e-ISSN: 2582-5208

International Research Journal of Modernization in Engineering Technology and Science

( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com

DOCUMENTATION IN PHARMACEUTICAL INDUSTRY

Baratam Sandhya Rani*1, Uppada Harini*2, M. Jahnavi*3, V. Dihitha*4, P. Triveni*5,
K. Deepak*6, B. Mohan*7, Jagadeesh Panda*8
*1Associate Professor, B. Pharmacy, Raghu College Of Pharmacy, Dakamarri, Visakhapatnam, India.
*2Associate Professor, B. Pharmacy, Raghu College Of Pharmacy, Dakamarri, Visakhapatnam, India.
*3,4,5,6,7Student, B. Pharmacy, Raghu College Of Pharmacy, Dakamarri, Visakhapatnam, India.
*8Principal, B. Pharmacy, Raghu College Of Pharmacy, Dakamarri, Visakhapatnam, India.
DOI : https://www.doi.org/10.56726/IRJMETS62972
ABSTRACT
Documentation plays a crucial role in pharmaceutical industries. This article aims how to make effective
documents in various processes of pharma industries. This article also gives information about various types of
documents and their contents in industry. Article explains importance and need to prepare a document in
industry. As industry faces a stringent regulatory requirements making documentation is a critical aspect of
operations. Traditional paper work of documentation is sometimes error-prone, this article shows the benefits
of electronic technical documents in which documents are digitalized. The main objective of this article is to
support pharmaceutical industries to maintain documents for good manufacturing practices that ensures
product quality and promoting safety.
Keywords: Good Manufacturing Practices, Documentation, Regulatory Requirements, Electronic Technical
Documents, Product Quality, Safety.
I. INTRODUCTION
DOCUMENTATION:
 Documentation provides information on when, where, who, why, & how to complete tasks and evidence
providing that the tasks have been completed.
 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 defining the specification for all materials,
method of manufacturing and control. These documents should be approved, signed, dated by appropriate
and authorised person.
Related Definitions:
DOCUMENT: A piece of written, printed, or electronic matter that provides information or evidence or that
serves as an official record.
DOCUMENTATION: Documentation is any communicable material that is used to describe, explain or instruct
regarding some attributes of an object, system or procedure, such as its parts, assembly, installation,
maintenance and use.
RECORD: Provide evidences of various actions taken to demonstrate compliance with instructions, e.g.
activities, events, investigation, and in the case of manufactured.
PROTOCOL: The official procedure or a system of rules governing affairs of state or diplomatic occasions.
REPORT: An account given of a particular matter, especially in the form of an official document, after thorough
investigation or consideration by an appointed person or body.
II. NEED OF DOCUMENTATION
 Defines specifications and procedures for all materials and methods of manufacture and control.
 Control of process-ensures all staff knows what to do and when to do it.
 Ensure that authorised persons have all information necessary for release of product.
 Ensures documented evidence traceability, provide records and audit trail for investigation.
 Ensures availability of data for validation, review and statistical analysis.
 To improve performance.
 Regulatory requirements.
www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science
[5150]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
Importance of documentation:
Proper documentation is the backbone of current good manufacturing practices (cGMP) and in the regulatory
world, it is commonly held that
“If it isn’t documented, it wasn’t done!”
Documentation is the most essential part of a quality management and quality assurance system for the
following reasons:
 Written procedures provide clarity and ensure there are no errors that may arise during spoken
communication.
 Records, documents, and reports give a clear picture of what has been done and is ongoing work, and it also
helps to plan better for the future.
 A comprehensive review of the documents maintained in a pharmaceutical facility is often the key used by
regulatory bodies to assess the quality function of the facility.
 Accurate and clear records allow the critical reviewing of processes, which can help to improve quality and
create cost-saving measures too
 Good documentation is a must to attain ISO certification and any other industry- specific certificates.
 It provides necessary working details.
 Reduces risk of mistakes.
 Help in tracing the deviation from the expected yield.
 They help in decreasing the batch-to-batch variation so that quality of product is kept within the limits of
acceptability.
 Considered as the history of batch operations.
 Self-inspection of procedure.
Good Documentation Practices/ Maintenance of Documents in pharmaceutical industry:
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 authorised person
 Have the date of issue
 Have a due date of revision
 List to whom it has been issued
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 weigh materials
into the blend
 Instructions shall be in imperative manner
Where entry of any data(e.g. temperature, weight) is expected to be made by the person using the
document
1. Sufficient space shall be provided for making the entry
2. Heading shall clearly indicate what is to be entered, and who is responsible
3. All entries shall be in ink
4. All entries shall be clear and legible
5. Person making the entries shall confirm the entry by initialling/signing the same
6. An error in entry shall be so corrected that the original (wrong) entry is not lost. Such correction shall also
be initialled and dated.
7. Where necessary reason for correction shall be recorded initialled and dated.
Such revised versions shall also be approved by the authorised persons.
Updated/revised versions shall also be superseding the previous edition, and the document shall
clearly indicate this.

