INTRODUCTION TO MANUFACTURING AND independently by means of chemical or

INDUSTRIAL PHARMACY biological synthesis.

➢ And includes any packaging or
Manufacturing Pharmacy – is presently repackaging of the substances or
considered as an advance course, it deals with labeling or relabeling of its container and
the technology of various official and non-official the promotion and marketing of such
products manufactured in a semi commercial drug or devices.
and commercial scale. ➢ Also includes the preparation and
Industrial Pharmacy – refers to pharmaceutical promotion of commercially available
research and manufacturing companies production from bulk compounds for
providing pharmacists with medicines in pre- resale by pharmacies practitioners or
fabricated or ready to take forms. other persons.

This relates to the following United States Pharmacopeia (USP) defines:

1. Practice of pharmacy in some hospitals Preparation is used to Products is used to refer

2. Large scale production carries out in refer to compounded to manufactured
modern pharmaceutical plants. prescriptions. pharmaceuticals.

COMPOUNDING (as defined by NABP) For stability purposes, For stability purposes,
preparations are assigned manufactured products
➢ Is the preparation, mixing, assembling, a Beyond use date are assigned an
packaging, or labeling of drug or device Expiration date.
as the result of a practitioner’s
prescription drug order or initiative Manufacturing Pharmacy
based on the pharmacist or patient or Elements of an Organization
prescriber relationship in the course if
professional practice. 1. Organization
➢ Also includes the preparation of drugs ➢ A mechanism for determining and
and devices in anticipation of assigning duties to people, in order to
prescription drug orders based on work effectively.
routine, regularly observed patterns.
➢ For the purpose of, as an incident to 2. Business Organization
research, teaching or chemical analysis ➢ Combination of manpower, money,
and not for sale or dispensing. machines and methods

Manufacturing

➢ Has been defined as the production,

preparation, propagation conversion of
processing of a drug or device, either by
directly or indirectly by extraction from
substances of natural origin or
 BASIC ELEMENTS OF AN ORGANIZATION Interpreted in a chart

1. Division of Responsibility (Obligation or

Duty)
➢ Responsibility must be delegated
➢ The company objectives must be
determined and the organizational
plan must be consulted with the aim
of achieving them.
CHARACTERISTICS OF AN ORGANIZATIONAL
CHART
2. Delegation of Authority
➢ Authority must be defined and A. It lists all important positions and
delegated to avoid negligence of functions of each divisions or
duty. department
B. it is means of quickly showing the shape
3. Determination of the interrelationship or structure of the company to
among the functions of each of the employees and other interested parties
component of the organizational plan outside the company
➢ To promote harmonious teamwork
IMPORTANCE OF A CHART
BASIC TOOLS IN AN ORGANIZATION
A. can analyze organizational problems like
I. Organizational Planning overlapping of functions
II. Position Description B. can assess the strengths and weaknesses
- It is a basic tool of an organization in the functions and personnel
that clearly define authority, duty or C. can plan changes in the structure, if not
responsibility. applicable
III. Organizational Manual
Some Drawbacks in the Chart
I. ORGANIZATIONAL PLANNING
a. cannot reveal company objective and
President policies
b. cannot indicate a delegated authority
- Personnel c. reveals little about working relationships
- Finance
- Marketing II. POSITION DESCRIPTION
- Technical director ➢ Describes the knowledge, skills,
o Research and product abilities and duties of a specific
development position not the characteristics or
o Quality control traits of the current incumbent.
- Plant ➢ Summary of the most important
features of a position including: the
general nature of the work
 performed, the specific duties and 3. They embrace the topmost level of
responsibilities and the executives concerned with a particular
qualifications needed to do the job. division of the company rather than the
enterprise as a whole.
III. ORGANIZATIONAL MANUAL
➢ Management Guide Forms and Organizational Structure
➢ It combines the chart and position 1. Functional Structure
descriptions, with description ✓ It groups all activities on the basis of
materials about the organization the functions alone. This is more
BASIC LEVELS OF TOP MANAGEMENT AND appropriate for a small company or
THEIR FUNCTIONS one with closely related products.
✓ All production, sales and financial
Level I: Board of Trustees or Board of Directors activities are under one head. It is
flexible, facilities and coordination
Functions: and encourage specialization the
1. To protect and make the most effective field.
use of the assets of the company 2. Divisionalized Structure
2. Establishes objective and determines the ✓ It combines into one unit, all
basic policies and general course of the different kinds of work necessary to
business accomplish a specific result. The
3. Represents and safeguards the interests kinds of work necessary may be
of the stockholders grouped on a geographical basis or
more commonly on a product basis.
Level II: President
Definition of Line and Staff
Functions:
LINE
1. Active planning, direction, coordination
and control of the business within the ✓ It is identified as the chain of
scope of policies established and command from to the bottom of the
authorized by level management. organization.
✓ Constitutes the framework of the
Level III: Vice President, General Management & organizational structure have direct
Department Managers responsibility to accomplish the
objectives of the enterprise
Functions:
✓ Have the power or authority to
1. Manages the major department of the initiate and carry through other
company primary activities necessary to reach
2. They are fully responsible and the stated goal of the company.
accountable to level II management for
the success of their respective
operations
STAFF

