INTRODUCTION

The development of a drug product is a lengthy process involving drug discovery,

laboratory testing, animal studies, clinical trials and regulatory registration. To
further enhance the effectiveness and safety of the drug product after approval,
many regulatory agencies such as the United States Food and Drug
Administration (FDA) also require that the drug product be tested for its identity,
strength, quality, purity and stability before it can be released for use.
For this reason, pharmaceutical validation and process controls are important in
spite of the problems that may been countered. Process controls include raw
materials inspection, in-process controls and target so for final product. The
purpose is to monitor the on-line and off-line performance of the manufacturing
process and then validate it.
Even after the manufacturing process is validated, current good manufacturing
practice also requires that a well-written procedure for process controls is
established to monitor it performance. The QA/QC good practice guidance
outlined here reflects practicality, acceptability, cost-effectiveness, existing
experience, and the potential for application on a worldwide basis. A QA/QC
programme contributes to the objectives of good practice guidance, namely to
improve transparency, consistency, comparability, completeness, and confidence
in national inventories of emissions estimates.
The outcomes of the QA/QC process may result in a reassessment of inventory
or source category uncertainty estimates. For example, if data quality is found to
be lower than previously thought and this situation cannot be rectified in the
timeframe of the current inventory, the uncertainty estimates ought to be re-
evaluated.
QUALITY CONTROL
Quality control is an essential operation in the pharmaceutical industry.
Pharmaceutical drug products must be marketed as safe and therapeutically active
formulations with consistent and predictable properties and performance. As new
and better medicinal agents are rapidly evolving, so are there more exacting and
sophisticated analytical methods being developed for their evaluation.

According to the World Health Organization (WHO), the term quality control
refers to the sum of all procedures undertaken to ensure the identity and purity
of a particular pharmaceutical.
Quality control in particular is the area of good manufacturing practices (GMP)
which deals with processes involving sampling, specifications and testing, and
with the organization, documentation and release procedures. These helps ensure
that the necessary and relevant tests are executed and that materials are not
released for use, nor products released for sale or supply, until their quality has
been confirmed to comply with international standards.

This attribute of a pharmaceutical preparation cannot be easily measured and

assured during in-process inspection and finished-product testing, since every
stage of the manufacturing process affects the properties of the drug. This key
fact opens up the necessity to properly train all personnel-- from the basic
concepts of assuring quality like donning on their personal protective equipment
(PPE) prior to entering production sites; up to the complex protocols of aseptic
technique.

Additionally, a consistent yield of products of the highest calibre will not only
depend on the operators, rather, even the material of construction of the
cleanrooms and various equipment used for handling and preparing the final
products can be of influence. As such, a keen sense of attention to detail is
essential.
It is also important to note that quality control is not confined to laboratory
operations but must be involved in all decisions concerning the quality of the
product; from the purchasing and storage of raw materials, to the in-process
quality control testing, up until the labelling and packaging of the final product.
Quality assurance
Quality assurance is one of the most important aspects of the entire drug
manufacturing process. Not only will it help companies protect their reputations,
but it will allow them to avoid hefty penalties from regulatory organizations.
This is exactly why anyone involved with quality assurance should receive
pharma training that helps ensure compliance.

The purpose of pharmaceutical quality assurance is to ensure that the medication

being manufactured will provide the desired effect to the patient. Quality
assurance also guarantees that there are no contaminants present and that the
medications will meet quality requirements and all relevant regulations.

There are several objectives that must be met with pharmaceutical quality
assurance. If a manufacturer falls short of these objectives, they may face heavy
fines and possible legal actions that can jeopardize the business.

Today, we’re going to go over the common objectives of pharmaceutical

importance. Understanding these objectives will shed light on how important
pharmaceutical quality assurance truly is.

