.
Processing: Individual Steps In The Process Of Manufacturing Including
Controls Thereof.
Finished Goods: Specifications, Testing, Storage, Distribution, and
Rejection/Disposal. 7
10. TYPES OF DOCUMENTS
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Quality manual
Logbooks
Specifications
Test methods
Standard operating procedures (SOPs)
Policies
Batch records
11. CHARACTERISTIC OF DOCUMENT
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For effective useof documents, they should be designed and prepared with utmost
care. Eachdocumentshall:
(i) Haveacleartitle.
(ii) Havean identificationnumber.
(iii) Beapproved by authorizedperson.
(iv) Havethe date ofissue
(v) Haveadue date ofrevision.
(vi) List to whom it hasbeen issued.
12. “WHERE THE DOCUMENTS CARRY
INSTRUCTIONS”
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(i)Theinstructions shallbe precise and not ambiguous.
(ii)Theyshall be for eachindividual step and not combined.
E.g.Weigh the materials; charge the weighed materials into the blend
(iii)Instructions shallbe in imperative mood.
13. “WHERE ENTRY OF ANY DATA IS EXPECTED”
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(i)Sufficient space shall be provided for making the entry.
(ii)Heading shall clearly indicate what is to be entered, and who is responsible.
(iii)All entries shall be in ink.
(iv) All entries shall be clear and legible.
(v) Person making the entries shall confirm the entry by initialing/signing the
same.
(vi)An error in entry shall be so corrected that the original (wrong) entry is not lost.
Such correction shall also be initialed and dated. Where necessary, reason for
correction shall also be recorded, initialed and dated
14. DOCUMENTATION REVIEW
Documentation system should provide for a periodic review, and revision, if necessary, of any
document, or part thereof.
Such revised versions shall also be approved by the authorized persons.
Updated/revised versions shall also be superseding the previous edition, and
the document shall clearly indicate this.
Outdate/superseded document shall be immediately removed from active use, and copy retained
only for reference.
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15. ELECTRONIC DATA
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If documentation is through electronic data processing system
(computerized system) there shall be adequate, reliable systems in place:
1.To check and ensure correctness of data.
2. To record changes (addition/deletion)
3. That meets other regulation requirement, if any
16. “DOCUMENTS” MODEL
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D= Design, development, deviations, dossiers and Drug Master Files for regulated markets, distribution
records
O= Operational procedures/techniques/methods, Out of specifications (OOS), Out of trend (OOT)
C= Cleaning, calibration, controls, complaints, containers and closures, contamination and change control
U= User requirement specifications, utilities like water systems, HVAC, AHU etc.
M= Man, materials, machines, methods, maintenance, manufacturing operations and controls, monitoring,
master formula, manuals (quality, safety and environment), medical records
E= Engineering control and practices, Environment control, Equipment qualification documents
N= Non-routine activities, New products and substances
T = Technology transfer, training, testing, Trend analysis, Technical dossiers supplier qualification,
S= SOPs, safety practices, sanitation, storage, self-inspection, standardization, specifications and
standard test procedures and site master file
17. STANDARD OPERATING PROCEDURES (SOP’S)
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A typical Pharmaceutical Industry has an average of 1200- 1300 SOPs.
A Parenteral Drug Association (PDA) survey found that a typical
pharmaceutical company must manage an average of 1250 SOPs.
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.
18. BENEFITS OF SOP
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To provide people with all the safety, health, environmental and operational information necessary to
perform a job properly.
To ensure that production operations are performed consistently to maintain quality control of processes
and products.
To ensure that processes continue uninterrupted and are completed on a prescribed schedule.
To ensure that no failures occur in manufacturing and other processes that would harm anyone in the
surrounding community
To ensure that approved procedures are followed in compliance with company and government regulations.
To serve as a training document for teaching users about the process for which the SOP was written
To serve as a checklist for co-workers who observe job performance to reinforce proper performance.
To serve as a checklist for auditors.
To serve as an historical record of the how, why and when of steps in an existing process so there is a
factual
basis for revising those steps when a process or equipment are changed.
20. “HOW TO WRITE?”
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OBJECTIVE:
To lay down procedure for the preparation of Standard Operating Procedures.
