Documentation In Pharmaceutical Industry.pptx

Documentation In Pharmaceutical Industry
F.Y. M. Pharm (Pharmaceutical Analysis)

Syllabus
• Three tier documentation i.e., Policy, Procedures and Work instructions, and
records (Formats),
• Basic principles- How to maintain, retention and retrieval, etc.
• Standard operating procedures (How to write), (Reduced Syllabus)
• Master Formula Record,
• Batch Formula Record, (Reduced Syllabus)
• Quality audit plan and reports.
• Specification and test procedures, Protocols and reports.
• Distribution records.
• Electronic data.

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.
Documentation provides information on when, where, who, why & how to complete
tasks and evidence providing that the tasks have been completed.
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
defining the specification for all materials, method of manufacturing and control.
These documents should be approved, signed, dated by appropriate and authorized
person.

Need Of
Documentation
1. Defines specifications and procedures for all
materials and methods of manufacture and
control
2. Control of Process - Ensures all staff knows
what to do and when to do it.
3. Ensure that authorized persons have all
information necessary for release of product
4. Ensures documented evidence, traceability,
provide records and audit trail for
investigation
5. Ensures availability of data for validation,
review and statistical analysis.
6. To improve performance
7. Regulatory requirements
1. It provides necessary working details
2. Reduces the risk of mistake
3. Help in tracing the deviation from the
expected yield
4. They help in decreasing the batch-to-batch
variation so that quality of product is kept
within the limits of acceptability
5. Considered as the history of batch operations
6. Self-inspection of procedure
Importance Of
Documentation

Maintenance of Documents
For effective use of documents, they should be designed and
prepared with utmost care. Each document shall:
a. Have a clear title
b. Have an identification number
c. Be approved by authorized person
d. Have the date of issue
e. Have a due date of revision
f. List to whom it has been issued
Where the documents carry instructions (e.g., batch processing)
a. The instructions shall be precise and not ambiguous
b. They shall be for each individual step and not combined. e.g.,
Weigh the materials, charge the weighed materials into the blend
c. 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:
a. Sufficient space shall be provided for making the entry.
b. Heading shall clearly indicate what is to be entered, and who is responsible.
c. All entries shall be in ink.
d. All entries shall be clear and legible.
e. Person making the entries shall confirm the entry by initialling/signing the same.
f. An error in entry shall be so corrected that the original (wrong) entry is not lost.
Such correction shall also be initialled and dated.
g. Where necessary reason for correction shall also be recorded initialled and dated.
Documentation system should provide for a periodic
review and revision, if necessary, of any document or
part thereof.
Such revised versions shall also be approved by the
authorized persons.
Updated/revised versions shall also be superseding the
previous edition, and the document shall clearly
indicate this.
Outdate/superseded document shall be immediately
removed from active use and copy retained only for
reference.
If documentation is through electronic data processing
system (computerized system) there shall be adequate
reliable systems in place:
a. To check and ensure the correctness of data.
b. To record changes (addition/deletion)

Retrieval Of Documents
1. All documents should be stored in the department in such a fashion that their
retrieval is easy
2. For this purpose, following system may be adopted: A total list (may be
alphabetical) of documents should be made. This list should show: The name of
the document, Location of availability and Person to be contacted for retrieval.
3. Any document on demand, if available should be made available to the
demanding authority in reasonable period.
4. Complete Batch production and control record (B.P.C.R) must always be kept
under lock and key under the control of Q.A.
5. Retrieval of any master production and control record (M.P.C.R) and other
important documents should be possible only on proper authorization of Q.A.

Documentation In Pharmaceutical Industry.pptx

Tier Of Documentation
1. Quality Manual/ Policies
2. Procedures
3. Work Instructions
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.
Policies: Documents that describe in general
terms, and not with step-by-step instructions,
how specific GMP aspects (such as security,
documentation, health, and responsibilities) will
be implemented.
Objectives of Quality Manual
1. Describe the quality system structure.
2. Declare the quality policy and organization goal.
3. Describe how the organization meets the quality goal.
4. Content of quality manual: The quality policy declaration,
The goal of quality, and The organizational structure
including responsibility and authority of each key personnel
Procedures, instructions and resources for implementing the
quality management.
5. User: All personnel in the organization, Another parties,
auditors, and customers

Procedures (SOP)
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:
1. What the process is and its purpose
2. Where activity is operating
3. Who is responsible for every activity
4. When activity is completed, sequential of the
activities, frequency, etc.
5. Reference to the other relevant documents
User: All personnel who set up and run the processes
Working Instruction
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 operates the certain task
Supporting documents: Worksheet, checklist; Visual
(illustration, flow chart, layout plan, photo)