DEFINITION OF IPQC
IPQC stands for IN PROCESS QUALITY CONTROL. These are checks that
are carried out
before the manufacturing process is completed. The function of in -process
controls is monitoring and if necessary, adaption of the manufacturing process in
order to comply with the specifications .this may include control of equipment
and environment too.
In-process materials should be tested for identity, strength, quality and purity as
appropriate and approved or rejected by the quality control unit during the
production process. Rejected in-process materials should be identified and
controlled under a quarantine system designed to prevent their use in
manufacturing .Written procedure should be established he in-
process controls and tests as specified.
• Tablet or capsule weight variation.
• Disintegration time.
• Content uniformity and homogeneity.
• Dissolution time and rate.
• Clarity, Completeness or pH of solutions.
PRACTICAL CONSIDERATION IN DEVELOPING QA/QC
SYSTEMS
Implementing QA/QC procedures requires resources, expertise and time. In
developing any QA/QC system, it is expected that judgements will need to be
made on the following:
Resources allocated to QC for different source categories and the compilation
process;
Time allocated to conduct the checks and reviews of emissions estimates;
Availability and access to information on activity data and emission factors,
including data quality; Procedures to ensure confidentiality of inventory and
source category information, when required;
Requirements for archiving information; Frequency of QA/QC checks on
different parts of the inventory; The level of QC appropriate for each source
category; Whether increased effort on QC will result improved emissions
estimates and reduced uncertainties; Whether sufficient expertise is available to
conduct the checks and reviews. In practice, the QA/QC system is only part of
the inventory development process and inventory agencies do not have unlimited
resources.
Quality control requirements, improved accuracy and reduced uncertainty need
to be balanced against requirements for timeliness and cost effectiveness. A good
practice system seeks to achieve that balance and to enable continuous
improvement of inventory estimates.
Within the QA/QC system, good practice provides for greater effort for key
source categories and for those source categories where data and methodological
changes have recently occurred, then for other source categories3. It is unlikely
that inventory agencies will have sufficient resources to conduct all the QA/QC
procedures outlined in this review on all source categories.
In addition, it is not necessary to conduct all of these procedures every year. For
example, data collection processes conducted by national statistical agencies are
not likely to change significantly from one year to the next.
Once the inventory agency has identified what quality controls are in place,
assessed the uncertainty of that data, and documented the details for future
inventory reference, it is unnecessary to revisit this aspect of the QC procedure
every year.
However, it is good practice to check the validity of this information periodically
as changes in sample size, methods of collection, or frequency of data collection
may occur.
The optimal frequency of such checks will depend on national circumstances.
While focusing QA/QC activities on key source categories will lead to the most
significant improvements in the overall inventory estimates, it is good practice to
plan to conduct at least the general procedures.
General QC Procedures on all parts of the inventory over a period of time. Some
source categories may require more frequent QA/QC than others because of their
significance to the total inventory estimates, contribution to trends in emissions
over time or changes in data or characteristics of the source category, including
the level of uncertainty.
For example, if technological advancements occur in an industrial source
category, it is good practice to conduct a thorough QC check of the data sources
and the compilation process to ensure that the inventory methods remain
appropriate. It is recognised that resource requirements will be higher in the initial
stages of implementing any QA/QC system than in later years. As capacity to
conduct QA/QC procedures develops in the inventory agency and in other
associated organisations, improvements in efficiency should be expected.
The general procedures require no additional expertise in addition to that needed
to develop the estimates and compile the inventory and should be performed on
estimates developed using Tier 1 or higher tier methods for source categories.
A review of the final inventory report by a person not involved in the compilation
is also good practice, even if the inventory were compiled using only Tier 1
methods. More extensive QC and more rigorous review processes are
encouraged if higher tier methods have been used. Availability of appropriate
expertise may limit the degree of independence of expert reviews in some cases.
The QA/QC process is intended to ensure transparency and quality.

ELEMENTS OF QA/QC SYSTEM

The following are the major elements to be considered in the development of a
QA/QC system be implemented in tracking inventory compilation:
• an inventory agency responsible for coordinating QA/QC activities;
A QA/QC plan;
• General QC procedures
• Source category-specific QC procedures
• QA review procedures;
• Reporting, documentation, and archiving procedures.
For purposes of the QA/QC system, the QC approach includes all procedures in
plus additional
QUALITY CONTROL EQUIPMENTS
Friabilator
Friabilator is the instrument which is used to detect the friability of the tablets.
Friability is the combined effects of shock and abrasions. So, to resis t shock and
abrasions friability test is done for the tablets. In this a no. of tablets is put in the
friabilator and revolves at 25rpm, dropping the tablets a distance of six inches
with each revolution. Conventional compressed tablets that lose less than 0.5 to
1.0% of their weight are generally considered as acceptable. When capping is
considered on friability testing, the tablet should not be considered as for
commercial use, regardless of the %age of loss seen.

