Pharmaceutical Quality Management-I
Table of Contents
CHAPTER 1 ................................................................................................................................... 2
GOOD MANUFACTURING PRACTICES IN INDUSTRY ......................................................... 2
INTRODUCTION ......................................................................................................................... 2
General Terms ................................................................................................................................ 2
Quality Management ..................................................................................................................... 2
Quality Assurance ........................................................................................................... 3
Quality Control ................................................................................................................ 4
Good Manufacturing Practices ....................................................................................... 5
INFRA STRUCTURE OF PHARMACUTICAL INDUSTRY .................................................. 5
Research and development department ......................................................................... 5
Material management department .................................................................................. 6
Production department .................................................................................................... 6
Quality Assurance department ....................................................................................... 6
Quality control department ............................................................................................. 7
Marketing department ..................................................................................................... 7
Standard .......................................................................................................................................... 7
Standardization ................................................................................................................ 7
Type of Standard ............................................................................................................. 7
Validation ....................................................................................................................................... 8
Types of validation ......................................................................................................... 9
Steps for Validation Procedures: ................................................................................. 10
Scope of Validation Applications: ............................................................................... 10
Selection of analytical method: .................................................................................................. 10
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Pharmaceutical Quality Management-I
CHAPTER 1
GOOD MANUFACTURING PRACTICES IN INDUSTRY
INTRODUCTION
General Terms
Quality
Quality is generally known as “fitness for use” The word quality is derived from Latin
“Qualitas” which means “general excellence” or “distinctive feature”.
Quality refers to the characteristics of a product from both points of view, Qualitative and
Quantitative. It also refers to the quality of a process as well as the product itself.
Management
It is the activity which plans organizes and controls operations of basic elements of
materials, machines, methods and market providing the directions with co-ordination and
giving leadership to human efforts so as to achieve the objectives of an enterprise
(organization).
In pharmacy it refers to “to manage the quality of the pharmaceutical product and dosage
forms”.
Control
The word “control” implies a procedure by which decisions maybe made regarding whether
product testing is proceeding according to the plan and meeting standards established
previously.
Quality Management
Quality management is the system within organization in which management take steps to
maintain the quality of the final product. Management defines and implement ‘quality
policy’ for the drug products. Quality system in an appropriate infrastructure comprises of
organizations structure, procedures, processes and resources. Stepwise actions of quality are
very important that provide confidence that final product will be of required quality and
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fulfill all the necessary quality requirements needed for specific product. E.g parentrals
should have to be sterile. And actions taken for a sterile parentral started from the raw
material till the final unit dosage form. At all steps sterility is the main point to be consider
and it maintains quality.
Quality management system involves three basic concepts:
1) Quality assurance
2) Quality control
3) Good manufacturing practices (GMPs)
Objectives
There are three main objectives of quality management of the pharmaceuticals:
1. To produce quality products
2. To satisfy the customers and consumers
3. To achieve the objective of the organization (profit of industry)
Quality Assurance
Totality of all the quality actions.
It is a wide-ranging concept that covers all the matters that individually or collectively
influence the quality of a drug. It is the total of the organized arrangement made with
objectives of ensuring that drug of quality require for their intended use.
Quality assurance therefore incorporates good manufacturing practices along with other
factors to achieve the objectives of organization.
The main role of quality assurance is as follows:
To inspect each regulatory process and control the documentation during all the steps.
Quality assurance system must comprise of GMP (good manufacturing practices) which
includes GLP (good lab practices) and GCP (good clinical practices). All control operations
for product development must be in written form and GMPs must follow. Calibration and
validation must be carried out for the in-process actions during the handling of starting,
intermediate and final materials for the drug formulation. Final product must be formulated
and patterned according to written procedures. Final products are marketed only after
marketing authorization and sold to an authorized person which ensures that product is
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manufactured in accordance with marketing authorization. Pharmaceutical product must
keep in such conditions that it remain active throughout its shelf life. Self -inspection and
quality audits are being done for maintaining the effectiveness of the formulations and
counter checking the QA process. Deviations inspected must be reported and recorded and
investigated for solutions. Regular checks for the quality are done and maintain
pharmaceutical products effectiveness.
Owner must ensure that product is safe to use. For this a qualified staff, competent
personals, suitable premises, sufficient equipment and all necessary facilities must present.
Quality Control
Maintain standards of final products by testing against specifications.
It is mainly concerned with the analytical measurement processes and focus on technical
aspects of the testing of drugs at all stages.
Difference between quality assurance and quality control
Quality assurance
Quality control
1. 1-Inspects and regulates every
1. 1-Mainly involves analytical
process
and
step
during
measurements.
manufacturing.