Comparison between SOP and Working
Instructions
SOP Working Instruction
Process oriented. Task oriented.
Describe step of procedure. Describe detail instruction.
Supporting the quality manual. Operation guidance.
Explaining general description on certain process and
give systematic action to ensure product quality.
Dedicated to explaining special task, method, or
technique which should be done to achieve target
quality.
Procedure guideline which involves several
departments and/or sections.
Instruction guidance which dedicated for certain
department or section only.
During implementation need other supported
documents.
During implementation can stand alone.
Guideline at organization level. Guidance at operational level.

Records
Records, including charts and data pertaining to design, inspection, testing, survey, audit, review or related results.
Demonstrate: Quality System has been effectively implemented, Products and services have been developed and
delivered appropriately with the requirements.
All Records should be:
a. Legible and clear
b. Dated
c. Readily identifiable and retrievable
d. Carry authorization status
e. Retained for a designated period
f. Protected from damage and deterioration while storage
g. All calculations should be duly recorded

Basics Principles
Maintenance
1. Each specification for raw materials,
intermediates, final products, and packing
materials should be approved and
maintained.
2. The issuance, revision, withdrawal of all
documents should be controlled, with
maintenance of revision histories.
3. Things to be maintained. The name of the
manufacturer; identity and quantity of each
shipment of each batch of raw materials,
intermediates, or labelling and packaging
materials; the name of the supplier; the
supplier’s control number(s)
Retention:
1. All production, control, and distribution
records should be retained for at least 1 year
after the expiry date of the batch.
2. For APIs with retest dates, records should be
retained for at least 3 years after the batch is
completely distributed.
3. During the retention period, originals or
copies of records should be readily available
at the establishment where the activities
described in such records occurred.
4. 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.

Master production and control record (MPCR)
It is also said and written as “Master formula record/ Manufacturing formula/ Master production and
control record”. (CFR 211.186)
Definition: “An approved master document that describes the full processes of manufacturing for the
batch of specific product.” It included all the materials used in any batch manufacturing and step by
step processes of manufacturing.
General Principles:
1. To ensure product uniformity from batch to batch the master product instruction for each API,
Intermediate and finished product should be- Prepared, dated and signed by one person and
checked, dated and signed by another person.
2. Person experienced from QC and production responsible for content and distribution within firm.
3. Outdated MPCR should be withdrawn and retained for reference.
4. Any amendment in master formula should be formally authorized by competent person.

Master production instructions include:
1. Name of intermediate/API/formulation and identifying documents with reference code.
2. List of raw materials and intermediates.
3. Accurate statement of quantity of ratio of each raw material with unit of measure.
4. The production location and major production equipment used.
5. Detailed production instructions including:
Sequences to be follow:
a. Ranges of process parameters.
b. Methods to be used for critical equipment
c. Time limit of individual processing step.
d. Sampling instructions and in-process control with acceptable limits.
e. Instruction for storage of the intermediate or API/semi- finished formulations to assure its suitability
for use.
f. Description of drug product containers, closures, and packaging materials, including specimen copy
signed by authorized person.

Master formula record (MFR) is a master document for any pharmaceutical product.
It contains all information about the manufacturing process for the product and is
prepared by the research and development team of the company. It is used as a
reference standard for preparing batch manufacturing record (BMR) by
manufacturing units. MFR is also called Master Manufacturing record or Master
production record.
“A document or a set of documents specifying the starting materials with their
quantities and the packaging materials, together with a description of the procedures
and precautions required to produce a specific quantity of a finished product as well
as the processing instructions, including the in-process control”.

Preparation of MFR
MFR should have following parts:
Product Details:
i. Name, logo and address of the manufacturing
process
ii. Dosage form name
iii. Brand name
iv. Generic name
v. Product code
vi. Label claim of all ingredients
vii.Product description
viii.Batch size
ix. Pack size and packaging style
x. Shelf life
xi. Storage conditions
xii.MFR number and date
xiii.Effective batch number
xiv.Authorization by the production and quality
assurance head
Flow chart:
i. Steps of the manufacturing process to be monitored.
ii. Flowchart of the material movement from dispensing to the
final product to stores.
Equipment: Create a list of all required equipment and
machines required in the manufacturing process with their
capacity.
Special Instructions
i. Write down the precautions special instructions to follow
during the product manufacturing and packing and these
should also be added in the batch manufacturing formula.
ii. Batch manufacturing formula should include the following:
Name of the ingredient with test reference (As IP, BP, USP etc),
Quantity to be added, and Overages to be added (%).

