Pharmaceutical documentation

PHARMACEUTICAL DOCUMENTATION
A Project Submitted
In Partial Fulfillment of the Requirements
for the Degree of
BACHELOR OF PHARMACY
by
Rahul Sharma Rool No. 1226650033
Under the supervision
Of
Mr. Shailesh Kumar Singh
(Assist.Professor & HOD)
LTR Institute of Technology Kurali, Meerut (UP)
FACULTY OF PHARMACY
Dr. A. P. J. ABDUL KALAM TECHNICAL UNIVERSITY,
LUCKNOW
(Formerly Uttar Pradesh Technical University, Lucknow)
May, 2016

CERTIFICATE
Certified that Rahul Sharma (1226650033) has carried out the project work
presented in this entitled “Pharmaceutical Documentation”, for the award of Bachelor of
Pharmacy from Dr. A.P.J. Abdul Kalam Technical University, Lucknow under my
Supervision. The project embodies results of original work and studies are carried out by the
student himself and the contents of the project do not form the basis for the award of any
other degree to the candidate or to anybody else from this or any other University/Institution.
Supervisor: Date:- …....
Mr. Shailesh Singh Place :- Kurali
(Assistant Professor & HOD) (Meerut)
Department of Pharmacy
LTR Institute of Technology Kurali Meerut (UP

DECLARATIOAn hereby declare that works embodied in this project entitled
“Pharmaceutical Documentation” has been carried out by us in the Department of
Pharmacy, LTR Institute of Technologyn Kurali Meerut (UP) affiliated to Dr. A.P.J.
Abdul Kalam Technical University, Lucknow, during our B. Pharm. Final Year 2016.
Name Rool No.
Rahul Sharma 1226650033
signature
Date :-
Place :-Kurali (Meerut)

ACKNOWLEDGEMENT
We take privilege to acknowledge to all those who have helped us in completion of
the work. At first we express our deep sense of gratitude indebtedness to Mr. Anil Gupta
(Chairman) LTR Institute of technology who gave permission and accompanied to
complete our work. We are specially thanks full to Mr. Pratik Kansal (Education
directior) for accompanied to complete our work.
We are extremely grateful to Mr. Shailesh Kumar Singh & Mr. Prem Kumar
Singh for his guidance, constant encouragement and valuable suggestion which made us to
complete our work.
We are also grateful of Mr. Rubal Rathi & Mis. Farheen Malik for their personal
care, guidance & good education.
We are grateful to LTR Institute of Technology Kurali, (Meerut) for providing
infrastructure, computer lab, internet, library & other facility. We express our sincere thanks
to one and all that accompanied and helped throughout our educational career.
I am also thankful to our parents and entire classmate for their kind cooperation & the
author whose book I had consulted while making the project and to my teacher and my dear
friends.

ABSTRACT
Documentation is an integral part of good manufacturing practices. It defines a system
of information and control so that risks so inherent in misinterpretation and/or error in oral
communication are minimized. It consequently strengthens the quality and its consistency of
all goods and services as those responsible for the specific operations have clear
unambiguous instructions to follow including active drug substances is legally mandatory.
The purpose of this work is to specify the GMP requirements on documentation
within pharmaceutical industry. In this article firstly Processing of documents like
(preparation, issue, use, storage, retrieval, retention, and disposal) and briefly information
about the PMD is described. Secondly specification about key documents concerning
Manufacturing, testing, packaging and other aspects like (distribution, complaints, and labels)
are described. Documentation within pharmaceutical industry is an essential part of both the
Quality assurance and Quality control system. Documentation describes the specifications for
all materials, methods of manufacturing and control. It will allow the personnel to decide
whether or not to release batch for sale and also to permit investigation of history of batch of
product through tool of audit trails.
The Pharmaceutical industries are in a highly regulated environment hence it requires
effective document management processes. In addition to the strict regulatory environment
the Pharmaceutical companies must find ways of dealing with the increasing amount of
information that must be processed. 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. Along with the documentation management the security of data is also crucial. Note
that electronic information includes everything such as emails, adverse event reports,
complaints, batch records, quality control records – everything that is stored electronically. A
document management system is designed to automate a business process. In its simplest
form this involves capturing of paper documents so that an end user can retrieve the image of
paper document from their computer. Several technologies are being used currently in
pharmaceutical industry to manage their huge volumes of data generated on daily basis. Some
of the latest technologies are discussed in this review article along with their advantages and
disadvantages.
Keywords: PMD, Specifications, Quality Assurance, Quality Control, Batch, SOP, Record,
Document management, electronic records, Technology.

1. TABLE OF CONTENTS
S. No. Contents Page. No.
1 Documentation 1-8
2 Literature Review 9-11
3 Aim of Study 12
4 Good documentation practices 13-26
5 Type of documentation used in pharmaceutical industry 27-40
6 Document required as per ICH guideline 41-46
7 Document required as per WHO guideline 47-55
8 Document required as per USFDA guideline 56-59
9 GMP guidelines for records and reports 60-64
10 Documentation according to inspection and standards division of
the medicine and health care products regulatory agency
65-71
11 Implementation in documentation 72-82
12 Document for new drugs approval 83-102
13 Conclusion &Reference 102-105
2. LIST OF FIGURE
Fig. No. Figure Name Page. No.
1 Classic documentation hierarchy 17
2 Documentation flow path 18
3 Procedure approval of new druds 85
4 Flow chart approval of drug 88
5 The drugs approval process 88
LIST OF RECORD FORMAT
S. No. Name of Format Page. No.
1. Format for master formula record 29
2. Format for batch manufacturing record 32-35
3. Format of batch packaging record 36
4. Format for SOP 39-40

5. Format for form 44 96
6 Format for form 45A 99
7 Format for form 46 100
8 Format for form 46A 101
3 .LIST OF ABBREVIATIONS

S. No. Symbols Full Name
1. OPPI Organization of Pharmaceutical Producers of India
2. GMP Good Manufacturing Practice
3. WHO World Health Organization
4. GLP Good Laboratory Practice
5. ISO International Orrganization for Standardization
6. FDA Food and Drug Administration
7. OOS Out Of Specification
8. OOT Out Of Trend
9. HVAC Heating Ventilation and Air Conditioning
10. AHU Air Handling Unit
11. SOPs Standard Operating Procedures
12. BMR Batch Manufacturing Record
13. URS User Requirement Specification
14. BOMs Bills Of Materials
15. WIs Work Instructions
16. GDP Good Documentation Practices
17. FAT File Allocation Table
18. DQ Design Qualification
19. PQ Performance Qualification
20. IQ Installation Qualification
21. OQ Operational Qualification
22. PMD Pharmaceutical Manufacturing Documentation
23. USA United State of America
24. QA Quality Assurance
25. QC Quality Control
26. CFR Code Of Federal Regulations
27. LIMS Laboratory Information Management System
28. CD Compact Disk
29. ROM. Read Only Memory
30. CFR Code Of Federal Regulations
31. ICH International Conference on Harmonization
32. USFDA United State Food and Drug Administration
33. APIs Active Pharmaceutical Ingredients
34. INN International Non-proprietary Name
35. DMR’s Device Master Records
36. DHR’s Device History Records
37. QSR Quality System Record
38. MWFP Manufacturing Working Formula Procedure
39. ROI Return On Investment

40. CAPA Corrective And Preventive Action

41.DOCUMENTATION
Introduction
41.1. Objectives of documents
41.2. Scope
41.3. Characteristic of document
41.4. Different types of documents and records
41.5. Preparation, issue and use of documents
41.6. Pharmaceutical manufacturing documentation
41.7. Steps involved in total PMD programme
41.8. Storage and retention of documents
41.9. Storage and retrieval of documents
41.10. Disposal of documents

5. DOCUMENTATION:
5.1. Introduction: (17)
Documentation 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.
Documents are a mirror to show actual image of any pharmaceutical company. Documents
and products are produced in pharmaceuticals but regulatory bodies are interested to see
documents first. Different documents can describe the different activity in pharma and its
actual image.
Document is any written statement or proof. Documentation is an essential part of
Quality Assurance and Quality Control system and it is related to all aspects of Good
Manufacturing Practices (GMP). It is mainly defines the specification for all materials,
method of manufacturing and control. It also ensures that personnel concerned with
manufacturing should know information to decide whether to release the batch or not for sale
it also provides an audit trail which also allows the investigation of history of any suspected
defective batch. These documents should be approved, signed, dated by appropriate and
authorized person.
These documents shall specify their title, purpose and nature. They should be
regularly reviewed and kept up to date and if any alterations are made in their entry shall be
signed with date. For any organization it is very difficult to make a consolidated list of
documents which will meet all requirements of company. (32)
Objectives of documents: (26)
1. To define the specifications and procedures for all materials and method of manufacture
and control.
2. To ensure that all personal concern with manufacture know what to do and when to do it.
3. To ensure that authorized persons have all the information necessary to decide whether
or not to realize a batch of a drug for sale.
4. To ensure the existence of documented evidence, trace ability and to provide records and
an audit trail that will permit investigation.
5. It ensures the availability of the data needed for validation, review and statistical
analysis.