✓ Constitutes the work functions or the Five (5) Major Departments

organization component that are
required to supply information and 1. Personnel
services to the line components. 2. Finance
3. Marketing
Organizational Chart 4. Technical Director
- Research and product development
• Research and Development Division and quality control
• Production Management 5. Plant
• Maintenance Division
• Manufacturing Division 1. Personnel Department
• Quality Assurance Division - Coordinate labor and management
• Affiliate Business Division relationship
• Health Food Division 2. Finance Department
• Market Research Division - Consists of cost accounting, forecast
• Regulatory Affairs Division and budget and general accounting
• Sales and Development and Division 3. Marketing Department
• Accounting Division - Consists of market research, sales
• General Affairs Division and detailing and advertising
4. Technical Director
- Research and product development,
quality control of drugs and
cosmetics
5. Plant Department
- Production control, warehouse
manufacture of pharmaceuticals,
manufacture of cosmetics and
maintenance.

Research and product Development

1. Chemical Research
- Chemical Development, Chemical
Synthesis, Analytical Chemistry
2. Biological Research
- Pharmacology, Animal Research,
Microbiology
3. Pharmaceutical Research
- Pharmaceutical Development,
Chemical Synthesis
 A. 1 RAW MATERIALS
3 STAGES OF RESEARCH ➢ Usual criteria: description, solubility, ID,
•
PRELIMINARY STAGE melting point, loss on ignition, residue on
➢ Consist of market research literature a ignition specific rotation, refractive index,
review, patient search and raw materials. specific gravity, assay.
❖ Additional: particle size, crystal
• APPLIED RESEARCH STAGE
shape, surface tension, viscosity,
➢ Consist of chemical studies development
irritation, foreign substance,
of chemical process and cost research
allergenic substance, toxicity
• CLINICAL RESEARCH STAGE
➢ Consist of manufacturing requirements,
A. 2 CONTAINERS SPECIFICATION
research on label, review of basic
a. Physical changes of containers upon
information, product control, contract
prolonged contract with product
with therapeutic trial committee, patent
b. Moisture and gaseous permeability
application and cost of clinical trial.
c. Compatibility between container and
QUALITY CONTROL FOR DRUGS AND product
COSMETICS d. Toxicity and safety considerations

I. Specifications and Assay B. FINISHED PRODUCT SPECIFICATION

Department Section Developed jointly by:
II. Central Release Section • Quality control
III. Chemical Control Section
• Research and product development
IV. Plant Inspection Section
• Sales or marketing production
V. Biological Microbiological Section
• Management individuals
➢ Description, ID, moisture content, pH,
I. Specifications and Assay
specific gravity, alcohol content,
Department Section
hardness, disintegration time, weight
PURPOSE: variation, sterility, pyrogenicity, safety,
assay
1. Confirm to appropriate standard if ❖ Additional: Dissolution rate, content
identity, purity, potency, quality, uniformity, related foreign
physiological availability and substances, irritation, microbial
therapeutic activity content stability
2. Meet government rules and
regulations Specifications for a product are development
3. Prevent potential hazard to public not only to assure quality but to detect and
health identify impurities
a. Raw materials and containers
2 Kinds of Impurities
specification
b. Finished product specifications 1. PRODUCT SPECIFIC IMPURITIES
 • Example: degradation manufacturing and packaging for
completeness and accuracy and to
2. PRODUCT UNSPECIFIC IMPURITIES assume responsibility for their
• External safekeeping and storage
2. To investigate customer complains or
Factors to be considered in the development of inquires on product quality since this
specifications for dosage form of finished section has an easy access to records of
products: manufacturing and packaging operations
3. To maintain complete and accurate
1. Ascertain which physical, chemical and
records of the receipt and distribution of
biological characteristics of dosage
every lot of raw material and finished
forms are critical which are important
product
which are helpful, and which are not
4. To keep retention samples in locked area
particularly important but useful.
under similar conditions comparable to
2. Decide which dosage form
the market conditions
characteristics shall be established as the
5. To properly record and handle finished
criteria for evaluating routine production
products returned by pharmacies and
batches.
hospitals
3. Establish appropriate test methods
4. Determine the acceptable tolerances for
III. Chemical Control Section
each of the dosage form characteristics
FUNCTIONS:
Assay Development Section
1. To test and assay every lot of raw
Purpose of varying or completely changing assay
material in-process products and every
methods:
lot of finished product
1. Greater accuracy in testing 2. To conduct stability studies
2. More rapid result thus contributes to
reduction in cost of operation IV. Inspection and Checking Section
3. Increase in the number of samples
FUNCTIONS:
tested without increase in cost or time
especially with the growing use of 2. To inspect sample every shipment of raw
automation in testing materials and every lot of finished
product
QUALITY CONTROL FOR DRUGS AND
3. To conduct stability studies
COSMETICS
4. To inspect and check all manufacturing
II. Central Release Section operations, including in-process filling
and labeling as well as periodic
FUNCTIONS: examination on the quality of stocks in
1. To examine meticulously the records the warehouse
resulting from the exercise of Quality 5. To sample retention or reserved samples
control functions throughout all steps of withdrawn from the packaging line for
 finished products and from warehouse
for raw materials
▪ QUALITY CONTROL
✓ Is a staff function as a service
RETENTION SAMPLES department supporting but not
subordinate to production supervision
➢ Are portions of materials or finished ✓ Responsibility for quality is shared by
products taken from the same lot tested all but Quality control has ultimate
and assayed are kept in locked areas jurisdiction over the release of every
under the same conditions comparable to product manufactured and/or filled
market conditions. packaged
➢ The quantity of reserved samples include
at least 2 labeled containers of the final PLANT DEPARTMENT
dosage form or 2 times the quantity I. Production control
required for testing. These samples are to II. Warehouse division
be retained for at least 2 years after III. Engineering and Maintenance
distribution 2 years after expiry. IV. Manufacture of pharmaceuticals
Whichever is shorter. V. Manufacture of cosmetics