Preparation of MFR
Calculations
i. Include the calculation steps of all active material to get the 100% of the active material.
ii. The calculations shall be done using water content or LOD to get 100% potency
Manufacturing Process
i. Write all steps in all stages of the manufacturing process.
ii. All process steps like shifting, milling, mixing, lubricating, granulation, compression and coating should be written in detail
including the process time and yield.
iii. Include atmospheric conditions as temperature, humidity and storage conditions for every step.
Packing Process
i. List of all packing materials with their quantity is written.
ii. Line clearance, reconciliation of printed and unprinted packing material should be included in detail.
Yield
i. Include the theoretical, actual yield and acceptance limit of the batch
ii. The detail given above should be included in a general master formula record. Other details should be added as per company
requirements in the master formula record.

GMP Guidelines on MPCR:
WHO: WHO Technical report series no-908,
2003
EU- EudraLex - Medicinal products for human
and veterinary use, good manufacturing
practices, Chapter- 4
Pharmaceutical inspection convention (PIC):
January 2006, GMP for medicinal products.
Canada - Health Canada health products and
food branch inspectorate, GMP guidelines
2002
USA - US code for federal regulations

Quality Audit Plan
Audit: It is periodic, independent and documented
examination and verification of activities, records,
processes and other elements of quality system to
determine their conformity with requirements of quality
standard such as ISO 9000.
As per ISO, Systematic, independent and documented
process for obtaining audit evidence and evaluating them
objectively to determine the degree to which the
verification criteria are met
Audit compliance: Ensure compliance with ISO
9001:2008; Ensure compliance with organization
requirements; Ensure compliance with regulatory
requirements.
Reason for audit:
1. Build confidence in GMP and QA
2. Measures for necessary improvement
3. Absolute reliability, in optimal conditions
4. Build interdepartmental trust
5. Providing corrective action
6. Promote understanding between parties
Objectives:
1. Evaluating conformity of requirements to ISO 9001
2. Judging conformity of implementation to
documentation
3. Determining effectiveness in meeting requirements and
objectives
4. Meeting any contractual or regulatory requirements for
auditing
5. Providing an opportunity to improve the quality
management system
6. Permitting registration and inclusion in a list of
registered companies
7. Qualifying potential suppliers
Audits and regulatory standards:
1. ISO 9000: published in 1987 for all business activities
2. Today, popular standards such as ISO 9001: 2000, ISO
14001: 2004, and ISO 13485
3. 21 CFR part 820
4. FDA regulation

Quality Audit Plan
Types of audits:
i. Internal audit
ii. External audit
iii. Regulatory audit
iv. Product audit
v. Process audit
vi. System audit
Internal audit: (First Party): Internal auditing is an independent, objective assurance and consulting activity designed to add value
and improve an organization’s operations.
Internal control: A process which is performed by the employees of the company as well as the information technology systems that
are used to assist the company in achieving its objectives.
Management tool: These monitors and evaluates the effectiveness of operational processes and risk management of a company.
Purpose:
1. Early identification of regulatory concern
2. Identify compliance deficiency and deviation from quality standard and company requirement.
3. Inform management about regulatory risk
4. Foster continuous improvement
Benefits:
1. Identify root problem and plan for corrective action
2. Better allocation of resources
3. We can understand health of quality system
Three Tier Approach in Internal Audits
Tier 1: Audits carried out by the staff of a section or department on themselves. Such audits will typically be of only short duration and
of limited scope. They focus on ‘visibles’, e.g., housekeeping and documentation.
Tier 2: Audits, typically led by a local quality assurance group, comprising staff independent of the department being audited. Such
audits will typically be of longer duration, but less frequent. They are likely to focus more on systems than on warehousing (which
should be well controlled because of the tier 1 audits).
Tier 3: Audits carried out by a corporate compliance group. Alternatively, external consultants may be asked to carry out such audits.
Such audits will often be carried out to assess readiness for a regulatory audit but may also be used to obtain an expert view on a
specific critical activity, e.g., sterile products manufacture.