6. The design of documents as per the uses need of manufacturer.
7. To defines manufacturers system of information and control.
8. To allows the calculation to be checked.
9. To will prevent the risk of errors and misinterpretation which are inherent in oral or
casual written communication.
10. To trace the history of any product.
11. To provide confirmation of performance of task.
1.3. Scope: (17)
Good documentation encompasses practically all the aspect of pharmaceutical
production:
1. Building and premises: Installation, validation, cleaning and maintenance.
2. Personnel: Training, hygiene etc.
3. Equipment: Installation, calibration, validation, maintenance, cleaning.
4. Materials: Specification, testing, ware-housing, use, rejection/disposal.
5. Processing: Individual steps in the process of manufacturing including controls thereof.
6. Finished goods: Specifications, testing, storage, distribution, and rejection/disposal.
7. Complaints: Investigation, actions (including recall, if necessary).
1.4. Characteristic of document: (15)
1. For effective use of documents they should be designed and prepared with utmost care
each document shall:
 have a clear title.
 have an identification number.
 be approved by authorized person.
 have the date of issue.
 have a due date of revision.
 list to whom it has been issued.
2. Where the documents carry instructions (e.g. batch processing)
 The instructions shall be precise and not ambiguous.
 They shall be for each individual step and not combined. e. g. Weigh the materials,
charge the weighed materials into the blend.
 Instructions shall be in imperative manner.

3. Where entry of any data (e.g. temperature, weight) is expected to be made by the person
using the document:
 sufficient space shall be provided for making the entry.
 heading shall clearly indicate what is to be entered, and who is responsible.
 all entries shall be in ink.
 all entries shall be clear and legible.
 person making the entries shall confirm the entry by initialling/signing the same.
 an error in entry shall be so corrected that the original (wrong) entry is not lost. Such
correction shall also be initialled and dated. Where necessary reason for correction
shall also be recorded initialled and dated.
4. Documentation system should provide for a periodic review and revision if necessary of
any document or part thereof.
5. Such revised versions shall also be approved by the authorized persons.
6. Updated/revised versions shall also be superseding the previous edition, and the
document shall clearly indicate this.
7. Outdate/superseded document shall be immediately removed from active use and copy
retained only for reference. If documentation is through electronic data processing system
(computerized system) there shall be adequate reliable systems in place:
 To check and ensure the correctness of data.
 To record changes (addition/deletion)
8. For implementing efficient documentation practices which meet full GLP/GMP/ISO and
FDA requirements.
9. Here is a hint from the “DOCUMENTS” model, which lists out the areas required for
GMP document implementation :( 20)
 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
 S- SOPs, safety practices, sanitation, storage, self-inspection, standardization, supplier
qualification, specifications and standard test procedures and site master file.
1.5. Different types of documents and records:
Documentation and records used throughout the manufacturing process, as well as
supporting processes (e.g. Quality Control or Quality Assurance), must meet the basic
requirements of GDP. These include (but are not limited to):
1. Batch Record Forms
2. Bills of Materials (BOMs)
3. Specifications
4. Policies
5. Protocols
6. Standard Operating Procedures (SOPs)
7. Work Instructions (WIs)
8. Checklists
9. Forms/Log sheets
10. Certificate of Analyses or Certificate of Compliance
11. Technical transfer reports
12. Technical agreements
13. Technical reports
14. Test Methods
15. Training Assessments
16. Records
17. Worksheets, note books, and log books
18. Validation documentation
19. Manufacturing and packaging instructions

20. Confidentiality agreements
21. Change control
22. Quality system related documents
23. Quality manual
24. Validation protocols and reports
25. Deviation reports
26. Audit plans
27. Electronic and hard-copy Quality records (e.g. non-conformance, corrective and
preventative actions, internal inspection, change control, training records etc.)
28. Validation Master Plans and validation documents including URS, DQ, FAT, IQ, OQ,
PQ, and Validation reports.
29. Test material related documents including product specification, test material receipt and
reports.
30. Personnel related documents including training records.
31. Facility related documents including floor plans, HVAC plans, and environmental
specifications.
32. Deviation forms including unplanned deviations and system failure investigation.
1.6. Preparation, issue and use of documents(32):
Documents should be carefully and logically set out to allow their correct use and
easy to check. Each document should include.
1. The name of company.
2. Purpose and title of documents.
3. The document identity number.
4. Date of its authorization.
5. Date of its expiry or Review.
6. Signature of authorizing person.
7. Page number
8. The distribution list where copies are distribute.
9. The way in which it is used and by whom.
10. The reason for its revision.
11. References used in its preparation.
12. Issued documents should not be hand written.

Reproduced computer printed documents should be clear and legible. If any
corrections are made in entry of document should be signed and dated. Where the documents
which bears instructions should be written as imperative. Master documents which have
direct bearing on product quality should be authorized by person responsible for Quality
Assurance. Documents should allow sufficient space for entry, sufficient space between the
entries and should clearly indicate what is to be entered. (32)
1.7. Pharmaceutical Manufacturing Documentation (PMD):
It is a really complex subject. For a PMD programme one needs to carefully study
organizational environment and for this following need to be consider.
1. Manufacturing activities taken under that organization.
2. Which country’s requirements of documentation the company needs to fulfil e.g. W.H.O.,
U.S.A. or any other.
3. Level of computerization available in that organization.
4. Any other consideration.
1.8. Steps involved in total PMD programme:
Step 1: Identify at least 2 knowledgeable persons from production and Q.A/Q.C. who
are familiar with organization product profiles and Q.A/Q.C. Activities.
Step 2: List out the manufacturing formulation departments.
Step 3: List out the Q.A/Q.C. Activities.
Step 4: List out the countries where the product is likely to be sold and their PMD
requirements.
Step 5: Categories the documents so as to meet the requirements of step 4.
Step 6: Design the document.
Step 7: Explain the document to concerned persons and train them for using same.
Step 8: Trial run the document, study difficulties, modify if required.
Step 9: Implement the document.
Step 10: Review it by receiving feedback from users at regular intervals.
1.9. Storage and retention of documents: (32)
The completed documents and records of each batch should be retained for at least 1
year after expiry date of batch if expiry date is not mentioned then they should be retained for

at least 6 years from the date of its manufacturing. Master documents should be kept secured
from theft loss or alteration of information. Even the storage and retention of documents and
records can be done in electronic format in the form of microfilms and microfiche that are
photo reduced copies
1.10. Storage and retrieval of documents: (32)
The documents should be stored in such manner that their retrieval is easy and for this
purpose a system is adopted in which a list of documents are prepared as per their name,
location, person to be contacted for its retrieval. Retrieval of master documents should be
possible with proper authorization of Q.A.
1.11. Disposal of documents: (32)
The expired Documents must be destroyed by Q.A. with proper record and
authorization by suitable methods like shredding, burning.

PHARMACEUTICAL DOCUMENTATION PRACTICE
LTR INSTITUTE OF TECHNOLOGY KURALI, MEERUT (UP)
8. LITERATURE REVIEW
 Jones et al., (2010) suggested that the types of controls and the records and reports
that support them for the manufacture of finished drug products are well defined both
in terms of regulatory requirements and in industry practice. Adequate review of
executed BPRs serves at least two important purposes. The process satisfies the
regulatory requirement for such a step, and the process provides useful feedback to the
functional group responsible for the manufacturing step. As noted a high error rate
may indicate improper training or inadequate supervision, but it may also indicate a
poorly written procedure. Properly trained reviewers and approvers of BPRs provide a
valuable service to the quality assurance unit of a manufacturing organization.
 Brussels et al., (2011) suggested that good documentation constitutes an essential part
of the quality assurance system and is Key to operating in compliance with GMP
requirements. The various types of documents and media used should be fully defined
in the manufacturer's Quality Management System. Documentation may exist in a
variety of forms including paper-based electronic or photographic media. The main
objective of the system of documentation utilized must be to establish, control,
monitor and record all activities which directly or indirectly impact on all aspects of
the quality of medicinal products. The Quality Management System should include
sufficient instructional detail to facilitate a common understanding of the requirements
in addition to providing for sufficient recording of the various processes and
evaluation of any observations so that ongoing application of the requirements may be
demonstrated.
 Welankiwar et al., (2013) suggested that the design of documents depends upon the
manufacturer. Documentation also serves as existence of evidence and allows
traceability. Documentation is essential to achieve total approach towards GMP. It also
ensures the availability of necessary data needed for validation, review and statistical
analysis. It also allows audit trail which will permit the investigations. Master
documents like Master Formulae record, batch production record which have direct
bearing on the product quality should always protected against theft, loss and alteration
of information. Even the design of the PMD depends upon the manufacturing
activities, regulatory agencies certification, and computerization. These documents