SCOPE:
This procedure is applicable to all the SOP’s throughout the organization.
RESPONSIBILITY:
Person Performing: Respective HOD’s of concerning departments
Person Monitoring: QA officer/ HOD QA
PROCEDURE:
All SOP’s shall be computer typed using Times New Roman font.
21. “HOW TOWRITE?”
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Format of SOP shall be as per Annexure SOP/QA/002/1.
Each SOP has:
I) Header,
II)Signature block and
III)Body
Header: Present on all the pages of SOP and includes
Company Logo, Name, address & Concerned Dept.: Company Logo, CHARAK Pharma
Limited, Wagholi-Pune & Name of Concerned Department.
22. “HOW TOWRITE?”
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Document Type: STANDARD OPERATING PROCEDURE (In capital bold letters of font size 14)
Ref. No.: It is like SOP/DC/YYY-Z Where DC depicts the department code as below:
PE: Personnel Department PD: Production Department
MT: Maintenance Department QA: Quality Assurance Department
QC: Quality Control Department ST: Store Department
PU: Purchase Department
YYY is the sequential number starting from 001 for each department.
And Z is the revision status, starting from 0 for the original version and 1 for the next version
and so on. (In capital letters of font size 12).
23. “HOW TOWRITE?”
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Supersedes: It is the Ref. No. of the earlier version. (In capital letters of font size 12).
Effective Date: It is the date from which the SOP shall be put in use. The date format has to be
DD/MM/YYYY, where DD indicates the date, MM indicates the month & YYYY indicates the
year (e.g. 01/11/2007). Date shall be written with blue indelible ink pen.
ReviewDate: It is the Month & Year during which the SOP shall be revised e.g. 21/2013,
written with blue indelible ink pen. It shall be maximum 2 years from the effective date.
Page No.: It is like X OF Y. Where X is the individual page number and Y is the total number of
pages. (In capital letters of font size 12)
24. “HOW TOWRITE?”
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Title: It shall be clear and descriptive. (In bold capital letters of font size 12).
Signature Block: It shall be below the header and only on the first page of the SOP.
(Titles in the rows & columns shall be in bold letters & other text in normal letters of font size
12. Name and designation shall be typed. And signature and date shall be put in blue indelible
ink pen)
Prepared by: Signature with date, name and designation of the person from user department
who has drafted the SOP.
Verified by: Signature with date, name and designation of the HOD or the person from user
department who has verified the draft of the SOP.
Authorized by: Signature with date, name and designation of the person authorizing SOP,
DGM QA or HOD QA.
25. “HOW TOWRITE?”
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BODY: It shall contain the subject matter, which is written in the following manner.
(Subtitles in capital bold letters and text matter in normal letters of font size 12).
Objective: It shall define the purpose of the SOP.
Scope: It shall define the area of application.
Responsibility: It shall specify the person responsible for carrying out and monitoring the
activity as per the SOP.
26. “HOW TOWRITE?”
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PROCEDURE:
It shall give all steps required by the process in a proper sequence and instructions to be
followed while carrying out the activity so as to achieve the desired goals.
Procedure shall be:
a) Logically lay out.
b) Written in the imperative (authoritative) tense.
c) User friendly.
d) Simple to understand and in plain unambiguous English.
e) To the point with no unnecessary information.
f) In standardized terminology.
27. “HOW TOWRITE?”
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ABBREVIATION: This shall include list of abbreviations used and their meaning.
ANNEXURE: This shall include list of annexure attached.
REFERENCE: This shall include list of reference documents.
ABBREVIATION:
HOD : Head of the Department SOP : Standard Operating Procedure.
QA : Quality Assurance DGM : Deputy General Manager
ANNEXURE:
Annexure – SOP/QA/002/1 - ‘Standard Operating Procedure’ Form.
REFERENCE:
SOP issuance logbook
Standard SOP format.
29. MASTER FORMULA RECORD
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Master formula record (MFR) is a master document for any pharmaceutical
product.
It contains all information about the manufacturing process for the product.
MFR is prepared by the research and development team of the company and all
other documents like BMR and BPR (Batch packaging record) are prepared using
MFR by the manufacturing units.