V. Chemical Control Section I. PRODUCTION CONTROL

FUNCTIONS: 1. Purchasing
➢ Requisitioned items for the company
1. To perform and evaluate microbiological both from local and imported sources
and pharmacological assays 2. Inventory control
2. To do sterility, pyrogenicity, ➢ Watches closely and records all
bacteriological, irritation, and safety/ materials used in production; controls
toxicity tests. the stock of both raw materials and
✓ Biological tests are required for finished; in charge of checking stocks
biological products, parenteral and regularly
eye preparations. 3. Planning and Scheduling
➢ Coordinates with market on what
Description of Quality Control Department
products are required for supply and
▪ Director of Quality Control then plans and schedules the
➢ Is the individual directly responsible for manufacturing order (MO);
the quality of drug products in a manufacturing at the time limit
manufacturing company. allowed
➢ He should report directly only to the
President, Vice President or Technical
director (same level as the Production
manager)
 ➢ Are where raw materials for use in
production are weighed and/or
measured
o Supervisor should be pharmacist
checker is required to avoid errors
o Quality control inspectors do
II. WAREHOUSE DIVISION routine checks on all areas of
warehouse
Consist of 5 sections
Manufactured of Pharmaceuticals
1. Raw material
1. Consist of 3 subdivisions ▪ LIQUIDS
✓ Quarantined area ▪ MEDICATED APPLICATION
✓ Approved for use area ▪ SOLIDS
✓ Rejected area ▪ STERILE PRODUCTS
▪ PACKAGING & FINISHING

Manufactured of Cosmetics

▪ HAIR PREPARATION
▪ FACE CREAMS POWDERS
▪ SHAVING PREPARATIONS
▪ PERSONAL CLEANLINESS ITEMS

III. Engineering and Maintenance

section
➢ Care and maintenance of all machines
2. In process
used in the plant department
➢ Consist or products which have been
including electric lines water lines,
bottled or stripped packed but not yet
repair of defective equipment
labeled or packed into boxes pr
IV. Manufacturing of Pharmaceuticals
cartons because they are awaiting
➢ Prepares master formula
quality control tests and assays for
final disposition
3. Finished Product
➢ This are contains the products PRODUCT LIFE CYCLE MANAGEMENT
packaged and finished and are ready
• Process of managing the entire
for distribution and sale
lifecycle of a product from its
4. Returned goods
conception, through design and
➢ In as much as returns cannot be
manufacture to service and disposal
avoided, goods returned are stored in
a section of the warehouse pending
disposition by quality control
5. Dispensing
ELEMENTS IN INVOLVES IN PLM for repair and maintenance as well as
waste management/ recycling
• Foundation technologies and information.
standards
• Information authoring and analysis PHARMACEUTICAL QUALITY SYSTEM
tools
PHARMACEUTICAL QUALITY SYSTEM
• Core functions
• Functional applications ➢ also known as ICH Q10 model
• Business solutions ➢ describes one comprehensive model for
an effective pharmaceutical quality
PHASES OF PRODUCT LIFE CYCLE
system that is based on International
MANAGEMENT
Organization for Standardization (ISO)
• Phase 1: Conceive quality concepts
• Phase 2: Design ➢ a model for a pharmaceutical quality
• Phase 3: Realize system that can be implemented
• Phase 4: Service throughout the different stages of a
product lifecycle
Phase 1: Conceive ➢ demonstrates industry and regulatory
authorities' support of on effective
➢ The first stage is the definition of the
pharmaceutical quality system to
product requirements based on
enhance the quality and availability of
customer, company, market and
medicines around the world in the
regulatory bodies’ viewpoints
interest of public health
Phase 2: Design
Implementation of the Q10 model should result
➢ This is where the detailed design and in achievement of three main objectives that
development of the products form complement or enhance regional GMP
starts, progressing to prototype requirements:
testing, through pilot release to full
1. Achieve Product Realization
product launch 2. Establish and Maintain a State of Control
Phase 3: Realize 3. Facilitate Continual Improvement