also serve as written statements and proofs and should be carefully handled and kept
up to date. If any alteration is made in their entry should be signed and dated.
 Parikh et al., (2013) suggested that documentation consequently strengthens the
quality, and its consistency, of all goods and services, as those responsible for the
specific operations have clear unambiguous instructions to follow including active
drug substances, is legally mandatory. It is an integral part of good manufacturing
practices. It defines a system of information and control so that risks inherent in
misinterpretation and/or error in oral communication are minimized.
 Khan et al., (2013) suggested that Good documentation is a systematic procedure of
preparation, checking, verifying, issuing, storing and reviewing of any documents.
Documentation 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. It is any written statement or proof of any activity in pharmaceuticals.
Documents are a mirror to show actual image of any pharmaceutical company.
Documents and products are produced in pharmaceuticals but regulatory bodies are
interested to see documents first. Due to the importance given to documentation in
Pharma “good documentation practices” is required.
 Peters et al., (2014) suggested that the definition of Good Documentation Practice
(GDP) describes standards by which documentation is created and maintained in the
pharmaceutical industry. Although the U.S. Food and Drug Administration (FDA) set
some GDP standards, others fall under the current Good Manufacturing Practice
(cGMP). All pharmaceutical, bioscience and healthcare companies, as well as their
vendor partners, must observe GDP or face warnings or penalties levied by the FDA.
 Sandle et al., (2014) suggested that good documentation practices are an essential part
of GMP and compliance. When implemented the recommendations presented will help
with maintaining control and ensuring compliance in a GMP environment. The
effective control and management of documentation is a critical part of the GMP
program within the organization. An overview of good documentation practices
applicable to those working in the pharmaceutical and healthcare sectors is presented.

Specific topics for discussion include documentation fundamentals, document
creation, document management, best practices in style and layout, completing
documents and record-keeping, electronic records, storage, errors including error
correction, and associated topics.
 Panzade et al., (2014) suggested that uses good Manufacturing Practices (GMP)
numerous types of documentation exist and serve a variety of functions. Examples of
the functions of documentation include: providing a record of what was done,
instructing an individual on how to perform tasks, defining specifications, ensuring
traceability, and providing evidence that a product was made according to regulatory
or in house requirements. Although the U.S. Food and Drug Administration (FDA) set
some GDP standards, others fall under the current Good Manufacturing Practice
(cGMP). Any document required in accordance with regulations, especially the Good
Manufacturing Practice (GMP) regulations must be kept and made available for the
FDA upon an inspection or investigation.
 Abbas et al., (2014) suggested that proper documentation and record maintenance is a
principle step in good manufacturing practices regulations that a pharmaceutical
manufacturer must follow. Documentation provides a thorough knowledge of the
history and the present status of the manufacturing batch. Thus it provides a basis of
what should be done in future or for the improvement in the process. Effective
documentation provides the required information to the authorized personnel for the
release of the batch. I also provide the specification or the procedures for
manufacturing and control of the drug produces. The main purpose of the
documentation is to define procedures in written to the pharmaceutical so as to
minimize the errors, and this quality of the products is ultimately beneficial to the
company.
9. AIM OF STUDY
The main objective of the documentation, to increases the productivity and profits of
the pharmaceutical products & minimize the loss of investments. The documents are help in
planning, controlling, and co-coordinating of the material & production management in any

firm. They are also helps to increase the quality & quantity of the medicinal products and
formulation. The pharmaceutical documentation is essential for products demand estimation
in the market & also helps in the pharmaceutical marketing to selling history.
Documentation utilized must be to establish, control, monitor and record all activities
which directly or indirectly impact on all aspects of the quality of medicinal products in
pharmaceutical industry. Documentation are give 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 in pharmaceutical companies.
Documentation is ensuring that all personnel concerned with manufacturing know
what to do and when to do it. It ensures that authorized persons have all the information
necessary to decide whether or not to release a batch of a drug for sale in the market. The
purpose of these documents is to ensure the traceability of all data acquired and unusual
events during production and analysis. Documentation is give systematic procedure of
preparation, checking, verifying, issuing, storing and reviewing of any documents. Control of
document is also an important part of GDP to reduce error and misuses of any documents.
 GOOD DOCUMENTATION PRACTICES
a. Introduction
b. Good manufacturing practice and documentation
c. Types of documents
d. Document errors
e. Document fundamentals
f. Document creation
g. Document management
h. Document control
i. Best practices for document creation and use
j. Document style and layout

k. Completing documents and record-keeping

 GOOD DOCUMENTATION PRACTICES
1. Introduction:
The effective control and management of documentation is a critical part of the good
manufacturing practice (GMP) program within the organization. The accurate capture of
information plays an important part in the manufacture of pharmaceuticals and medical
devices (1). GMP is that part of quality assurance which ensures that products are consistently
produced and controlled to the quality standards appropriate for their intended use (2).
To comply with GMP, facilities require documented systems based on specifications,
manufacturing and packaging instructions, procedures, and records. In particular, specific
batch manufacturing documentation must be in place. These documents must make it
possible to trace the history of each batch. This traceability needs to be possible for a
minimum defined period that is typically one year after expiry of the batch. These types of
records are essential for the quality assurance system.
Documentation is also Key to GMP compliance for it ensures traceability of all
development, manufacturing and testing activities. Documentation provides the route for
auditors to assess the overall quality of operations within a company and the final product (3).
For example, with the FDA Code of Federal Regulations (CFR), 21CFR 211.180(e), records
and reports, states: "written records shall be maintained so that data therein can be used for
evaluating the quality standards of each drug product” This extract thereby links the
importance of good documentation to GMP.
This paper presents an overview of good documentation practices applicable to those
working in the pharmaceutical and healthcare sectors.
2. Good manufacturing practice and documentation:
There are a number of aspects of GMP that relate to documentation. GMP requires that
documents should be:
Controlled within the quality system
Approved, signed and dated
Regularly reviewed
Retained
Can be superseded within the quality system.

Pharmaceutical and other healthcare organization must have "good" documentation
practices. Whether the term "GDP' should be used to represent "good documentation
practice" is contentious since GDP is more commonly used as an acronym for "good
distribution practice"' in relation to the distribution of medicinal products.
3. Types of documents:
The different types of documents found within pharmaceutical and medical device
facilities were described earlier. The main types of documents are now discussed in more
detail with differences between the different types noted.
 Specifications:
Specifications are documents related to starting materials, packaging components, and
finished products. They describe the standards to which these materials and products must
comply if they are to be approved for use in manufacturing or for commercial sale. For
example, the finished product specification should contain:
33. The designated name of the product and the code reference where applicable.
34. The formula or suitable a reference.
35. A description of the pharmaceutical form and package details.
36. Directions for sampling and testing or a reference to procedures.
37. The qualitative and quantitative requirements with the acceptance limits. For example, the
sterility test or absence of specified pathogens.
38. The storage conditions and any special handling precautions, where applicable.
39. Shelf-life.
 Instructions:
All instructions to personnel (for example, media manufacture, bacterial
identification, analytical methods, and so on) should be clear, precise, unambiguous, and
written in numbered steps. They should be written in a language and style that the user can
readily understand. Associated with instructions are records. These can be either combined
with the instruction or in a separate document.
 Batch documentation:
A major element in final product release should be a review of all the relevant batch
documentation to ensure the presence of all necessary information and the satisfactory

completion of all necessary records. This will include sterilizer charts, microbiological testing
certificates of analysis, process records, test results, and so on.
 Procedures and records:
In addition to the instruction and associated records described above, specific
procedures including material receipt, sampling, testing rejection, complaints, and other
documents are also required. Depending of the type of document GMP expectations are that
the document carries:
 Product name
 Description of the item
 Reference number and item code
 Pack or batch size
 List of materials
 Specific precautions or instructions
 Names of associated personnel
 Dates and times
 Version number
 Approvals.
4. Document errors:
Common documentation errors that commonly appear in FDA warning letters and
reports from other regulatory authorities include (4):
 Documentation not contemporaneous
 Use of ditto marks
 Use of signature stamp
 Failure to use ink as specified by procedure
 Incorrect ink used for entries causing illegible data when a substance was spilled
 Logbook corrections failed to identify person who made the changes
 Obscured original data
 Use of pencil
 Inaccurate records

 Sample sequence table and audit trail not documented. (to draw on the commonly used
phrase: "if it is not documented, it didn't happen")
 Handwritten changes not dated
 Write-over, multiple line-through, and use of "white-out" or other masking device.
 The most common GMP citation occurs with correction of errors when information is
recorded.
Correction of documentation errors should include:
 Draw a single line through the error.
 Make the correction next to the error.
 Write an explanation for the error.
 It is recommended that these common errors are highlighted in training on the creation
and use of documentation.
5. Document fundamentals:
There are many different types of documents found within pharmaceutical
organizations, each serving a different purpose (5). Although there are different document
types, documents can generally be placed into a small number of categories cascading down
the quality system. With the types of documents and some of the errors relating to
documentation use, it is useful to consider at this point how documents come together and
what the basics of a document are.