32. BATCH FORMULA RECORD
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A batch manufacturing record is a document designed to provide a
complete record of the manufacturing history of a batch of product.
The US Food and Drug administration defines a batch as “a specific
quantity of a drug or other material that is intended to have uniform
character and quality, within specified limits, and is produced according
to a single manufacturing order during the same cycle of manufacture”.
33. PREPARATION OF BMR
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They normally contain information that relates to the following aspects of the manufacture of a batch of product:
Dates of start and finish of manufacture.
Lists all materials used and amounts of each used.
Lists of packaging materials used.
Details of the steps completed in the manufacturing process and times of completion.
Initials of the person responsible at every stage.
Details and results of all in-process checks.
Reference to any equipment used.
Batch yield and reconciliation.
Any deviations.
Quality Control information.
34. QUALITY AUDIT PLAN AND REPORTS
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Conducting internal audits (self inspections) and external audits of suppliers
and outsourcing operations are key elements of a good quality system.
One aspect of a quality system that is identified in the recently released
International Conference on Harmonisation (ICH) Q10, “Pharmaceutical Quality
System”, and in other quality system standards such as ISO 9001, is that of
conducting audits as a means of evaluating compliance with the objectives of the
quality system.
Implementation of the quality management system model defined in ICH Q10
should result in achievement of the three main objectives stated in ICH Q10:
Achieve product realization, establish and maintain a state of control, and
facilitate continual improvement.
35. DOCUMENTATION AND
COMMUNICATION
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Theaudit results should be documented and communicated to management.
The method of documentation and communication including the security and confidentiality of
the audit reports should be defined in the procedure.
It is important to remember that those responsible for the audited operation should always
receive acopy of the report, including outsourcing management and supplier management.
Such reports should clearly describe the audit team observations including specific examples when
possible.
If commitments have been made to implement corrective actions, such commitments should be
included in thereport.
Security of audit reports should be strictly enforced and distribution of the report should be
limited.
When providing audit reports to external sources such as outsourcing companies or suppliers, a
subset of the internal report may be provided aslong asthe observations are included
36. SPECIFICATION AND TEST PROCEDURES
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A specification is defined as a list of tests, references to analytical procedures, and
appropriate acceptance criteria, which are numerical limits, ranges, or other criteria
for the tests described.
It establishes the set of criteria to which a drug substance or drug product should
conform to be considered acceptable for its intended use.
"Conformance to specifications" means that the drug substance and / or drug
product, when tested according to the listed analytical procedures, will meet the
listedacceptance criteria.
Specifications are critical quality standards that are proposed and justified by the
manufacturer and approved by regulatory authorities asconditions of approval.
38. PROTOCOLS AND REPORTS
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A protocol is a written statement to conduct the process along with the
procedure, test method, equipment handling, specifications, acceptance
criteria, report andapproval.
The report summarizes all results, gives recommendations for fixing errors
and/or improving the overall quality of the speech corpus and gives an
executive summary.
39. DISTRIBUTION RECORDS
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Distribution forms an important activity of the integrated supply chain management of
pharmaceutical products.
Various persons and entities are often responsible for the handling storage and distribution
of suchproducts.
The guidelines are intended to apply to all steps in the entire distribution/supply chain
Permanent information, written or electronic, should exist for each stored product
indicating recommended storage conditions, any precautions to be observed and retest
dates.
Pharmacopoeial requirements and current national regulations concerning labels and
containers should be respected at all times.
Procedures should be in place for temperature mapping, security services at the
warehouse, destruction of unsaleable stocks and on retention of the records.
40. ELECTRONIC DATA
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Electronic data can stand for
data in general that is exchanged via electronic communication lines
digital data inparticular
Data (computing), i.e. computer -processable data asopposed to executable code
The Pharmaceutical industries are in a highly regulated environment, hence it requires effective
document management processes.
Having timely accurate data is critical for the success of any company.
Data has never been easy to manage, and is especially true in pharmaceutical industry.
Note that electronic information includes everything such as emails, adverse event reports,
complaints, batch records, quality control records -everything that is stored electronically.
Several technologies are being used currently in pharmaceutical industry to manage theirhuge
volumes of data generated on daily basis.