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5151]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
Outdate/superseded document shall be immediately removed from active use and copy retained only
for reference.
If documentation is through electronic data processing system (computerised system) there shall be
adequate reliable systems in place
 To check and ensure the correctness of data.
 To record changes (addition/deletion)
Common documentation errors:
o Illegible entries.
o Falsified data(date/time/version number).
o Signatures missing.
o Raw data to support results missing.
o Missing documents.
o Discarding data that does not match requirements.
o Invalid and fabricated data.
o No recording of activities.
o Data manipulation/deletion.
o Incomplete records.[1]
Type of GMP documents:
The records and documents in the pharmaceutical industry are categorised into the following
classes:[5]

1. Primary records (contracts, production formulae, packing instructions, supply source documents etc).
2. Procedures or supporting documents (SOPs, instructions, manuals, guidebooks).
3. Subsidiary records (equipment/instrument printouts, calibration reading reports etc).
4. Quality control records (test methods, test results, investigations, internal audit reports, Corrective and
Preventive (CAPA) reports, recall files etc).
Document name Description
Describes the regulations (USFDA/Schedule M/ ICH/ WHO) the company
Quality manual must follow to achieve desired level of compliance with cGMP in all
operations and products.
Company policy general description of company’s outlook on different aspects of the

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5152]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
company’s business and their implementation.
Standard operating
Stepwise instructions to perform a given task.
procedures(SOPs)
Stepwise instruction for production and packaging of drug product.
Batch records Include records relating to each batch, and contain entries made during
these processes.
Bound books or collection of forms in which operation, maintenance and
Log books
calibration details of equipment is recorded.
List of requirements that materials and products must meet to be
Specifications
considered acceptable.
Test methods Stepwise instructions for testing of materials and products.
THREE TIER DOCUMENTATION:
Broadly, all documents relating to quality fall into the following categories:[3]
1. Quality manual (optional)
2. Procedures (QSP and SOP)
3. Work instructions( can be merged with procedure)
4. Records

Quality manual:
A global company document that describes, in paragraph form, the regulations and/or parts of the regulations
that the company is required to follow.
Objectives of quality manual:
1. Describe the quality system structure.
2. Declare the quality policy and organisation goal.
3. Describe how the organisation meets the quality goal.