Figure 1: Classic documentation hierarchy
The vast majority of documents are procedures or records. The most common
examples of a procedure within the pharmaceutical organization are standard operating
procedures (SOP) (6). A record is often related to a specific SOP and carries the confirmatory
details required of that SOP. For example the SOP for a sterility test record should require
details such as the product name, its batch number, and its test result.
6. Document creation:
The creation of documentation can be conceived very much like a process. In doing
so, the first stage can be described as event capture. However, the information or event has no
status unless it can be verified or approved which is the second stage. The last part of the
process is to communicate the event in this context by circulating and implementing the
document. To illustrate this consider a laboratory test common to many microbiology
laboratories - the gram stain technique. To document the procedure we need to write down
the steps which capture the process. As part of a controlled system the steps need to be
verified as being correct and the procedure "signed of" (approval stage). The procedure can

then be issued in into routine use along with associated training which is the communication
stage.
Figure 2: Documentation flow path
7. Document management:
Each pharmaceutical organization should have a system for documentation
management. This sets out the rules and mechanisms for creating and controlling a document.
GMP makes certain requirements of a documentation system such as:
 Assigning responsibility to an individual for control of the system.
 Ensuring layout, approval, authorization and unique identification of all documents is
provided for often by a master documentation SOP.
Having a master documentation SOP to include:
 Procedures for issue, retrieval, re-issue, maintenance of currency and traceability.
 Procedures for determining the need for documents.
 Identification of documents to be included in batch dossiers (for batch release).
 Linkage of documents to licenses and regulatory requirements.
 Outlining audit requirements for the documentation system.
 Ensuring that only the most up to date version is ever used.
 Retention times and archiving.
8. Document control:
Further considerations regarding the system controlling documentation include:
 Documents should be available at point of use.
 Masters, including electronic versions, are held under control.
 There is control over format.
 There is a system for changes, approval, and re-issue.
 There is control of documents of an external origin.

The majority of these requirements also make up the elements of the "documentation
lifecycle" From document creation, through its use, to its storage and archiving, and then to
its eventual retirement and possibly replacement by a revised version.
The control of documents necessitates the following steps:
4. Documentation creation:
5. Documents must be contemporaneous with the event they describe.
6. Documents must not be handwritten (except for handwritten entries).
7. When electronically produced, the documentation must be checked for accuracy.
8. Free from errors.
9. For some types of data, the documentation must be in a format that permits trend
evaluation.
5. Document approval:
13. Documents must be approved for use. They must be approved, signed, and dated by
appropriate authorized personnel.
8. Handwritten entries:
14. Adequate space needs to be provided for expected handwritten entries.
15. Handwritten entries must be in indelible ink.
16. Proper writing instrument-no pencils, no felt tip pens.
17. Use Permanent ink-blue or black.
18. Critical entries must be independently checked (second person verified).
19. No spaces for handwritten entries should be left blank. If unused, they are crossed out or
"n/a" (or similar text) entered.
20. Ditto marks or continuation lines are not acceptable.
21. A stamp in lieu of a handwritten signature is not acceptable.
9. Document copies:
10. Copies need to be clear and legible.
11. Errors must not be introduced.
12. Documents should be regularly reviewed and kept current.
13. Documents should be retained and readily available for audits.
14. Archived documents must be retrievable for the appropriate duration.
15. Electronic document management systems must be validated.

16. Electronic records must be backed up.
10. Document modification:
 Handwritten modifications are signed and dated
 Altered text should not be obscured (e.g., no obliterating the text through crossing-out)
 Where appropriate, the reason for alteration must be noted (for example, "e.e." is a
common abbreviated reason, indicating "entry error").
 Controls exist to prevent the inadvertent use of superseded documents.
 Electronic versions should only be modified by authorized personnel.
 Access to electronic documents must be controlled by password or other means.
A history (audit trail) must be maintained of changes and deletions to electronic
documents. Well-designed documentation and appropriate documentation are paramount. It is
necessary to document every aspect of the process, activities, and operations involved with
drug and medical device manufacture. If the documentation showing how the product was
made and tested (which enables traceability and, in the event of future problems, recall from
the market) is not correct and in order, then the product does not meet the required
specification and could be considered to be adulterated.
9. Best practices for document creation and use:
A company should continually evolve good practices for creation of documents. It is
important that documents are designed, prepared, reviewed, and distributed with care.
Documents also must be approved, signed, and dated by the appropriate competent and
authorized persons. Further, documents must be regularly reviewed and kept up-to-date.
When a document has been revised, systems must be operated to prevent inadvertent use of
superseded documents. It is especially important that only current documentation should be
available for use (7). A further important consideration is to ensure that the records can be
kept in an orderly fashion to facilitate retrieval at some unspecified time in the future.
Best practices extend to the writing of the document. Using words that everyone can
understand minimizing jargon, acronyms, and abbreviations and using words with
unambiguous meaning can help the reader to more easily understand and interpret the
document(8).
Key "readability" qualities for a document include (8):

6. Concise: Present information clearly so it can be easily understood with no room for
misinterpretation. For example, the date format "06/05/14" can cause confusion. It is
better to use one that is unambiguous, such as "05 June 2014," especially if the document
is used in the US and Europe.
7. Legible: Information should be readable and leave no room for error. For example, hand-
written data that are not legible may create errors in data analysis or result in missing
data.
8. Accurate: Documentation should be error-free-properly reviewed, verified and approved.
Information should be recorded as an event happens and not after the fact to avoid
recording "what you remember" rather than "what actually happened."
9. Traceable: Documentation should be traceable. It should be made clear who logged the
information, what it was, and when and why it was documented.
10.To help with efficient location of records, attention should be paid to numbering
including the version number for traceability. Simple sequential number of documents
only works for a small number of documents. In most cases a defined structure to the
numbering system is needed. For example, 001-100 could represent regulatory
documents, 101-200 could represent QC testing documents, and 201 -300 could represent
production documentation. This system may still limit. The numbering system may need
to include references to the site, a system (production, QC, validation, and so on) as well
as its sequential number.
10.Document style and layout:
It is often helpful to adopt a specific document style for consistency of operations.
Elements of the style should be specified in an approved procedure. These might include: (9)
2. Logo
3. Pagination/ layout to prevent confusion and ensure the document are kept in order.
4. Headers and footers.
5. Font including the size is useful to minimize errors introduced when changing between
fonts.
6. Page numbers
7. Executive summary

8. Changes - Change control is important for traceability
9. Circulation list - to ensure the document is reviewed and received by the appropriate
personnel.
10. Table of contents
11. Authorization levels stated on document.
12. Cross references
13. Revision history
14. Definitions
15. Content (context and meaning)
16. A clear area for recording problems/ incidents.
17. Use of pictures, flow charts, diagrams as suitable alternatives to text.
Care should be taken in designing and stylizing documentation. Documents must have
unambiguous contents. The title, nature, and purpose should be clearly stated. They must be
laid out in an orderly fashion. Documents must be easy to check. Reproduced documents
must be clear and legible. Many people do not consider the importance of how key
information is presented within a document. This can result in the reader wasting time or not
conducting the correct tasks. For example, a poorly structured document could ask the user to
conduct a task that requires some action to be performed prior to the subject task – but only
mentions the pre-work at the end of the document and with no reference to the pre-work at
the beginning.
Helpful considerations for layouts include the following:
 Cover page with identifiers and status.
 Table of contents – creating a road map through the document.
 Scope and applicability section
 Introduction
 Information and instructions in a logical sequence.
 Additional information and detail.
Numerical information must include the correct use of units. The use of color coding
in graphical information, such as black lines for existing pipework and red lines for new
pipework, might also be useful.