Quality Audit Plan
External audits: (Second party and third party)
1. Carried out by company on its vendors or subcontractors
2. Although there are no strict legal requirements for this
control.
3. It is always advisable to evaluate the competence of the
contractors in which we produce our products or carry
out the analysis of our products or any other activity
according the GMP.
Benefits:
1. Develop knowledge and confidence in the partnership
agreement
2. Ensures that requirements are understood and met
3. Reduce the risk of failure.
Regulatory audits: (Third-Party Audit)
This type of audit is also known as Third-Party Audit.
Neither customer nor supplier conducts this type of audit.
A regulatory agency or independent body conducts a third-
party audit for compliance or certification or registration
purposes.
Regulatory Bodies:
Medicines and healthcare products regulatory agency
(MHRA)
United States food and drug administration (USFDA),
Therapeutic goods administration (TGA), Australia,
Medicines control council (MCC), South Africa, etc. are
responsible for carrying out these checks
Auditors must be representative from production, quality
control, warehouse, maintenance, administration/personnel
and marketing/sales.
Inspectors: Extensively trained, competent and professional;
All MHRA inspectors are professionally qualified and have a
minimum of five years of appropriate experience in a
production operation
Failure of regulatory audit: Restrictions (or revocation) of
production or import/export license.

Quality Audit Plan
Product audit
In depth examination of product if it meets
specifications, performance, standard and
customer requirements.
Process audit
An analysis of elements of the process and
appraisal of completeness, correctness of a
condition and probable effectiveness.
System audit
A documented activity performed to verify by
examination and evaluation of quality system
implemented by company.

Quality Audit Plan
Steps of Quality Audit:
Notification: Alerts the party to be audited of the date and time of the
process. The notification also will list the documents that the order
wishes to review in order to understand the organization of the
company.
Planning: Planning is the steps the auditor takes, before the audit, to
identify key areas of risk and areas of concern. schedule of the
employees that must be consulted.
Opening meeting: Meeting between the auditing staff and senior
management of the auditing target as well as administrative staff.
Field work: Initial investigation begun after learning of business
procedures, interviewing key staff, testing current business practices by
sampling, reviewing the law and testing internal rules
Communication: The audit team should consistently be in
contact with the corporate auditor to clarify processes, gain
access to documents and clarify procedures
Draft audit: The draft audit detail what was done and what
was found, a distribution list of parties to receive preliminary
results, and a list of concerns.
Management response: The draft is given to management to
review, edit and suggest changes, probe areas of concern and
correct error
Final meeting: The final meeting is designed to close loose
ends, discuss the management response and address the scope
of the audit.
Report distribution: Final audit report is sent to appropriate
officials inside and outside the audit area
Feedback: Audited company implements the recommended
changes and the auditors review and test the quality,
adherence and effects of the adopted changes.

Specifications
A specification is defined as list of tests with references to
analytical procedures, with appropriate acceptance criteria
which are numerical limits or ranges, or other criteria for the
tests described.
Specifications are critical quality standards that are proposed
and justified by the manufacturer and approved by the
regulatory authorities as conditions of approval.
Specifications are legally binding criteria that a medicinal
product must meet.
Set of criteria that a drug substance and drug product must meet
to fulfil pre-defined standards for commercial use.
Assurance that the quality is safe and efficacious over its shelf-
life.
ICH Q6A Specifications: Test procedures and
acceptance criteria for new drug substances and
new drug products: Chemical substances
ICH Q3A - Q3D: Impurities
Pharmacopoeia USP, IP, BP, EP, JP
Universal tests/criteria:
1. Description / Appearance
2. Identification (IR, HPLC/ UV diode array,
etc.)
3. Assay
4. Impurities

Specifications
Specification test criteria
API:
1. Polymorphism
2. Physico-chemical properties: pH, melting point
3. Water content (KF preferred)
4. Inorganic impurities, Heavy metals
5. Microbial limits Finished Product
FINISHED PRODUCT:
1. Performance tests: e.g., dissolution, disintegration (where
applicable)
2. Uniformity of dosage units: mass or content uniformity, fill
volume
3. Physical tests: e.g., LOD/water content, pH, friability, hardness,
particle size
4. Content of preservatives
5. Microbial contamination
6. Sterility, bacterial endotoxins, particulate matter (parenteral)
Specification Parameters
Description: Should be detailed (colour, shape, coating, marking
(ink, embossing)
Identification: should be able to discriminate betwee
compounds of closely related structure done HPLC/UV
HPLC/MS or GC/MS
Assay: should be stability indicating. May be non- specific, e.g
titration, but need to achieve overall specificity, e.g., non-specif
assay plus suitable related substances test
Related substances:
- Specified (identified and unidentified)
- Unspecified (individual unknowns), and
- Total related compounds
Dissolution: Dissolution specs at release and shelf-life should b
identical ± 5 %
Hardness and friability
Content uniformity