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5153]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
Content of quality manual:
The quality policy declaration, the goal of quality, and the organisational structure including responsibility and
authority of each key personnel procedure, instructions and resources for implementing the quality
management.
User:
All personnel in the organisation, Another parties, Auditors, and customers.[1]
POLICY:
Documents that describe in general terms, and not with step-by-step instructions, how specific GMP aspects
(such as security, documentation, health, and responsibilities) will be implemented.[1]
PROCEDURES:
Step-by-step instructions for performing operational tasks or activities.
Objectives:
Describe in detail how activities should be done, controlled and recorded in implementing the definite policy.
Standard operating procedures explains:
 What the process is and its purpose
 Where activity is operating
 Who is responsible for every activity
 When activity is completed, sequential of the activities, frequency, etc..
 Reference to the other relevant documents
USER:
All personnel who set up and run the processes.[1]
WORK INSTRUCTIONS:
The operational document containing instructions specifying how the activities are performed or products are
accepted.
Objectives:
It is an instruction document, step by step for guideline to execute the daily activity or operation for personnel
in every function. It is used departmentally, every task or every line.
Content of work instructions:
Detailed explanation of instructions to finish the job, detailed handling of method, equipment and machine and
related to the technical matters with stressing for operation, inspection & testing.
User:
All personnel who operate the certain task.
Supporting documents:
Worksheet, checklist; Visual(illustration, flowchart, layout plan, photo)[1]
Comparison between procedure and Working instructions:[1]
Procedure working instructions
Process oriented task oriented
Describe step of procedure describe detail instruction
Supporting the quality manual Operation guidance
Dedicated to explaining special task, method, or
Explaining general description on certain process
technique which should be done to achieve target
and give systematic action to ensure product quality
quality.
Procedure guideline which involves several Instruction guidance which dedicated for certain
departments and/ or sections department or section only.
During implementation need other supported During implementation can stand alone
www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science
[5154]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
documents
Guideline at organization level Guidance at operational level.
RECORD:
Records, including charts and data pertaining to design, inspection, testing, survey, audit, review or related
results.
All the records should be:
 Legible and clear
 Dated
 Readily identifiable and retrievable
 Carry authorization status
 Retained for a designated period
 Protected from damage and deterioration while storage
 All calculations should be duly recorded.[1]
BASIC PRINCIPLES- MAINTENANCE, RETENSION & RETRIEVAL :
MAINTENANCE:
 Each specification for raw materials, intermediates, final products, and packaging materials should be
approved and maintained.
 The issuance, revision, withdrawal of all documents should be controlled, with maintenance of revision
histories.
 Things to be maintained:
 The name of the manufacturer
 Identity and quantity of each shipment of each batch of raw materials, intermediates
 Labelling and packaging materials
 The name of the supplier
 The supplier’s control number(s)[1]
RETENSION:
 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 batch is completely
distributed.
 During the retention period, originals or copies of records should be readily available at the establishment
where the activities described in such records occurred.
 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.[1]
RETRIEVAL OF DOCUMENTS:
 All documents should be stored in the department in such a fashion that their retrieval is easy.
 For this purpose, following system may be adopted: a total list (may be alphabetical) of documents should be
made. This list show: the name of the document, location of availability and person to be contacted for
retrieval.
 Any document on demand, if available should be made available to the demanding authority in reasonable
period.
 Complete batch production and control record (B.P.C.R) must always be kept under lock and key under
control of Q.A.
 Retrieval of any master production and control record (M.P.C.R) and other important documents should be
possible only on proper authorisation of Q.A.[1]
Distribution Records:
 It contains name and strength of the product and description of the dosage form, name and address of the
consignee, date quantity shipped, and lot or control number of the drug product.

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5155]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
 Distribution records include a wide range of documentation such as invoices, bill of lading customer
receipts, and internal warehouse storage and inventory records.
 The information required need not be on document.
 Also customer codes and product codes may be used as alternates to customers name and addresses and
product names.
 Records for distribution shall be maintained in a manner such that finished batch of a drug can be traced to
the retain level to facilitate prompt and complete recall of the batch, if and when necessary.[2]
III. CONTROLLED DOCUMENTS
Definition: Controlled documents are official records subject to rigorous management to ensure they meet
predefined standards and regulations. This control ensures that the documents remain accurate, consistent and
up-to-date.
Features and Processes :
1. Version control:
➢ Tracking changes : Each document undergoes versioning to track changes and updates. This ensures that
users always access the latest approved version and historical records are preserved for audit purposes.
➢ Audit trail : Previous versions are retained for reference and accountability ,showing who made
changes ,when and why .
2. Approval workflow:
➢ Review process : A formal review and approval process is mandatory. This typically involves subject matter
experts, managers or legal teams who approve content for compliance, accuracy and relevance.
➢ Approval signatures : Final approval is documented ,often with digital or handwritten signatures
,confirming that the documents meet all necessary standards.
3. Distribution control :
➢ Monitored distribution: Only authorized individuals or departments have access to controlled documents.
Their distribution is monitored to prevent unauthorized or outdated versions from circulating.
4. Retention :
➢ Defined retention periods : Controlled documents are often subject to specific retention schedules ,usually
dictated by legal ,regulatory or industry standards (e.g. ISO , FDA ). These schedules specify how long a
document must be kept after it is no longer actively used.
➢ Legal and regulatory compliance :Certain laws and regulations ,such as the GDPR (general data protection
regulation) or specific industry regulations, mandate the retention of certain documents for a fixed period.
➢ Retention policies : Organizations establish formal retention policies that define the lifecycle of documents ,
from creation and active use to archiving and final disposal .
➢ Examples: Standard Operating Procedures (SOPs), policies, contracts, quality manuals, work instructions,
and safety protocols.
5. Access control :
➢ Restricted access: Only authorized individuals or departments are allowed to view ,edit or distribute
controlled documents ,minimizing the risk of unauthorized changes or misuse.
➢ Permission levels : Different permission levels can be applied ,such as “view only” access for general users
and “edit” access for document owners .
6. Document identification :
➢ Unique identifiers : Each controlled document is assigned a unique identifier to ensure easy tracking and
retrieval .
➢ Meta data : Additional information ,such as document title ,version number ,creation date and responsible
department ,is often included for better organization .