The narrative must consider writing style, nomenclature, and dealing with errors and
corrections. When considering the numerical issues what are viewed as standard units. Think
about mathematical symbols and the order in which calculations are performed. For example,
the bodmas approach (b)rackets (o)rder (d)ivide (m)ultiply (a)ddition (s)ubtraction, is useful.
If someone gets the sequence wrong, they will get the wrong result. It is also important to
think about the rules on rounding, i.e., above 0.5, round up, etc. Finally, consider
standardizing symbols in drawings.
It is useful to consider different styles to accommodate the different reading styles of
readers. There are thought to be three styles based on the linguistic, logical and spatial talents.
These can be summarized as (10):
12. Linguistic talent. There is a strong ability to write and talk fluently. Phrases like "gift of
the gab" often apply. Individuals in this category can also write and read well.
Shakespeare had linguistic talent.
13. Logical talent. There is strong ability to think logically and are quick in calculating
odds and statistics. Albert Einstein had logic talent.
14. Spatial talent. There is strong ability to image things in the "mind's eye." These people
often have good navigational skills such as Christopher Columbus.
The following should be considered whenever possible:
 Narrative – written text
 Tabular – tables
 Charts – bar charts, pie charts
 Colour – bold – underlined text
 Pictures – photographs, images
 Diagrams – 2d, 3d
 Process logic – flowcharts
Including various combinations of the above is extremely useful. A flow chart might
help with navigating the document while pictures are very useful in dressing procedures for
entry into clean rooms. Tables are useful for summarizing data such as microbial limits for
environmental monitoring.
The use of cross referencing in documents is helpful in keeping the document short
and manageable. Be careful of cross referencing too many documents as this can be self-

defeating. The user will not follow the procedure if they have to locate too many other
documents.
Finally, consideration of the end user when writing is also extremely important. Too
often documents are written by managers or technical staff without thought for the people
that will be using them. Ideally it is recommended that the end user writes the document.
11. Completing documents and record-keeping:
After documents have been designed, prepared, and approved, they must be used and
completed properly. For example, where documents require the entry of data, these entries
must be made in clear legible handwriting using a suitable indelible medium not a pencil.
Sufficient space must be provided for entries. With such entries, it is important that any
correction made to a document or record must be signed or initialled and dated; the correction
must permit the reading of the original information. Where appropriate, the reason for the
correction must be recorded.
With record-keeping in general, a record must be kept at the time each action is taken.
All activities concerning the conduct of preclinical studies, clinical trials, and the
manufacture and control of products must be traceable.
 Electronic records:
The advent of computerized systems caused industry to move away from paper-based
systems to paper-less systems. Electronic records offer many advantages. The reality is that
typically there is a balance between the two. For example, consider a record for the absence
of pathogen test on a non-sterile product. Recording the test result presents us with two
options. Firstly it can and often is written on a log sheet. Secondly we can use a laboratory
information management system (LIMS) to record the result electronically (11).
As a controlled form it will be created in Microsoft Word (electronic) and printed
onto paper to check it so it can be signed for approval giving it status. This can be done on
screen but many people prefer to review a hard copy. Approval can be electronic recording
user name and password, or the printed document can be physically signed. In the latter case,
the approved document could be scanned so it can be stored, distributed, and referenced
electronically. A physically approved document will need photocopying if it is to be

distributed in the "paper world." Electronic distribution of a physically signed document can
save on paper but does present problems mainly from the scanning process.
A scan that creates a picture of the original will be a very large file. Use of optical
character recognition in the scanning process produces small files, but the scanning process
introduces errors where characters may get missed or replaced requiring a further proof read
often from a paper printout. During the active stage, personnel may prefer a hard copy to
work from so that an electronic document will be printed onto paper.
Archiving of paper records is costly in terms of space and to some degree
retrievability, but little more in terms of maintenance. Archiving of electronic records
presents more challenging problems. They only exist as a series of "1's" and "0's" (binary
code) on storage media like a CD ROM. With electronic record archiving, the technology
window must be understood. This means that the data might be available on the CD but after
5 years there may not be any hardware that can read it. Essential to electronic record
archiving is that companies have an adequate migration strategy. Paper records are still
usable after several thousand years but data on discs may be lost after only 5-10 years or a
shorter period if the discs are not properly controlled. The migration strategy should also
include the regular transfer of data onto fresh media even if the hardware has not changed.
The requirements for electronic records and signatures within the US title 21 parts 11
of the Code of Federal Regulations (CFR). Although organizations do not have to use
electronic records and signatures, if they do, they must comply with the CFR. It is important
that such records are afforded the equivalence to paper records and hand written signatures.
The CFR make it clear that procedures shall be followed records should be documented at the
time of performance, and deviations recorded and justified.
 Document storage:
Storage of critical records must at secure place, with access limited to authorized
persons. In relation to this, 21CFR 211.180(d) states "these records or copies shall be subject
to photocopying or other means of reproduction as part of such inspection. Records that can
be immediately retrieved from another location by computer or other electronic means shall
be considered as meeting the requirements of this paragraph."
The storage location must ensure adequate protection from loss, destruction, or
falsification, and from damage due to fire, water, and other disasters. Records which are

critical to regulatory compliance or to support essential business activities must be duplicated
on paper, microfilm, or electronically, and stored in a separate, secure location in a separate
building from the originals.
Data may be recorded by electromagnetic or photographic means but detailed
procedures relating to whatever system is adopted must be available. Accuracy of the record
should be checked as per the defined procedure. If documentation is handled by electronic
data processing methods only authorized persons should be able to enter or modify data in the
computer, access must be restricted by passwords or other means, and entry of critical data
must be independently verified.
If electronic, photographic or other data processing systems are used for the retention
of documents an appropriate storage for required duration is necessary to protect against loss
or damage. It is particularly important that during the period of retention, the data can be
rendered retrievable and legible within an appropriate period of time. This means having a
validated system of data recall. The data should also be available in a legible form. Rapid
retrieval of reports and data is essential for audits.

40. TYPE OF DOCUMENTATION USED IN PHARMACEUTICAL
INDUSTRY
a. Master formula record
b. Master packaging records
c. Batch production record
d. Batch manufacturing record
e. Batch packaging records
f. Standard Operating Procedures (SO
a. Master formula record: (22, 23
Master formula record is a product specific document compiled, checked, authorized
and approved by competent technical personnel from different. But interlinked, functions
such as development, production, packaging and quality control as necessary and appropriate.
As with any other documentation master formula record shall also be open for review.
Changes, if any shall also be approved by designated persons responsible for production and
quality control.
Such Type of master formula record is prepared for each product and batch size to be
manufactured. These shall be prepared by competent technical staff like head of production
and Quality control. These documents are prepared to achieve uniformity within batch to
batch. Master formula record shall: (32)
Give patent/proprietary name of the product, and its strength.
Give Pharmacopoeial/generic name of the product, and its strength.
Give dosage form (e.g. tablet, capsule) and physical characteristics of the product.
Give sufficient detailed information of product pack and primary packaging materials.
Give identity, quality and quantity of every ingredient, including over ages/assay value based
quantities, if any, irrespective of whether, or not, the material:
 is an active drug substance in the formulation/product.
 is used as a pharmaceutical aid (excipient).
 appears, or is detected/tested in the final product.

Briefly describe all the raw materials.
Give broad outlines of the process of manufacture (as a flow- chart, for example).
Give brief description of equipment/ machinery used for manufacturing the product.
Give step-wise manufacturing process.
Give theoretical and practical (expected) yields at different stages of manufacture.
Bring out in sufficient details precautions to be taken during manufacturing to ensure birth
product quality and personnel safety.
Give all analytical controls, including limits thereof, applicable to the finished product.
Give stability test results covering the assigned shelf life.
Have a ‘product history’ data giving references in manufacturing/packaging introduced over
the year.
(Preferably) contain samples of printed packaging components.
A format, which may be used as guideline for preparing master formula record, is as
below: (32)
Format for master formula record:
M/S (name & address of the company)
Name of product:________________________________________________________
Trade name, if any:_______________________________________________________
Master formula record No. ________________________________________________
Effective Date :__________________________________________________________
Approved By:
Sign Sign
Q.C. Manager Production Manager
Specification of Raw Material:
Name of Raw Material: Specification
Specifications of container, Closure, Labelling and Packaging Material:
Name of item: Specification
Such type of records shall contain: (32)
9. Name of product along with its reference code which relate to its specifications.
10. The patent or proprietary name of product along with its generic name.
11. Description of dosage form, strength, composition of product and batch size.
12. Specifications for all starting material used.