Specifications
 Active and inactive starting material.
 Primary printed and other packaging materials.
 Intermediate and bulk products.
 Finished pharmaceutical products.
Common contents in specification format:
i. Name of company and address of location.
ii. Title of document viz-Specification.
iii.Effective date, date of preparation, checking,
authorization, date of review.
iv.Name and signature of person checking and
authorizing specification.
v. Pharmacopeia reference.
vi.Unique identification number
Acceptance limits:
Active substance: ± 5 % release limit without
justification; > ± 5 % needs justification
Excipients: Excipient should not affect bioavailability
of active substance; Preservatives content limits of 90-
110 % acceptable; Routine test: Carried out on each
batch of intermediate, bulk and finished product;
Periodic test: Not carried out batch to batch but
periodically.

Specifications
Product release specifications
i. Finished product is product in marketable pack, practically
transportable, one can sale.
ii. Specifications for finished dosage form:
a. Designated names and identification and assay of active
substances, excipients, colorants used.
b. Formula or reference to formula.
c. Description of dosage form and packing details.
d. General physical test with acceptable limit.
e. Identification and assay of antimicrobial and antioxidants
preservatives.
f. Purity test.
g. Pharmaceutical test (e.g., dissolution)
h. Maximum acceptable deviation +/- 5 % at the time of
manufacture.
Safety test including abnormal or specific toxicity test.
WHO guideline for storage:
a. Finished product should be held in quarantine
area.
b. Satisfactory lab determinations of batch before
release.
c. Product failing to meet the established
specifications should be rejected and
reprocessed if feasible.

Specifications
Product release specifications: SOP on releasing finished product:
a. Authorized person/QA head as per regulatory requirement.
b. Before releasing finished product following points to be considered.
i. Completed B.P.C.R
ii. Test reports I.P.Q.C
iii. Test reports of finished product/analysis.
iv. Stability report along with environmental conditions.
v. Reports related to manufacturing and packaging of batch.
Test and acceptance criteria for new drug product:
Description: Qualitative description of dosage form e.g., Size, shape and
color and final acceptance color.
Identification: I.R, HPLC/UV, HPLC/MS or GC/MS
Assay: Stability indicating assay with quantitation of impurities.
Impurities: Organic or inorganic impurities and residual solvents.
Additional test and acceptance criteria:
i. Dissolution: single time point, multiple time point
ii. Disintegration:
iii. Hardness
iv. Friability
v. Uniformity of dosage
vi. Water content
vii. Microbial limit

Distribution Record
Distribution records shall contain the name and strength of the
product and description of the dosage form, name and address
of the consignee, date and quantity shipped, and lot or control
number of the drug product. For compressed medical gas
products, distribution records are not required to contain lot or
control numbers.
The primary purpose of this section is to ensure that adequate
data are available to access trade customers should a recall be
initiated. The recording of lot number to each order will
certainly accomplish this purpose; other approaches can
achieve the same result. The recording of dates on which a
specific lot of products commenced and ceased distribution
may be used. All customers receiving the product between
these dates could then be contacted. Obviously on the first and
last days of distribution some of the customers may have
received product from the end of the previous lot or the
beginning of the next lot. This overlap should in no way
adversely impact on the effectiveness of a recall.
Whatever system is used, it must accommodate the
reintroduction of re- turned goods into the distribution chain.
Distribution records include a wide range of documentation
such as in- voices, bills of lading, customers receipts, and
internal warehouse storage and inventory records. The
information required need not be on every document. Also,
customer codes and product codes may be used as alternates
to customer names and addresses and product names.
Compendial articles are to follow the current compendium
when shipped. This can create some difficulties with respect
to inventories of components, labelling or products when
there are compendial changes. Compliance Policy Guide
7132.02 does suggest that regulatory action should not be
taken if a company is using up existing stock of labels in a
reasonable time and that the product or material is otherwise
in compliance with the new monograph.