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5156]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
7. Archiving :
➢ Long-term storage: Once a document is no longer actively used but still needs to be retained (for regulatory
or historical purposes ) , it is moved to an archive . Archived documents are often stored in a secure and
controlled environment .
➢ Access restrictions: Archived documents typically have limited access , with only authorized personnel able
to retrieve them when necessary.
➢ Preservation of integrity : Archived documents must remain unaltered to preserve their integrity ,ensuring
they can be used as evidence if required.
➢ Format consideration: Digital archives often ensure documents are stored in non-editable formats to
maintain their original form and prevent tampering.
Importance: Controlled documents are essential for ensuring compliance with external regulations like
ISO (international organization for standardization ) standards, FDA(food and drug administration ) guidelines,
or GDPR requirements. Without controlled documentation, organizations risk non-compliance, fines, or
operational inefficiencies.[9]
IV. UNCONTROLLED DOCUMENTS
Definition:- These are informal documents not subject to the same stringent management as controlled
documents. They are generally considered lower risk in terms of regulatory impact but still play a role in daily
operations.
Features and processes:
1. No Formal Approval or Version Control :
➢ Uncontrolled documents are not required to follow formal approval workflows or version control processes.
They can be distributed without tracking who has access to them or whether they've been updated.
➢ Users need to ensure that the document they are referencing is the latest version, as there’s no formal
system to verify this.
2. Informational/Reference Purposes Only :
➢ These documents are typically intended for reference or informational purposes, such as industry standards,
external publications, articles, or guidelines that do not directly impact the organization's compliance or
operations.
➢ Examples:
External publications (e.g., research papers, textbooks)Vendor brochures or user manuals, general
reference materials , industrial guidelines that do not require internal compliance.
3. Not Tracked or Audited :
➢ Uncontrolled documents are not tracked in the same way that controlled documents are, meaning there’s no
centralized system monitoring when they’re accessed, revised, or distributed.
➢ Implication: Since they are not part of the formal document management system, they can’t be audited for
changes or accuracy in real time.
4. No Expiry or Review Dates
➢ These documents typically do not have formal review or expiration dates. This is because they are external
or not critical to the core functioning of regulated operations.
➢ Risk: There is a risk of using outdated or inaccurate information, which could affect decision-making if the
document becomes obsolete without users being aware.
5. Distribution is Informal:
➢ Uncontrolled documents can be distributed without the need for a formal system to ensure that everyone
who needs the document has the correct version. Distribution might happen via email, downloads from
external websites, or printouts.