13. A statement of expected final yield along with its acceptable limits.
14. A statement of processing location.
15. Methods or reference to methods used for preparing and operating critical equipments to
be used.
16. Dispensing instructions.
17. Detailed stepwise processing instruction.
18. Instructions for in process controls.
19. Instructions for storage conditions of product including container, labelling and special
storage conditions.
20. Any special precautions to be observed.
21. Packing details with specimen labels
22. Precautions to be taken
23. Finished product specification
24. Expiry date
b. Master packaging records: (22, 23)
They should contain:
 Name of the product.
 Description of dosage form, strength and composition.
 The pack size in terms of number of doses, weight or volume of product.
 Complete list of all packaging materials required for standard batch size. Special
precautions to be observed including careful examination of area and equipments in
order to ascertain line clearance.
 Description of packaging operation.
 Details of in-process controls with instruction for sampling.
 Reproduction of relevant packaging materials and specimen indicating batch number
and expiry date of product.
 Detailed investigation of unexplained events e.g. discrepancy in number of units
labeled and packaging units issued.
c. Batch production record: (22), (23)
It is a product and batch specific document designed to provide information on
History of any batch of Product. It is a recurring document. It is based on the Master formula
record and shall be compiled, checked and approved by competent technical persons

responsible for Production, Quality control. The computer printout of such documents should
prefer to avoid transcription errors.
Such type of documents should contain:
 Date and time of all activities which are carried out concerning the production and
control of batch
 Identification of major lines and equipments to be used. Identification of rooms with
their unique identification number.
 Specific identification of in-process materials.
 Weights and measures of components used in processing.
 Inspection status of packaging and labelling area before and after it use.
 A statement of actual yield and percentage theoretical yield at every stage of processing.
 Complete labelling control records.
 Description of container and closure system.
 Any sampling which is performed during production and packaging activities.
 Identification of persons supervising significant steps of operation.
 Any investigation made of unexplained events like yield variation.
 Results of examination made.
 In-process and laboratory control results.
d. Batch manufacturing record: (22, 23)
Batch manufacturing record is a product and batch specific document designed to give
a complete and reliable picture of the manufacturing history of each batch of every product.
Batch manufacturing record shall be essentially based on the master formula record and shall
be compiled, checked, approved and authorized by competent technical person responsible
for production and quality control. Photo reproduction, or such other system (e.g. computer
printouts) shall be preferred to avoid transcription errors provided, however, there are
adequate safeguards to prevent unauthorized re-production.
 Name of the product
 Batch number
 Date of commencement & completion of significant intermediate stage.
 Name of the person responsible for each stage of production.
 Initials of operators who carried out significant processes and initial of persons who
checked, wherever applicable.

 Quantity, batch number, quality control report number of each ingredient actually
weighed and amount of any recovered material added.
 In-process controls carried out their results and signature of person who performed
 Theoretical yield & actual yield at appropriate stage of production together with
explanation, if variation beyond expectation observed.
 Authorization of any deviation, if made.
Format for batch manufacturing record:
FOR TABLETS:
M/S (name & address of the company)
Name of
product:______________________________________
__________________
Trade name, if
any:_________________________________________
______________
(MFR NO.)
_____________________________________________
__________
Batch No. :_______________________Batch size:
_____________________________
Date of expiry:
_____________________________________________

____________
Date of commencement:
_____________________________________________
_____
S.NO.
Ingred
ients
In
order
of
mixin
g
Stand
ards
Q/
C
rep
ort
No
.
La
bel
Cla
im
Qua
ntity
requi
red
Qua
ntity
Actu
ally
Used
Rem
arks
%
Over
ages
1 2 3 4 5 6 7 8
MIXING:
Equipment
Used:_______________________
_____________________________________________
____________________________
Date: Time:
Duration:
_____________________________________________
____________________________
_____________________________________________
____________________________
Result of uniformity of mixing (in case of tablets,

containing small quantity of active medicament):
_____________________________________________
__________

WET GRANULATION:
Equipment
Used:__________
_____________
_____________________________________________
____________________________
Date: Time:
Duration:
_____________________________________________
____________________________
_____________________________________________
____________________________
DRYING:
Equipment
Used:__________
_____________
_____________________________________________
____________________________
Date: Time: Temp. at which dried :
duration:
_____________________________________________
____________________________
_____________________________________________
____________________________
(If tray dryer has been used, use this chart):
_____________________________________________
____________________________
Time:

Temperature:
_____________________________________________
____________________________
_____________________________________________
_____________________________
Moisture content of
granules:_____________________________________
______________
Actual yield of
granules:_____________________________________
__________________
Theoretical yield of
granules:_____________________________________
______________
Whether within permissible
limits:_______________________________________
________
COMPRESSION:
Compression machine
used:________________________________________
___________
Punch
size:_________________________________________
________________________
Appearance:
_______________________________________
________________
Humidity (In case of moisture sensitive product) :
__________________________________
Hardness (Kg) :

_______________________________________
________________
Disintegration time (min.) :
_____________________________________________
____
Friability (%):
_______________________________________
________________
Weight of tablet: _____________________Average
weight per tablet:_________________
Date of compression:
_______________________________________
________________
Result of test analysis of
tablets:_______________________________________
__________
COATING:
Nature of
coating:______________________________________
______________________
Material used for coating:
_____________________________________________
________
_____________________________________________
______________________________
S. No. Ingredient Q.C. report
no. Quantity used
_____________________________________________
_____________________________
_____________________________________________

_____________________________
Date of coating:
_____________________________________________
________________
Date of polishing:
_____________________________________________
_______________
Name of coater:
_____________________________________________
_______________
Result of test/ analysis of bulk finished
project:____________________________________
PACKAGING:
Packaging
Description:___________________________________
____________________
Precoding of labels and printed packaging material
examined & verified by: _____________
_____________________________________________
____________________________
(Attach specimen)
No. of precoded:
17. Labels received
:_________________________________________
______________
18. Printed packaging material received:
_____________________________________

Date
Start
Time
Close
Time
Name of persons
responsible for
Stripping
Other
package.
Stripping Checking Counting & filling In boxes
e. Batch packaging records: (23)
In fact, batch packaging record is a part of batch process record. These records are
based on packaging instruction. One important operation that should be carried out before
packaging operation is line purging. It should be kept for each batch which is produced
/processed. It should be based on relevant parts of packaging instructions. And method of its
preparation shall avoid transcription errors. As per the schedule M before any packaging
operation begins checks shall be made and recorded that work stations are clear of previous
products and equipment is clean and suitable for use.
WHO guidelines require that following information should be recorded at the time of
each action:
 The name , batch number & quantity of the bulk finished product to be packed
 Theoretical yield & actual yield and reconciliation
 The date and time of the packaging operations
 The name of the responsible person carrying out the packaging operations
 Initial of the operators of the different significance step
 In-process control checks & the checks made for identity & conformity with the
packaging instruction
 Detail of packaging operation like equipment and the packaging lines used, when
necessary, the instruction for keeping the product unpacked or a record of unpacked
product sent back to storage area.

 Sample of printed packaging material used, bearing the batch number, expiry date and
any additional over printing.
 In any case of problem, if any deviation made, written authorization for the same.
 Quantity along with identification of different packaging materials issued, used,
destroyed and/ or returned to store and reconciliation.
Format of batch packaging record:
Total quality packed:
___________________________________________________
Date of completion:
____________________________________________________
Quantity collected as sample by Q/C department:
_____________________________
Reconciliation of labelling and packaging material:
___________________________
Label Foil Printed
cartons
Requisitioned:
Received:
Used :
Retuned:
Destroyed :
Destroyed on:
Destroyed by:
Actual yield (%)
____________________________________________________________
Theoretical yield (%)
________________________________________________________
Whether within
limits:_____________________________________________________
Q/C report finished product
:________________________________________________

Status No. & date and release
order:_________________________________________
Sign of
supervisor____________________________
Date of released
:________________________________________________________
Quantity released:
_______________________________________________________
Date of transfer of finished product to
warehouse:______________________________
f. Standard Operating Procedures (SOP): (28)
The terms standard operating procedure and standing operating procedure, both
abbreviated by the initialise, SOP, occur in a variety of different contexts such as healthcare,
education, industry, the military, etc.
One of the important activities in the implementation GMP is preparation of SOPS.
One may very well ask why should there be SOPS. One of the objectives of GMPS is
consistency in quality. Consistency in quality can be achieved by minimizing sources of
quality variation. SOPS can be defined as written documents specifying the procedure that
must be followed to carry out operation. One of the purposes of SOPS is to reduce the
introduction of errors and variation in the operation. The other purpose of sops is of historical
perspective i.e. how an operation was carried out.
An SOP is a written document or instruction detailing all steps and activities of a
process or procedure. These should be carried out without any deviation or modification to
guarantee the expected outcome. Any modification or deviation from a given SOP should be
thoroughly investigated and outcomes of the investigation documented according the internal
deviation procedure.
All quality impacting processes and procedures should be laid out in Standard
Operating Procedures (SOPs).
The best way to prepare SOPs is to involve at least one person from each work area.
The person selected should be asked to write down the procedure of the operation with details
and the precautions to be taken.