Electronic Data
Data has never been easy to manage and is especially true in
pharmaceutical industry. The FDA uses the acronym ALCOA
to define its expectations of electronic data.
ALCOA
A: Attribute;
L: Long lasting;
C: Contemporaneous;
O: Original;
A: Accurate
21 CFR Part 11: Electronic records and electronic signatures
must control the electronic data record security, integrity,
traceability and the proper use of electronic signatures
Management: Hardware and software that converts paper
documents into electronic documents, manages and archives
those electronic documents and then indexes and stores them
according to company policy.
Software's used:
1. Laboratory information management systems (LIMS).
2. Electronic data capture (EDC)
3. Paper Data Capture (PDC)
4. Share point document management system
5. Enterprise content management
Laboratory information management systems LIMS:
1. Commercially available for 20 years
2. Software based laboratory and information
management system that offers a set of key features
that helps supporting modern laboratory’s operations
3. Key features of LIMS: Workflow, data tracking, data
exchange interface, assay data management, data
mining, data analysis, electronic laboratory notebook
(ELN) integration etc.

Electronic Data
Advantages of LIMS:
1. Makes ergonomically for individuals working in
laboratory.
2. Reduction in ambiguity and improvement in
consistency of laboratory practices
3. Increase in productivity occurs when the system is
properly integrated into the daily routine of laboratory
operations.
4. All the information can be stored and retrieved from the
central database
5. Real time control of data with built in QC specifications
Disadvantages of LIMS:
1. Adequate validation to ensure data integrity
2. Limited interface between lab & field computers
3. Cost of LIMS
Electronic data capture (EDC):
1. EDC computer-based system acts as tool for collection of
clinical data in electronic format based upon software
program.
2. Streamline the data collection and reduction in time to market
drugs and medical devises.
3. Adopted by many pharmaceutical companies and clinical
research organizations where it is used for clinical trial data
management.
Objectives for implementing an EDC system in clinical trial
1. Real time data access
2. Efficient data transfer and faster impact on marketing a drug
3. Overcoming the shipping of paper CRFs (case report forms)
from remote area
Paper Data Capture (PDC): PDC works similar to EDC and
used for data gathering in terms of paper case report forms;
Reviewed case report forms are stored in central data base in
digital format
Advantage
1. Cost and maintenance is low compared to EDC
2. Improve/modify the data collection

Electronic Data Share point document management system:
1. It is a web-based application developed by
Microsoft in 2001.
2. Provide functions like document and file
management, intranet portal, enterprise
search, business intelligence
3. Unique features like system integration,
process integration, and workflow
automation capabilities.
4. Application is being used by 78% of fortune
500 companies
5. Using share point document management
system one can create document libraries
where you can store/ share variety of files.

Electronic Data
Enterprise content management: It is a software application
with collection of different tools like capture, manage, store,
preserve, and deliver content and documents related to
organizational processes.
ECM covers web content management, search, workflow
management, capture and scanning, and it primarily aims at
managing the life cycle of information from initial publication
or creation to archival and eventually disposal.

Site Master File
1. The Site Master File is prepared by the pharmaceutical manufacturer and
should contain specific information about the quality management policies
and activities of the site, the production and/or quality control of
pharmaceutical manufacturing operations carried out at the named site and
any closely integrated operations at adjacent and nearby buildings.
2. Site Master File should provide clear information on the manufacturer’s
GMP related activities that can be useful in general supervision and in the
efficient planning and undertaking of GMP inspections.
3. The Site Master File should be a part of documentation belonging to the
quality management system of the manufacturer and kept updated
accordingly.
4. The Site Master File should have an edition number, the date it becomes
effective and the date by which it has to be reviewed.
5. It should contain adequate information but not exceeds 25-30 pages.
6. Simple plans and layouts should be preferred instead on narratives.
Purpose: It is useful to the regulatory authority in planning and
conducting GMP inspections.
Scope: These Explanatory Notes apply for all kind of manufacturing
operations such as production, packaging and labelling, testing,
relabelling and repackaging of all types of medicinal products.

Site Master File
Content of Site Master File:
General Information on the Manufacturer
1. Contact information on the manufacturer: Site address, phone numbers,
geographical location
2. Authorized pharmaceutical manufacturing activities of the site: Brief about
manufacture, import, export, distribution and other activities as authorized by the
relevant Competent Authorities including foreign authorities with authorized dosage
forms/activities, respectively
3. Any other manufacturing activities carried out on the site
Quality Management System of the Manufacturer
1. The quality management system of the manufacturer Information of activities for
which the site is accredited and certified, including dates and contents of
accreditations, names of accrediting bodies.
2. Release procedure of finished products: General description of batch certification
and releasing procedure.
3. Management of suppliers and contractors: A brief summary of the
establishment/knowledge of supply chain and the external audit program.
4. Quality Risk Management (QRM): Activities which are performed at corporate
level, and those which are performed locally.
5. Product Quality Reviews: Brief description of methodologies used
Personnel: Number of employees engaged in the
quality management, production, quality control,
storage and distribution respectively including
senior management
Premises And Equipment
1. Premises: Short description of plant; size of
the site and list of buildings. Lay outs and
flow charts of the production areas,
warehouses and storage area. heating,
ventilation and air conditioning (HVAC)
system, water systems steam, compressed air,
Nitrogen etc.
2. Equipment: Listing of major production and
control laboratory equipment with critical
pieces of equipment identified. Cleaning and
sanitation, GMP critical computerized
systems