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5157]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
➢ Risk: Without a controlled distribution mechanism, different users may end up with different versions of the
document, leading to inconsistencies in usage or interpretation.[9]
Key Differences Between Controlled and Uncontrolled Documents
Level of Control: Controlled undergo strict oversight, whereas uncontrolled documents are handled more
flexibly.
Versioning: Controlled documents have formal version control to ensure the most current information is used,
while uncontrolled documents do not.
Review and Approval: Controlled documents are subject to a structured review and approval process, while
uncontrolled documents can be created or revised without formal oversight.
Distribution: Controlled documents are distributed according to strict guidelines, ensuring only authorized
personnel can access them. Uncontrolled documents are typically distributed more freely.
Regulatory Impact: Controlled documents are necessary for regulatory compliance (e.g., ISO, FDA), while
uncontrolled documents generally have no direct regulatory implications.
The Importance of Managing Both Types in an Organization
Compliance and Auditing: Organizations in highly regulated industries need controlled documents to ensure
compliance with industry standards and legal regulations. Regular audits ensure that these documents are
accurate and properly managed.
Operational Efficiency: Controlled documents provide clear instructions, standards, and procedures that
improve consistency and reduce errors. Uncontrolled documents, on the other hand, foster flexibility and
innovation, allowing teams to share ideas and collaborate efficiently without the constraints of a formal
approval process.
Risk Mitigation: Mismanaging controlled documents could lead to serious compliance violations, while poor
handling of uncontrolled documents could lead to confusion, inefficiencies, or even reputational damage.
Challenges and Best Practices in Managing Controlled and Uncontrolled Documents
Document Overload: Without proper categorization, organizations might become overwhelmed by the volume
of both controlled and uncontrolled documents.
Unintended Document Circulation: Uncontrolled documents, especially if treated informally, could lead to
the circulation of inaccurate or outdated information.
Implementing a Document Management System (DMS): A robust DMS can streamline document
categorization, version control, approval workflows, and retention scheduling, making it easier to manage both
controlled and uncontrolled documents.
Regular Audits: Conducting regular audits ensures that controlled documents are updated and compliant, and
uncontrolled documents are not misused.
Clear Policies and Training: Organizations should implement clear policies on how to handle both types of
documents and provide staff training to ensure everyone understands the distinction.[9]
V. INTRODUCTION TO REGULATORY SUBMISSIONS IN PHARMACEUTICALS
❖ Purpose and Importance:
➢ Regulatory submissions are crucial for obtaining approval to market and distribute pharmaceutical
products. These submissions provide evidence to regulatory authorities that the drug product is safe, effective,
and of high quality.
❖ Key Regulatory Bodies:
➢ FDA (United States Food and Drug Administration)
➢ EMA (European Medicines Agency)
➢ PMDA (Pharmaceuticals and Medical Devices Agency, Japan)
➢ Health Canada, TGA (Therapeutic Goods Administration, Australia), and others.