The written down procedure should be discussed by a group of persons intimately
connected with the operation. Modifications, if any, should be made. This should be handed
over to the person who has been designated as coordinator. The coordinator should rewrite it
is needed to bring uniformity in style & format. It will be advisable to first prepare SOP for
SOP.
42.Benefits of SOP: (29)
11.To provide people with all the safety, health, environmental and operational information
necessary to perform a job properly.
12.To ensure that production operations are performed consistently to maintain quality
control of processes and products.
13.To ensure that processes continue uninterrupted and are completed on a prescribed
schedule.
14.To ensure that no failures occur in manufacturing and other processes that would harm
anyone in the surrounding community.
15.To ensure that approved procedures are followed in compliance with company and
government regulations.
16.To serve as a training document for teaching users about the process for which the SOP
was written.
17.To serve as a checklist for co-workers who observe job performance to reinforce proper
performance.
18.To serve as a checklist for auditors.
19.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.To serve as an explanation of steps in a process so they can be reviewed in accident
investigations.
43.Some guidelines are given below to prepare SOPS:
(23)
18.Give a clear & descriptive title to each SOP.
19.Provide sufficient details the SOP should meet the need of an individual; all the same, it
should be general enough for more than one user.
20.Flexibility should be written in the SOP wherever appropriate but it should not be made
too general for, it may be useless in meeting its intended purpose.

21.Organize SOPs according to order of sequence of events involved in performing the
operation. Write the text in straight forward and easy to follow manner.
22.After drafting SOP, use it in performing the operation to ensure that it has sufficient
details to perform the operation in intended manner.
23.Take into account the instructions from the manufacturer of the equipment which is
employed in performing the operation while drafting SOP.
24.Indicate total number of pages so that user is certain that he is performing the complete
operation.
25.Indicate the effective date of the SOP.
The following explanatory notes will be useful in preparing SOP for SOP.
6. Design a format for SOP. This will maintain uniformity in writing SOPs.
7. Device a system of assigning number to SOP. This may include a code for the
department, activity to which it is related & version. For example, SOP for equipment
cleaning in production department may be numbered as PR/EC/01/V1 or PR.EC01.V!
8. Device a date format. Date format could be: DD/MM/YY or DD/MM/YYYY.
9. Define elements of SOP, usually the following elements are included in a SOP:
10. SOP number
11. Title of SOP
12. Department
13. Prepared by, approved by, authorized or issued by:
14. Purpose/object
15. Scope
16. Responsibility
17. Procedure
18. References
19. Distribution
10. A format given on next page may be seen for guidance. It will be useful if a history page
has record of revision to that SOP. This page may contain the following information:
22. Version number
23. Reasons for revision
24. Nature of revision
25. Revised by
26. Retrieval and distribution of obsolete copies.

Format for SOP:
Name of
company________________________________________________________
Site____________________________________________________________
________
SOP No._______________________ Total
pages_______________________________
Title: SOP for
___________________________________________________________
Department_____________________________________________________
_______________________________________________________________
_________________
Effective Date_____________________ Review
Date___________________________
_______________________________________________________________
________
Prepared by:
Approved by:
Authorized or issued by:
Purpose:
Scope:
Responsibility:
Procedure:
Reference:
_______________________________________________________________
________
Distribution:
_______________________________________________________________
____

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 DOCUMENT REQUIRED AS PER ICH GUIDELINE
a. Documentation systemand specifications
b. Equipment cleaning and use record
c. Records of raw materials, intermediates, API labelling and packaging materials
d. Masterproduction instructions (Master production and control records)
e. Batch production records (Batch production and control records)
f. Laboratory control records
g. Batch production record review

 DOCUMENT REQUIRED AS PER ICH GUIDELINE: (13, 19)
1. Documentation system and specifications:
All documents related to the manufacture of intermediates or APIs should be prepared,
reviewed, approved and distributed according to written procedures. Such documents can
be in paper or electronic form.
The issuance, revision, superseding and withdrawal of all documents should be controlled
with maintenance of revision histories.
A procedure should be established for retaining all appropriate documents (e.g., development
history reports, scale-up reports, technical transfer reports, process validation reports,
training records, production records, control records, and distribution records). The
retention periods for these documents should be specified.
All production, control, and distribution records should be retained for at least 1 year after the
expiry date of the batch. For APIs with retest dates, records should be retained for at
least 3 years after the batch is completely distributed.
When entries are made in records, these should be made indelibly in spaces provided for such
entries, directly after performing the activities, and should identify the person making the
entry. Corrections to entries should be dated and signed and leave the original entry still
readable.
During the retention period, originals or copies of records should be readily available at the
establishment where the activities described in such records occurred. Records that can
be promptly retrieved from another location by electronic or other means are acceptable.
Specifications, instructions, procedures, and records can be retained either as originals or as
true copies such as photocopies, microfilm, microfiche, or other accurate reproductions
of the original records. Where reduction techniques such as microfilming or electronic
records are used, suitable retrieval equipment and a means to produce a hard copy should
be readily available.
Specifications should be established and documented for raw materials, intermediates where
necessary, APIs, and labelling and packaging materials. In addition, specifications may
be appropriate for certain other materials, such as process aids, gaskets, or other
materials used during the production of intermediates or APIs that could critically impact

on quality. Acceptance criteria should be established and documented for in-process
controls.
If electronic signatures are used on documents, they should be authenticated and secure.
2. Equipment cleaning and use record:
19.Records of major equipment use, cleaning, sanitization and/or sterilization and
maintenance should show the date, time (if appropriate), product, and batch number of
each batch processed in the equipment, and the person who performed the cleaning and
maintenance.
20.If equipment is dedicated to manufacturing one intermediate or API, then individual
equipment records are not necessary if batches of the intermediate or API follow in
traceable sequence. In cases where dedicated equipment is employed the records of
cleaning, maintenance, and use can be part of the batch record or maintained separately.
3. Records of raw materials, intermediates, API labelling and packaging materials:
Records should be maintained including:
25.The name of the manufacturer, identity and quantity of each shipment of each batch of
raw materials, intermediates or labelling and packaging materials for API's.
26.The name of the supplier the supplier's control number, if known, or other identification
number the number allocated on receipt and the date of receipt.
27.The results of any test or examination performed and the conclusions derived from these
Records tracing the use of materials.
28.Documentation of the examination and review of API labelling and packaging materials
for conformity with established specifications.
29.The final decision regarding rejected raw materials, intermediates or API labelling and
packaging materials.
30.Master (approved) labels should be maintained for comparison to issued labels.
4. Master production instructions (Master production and control records):
 To ensure uniformity from batch to batch, master production instructions for each
intermediate and API should be prepared, dated, and signed by one person and
independently checked, dated, and signed by a person in the quality units.
 Master production instructions should include:

 The name of the intermediate or API being manufactured and an identifying document
reference code, if applicable.
 A complete list of raw materials and intermediates designated by names or codes
sufficiently specific to identify any special quality characteristics.
 An accurate statement of the quantity or ratio of each raw material or intermediate to
be used, including the unit of measure. Where the quantity is not fixed, the calculation
for each batch size or rate of production should be included. Variations to quantities
should be included where they are justified.
 The production location and major production equipment to be used.
 Detailed production instructions, including the:
o Sequences to be followed.
o Ranges of process parameters to be used.
o Sampling instructions and in-process controls with their acceptance criteria, where
appropriate.
o Time limits for completion of individual processing steps and/or the total process
where appropriate.
o Expected yield ranges at appropriate phases of processing or time.
 Where appropriate special notations and precautions to be followed or cross-references
to these.
 The instructions for storage of the intermediate or API to assure its suitability for use,
including the labelling and packaging materials and special storage conditions with
time limits where appropriate.
5. Batch production records (Batch production and control records):
 Batch production records should be prepared for each intermediate and API 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. If the batch production record is produced from a separate part
of the master document, that document should include a reference to the current master
production instruction being used.