➢ Once the design of the products The elements described below might be required
components is complete the method in part under regional GMP regulations.
of manufacturing is defined However, the Q10 model's intent is to enhance
these elements to promote the lifecycle
Phase 4: Service approach to product quality. These four
elements are:
➢ The final phase of the lifecycle involves
managing of in service information. • Process performance and product
Providing customers and service quality monitoring system
engineers with support information
 • Corrective action and preventive action preventive actions resulting from the
(CAPA) system investigation of complaints, product rejections,
• Change management system nonconformances, recalls, deviations, audits,
• Management review of process regulatory inspections and findings, and trends
performance and product quality from process performance and product quality
monitoring
I. Process performance and product quality
monitoring system III. Change Management System

Pharmaceutical companies should plan and Innovation, continual improvement, the outputs
execute a system for the monitoring of process of process performance and product quality
performance and product quality to ensure a monitoring, and CAPA drive change.
state of control is maintained. The process
• To evaluate, approve, and implement
performance and product quality monitoring
these changes properly, a company
system should
should have an effective change
a. use quality risk management to establish management system.
the control strategy. • The change management system should
b. Provide the tools for measurement and include the following, as appropriate for
analysis of parameters and the stage of the lifecycle:
c. attributes identified in the control a) Quality risk management should be
strategy c) Anglyze parameters and utilized to evaluate proposed changes.
attributes identified in the control The level of effort and formality of the
strategy to verify continued operation evaluation should be commensurate
within a state of control with the level of risk
d. Identify sources of variation affecting b) Proposed changes should be evaluated
process performance and product relative to the marketing authorbation
quality for potential continual Incuding design space, where
improvement activities to reduce or established, and/or current product and
control variation. process understanding
e. Include feedback on product quality c) Proposed changes should be evaluated
from both internal and external sources by expert teams contributing the
f. Provide knowledge to enhance process appropriate expertise and knowledge
understanding, enrich the design space from relevant areas to ensure the change
where established), and enable is technicaly Justified Prospective
innovative approaches to process evaluation criteria for a proposed change
validation. should be set
d) After implementation, an evaluation of
II. Corrective Action and Preventive Action the change should be undertaken to con
(CAPA) System the change objectives were achieved
•The pharmaceutical company should have a and that there was no deleterious
system for implementing corrective actions and impact on product quality.
 IV. Management Review of Process quality issues during development and
Performance and Product Quality manufacturing.

Management review should provide • It can facilitate better and more

assurance that process performance and informed decisions, can provide
product quality are managed over the regulators with greater assurance of a
lifecycle. company's ability to deal with potential
risks and can beneficially affect the
• The management review system should
extent and level of direct regulatory
include:
oversight
a) The results of regulatory inspections and • Two primary principles of quality risk
findings, audits and other assessments, management are:
and commitments made to regulatory 1. The evaluation of the risk to quality
authorities should be based on scientific knowledge
b) Periodic quality reviews, that can and ultimately link to the protection of
include: the patient; and
c) Measures of customer satisfaction such 2. The level of effort, formality and
as product quality complaints and recalls documentation of the quality risk
d) Conclusions of process performance and management process should be
product quality monitoring commensurate with the level of risk.
e) The effectiveness of process and product
changes including those arising from
corrective action and preventive actions
f) Any follow-up actions from previous
management reviews

PHARMACEUTICAL QUALITY SYSTEM

Should include the following:

A. Quality risk management

B. Contamination/Cross contamination
period
C. Good documentation practice Quality risk management should include
D. Good quality control laboratory practice systematic processes designed to coordinate,
E. Self-inspection facilitate and improve science-based decision
making with respect to risk. Possible steps used
A. QUALITY RISK MANAGEMENT to initiate and plan a quality risk management
process might include the following:
An effective quality risk management approach
con further ensure the high quality of the drug a. Define the problem and/or risk question,
(medicinal) product to the patient by providing a including pertinent assumptions
proactive means to identify and control potential identifying the potential for risk:
 b. Assemble background information and/ • Risk communication - the sharing of
or data on the potential hazard, harm or information about risk and risk
human health impact relevant to the risk management between the decision
assessment; maker and other stakeholders.
c. Identify a leader and necessary • Risk control-actions implementing risk
resources: management decisions (ISO Guide 73).
d. Specify a timeline, deliverables and • Risk evaluation - the comparison of the
appropriate level of decision making for estimated risk to given risk criteria using
the risk management process. a quantitative or qualitative scale to
determine the significance of the risk.
DEFINITION OF TERMS:
• Risk identification - the systematic use
• Harm-damage to health, including the of information to identify potential
damage that can occur from loss of sources of harm (hazards) referring to
product quality or availability. the risk question or problem description.
• Hazard - the potential source of harm • Risk management - the systematic
(ISO/IEC Guide 51). application of quality management
• Product lifecycle - all phases in the life of policies procedures, and practices to the
the product from the initial development tasks of assessing, controlling,
through marketing until the product's communicating and reviewing risk.
discontinuation. • Risk reduction - actions taken to lessen
• Quality - the degree to which a set of the probability of occurrence of horm
inherent properties of a product. system and the severity of that harm.
or process fulfills requirements (see ICH • Risk review - review or monitoring of
Q6A definition specifically for "quality" output/results of the risk management
of drug substance and drug (medicinal) process considering (if appropriate) new
products.) knowledge and experience about the
• Quality risk management - a systematic risk.
process for the assessment control, • Stakeholder - any individual, group or
communication and review of risks to organization that can affect, be affected
the quality of the drug (medicinal) by, or perceive itself to be affected by a
product across the product lifecycle risk. Decision makers might also be
• Risk-the combination of the probability stakeholders. For the purposes of this
of occurrence of harm and the severity guideline, the patient, healthcare
of that harm professional, regulatory authority, and
• Risk assessment - a systematic process industry primary stakeholders are the
of organizing information to support a
RISK MANAGEMENT METHODS AND TOOLS
risk decision to be made within a risk
management process. It consists of the 1. Basic risk management facilitation
identification of hazards and the analysis methods
and evaluation of risks associated with 2. Failure Mode Effects Analysis (FMEA)
exposure to those hazards.
 3. Failure Mode, Effects and Criticality 3. FAILURE MODE, EFFECTS AND CRITICALITY
Analysis (FMECA ANALYSIS (FMECA)
4. Fault Tree Analysis (FTA)
5. Hazard Analysis and Critical Control ➢ FMEA might be extended to incorporate
Points (HACCP) an investigation of the degree of severity
6. Hazard Operability Analysis (HAZOP) of the consequences, their respective
7. Preliminary Hazard Analysis (PHA) probabilities of occurrence, and their
8. Risk ranking and filtering detectability, thereby becoming a Failure
9. Supporting statistical tools Mode Effect and Criticality Analysis
➢ FMECA application in the
1. BASIC RISK MANAGEMENT FACILITATION pharmaceutical industry should mostly
METHODS be utilized for failures and risks
associated with manufacturing
➢ Some of the simple techniques that are
processes
commonly used to structure risk
management by organizing data and 4. FAULT TREE ANALYSIS (FTA)
facilitating decision-making are:
▪ Flowcharts; ➢ an approach that assumes failure of the
▪ Check Sheets; functionality of o product or process.
▪ Process Mapping; ➢ This tool evaluates system (or sub-
▪ Cause and Effect Diagrams system) failures one at a time but can
combine multiple causes of failure by
2. FAILURE MODE EFFECTS ANALYSIS (FMEA) identifying causal chains
➢ The results are represented pictorially in
➢ FMEA provides for an evaluation of the form of a tree of foult modes.
potential failure modes for processes ➢ FTA can be used to establish the pathway
and their likely effect on outcomes
to the root cause of the failure.
and/or product performance ➢ FTA can be used to investigate
➢ It is a powerful tool for summarizing the complaints or deviations in order to fully
important modes of failure, factors understand their root cause and to
causing these failures and the likely ensure that intended improvements will
effects of these failures. fully resolve the issue and not lead to
➢ FMEA can be used to prioritize risks and other issues
monitor the effectiveness of risk control
activities. 5. HAZARD ANALYSIS AND CRITICAL CONTROL
➢ FMEA can be applied to equipment and POINTS (HACCP)
facilities and might be used to analyze a
manufacturing operation and its effect ➢ HACCP is a systematic, proactive, and
on product or process. preventive tool for assuring product
quality, reliability, and safety.
➢ It is a structured approach that applies
technical and scientific principles to
analyze, evaluate, prevent, and control
 the risk or adverse consequence(s) of production and formulation as well as
hazard(s) due to the design, the upstream suppliers, equipment and
development, production, and use of facilities for drug substances and drug
products. (medicinal) products.
➢ HACCP might be used to identify and
manage risks associated with physical, 7. PRELIMINARY HAZARD ANALYSIS (PHA)
chemical and biological hazards ➢ PHA is a tool of analysis based on
(including microbiological applying prior experience or knowledge
contamination). of a hazard or failure to identify future
hazards, hazardous situations and events
that might cause harm, as well as to
HACCP consists of the following seven steps: estimate their probability of occurrence
for a given activity, facility, product or
1. conduct a hazard analysis and identify system.
preventive measures for each step of the ➢ PHA is most commonly used early in the
process; development of a project when there is
2. determine the critical control points: little information on design details or
3. establish critical limits: operating procedures; thus, it will often
4. establish a system to monitor the critical be a precursor to further studies.
control points; ➢ The tool consists of
5. establish the corrective action to be ➢ the identification of the possibilities that
taken when monitoring indicates that the risk event happens,
the critical control points are not in a ➢ the qualitative evaluation of the extent
state of control:
of possible injury or damage to health
6. establish system to verify that the HACCP that could result and
system is working effectively: ➢ a relative ranking of the hazard using a
7. establish a record-keeping system combination of severity and
6. HAZARD OPERABILITY ANALYSIS (HAZON) ➢ likelihood of occurrence the
identification of possible remedial
➢ HAZOP is based on a theory that measures
assumes that risk events are caused by
deviations from the design or operating 8. RISK RANKING AND FILTERING
intentions ➢ Risk ranking and filtering is a tool for
➢ It is a systematic brainstorming comparing and ranking risks. Risk
technique for identifying hazards using ranking of complex systems typically
so-called "guide-words". "Guide-words" requires evaluation of multiple diverse
are applied to relevant parameters to quantitative and qualitative factors for
help identify potential deviations from each risk.
normal use or design intentions. ➢ The tool involves breaking down a basic
➢ HAZOP can be applied to manufacturing risk question into as many components
processes, including outsourced
 as needed to capture factors involved in GOOD DOCUMENTATION PRACTICE
the risk.
➢ Risk ranking and filtering can be used to Documentation and records used throughout
prioritize manufacturing sites for the manufacturing process, as well as
inspection/audit by regulators or supporting processes (e.g. Quality Control or
industry. Quality Assurance), must meet the basic
requirements of GDP. These include (but are not
9. SUPPORTING STATISTICAL TOOLS limited to):