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5158]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
Common Technical Document (CTD):
History and Evolution: The CTD was established by the International Council for Harmonisation (ICH) to
harmonize the submission format across different regulatory agencies. Before the CTD, each country had its
own submission guidelines, leading to duplicative work for pharmaceutical companies.
Objective: Standardization aims to reduce complexity and facilitate simultaneous submissions to multiple
regions.
❖ CTD Structure and Content:
➢ Module 1 (Regional Administrative Information):
Includes documents specific to the region such as application forms , labelling , and risk management plans.
➢ Module 2 (Common Technical Document Summaries):
Contains summaries and overviews of the Quality (CMC), Nonclinical (Pharmacology/Toxicology), and Clinical
(Efficacy and Safety) sections.
➢ Module 3 (Quality):
Provides detailed information on the manufacturing and controls of the drug substance and product.
Data on stability, manufacturing site, and specifications are covered.
➢ Module 4 (Nonclinical Study Reports):
Contains animal pharmacology and toxicology studies, assessing the drug's safety.
➢ Module 5 (Clinical Study Reports):Includes data from human clinical trials demonstrating the drug’s efficacy
and safety.[10]
Electronic Common Technical Document (eCTD)
➢ Transition from CTD to eCTD : The eCTD was introduced to facilitate electronic submissions and improve
accessibility for regulatory authorities.
The FDA and EMA have mandated the use of eCTD for certain applications, including DMFs and new drug
applications.
❖ eCTD Structure:
➢ Similar to the CTD with the same five modules but with additional features such as an XML backbone,
metadata, and life cycle management (tracking changes and amendments to submissions).
❖ Advantages of eCTD:
➢ Navigation and Review: Facilitates quick review with hyperlinks, bookmarks, and structured document
organization.
➢ Lifecycle Management: Changes and updates to documents (like amendments, annual reports, and
supplements) are easier to track and manage.
➢ Cost and Time Efficiency: Reduces paperwork and speeds up submission processes, cutting down on
regulatory review times.
➢ Global Standardization: Adopted by all major regulatory agencies, including the FDA, EMA, PMDA, Health
Canada, and others.[11]
Drug Master Files (DMF):
Definition and Purpose: A DMF is a submission to a regulatory body (e.g., FDA) that provides detailed
information on the processes, facilities, or components used in the manufacturing of human drugs. This is often
used by third-party manufacturers of APIs (active pharmaceutical ingredients), excipients, or packaging
materials.
❖ Types of DMFs:
➢ Type I: Manufacturing Site, Facilities, Operating Procedures.
➢ Type II: Drug Substance, Drug Product, or Intermediates.
➢ Type III: Packaging Material.
www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science
[5159]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
➢ Type IV: Excipients, Colorants and flavours.
➢ Type V: FDA-Accepted Reference Information.
❖ Importance of DMF:
➢ DMFs allow third-party manufacturers to provide confidential information directly to regulatory authorities
without disclosing proprietary information to drug product manufacturers.
➢ For drug product applicants, DMFs offer an alternative to conducting their own exhaustive quality checks on
the components or materials sourced from third parties.
➢ Global Use of DMFs: While the US FDA uses the DMF system, other regions may have alternative or
equivalent systems, such as the European ASMF (Active Substance Master File).
❖ DMF Submission Process
➢ How to Submit a DMF:
The DMF is submitted to the FDA using the eCTD format. The DMF must include a Letter of Authorization
(LOA), which gives permission for third-party companies to reference the DMF in their drug applications.
➢ Requirements for DMF Submission:
▪ Confidentiality: DMFs contain proprietary information about manufacturing processes and materials.
▪ Responsibility: The DMF holder is responsible for keeping the file up to date, submitting annual reports, and
providing amendments when necessary.
❖ Lifecycle Management of DMFs in eCTD Format:
Amendments, updates, or additional information submissions can be easily tracked via the eCTD lifecycle
management tools.
❖ Key Considerations and Challenges in Regulatory Submissions
Harmonization vs. Regional Differences:
Despite the harmonization of the CTD/eCTD format, Module 1 is still specific to each region. Understanding
regional differences (such as the FDA’s requirements versus the EMA’s) is critical for successful submission.
➢ Data Integrity and Security:
With eCTD, electronic submissions must adhere to strict standards of data integrity. Ensuring that documents