Dissolution test apparatus

The dissolution test is conducted to assure that drug is properly breaks into their
parts in a respective medium. Dissolution testing can be continued through three
stages.
STAGE (1-3)-Six tablets are tested and are acceptable if all the tablets are not
less than monograph tolerance limit plus 5%. if the tablet fails, an additional six
tablets are tested. The tablets are acceptable if average of the twelve tablets are
greater than or equal to tolerance limit and no unit less than tolerance limit minus
15%, if tablet still fails the test, an additional 12 tablets are tested. The tablets are
acceptable if the average of all 24 tablets is greater than or equal to tolerance limit
and if not more than 2 tablets are less than tolerance limit minus 15%. Industrial
pharmacists routinely test their formulations for dissolution.

Digital pH meter
Digital pH meter is used in pharmaceutical industries to assure the pH of the
solutions which is needed for the preparation of the drug, pH is very important to
make assure the stability of the product. Solutions stability investigation usually
commence with probing experiments to confirm decay at the extremes of pH for
an e.g., 0.1N HCL, Water, and0.1N NaOH). These intentionally degraded
samples may be used to confirm assay specificity as well as to provide estimates
for maximum rates of degradation. This initial experiment should be followed by
the generation of a complete pH rate profile to identify the pH of maximum
stability. Aqueous buffers are used to produce solutions over a wide range of ph
values with constant levels of drug, cosolvent and ionic strength. Since most
solution pharmaceuticals are intended for parenteral routes of administration, this
initial ph. Rte. study should be conducted at a constant ionic stren gth that is
compatible with physiologic media. Ionic strength of an isotonic 0.9% NaCl
solution is 0.15.
Moisture analyser
A moisture analyser indicating by its name as to analyse moisture in a drug
content. The formula
which is used to detect moisture is as follows:
[% Moisture content (M.C) = (wt. of water in sample/wt. of dry sample)
*100]
Drying of solids
The moisture content in a solid can be expressed on a wet -weight or dry weight
basis. On a wet weight basis, the water content of a material is ca lculated as a
%age of the weight of the wet solid, whereas on the dry weight basis, the water
is expressed as a %age of the weight of the dry solid. In pharmacy loss on drying
is commonly referred as L.O.D, is an expression of moisture content on a wet
weight basis which is calculated.
Process viscometer
This instrument is capable for performing the rheologic studies of most
pharmaceutical preparations such as semi-solid preparations or formulations:
pastes, ointments and creams.
Digital refractometer
Digital refractometer is used for those products which are sensitive to light
refraction so it is simply used to check the refraction spectrum of drug product.
Leak test apparatus
A leak test apparatus is used for checking the crimping of the valve which must
be available to prevent defective containers due to leakage. For metal containers,
this is accomplished by measuring the “crimp” dimensions and ensuring that they
meet specifications. Final testing of the efficiency of the valve closure is
accomplished by passing the filled containers through the water bath.

IPQC TESTS FOR VARIOUS DOSAGE FORMS:

Tablets:
a) Drug contents determination.
b) Moisture contents of granules.
c) Assay of active ingredients.
d) Weight variation of uncoated tablets.
e) Hardness test.
f) Disintegration test
Drug Content Determination
A physically sound tablet may not produce the desired effects. To evaluate a tablet
potential for efficacy, the amount of drug per tablet needs to be monitored from
tablet to tablet and batch to batch, and a measure of the tablets ability to release
the drug needs to be ascertained.
Moisture Content of granules
Granules should possess sufficient strength to withstand normal handling and
mixing processes without breaking down and producing large amounts of fine
powder. On the other hand, some size reduction during compaction into tablets is
desirable to expose the areas of clean surface necessary for optimum bonding to
take place so moisture content is the very important factor for producing God
pharmaceutical product.