➢ Statistical tools can support and facilitate ✓ Batch Record Forma

quality risk management. They can ✓ Bills of Materials (BOM)
enable effective data assessment, aid in ✓ Specifications
determining the significance of the data ✓ Policies
set(s), and facilitate more reliable ✓ Protocols
decision making. ✓ Standard Operating Procedures (SOPs)
➢ A listing of some of the principal ✓ Work Instructions (Wa)
statistical tools commonly used in the ✓ Test Methods
pharmaceutical industry is provided: ✓ Checklists
▪ Control Charts ✓ Forms/Log sheets
▪ Design of Experiments (DOE) ✓ Training Assessments
▪ Histograms ✓ Electronic and hardcopy Quality records
▪ Pareto Charts (e.g. non-conformance, corrective and
▪ Process Capability Analysis preventative actions, internal inspection,
change control, training records etc.)
GOOD DOCUMENTATION PRACTICE
✓ Certificate of Analyses (COA) or
Documentation may be divided into: Certificate of Compliance (CoC)
✓ Technical transfer reports
➢ Documents - procedural or instructional ✓ Validation documentation
documentation
➢ Records - evidence of compliance. GOOD DOCUMENTATION PRACTICE

The following requirements should be applied to

all documentation within the GMP environment.

General elements GDP requirements

Clearly written All documents must be accurate written in
documentation a manner that prevents errors and
ensures consistency. If documents are to
be used together e.g an SOP a form then
each should refence the other.
Using indelible ink All records must be filled out in indelible
ink for long term legibility. Do not use
pencil or ink can be erased.

Legible A document is unusable if it cannot be

handwritten read so care must be made at the time the
entries tasks are performed and should be legibly
signed and dated.
Reviewing and Documents and records should be country. such as
approving reviewed by someone who did not Day/Month/Year (Australia) or
perform the task to ensure that the Month/Day/Year (USA).
information is correct and accurate Because of differences between
countries, it is recommended
Staff signature Handwritten signature must be unique to
that the month is denoted by its
the individual and listed within the site
first 3 letters for clarity
signature register to ensure that the
Time format Record time in 24 hour format
signature is traceable to a member of staff
(00.00-23.59) or denoting am
(or contractor).
or pm.
Signed delegation In the event that a critical member of staff
of responsibility is absent for a time they must delegate
responsibility to another qualification
person.
Page numbering GMP documents should have page
numbers using the following standard “X
or Y’ to indicate the total number of pages
in a document.

Handling attachments GDP requirements

Handwritten Corrections GDP requirements Attachments to forms Staple the attachment to the record
Making a legible correction If a correction needs to be Cross-reference the record and the
made, the original record must form with each other
still be legible: Ensure sufficient identification on
Make a single line through the the attachment to ensure
error-never use correction traceability in the event it becomes
fluid, multiple cross-outs or separated (cross-referencing)
marker pen to obscure the
original record.

Handling omitted doto If an entry was omitted and Attachments to Indicate on the original document
must be made at a time later workbooks/logbooks that there is an attachment. Sign and
than the activity was date both the workbook and
performed then: attachment.
Clearly indicate the date the
activity was performed and Thermal printouts All printouts mode on thermal paper
the date the activity is must be copied before attaching to a
recorded on the report or fling indicate 'copy of
documentation. Sign and date original "or true copy on the copy
the change and initial and date.