Site Master File
Documentation: Electronic, manual data including Pharmacovigilance data, when applicable
Production:
1. Type of products: list of dosage forms of both human and veterinary products which are manufactured on the
site including toxic and hazardous chemicals.
2. Process validation
3. Material management and warehousing Arrangements for the handling of starting materials, packaging
materials, bulk and finished products including sampling, quarantine, release and storage
Quality Control (QC) Description of the Quality Control activities carried out on the site in terms of
physical, chemical, and microbiological and biological testing.
Distribution, Complaints, Product Defects And Recalls
1. Distribution: Types (wholesale license holders, manufacturing license holders, etc.
2. Complaints, product defects and recalls: Brief description of the system for handling complains,
product defects and recalls
Self-Inspection

Drug Master File (DMF)
A Drug Master File (DMF) is a submission to the Food and Drug
Administration (FDA) that may be used to provide confidential detailed
information about facilities, processes, or articles used in the manufacturing,
processing, packaging, and storing of one or more human drugs. The
submission of a DMF is not required by law or FDA regulation. A DMF is
submitted solely at the discretion of the holder. The information contained in
the DMF may be used to support an Investigational New Drug Application
(INDA), a New Drug Application (NDA), an Abbreviated New Drug
Application (ANDA), another DMF, an Export Application, or amendments
and supplements to any of these.
A DMF is not a substitute for an IND, NDA, ANDA, or Export Application.
It is not approved or disapproved. Technical contents of a DMF are reviewed
only in connection with the review of an IND, NDA, ANDA, or an Export
Application.
This guideline does not impose mandatory requirements (21 CFR 10.90(b)).
It does, however, offer guidance on acceptable approaches to meeting
regulatory requirements.
Different approaches may be followed, but the applicant is encouraged to
discuss significant variations in advance with FDA reviewers to preclude
spending time and effort in preparing a submission that FDA may later
determine to be unacceptable.
Drug Master Files are provided for in 21 CFR 314.420.
This guideline is intended to provide DMF holders with
procedures acceptable to the agency for preparing and
submitting a DMF.
The guideline discusses types of DMF's, the information
needed in each type, the format of submissions to a DMF,
the administrative procedures governing review of DMF's,
and the obligations of the DMF holder.
DMF's are generally created to allow a party other than
the holder of the DMF to reference material without
disclosing to that party the contents of the file. When an
applicant references its own material, the applicant should
reference the information contained in its own IND, NDA,
or ANDA directly rather than establishing a new DMF.

Types of Drug Master Files: There are five types of DMF’s:
Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel
Type II: Drug Substance, Drug Substance Intermediate, and Material Used in their Preparation, or Drug Product.
Type III: Packaging Material
Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation
Type V: FDAAccepted Reference Information.
Each DMF should contain only one type of information and all supporting data. See Section IV.C of the guideline for more detailed descriptions
of the kind of information desired in each type. Supporting information and data in a DMF can be cross referenced to any other DMF.
Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel:
A Type I DMF is recommended for a person outside of the United States to assist FDA in conducting onsite inspections of their
manufacturing facilities. The DMF should describe the manufacturing site, equipment capabilities, and operational layout. A
Type I DMF is normally not needed to describe domestic facilities, except in special cases, such as when a person is not
registered and not routinely inspected. The description of the site should include acreage, actual site address, and a map
showing its location with respect to the nearest city. An aerial photograph and a diagram of the site may be helpful.
A diagram of major production and processing areas is helpful for understanding the operational layout. Major equipment
should be described in terms of capabilities, application, and location. Make and model would not normally be needed unless
the equipment is new or unique. A diagram of major corporate organizational elements, with key manufacturing, quality
control, and quality assurance positions highlighted, at both the manufacturing site and corporate headquarters, is also helpful.