2. 2-Documentation
only
2. 2-Control Documentation.
concerned with testing of the
3. 3-Sampling of the material.
materials.
It is the part of GMP and in this sampling and testing of the formulations has done.
Documentation for each step is maintained in the organization. Product is only released
when all the necessary test for quality check of the product are done. It is not only lab
oriented but also involves other decisions regarding the quality of the final product. QC
must be independent from all other departments in the firm. A qualified and experience
person should take the hold for activities performed in the department of QC. Quality
control operations need adequate resources and facilities to carry out all the necessary
operations.
Quality control actions are taken for initial, intermediate and final products. Record is
maintained at each step of inspection for quality. Purity of drug should maintain, and
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container should be labelled correctly. Deviation from specified protocol must be recorded
for future inspections. Quality control also perform other duties like participate in
investigation of complaints regarded drug’s quality.
Good Manufacturing Practices
GMPs are the parts of the quality assurance that ensures that drugs are consistently produces
and control in such a way to meet the quality standards appropriate to their intended use, as
required by the marketing authorization.
GMP is used for lowering the risks which could be present any pharmaceutical product.
These risks could be of two types like:
1. Cross contamination
2. Mix-ups (false label on containers)
Manufacturing processes must present for formulating final products intended for their use
and must be reviewed by experienced personal. Qualifications and validation must have
performed for all the processes carried out for the quality product. All required resources
such as: qualified person, appropriate premises, suitable equipment, material, container,
labels, written SOPs, storage places, transport, in-process control facilities and testing
personals must present for carrying out GMPs.
All the procedures must be written in easy and unambiguous language. Working personals
must be trained for performing their duties. Records maintain for each step and make sure
that quality is maintained, deviations are also recorded for investigation where the quality is
compromised so take steps to minimize the deviations. Record is maintained that history of
the batch can be traced and must present in accessible place. Proper storage places can
retain the quality of the product as it is intended. A system must available for recall of the
product from sale if any problem is detected. Whenever complaints make for the marketed
product, they are investigated for quality defects and make preventive measure to stop
recurrence.
INFRA STRUCTURE OF PHARMACUTICAL INDUSTRY
The following are important departments in a pharmaceutical industry:
Research and development department
The following are important functions:
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i.
ii.
iii.
Patents registration
Development of dosage form.
Developing the ready dosage form
Material management department
There are following sub departments under this department:
a) Purchase department
It controls purchasing of the materials.
b) Planning department
It plans the amount of material to purchase.
c) Warehouse
It has further sub department as follow
-Row material store (RMS)
-Packing material store (PMS)
-Finished Goods store (FGS)
Production department
It functions in the production of dosage form. There are two sub departments.
i.
ii.
Oral/Non-injectable department: Also knows as non-sterile department
and involves production of oral dosage form. (tablets, capsules, emulsions,
syrups)
Injectable department: Also known as sterile department and it Involves
the production of sterile ointments and injection.
Quality Assurance department
It involves:
-To inspect each process in manufacturing.
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-Sampling of each process.
Quality control department
It function is to Test the batch analytically.
Marketing department
Marketing of the finished product to the customers.
Assay
Assay is the determination of the amount of a particularly constituent of a mixture or of the
biological or pharmacological potency of the drug.
Test
It is a technical operation that consists of the determination of one or more characteristics or
performance of a given product, material; equipment, organism and process/service
according to a specified procedure.
Standard
Something established as a measure or model to which other similar things should confirm.
Standardization
The brining of any preparation to the specified standard is called as standardization.
Type of Standard
There are two types of standards:
i.
Reference standard:
Drug substances of highest purity reasonably attainable specifically prepared by
independent synthesis or by farther purification of existing production material and shown
to be authentic material by an extensive set of analytical test.
ii.
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Working standard:
Pharmaceutical Quality Management-I
Drug substances of established quality and purity as shown by comparison to the reference
standard material and used as the reference working standard or substances for the routine
quality control test.
Drug Product
Finished dosage forms such as tablet, capsules, lotions and syrups containing drug
substances with or without association of one or more other ingredients.
Specific Identification Test
These are the tests which are used identify the presence of a substances in a sample for
example infrared spectroscopy, nuclear magnetic spectroscopy and mass spectroscopy are
used to identify the specific substances to present in a sample.
Impurity Profile Limit (IPL)
Impurity profile limits are the test to detect, identify and quantities the presence of starting
material intermediates, by products, degradation products, solvents and other impurities as
well as recommended limit of each of such impurities. These impurities should not only be
detected but also quantitated.
Qualification
It is generally related to the equipment, instruments used to determine whether this
equipment and instruments operate as it was designed to a reproducible manner.