Completing all fields on a All fields on a record should

record have an entry even if its “N/A”
Record control

➢ Your site GDP procedure should describe

the types of workbooks/notebooks that
Recording numbers GDP requirements
Decimal numbers In general, if a decimal value is
may be used-typically these are hard-
a fraction of 1 then a zero must covered with sown/sturdy binding; avoid
be placed before the decimal
point. The number of decimal spiral bound workbooks or logbooks as
places to be recorded should be pages may be removed
outlined in a procedure.
Rounding Consider the number of
significant figures of the Using True Copies
specification and the error of
the instrument/equipment,
rounding averages etc.
➢ Sometimes there is a need to use a copy
Dates format Record dates following of an original document or record, e.g.
common practice of the
 attaching a copy of a report to a non- HISTORY
conformance record. So that it is
apparent that the record is not the ➢ The term GLP was first used in New
original: Zealand in 1972.
✓ Stomp or write on the front of the ➢ GLP was instituted in US following cases
copied documentation, 'True Copy'. of fraud generated by toxicology lobs in
✓ Sign and date the 'True Copy' data submitted to the FDA by
amendment. pharmaceutical companies. As a result of
these findings, FDA promulgated the
Modifying records in a compliant manner Good Laboratory Practice (GLP)
Regulations, 21 CFR part 58, on
➢ The company GDP procedure should December 22, 1978 (43 FR 59986). The
stipulate how data or entries may be regulations became effective June 1979.
amended. This should include details on:
Assure the quality and integrity of safety
✓ ✓ Any standard abbreviations used, e.g. Nonclinical laboratory studies
'not applicable' (NA or N/A) etc. ➢ In 1981 an organization named OECD
✓ Unacceptable practices, e.g. using 'ditto' (organization for economic co-operation
marks (") to indicate the same entry as and development) produced GLP
above, leaving empty fields in a form, principles that are international
etc. standard.
✓ Who is responsible for checking
documentation amendments or general Basic elements in GLP
GMP compliance of logbook pages over
❖ Personnel
time.
✓ Sponsor
GOOD LABORATORY PRACTICE ✓ Management
✓ Study director
➢ Good laboratory practice or GLP ✓ Quality assurance
specifically refers to a quality system of ❖ Facility
management controls for research ✓ Laboratory operation
laboratories and organizations to try to ✓ Animal care
ensure the uniformity. consistency, ✓ Equipment
reliability, reproducibility, quality, and ✓ Reagents
integrity of chemical (including ❖ Documents
pharmaceuticals) nonclinical safety ✓ Standard operating
tests; from physio-chemical properties ✓ Protocols
through acute to chronic toxicity tests. ✓ Reports
➢ GOOD LABORATORY PRACTICE applies ✓ Archiving
to nonclinical studies conducted for the ❖ Test and control articles
assessment of the safety or efficacy of ✓ Characterization
chemicals (including pharmaceuticals). ✓ Handling
➢ GLP helps assure regulatory authorities ✓ Storage
that the data submitted are true
PERSONNEL MAINTENANCE & CALIBRATION OF
EQUIPMENT
Qualification of personnel
➢ Equipment shall be adequately
➢ The assumptions is that in order to inspected. cleaned & maintained
conduct GLP studies with right quality a ➢ Equipment used for assessment of data
couple of things are important; shall be tested, calibrated and/or
✓ There should be sufficient standardized
✓ The personnel should be qualified ➢ Scales & balances should be calibrated at
Sponsor regular intervals (usually ranging from 1-
12 months
➢ person who initiates & supports
nonclinical laboratory study, a person REAGENT AND MATERIALS CERTIFICATION
who submits nonclinical study to FDA or
• This policy is to assure that reagents
testing facility that initiates & conducts
used are specified in the standard
the study.
operating procedure.
PERSONNEL • Purchasing and testing should be
handled by a quality assurance program.
Facility management • Requirements:
✓ Reagents and solutions shall be labeled
➢ Responsibilities of facility management
✓ Deteriorated or outdated reagents and
is well defined. They designate a study
solutions shall not
director, as well as assure quality
✓ be used
assurance unit is available, test and
✓ include Date opened
control articles are characterized.
✓ Stored under ambient temperature
Study Director ✓ Expiration date

➢ He has overall responsibilities for STANDARD OPERATING PROCEDURES (SOP)

technical conduct safety studies, as well
✓ Written procedures for a laboratories
as interpretation, analysis,
program.
documentation and reporting of results.
✓ They define how to carry out protocol-
Quality Assurance unit specified activities.
✓ Most often written in a chronological
➢ The quality assurance unit (QAU) serves listing of action steps.
an internal control function. It is ✓ They are written to explain how the
responsible for monitoring each study to procedures are suppose to work
assure management that facilities, ✓ Routine inspection, cleaning,
equipment, personnel, methods, maintenance, testing and calibration.
practices, records, controls. SOPs, final ✓ Actions to be taken in response to
reports (for data integrity), and archives equipment failure.
are in conformance with the GLP/GALP ✓ Analytical methods
 ✓ Definition of raw data ✓ Adequate space
✓ Keeping records, reporting, storage, ✓ Ventilation
mixing, and retrieval of data ✓ Storage
✓ Hygiene