are secure, properly signed, and maintained is critical.
➢ Regulatory Updates and Compliance:
Regulatory bodies frequently update submission guidelines. Companies must stay abreast of these changes to
maintain compliance, especially with the FDA’s Guidance for Industry on DMFs and the EMA’s eCTD Validation
Criteria.
❖ Conclusion and Future Trends:
➢ Increasing Role of eCTD: With more agencies mandating eCTD submissions, the industry trend is toward full
digitalization of regulatory processes.
➢ Potential Advances: The integration of advanced technologies like Artificial Intelligence (AI) for document
preparation and review, and enhanced lifecycle management tools, may further streamline regulatory
submissions in the future.
➢ Global Regulatory Convergence: Initiatives by the ICH and other regulatory bodies to align requirements
could lead to even greater harmonization, reducing the burden on pharmaceutical companies submitting across
multiple regions.
MASTER FORMULA RECORD:
Definition:
A document or set of documents specifying the starting material with their quantities and the packaging
materials, together with a description of the procedure and precautions required to produce a specified
quantity of a finished product as well as the processing instructions, including the in-process controls."

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5160]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
Master production instructions should include:
 The name of the intermediate/AP/ formulation being manufactured and an identifying document reference
code, if applicable
 A complete list of raw materials and intermediates (designated by names or code497 sufficiently specific to
identify any special quality characteristic)
 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 wherever justified.
 The production location and major production equipment to be used
 Detailed production instructions, including the:
 Sequences to be followed
 Ranges Of process parameters to be used
 The methods, or reference to the methods, to be used for preparing the critical equipment (e.g., cleaning,
assembling)
 Sampling instructions and in-process controls, with their acceptance criteria where appropriate
 Time limits for completion of individual processing steps and/or the total process, Where appropriate
 Expected yield ranges at appropriate phases of processing or time
 Where appropriate, special notations and precautions to be followed, or Cross references to these
 Instructions for storage of the intermediate or API/semi-finished formulations to assure its suitability for
use; instructions should cover the labelling (specimen label sand packaging materials and special storage
conditions with time limits, where appropriate).
 Master Formula Record is also called MFR, Master Production Record.
 MFR is used as reference standard for preparing batch manufacturing record (BMR) by manufacturing units.
 It is prepared by the research and development team of the company. It contains all Information about the
manufacturing process for the product.
 Master Formula Record (MFN) is a master document for any pharmaceutical product.
 MFR plays an important. Inconsistency for each batch manufacturing. There shall be Master Formula records
relating to all manufacturing procedures for each product and batch size to be manufactured.
 These shall be prepared and endorsed by the competent technical staff i.e., head of production and quality
control.
 A Master Formula Record is ether prepared based upon experience of qualified staff like manufacturing
chemist or analytical chemist or prepared based upon batch manufacturing record of a batch size.
MFR includes-
 Product Details: Name, logo and address of the manufacturing company
 Dosage form name. Brand name, Generic name. Product code and Label claim of all ingredients
 Product description: Batch size, Pack size and packing style
 Shelf life and Storage conditions.
 MFR number and date: Supersede MFR number and date
 Effective batch number
 Authorization by the production and quality assurance head
 Equipment: A list of all required equipment and machines required in the manufacturing with their capacity
 Special instructions: The precautions and special instructions to be followed during the product
manufacturing and packing
 Calculations: Include the calculation steps of all active materials to get the 100% of the active material. The
calculation is done using water or LOD to get 100% potency
 Manufacturing Process: All steps in all stages of the manufacturing process are written. All process steps like
shifting, milling, lubricating, granulation, compression and coating are written in detail including the process
time and yield. It also includes atmospheric conditions as temperature, humidity, and storage conditions for
every step