 These records should be numbered with a unique batch or identification number, dated
and signed when issued. In continuous production the product code together with the
date and time can serve as the unique identifier until the final number is allocated.
 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 (e.g., reactors, driers, mills, etc.) used.
 Specific identification of each batch, including weights, measures, and batch numbers
of raw materials, intermediates, or any 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 for intermediate or API.
 Representative label of API or intermediate if made commercially available.
 Any deviation noted its evaluation, investigation conducted (if appropriate) or
reference to that investigation if stored separately.
 Results of release testing.
 Written procedures should be established and followed for investigating critical
deviations or the failure of a batch of intermediate or API to meet specifications. The
investigation should extend to other batches that may have been associated with the
specific failure or deviation.
6. Laboratory control records:
11.Laboratory control records should include complete data derived from all tests conducted
to ensure compliance with established specifications and standards, including
examinations and assays as follows:

20.A description of samples received for testing, including the material name or source,
batch number or other distinctive code, date sample was taken and where appropriates the
quantity and date the sample was received for testing.
21.A statement of or reference to each test method used.
22.A statement of the weight or measure of sample used for each test as described by the
method. Data on or cross-reference to the preparation and testing of reference standards,
reagents and standard solutions.
23.A complete record of all raw data generated during each test in addition to graphs, charts,
and spectra from laboratory instrumentation, properly identified to show the specific
material and batch tested.
24.A record of all calculations performed in connection with the test including for example
units of measure, conversion factors and equivalency factors.
25.A statement of the test results and how they compare with established acceptance criteria.
26.The signature of the person who performed each test and the date the tests were
performed.
27.The date and signature of a second person showing that the original records have been
reviewed for accuracy, completeness and compliance with established standards.
12.Complete records should also be maintained for:
27.Any modifications to an established analytical method.
28.Periodic calibration of laboratory instruments, apparatus, gauges, and recording devices.
29.All stability testing performed on APIs.
30.Out-of-specification (OOS) investigations.
7. Batch production record review:
11.Written procedures should be established and followed for the review and approval of
batch production and laboratory control records including packaging and labelling to
determine compliance of the intermediate or API with established specifications before a
batch is released or distributed.
12.Batch production and laboratory control records of critical process steps should be
reviewed and approved by the quality unit before an API batch is released or distributed.
Production and laboratory control records of non-critical process steps can be reviewed

by qualified production personnel or other units following procedures approved by the
quality unit.
13.All deviation, investigation and OOS reports should be reviewed as part of the batch
record review before the batch is released.
14.The quality unit can delegate to the production unit the responsibility and authority for
release of intermediates except for those shipped outside the control of the manufacturing
company.
 DOCUMENT REQUIRED AS PER WHO GUIDELINE
1. Principle
2. General information
3. SOP, specifications and master formulae
4. Forms for recording data
5. Identification numbers
6. Specification for starting & packaging material
7. Specification for intermediate & bulk product
8. Specification for finished product
9. Master formulae and processing instructions
10. Packaging instruction
11. Batch processing record
12. Batch packaging records
13. Standard operating procedure (SOPs)
14. Other various analysis records

7. DOCUMENT REQUIRED AS PER WHO GUIDELINE: (12,) (13), (24)
7.1. Principle:
Good documentation is an essential part of the quality assurance system and, as such,
should exit for all aspects of GMP. Its aims are to define the specifications and procedures for
all materials and method of manufactured 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. The design and use of document depend upon the
manufacturer.
7.2. General information:
 Documents should be designed, prepared, reviewed and distributed with care. They
should comply with the relevant part of the manufacturing and marketing
authorizations.
 Documents should be approved, signed and dated by the appropriate responsible
persons. No document should be changed without authorization and approval.

 Documents should have unambiguous contents: the title, nature and purpose should be
clearly stated. They should be laid out in an orderly fashion and be easy to check.
Reproduced documents should be easy to check. Reproduced documents should be
clear and legible. The reproduction of working documents from master documents
must not allow any error to be introduced through the reproduction process.
 Documents should be regularly reviewed and kept up to date when a document has
been revised, a system should exist to prevent inadvertent use of the superseded
version superseded documents should be retained for a specific period of time.
 Documents should not be hand written .Where documents require the entry should be
clear, legible and indelible. Sufficient space should be provided for such entries.
 Any alteration made to a document should be signed and dated: the alteration should
permit the reading of the original information. Where appropriate, the reason for the
alteration should be recorded.
 Records should be made or completed when any action is taken and in such a way that
all significant activities concerning the manufacture of pharmaceutical products are
traceable. Records should be retained for at least one year after the expiry date of the
finished product.
 Data (and records for storage) may be recorded by electronic data processing systems
or by photographic or other reliable means. Master formulae and detailed standard
operating procedures relating to the system in use should be available and the accuracy
of the records should be checked. If documentation is handled by electronic data-
processing methods. Only authorized persons should be able to enter or modify data in
the computer, and there should be a record of changes and deletions: access should be
restricted by passwords or other means and the entry of critical data should be
independently checked. Batch records stored electronically should be protected by
back-up transfer on magnetic tape, microfilm, paper print-outs or other means. It is
particularly important that, during the period of retention, the data are readily
available.

 Each specification should be approved, signed and dated, and maintained by quality
control, quality assurance unit or documentation center. Specifications for starting
materials, intermediates and bulk, finished products and packaging materials.
7.3. SOP, Specifications and master formulae:
Descriptive documents give instructions on how to perform a procedure or a study, or
give a description of specifications. The instruction type documents are: standard Operating
procedures (SOP); protocols (for validation studies, stability studies, safety studies); and
master formulae (manufacturing instructions). Each of these gives instruction on how to
perform specific procedures. Specifications describe the required characteristics or
composition of a product or material or test. These kinds of documents provide the specific
details defining the quality of incoming materials, the quality of the production environment,
the quality of the production and control process, and the quality of the final product.
7.4. Forms for recording data:
Another type of documentation is the form used for recording data as it is taken
during the performance of tasks, tests, or events. These are forms (datasheets, or data record
forms) reports, batch processing records, and equipment log books. These documents provide
the evidence that the raw materials, facility environment, the production process, and the final
product consistently meet the established quality requirements.
7.5. Identification numbers:
There are also the identification systems or codes devised to number and track both
information and documents. These are SOP numbers, equipment numbers, form numbers,
receiving codes, and batch/lot numbers. These numbering systems should be designed so that
procedures, processes and materials can be traced throughout the data records.
7.6. Specification for starting & packaging material:
Specifications for starting, primary and printed packaging materials should include if
applicable:
41.A description of the materials. Including:
44.The designated name and internal code reference.
45.The reference, if any, to a pharmacopoeial monograph.

46.Qualities and quantitative requirement with acceptance limit.
21.Depending on the company’s practice other data may be added to the specification such
as:
26.The supplier and the original producer of the materials.
27.A specimen of printed materials
28.Direction for sampling and testing, or a reference to procedures.
29.Storage conditions and precautions.
30.The maximum period of storage before re-examination.
Packaging material should conform to specifications, and should be compatible with
the material and/or with the drug product it contains. The material should be examined for
compliance with the specification, and for defects as well as for the correctness of identity
markings.
7.7. Specification for intermediate & bulk product:
Specifications for intermediate and bulk products should be available. The
specifications should be similar to specifications for starting materials or for finished
products as appropriate.
7.8. Specification for finished product:
Specifications for finished products should include:
2. The designated name of the product and the code reference. Where applicable
3. The designated name of the active ingredients, if applicable with the INN(s).
4. The formula or a reference to the formula.
5. A description of the dosage from and package details.
6. Direction for sampling and testing or a reference to producers.
7. The qualitative and quantitative requirement, with acceptance limits.
8. The storage conditions and precautions, where applicable.
9. The self-life.
7.9. Master formulae and processing instructions:

Formally authorized manufacturing formula and processing instructions should exist
for each product and batch size to be manufactured. They are often combined in one
document.
The Manufacturing formula should include:
15.The name of the product, with a product reference code relating to its Specifications.
16.A description of the pharmaceutical form, strength of the product and batch size.
17.A list of all starting materials to be used, with the amount of each, described using the
designed name and a reference which is unique to that material, mention should be made
of any substance that may disappear in the course of processing.
18.A statement of the expected final yield with the acceptable limits, and of relevant
intermediate yield, where applicable.
The processing instructions should include:
2. A statement of the processing location and the principal equipment to be used.
3. The methods, or reference to the methods to be used for preparing the critical equipment
(e.g. cleaning, assembling, calibrating, sterilizing).
4. Detailed stepwise processing instructions (e.g. checks on materials, pre-treatment,
sequence for adding materials, mixing time, temperatures).
5. The instruction for any in-process controls with their limits.
6. Where necessary the requirement for bulk storage of the products. Including the
container, labelling and special storage conditions where applicable.
7. Any special precautions to be observed.
7.10. Packaging Instruction:
Formally authorized packaging instruction should exist for each product. Pack size
and type. These should normally include, or make reference to:
 The name of the product.
 A description of its pharmaceutical form, strength and, where applicable, method of
application.
 The pack size expressed in terms of the number. Weight or volume of the product in
the final container.

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