Calibration
Instrument/equipment: response according to prescribed test condition verses accepted
tolerance limit.
Validation
A process involving confirmation or established by laboratory studies that a method,
procedure, system or analyte gives accurate and reproducible results for intended analytical
application in a proven and established range.
Validation of a process is the demonstration that controls the critical steps of a process
result in products o repeatable attributes or causes a reproducible event. (e.g. sterilization).it
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is a systemic, documented program that provides a high degree of assurance that a specific
process will consistently provide a product meeting its predetermined specifications and
quality attributes.
A validated manufacturing process in one that has been proved to do what it purposes, or it
is represented to do. The proofs of validation is obtained through collection and evaluation
of data, preferably beginnings from the process development phase and continuing through
into production phase validation necessarily includes processes qualification, but it also
includes the control of entire process for repeated batches or runs.
The documentation including protocols data and results obtained from process validation
and equipment qualification are important, since the validation performed should be
available by an appropriate responsible individual who often reviewing records, should be
able to certify the validation of the process to produce product of defined attributes
consistently, provided that the system validated is not altered.
Types of validation:
There are three types of validation:
Prospective validation
Prospective validation is done prior to the release of new product under revised
manufacturing process. It can be employed when the historical data of the product is not
available or is not sufficient and in process and finished product testing is not adequate to
ensure reproducibility and high degree compliance product likely attribution.
Retrospective validation
It refers to the review and evaluation of existing information for comparison when the
historical data is sufficient and easily available.
Concurrent validation
Concurrent validation refers to the subsequent confirmation of a batch. It is based on the
information generated during implementation of a system
Importance of Validation
Reproduction in cost associated with process sampling and testing.
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Batch to batch consistency is achieved.
Establish scientific and effective communication between scientists on technical matters.
Setting of standard operating procedures(SOP’s)
Important of taking action in case of noncompliance.
Retrospective validation is useful for trend comparison of results, compliance to
CGMP/CGLP. International pharmacopeia harmonization is achieved.
Steps for Validation Procedures
I.
II.
III.
IV.
V.
Establish validation of proposed process
Perform experimental studies.
Evaluate analytical result
Carry out statistical verifications.
Prepare report documenting all results
Scope of Validation Applications
I.
II.
III.
IV.
Manufacturing process control
Evaluation of dosage forms
Stability studies
Environmental control
Selection of analytical method
Analytical method should be as simple as possible and most specific most productive,
economical and convenient also accurate and precise as required.
Multiple source of key component should be avoided (reagents, columns, TLC plates). To
be fully optimized before transfer for validation of characteristics are needed.
1. Accuracy
Accuracy is defined as closeness of test result to true value or it means measure of
exactness of analytical method.
2. Precision
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It is the degree of agreement among individual test result when method is applied to a
homogenous sample, usually express as a standard deviation.
Types of precisions
Precision may be:
i.
ii.
iii.
Repeatability:
Under the same condition and is easy to achieve.
Reproducibility: Under different conditions
Within the same laboratory conditions but different drugs, analyte test and
equipment.
3. Selectivity/Specificity
It is the ability of a method to measure accurately and specifically the analyte of interest
in presence of matrix and other components likely to be present (impurities)
Analysis of a component of a mixture may interfere with other component of mixture. If
this occurs, the analytic method is nonspecific for the component under investigation.
With specificity, the concentration of compound can be completely measured regardless
of what other compared are present in the sample.
4. Linearity
It is the ability of a method to elicit test results that are directly proportional to the
concentration of the analyte.
The linearity of a method gives the characteristic trend of such parameters as
absorbance, peak height, and peak area or response ratio as a function of concentration
of component to be measured.
5. Range
It is the lowest and highest level of analyte that a method can determine with reasonable
accuracy and precision.
6. Limit of Detection (LOD)
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It is the lowest concentration of analyte in a sample that a method can detect but not
necessarily quantify it under stated experimental condition. It simply indicates that the
sample below or above certain level.
Whenever a sample contains a compound in a very low concentration, the signal from
the instrument will be small.
This gives rise to term limit off detection. LOD is not only dependent on procedure but
also the instrument.
7. Limit of Quantification
It is the lowest concentration of a substance in a sample that can be estimated
quantitatively with acceptable accuracy and precision.
8. Sensitivity
It is defined as capacity of test procedure to record small variations in the
concentrations.
9. Ruggedness
It is the degree of reproducibility of test result by analyzing same sample under variety
of same conditions (normal test conditions) e.g. different analyst instruments, drugs,
reagents, columns etc.
10. Robustness
It is the measure of capacity of a method to remain unaffected by small but deliberate .
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