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5161]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
 Packing Process: List of all packing materials with their quantity is written. Line clearance, reconciliation of
printed and unprinted packing materials should be included in details.
 Yield: Include the theoretical, actual yield and acceptance limit of the batch.
 Primary Responsibility is of FD and Production Department and secondary responsibility is of Quality
Assurance Department. Accountability lies with Head-Quality Assurance for Implementation of SOP.
Steps in preparation of MFR:
 Production Department in association with PD prepares MFR. It is divided into two sections;
1) Manufacturing
2) Packaging
 The first page of both the sections shall have following details: Name, address and logo of the company.
Dosage form, Brand name Generic name Product code Label claim include all ingredients and text included
in product permission. Product Description, Shelf Life, Pack Size, Batch Size and Storage conditions.
 The secondary page of manufacturing section shall include-Processes to monitor. Subsequent pages shall
include the processes to be monitored. The list of equipment machines, utensils to be used, shall be
described. The subsequent page shall include any Special precautions to be taken for the product during
manufacturing and packing. The same should also include Batch Manufacturing formula
 At the end of every important stage, include a statement of the yield with the acceptable Limits. In-process
quality checks during and at the end of important steps and stages with their limits are included. The
process shall include the equipment to be used. The methods or the reference of the methods/procedures to
employed for preparing, cleaning assembling, operating the various equipment are given. Detailed stepwise
processing instructions (example: checks on materials, pretreatments, sequence for adding materials,
mixing times, temperatures, humidity etc.) is included. The requirements for storage conditions of the
products are also present.
 The secondary page of packaging section of MFR should include complete list of all then packaging materials
required for a standard batch size including quantities sizes and types Include line clearance checking
during batch cording and batch packaging operations. Includes reconciliation of printed and unprinted
packaging materials with acceptable limits. Includes
 destruction of excess or rejected printed packaging materials Includes description of packaging
 Operation including any significant subsidiary operations and equipment to be used. [8]
BATCH PRODUCTION RECORDS/BATCH PRODUCTION AND CONTROL RECORDS (BPCR)/BATCH
MANUFACTURING RECORD (BMR):
Definition:
 Batch manufacturing record is a written document of the batch, prepared during pharmaceutical
manufacturing process.
 It contains actual data and step by step process for manufacturing each batch.
 Batch manufacturing record is like a proof that batches were properly made and checked by quality control
personnel.
 Batch production records should be prepared for each intermediate and API/formulation and should include
complete information relating to the production and control of each batch.
 The batch production record should be checked before issuance to assure that it is the correct version and a
legible accurate reproduction of the appropriate master production instruction.
 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.
 Before any processing begins, a check should be performed and recorded to ensure that the equipment and
workstation are clear of previous products, documents, or materials not required for the planned process
and that the equipment is clean and suitable for use.
 These records should be numbered with unique batch or identification number and dated and signed when
issued.
 In continuous production, the product code together with the date and time can serve as the unique
identifier until the final number is allocated.
www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science
[5162]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
 The batch number should be immediately recorded in a logbook or by electronic data processing system.
 The record should include date of allocation, product identity, and size of batch.
 Documentation of completion of each significant step in the batch production records (batch production and
control records) should include:
o Dates and, when appropriate, times.
o Identity of major equipment used (e. g, reactors, driers, mills, etc.)
o Specific identification of each batch, including weights, measures, and batch numbers of raw materials,
intermediates, or by reprocessed materials used during manufacturing.
o Actual results recorded for critical process parameters.
o Any sampling performed.
o Signatures of the persons performing and directly supervising or checking each critical step in the operation.
o In-process and laboratory test results.
o Actual yield at appropriate phases or times.
o Description Of packaging and label.
o Representative label (commercial supply).
o Any deviation noted, its evaluation, and investigation conducted (if appropriate) or reference to that
investigation (if stored separately).
o Results of release testing.
o All analytical records relating to the batch, or a reference that will permit their retrieval.
o A decision for the release or rejection of the batch, with the date and signature of the person responsible for
the decision.
o The production record review.
 Production and quality control records should be reviewed as part of the approval process of batch release.
 Any divergence or failure of a batch to meet its specifications should be thoroughly investigated.
 The investigation should, if necessary, extend to other batches of the same product and other products that
may have been associated with the specific failure or discrepancy.
 A written record of the investigation should be made and should include the conclusion and follow-up
action.
 The following information should be recorded at the time each action is taken (the date must be noted and
the person responsible should be clearly identified by signature or electronic password):
 The name of the product, the batch number and the quantity of product to be packed, as well as the quantity
actually obtained and its reconciliation.
 The date(s) and time(s) of the packaging operations.
 The name of the responsible person carrying out the packaging operation. The initials of the operators of the
different significant steps.
 The checks made for identity and conformity with the packaging instructions, including the results of in-
process controls.
 Details of the packaging operations carried out, including references to equipment and the packaging lines
used and, when necessary, instructions for keeping the product unpacked or a record of returning product
that has not been packaged to the storage area.
 Whenever possible, the regular check for correctness of printing (e.g. batch number expiry date and other
additional overprinting) and specimen samples collected.
 Notes on any special problems, including details of any deviation from the packaging instructions, with
written authorization by an appropriate person.
 The quantities and reference number or identification of all printed packaging materials and bulk product
issued, used, destroyed, or returned to stock and the quantities of product obtained; this is necessary to
permit an adequate reconciliation.[8]
VI. CONCLUSION
Here by we conclude that documents made in industries are beneficial for further reference, auditing, review
and others. Documents made in industries are well thoroughly written in the paper work or digitalised by e-
documents and these are stored according to the requirement. All these guidelines for preparing specific type of
www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science
[5163]
 e-ISSN: 2582-5208
International Research Journal of Modernization in Engineering Technology and Science
( Peer-Reviewed, Open Access, Fully Refereed International Journal )
Volume:06/Issue:10/October-2024 Impact Factor- 8.187 www.irjmets.com
document are mentioned in this article. Various types of documents like BFR, MFR, controlled documents,
uncontrolled documents and others, their making procedures are explained. Effective documents can help in
error correction in the process hence preparation of documents is very necessary step in the pharmaceutical
industries.
VII. REFERENCES
[1] https://www.slideshare.net/slideshow/documentation-in-pharmaceutical-industrypptx-
258791091/258791091
[2] https://www.slideshare.net/slideshow/documentation-in-pharmaceutical-industry-
234521981/234521981
[3] https://www.scribd.com/presentation/518191480/Documentation-in-Pharmaceutical-Industry-
Yadav-Pooja-S
[4] https://www.slideshare.net/slideshow/pharmaceutical-documentation-233090722/233090722
[5] A TEXT BOOK OF PHARMACEUTICAL QUALITY ASSURANCE by ANUSUYA R. KASHI, BINDU
SUKUMARAN, VEENA P. from Nirali Prakashan.
[6] https://www.consepsys.com/2019/01/16/controlled-and-uncontrolled-documents/
[7] https://instantgmp.com/what-is-the-difference-in-controlled-uncontrolled-documents/
[8] https://tabraizullah.files.wordpress.com/2020/02/document-maintenance-in-pharmaceutical-
industry.pdf
[9] https://www.slideshare.net/slideshow/concept-of-controlled-uncontrolled-documents-
ctdpdf/258350426
[10] https://www.slideshare.net/slideshow/common-technical-document-ctd/131520156
[11] https://www.slideshare.net/MChandraMohan/ectd-234188409

www.irjmets.com @International Research Journal of Modernization in Engineering, Technology and Science

[5164]