DOCUMENTATION AND MAINTENANCE OF

TEST AND CONTROL ARTICLES RECORDS
• Control articles or reference substances
• Maintenance of all records provide
as they re-called in the OECD principles documentation which may be required
are of utmost importance as they are in the event of legal challenges due to
commonly used to calibrate the repercussions of decisions based on the
instrument original analytical results.
• Main requirements for control articles • General guidelines followed in regulated
are: the identity, strength, purity,
laboratories is to maintain records for at
composition and other characteristics least five years
should be determined for each batch
• Length of time over which laboratory
and documented.
records should be maintained will vary
• The stability of each test and articles with the situation
should also be determined.
• Certified reference standards can be SELF-INSPECTION
purchased from appropriate suppliers. If
➢ Self inspections should be conducted in
standards are not available, the
order to monitor the implementation
recommendation is to take a lot of your
and compliance with Good
own material and analyze, certify and
Manufacturing Practice principles and to
use it as the standard
propose necessary corrective actions.
ANALYST CERTIFICATION • Personnel matters, premises,
equipment, documentation, production.
• Some acceptable proof of satisfactory quality control distribution of the
training and/or competence with medicinal products, arrangements for
specific laboratory procedures must be dealing with complaints and recalls, and
established for each analyst. self inspection, should be examined at
• Qualification can come from education, intervals following a pre-arranged
experience or additional trainings, but it program in order to verify their
should be documented conformity with the principles of Quality
• Sufficient people Assurance.
• Requirements of certification vary • Self inspections should be conducted in
an independent and detailed way by
LABORATORY CERTIFICATION
designated competent person(s) from
• Normally done by an external agency the company.
• Evaluation is concerned with issues such • All self inspections should be recorded.
as: Reports should contain all the
 observations made during the ✓ If there is something to be done,
inspections and where applicable, correct it immediately.
proposals for corrective measures. 6. 2 If there is no operation:
Statements on the actions subsequently ✓ Determine if there is an SOP on display.
taken (ie., effective follow-up program) ✓ Observe if there is a log sheet to be
should also be recorded. filled up.
✓ Determine if inputs in the log sheet are
SELF-INSPECTION accurate and updated.
7. The result of the evaluation shall be
discussed by the team and agreements
and conclusions shall be reached.
8. The root cause should be determined for
non-compliance
9. Determine the risk caused by the non-
compliance
10. Corrective actions/preventive actions
shall be recommended.
METHODS OF THE PROCESS
11. A follow-up program shall be drawn
1. Each member of the self-inspection with:
team shall separately use checklist. 11.1 Identification of the person responsible
Observations shall be documented. for implementation
2. The inspection may be performed as 11.2 Timeliness and target date
short events in a day. It does not have to 11.3 Urgency of Corrective action are
be so comprehensive that would require classified into
disruption of regular work. 11.3.1 Immediate
3. Skip areas where compliance is ➢ started at the time non-
established to be consistent. compliance is observed and
4. Choice of inspection areas may be addressed
random and unpredictable 11. 11.3.2 Prompt
5. The inspector should be familiar with the ➢ addressed within 2 months
SOP through prior reading. Otherwise, 12. The findings or observation shall be
he/she should read the SOP on display classified into:
6. 1 If an operation is going on: ✓ Observe 12. 1 Critical - This finding is extremely
if the activities follow the SOP. serious and should be treated with
✓ Read the batch record or prescribed priority. Immediate corrective action is
forms to determine if the inputs are required. It could also be an encounter of
timely and accurate. repeated major finding.
✓ Interview the person(s) undertaking the 12. 2 Major - This finding is serious or
activity and determine status of the consists of a significant number of minor
activity. observations that have occurred in the
✓ Record the findings. same area or system. It requires prompt
corrective action. It is also a
 demonstration of a recurring minor
nonconformity.
12. 3 An observation that is not serious but
could become a problem if not corrected
in a timely manner. Management follow-
up is required to assure that a systematic
problem or repeated occurrence will
cease to exist.
13. Management led by the President shall
review the self- Inspection report and
monitor the corrective action as
necessary.
14. Implementation
14. 1 Implementation of recommended
oction shall be noted and dated when
completed.
14. 2 It should be verified by the person who
did the self-inspection.
14. 3 It should be signed by the person
implementing the corrective action
15. Documentation
15. 1 Self-inspection reports should be
logged.
15. 2 All documents related to self-
inspection shall be kept for at least five
years.