Type II: Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product
A Type II DMF should, in general, be limited to a single drug intermediate, drug substance, drug product, or type of material used in
their preparation. Drug Substance Intermediates, Drug Substances, and Material Used in Their Preparation. Summarize all significant
steps in the manufacturing and controls of the drug intermediate or substance. Manufacturing procedures and controls for finished
dosage forms should ordinarily be submitted in an IND, NDA, ANDA, or Export Application. If this information cannot be submitted in
an IND, NDA, ANDA, or Export Application, it should be submitted in a DMF.
Type III: Packaging Material: Each packaging material should be identified by the intended use, components, composition, and
controls for its release. The names of the suppliers or fabricators of the components used in preparing the packaging material and the
acceptance specifications should also be given. Toxicological data on these materials would be included under this type of DMF, if not
otherwise available by cross reference to another document.
Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation: Each additive should be identified and
characterized by its method of manufacture, release specifications, and testing methods. Toxicological data on these materials would
be included under this type of DMF, if not otherwise available by cross reference to another document. Usually, the official compendia
and FDA regulations for color additives (21 CFR Parts 70 through 82), direct food additives (21 CFR Parts 170 through 173), indirect
food additives (21 CFR Parts 174 through 178), and food substances (21 CFR Parts 181 through 186) may be used as sources for
release tests, specifications, and safety. Guidelines suggested for a Type II DMF may be helpful for preparing a Type IV DMF. The
DMF should include any other supporting information and data that are not available by cross reference to another document.
Type V: FDA Accepted Reference Information: FDA discourages the use of Type V DMF's for miscellaneous information, duplicate
information, or information that should be included in one of the other types of DMF's. If any holder wishes to submit information and
supporting data in a DMF that is not covered by Types I through IV, a holder must first submit a letter of intent to the Drug Master File
Staff. FDA will then contact the holder to discuss the proposed submission.

Contents of a DMF Submission
There are certain requirements for each DMF submission, such as a transmittal letter, administrative information about the submission, and the specific
information to be included in the DMF all of which must be written in English. DMFs from overseas firms that originate in a language other than English
must be accurately translated with a certification of translation included. Aside from the User Fee Form, no other forms should be filled out or submitted
along with a DMF submission. Letters of Authorization (LOAS) submitted with initial DMF submission must contain the DMF number. Each page of
each copy of the DMF should be dated and consecutively numbered and any updates should include an updated table of contents.
The transmittal letter for an original DMF should cover the following:
1. Identification of submission: Original, the type of DMF, and its subject;
2. Identification of the applications, if known, that the DMF is intended to support, including the name and address of each sponsor, applicant, or holder,
and all relevant document numbers;
3. Signature of the holder, authorized representative or agent;
4. Name and title of the signer.
The administrative information required is as follows: The names and addresses of the following must be provided:
1. DMF holder;
2. Corporate headquarters;
3. Manufacturing/processing facility;
4. Contact for FDA correspondence; this is the contact person and a telephone number; fax number and email address should be provided;
5. Agent(s), if any;
6. The specific responsibilities of each person;
7. A statement of commitment;
8. A signed statement by the holder certifying that the DMF is current and that the DMF holder will comply with the statements made in it.

The FDA regulations regarding DMFS states: "Any addition, change, or deletion of information in a drug master file is required
to be submitted in two copies and to describe by name, reference number, volume, and page number the information affected in
the drug master file".
The FDA ensures that DMFS are current. If a company has not submitted an annual report for three years, the agency sends an
"Overdue Notification Letters" to DMF holders. The holder has 90 days in which to respond and submit its annual report. If
they fail to respond, their DMF may be closed.
A note when filing new DMFS, FDA requires and provides a pre- assigned application number. While a pre-assigned number
will be required for a new DMF, those converting paper DMF submissions to electronic (eDMF) may use the originally
provided DMF number as the submission information is the same, only the vehicle for submission has changed. (Please note
that in cases where the originally assigned DMF number is fewer than six digits, zeros must be added to the beginning of the
number to conform to the 6-digit format).
Information on how to obtain a pre-assigned number can be found at FDA's website: "Requesting a Pre-assigned Application
number": http://www.fda.gov/Drugs/DevelopmentApproval Process/Forms Submission
Requirements/ElectronicSubmissions/ucm114027.html
(It should be noted that a request for a pre-assigned DMF number for a Type V DMF should include documentation that the
request for a Type V was cleared.)
Many firms choose to have DMF information reviewed by a regulatory consultant who specializes in pharmaceuticals and the
DMF process prior to submission to verify all DMF parts are included and any all technical information is thorough and complete.

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