Assay of active ingredient

In a tablet an active ingredient is present which is called active pharmaceutical
ingredient (A.P.I). So, to prepare the tablet assay has to be done to produce good
finished product.

Hardness test
The monitoring of tablet hardness is especially important for drug products that
possess real or potential bioavailability problems that are sensitive to altered
dissolution release profiles as a function of the compressive force employed. One
of the earliest testers to evaluate tablet hardness was the Monsanto hardness tester
to evaluate tablet hardness tester.
Disintegration test
A generally accepted maximum is that drug to be readily available to the body, it
must be in solution. For most tablets, the first important step towards solution is
break down of the tablet into smaller particles or granules, a process known as
disintegration. The U.S.P device to test disintegration uses 6 glass tubes that are
3 inches long, open at the top, and held against a 10-mesh screen at the bottom
end of the basket rack assembly. To test for disintegration time, one tablet is
placed in each tube, and the basket rack is positioned in a 1-L beaker of water,
simulated gastric fluid and at 37°-+2°c, such that tablet remains 2.5cm below the
surface of the liquid on their upward movement and descend not closer than
2.5cm from the bottom of the beaker. A standard motor driven device is used to
move the basket assembly containing the tablets up and down through distance
of 5 to 6cm at a frequency of 28 to 32 cycles per minute.

I.P.Q.C TEST FOR SYRUPS AND SUSPENSION

a) Drug contents determination.
b) Assay of active ingredients.
c) pH.
d) Weight per ml.
e) particle size

Drug content determination

Determination of drug content in suspension and syrups are important because
them concentration has to be sufficient itself that it produces the pharmacological
action. A suspension is much prescribed to paediatrics so their concentration has
to be sufficient not to less not to large.
Assay of active ingredient
Active ingredient means pure drug present in the product. An assay of active
ingredient must be done because it is the only which is responsible for
pharmacological action and in syrups and suspension a small and fine particle are
included in syrups and suspension
pH of the product
pH affects the stability of the product so before filling and after filling of
suspension and syrups pH has to be checked out for consistency of the product.
Particle size
In suspension and syrups a solute particle is dispersed in a suitable solvent so
particle size becomes the important factor for the suitability of the product and
all the particles has to be of same size and shape for proper dispersing in the
solvent.

I.P.Q.C TEST FOR SEMI- SOLIDS

a) Drug contents determination.
b) Assay of active ingredients.
c) Uniformity and homogeneity test.
d) Viscosity and specific gravity test.
e) Filling test.

Drug content determination

As all have discussed earlier drug content becomes important factor for active
pharmaceutical product. Drug content has to be of very suitable ratio that it can
give the pharmacological action.

Homogeneity test
The semi-solid preparations require further treatment are transferred or pumped
to the proper homogenizer, the selection of which is governed by the degree and
rate of shear stress required.
Viscosity and Specific gravity test
Once the desired semi-solid preparation has been chosen, a consistency that
provides the desired stability and has appropriate flow characteristics must be
attained. For emulsion it is routinely observed that the building up of viscosity in
a freshly prepared emulsion requires some time. The is recommended, therefore
that newly formulation emulsion be allowed to rest undisturbed for 24 to 48 hours
before it is determined whether its rheologic properties correspond to those that
are required. The viscosity of emulsions responds to changes in composition in
accordance with the following generalizations.
• There is a linear relationship between emulsion viscosity and viscosity of
continuous phase.
• The greater the volume of the internal phase, the greater is the apparent
viscosity.
• To control emulsion viscosity, three interacting effects must be balanced by the
formulator.
• the viscosity of o/w and w/o emulsions can be increased by the reducing
the particle size of
the dispersed phase.
• Emulsion stability is improved by a reduction in particle in particle size.
• Flocculation or clumping which tends to structure the internal phase, can
be stabilizing effect, it increases the viscosity.
I.P.Q.C TEST FOR INJECTABLES
a) Drug contents determination.
b) Clarity test.
c) pH.
d) Pyrogen test.
e) Stability test.
f) Leakage test.
g) Check-up of particulate matters.

Pyrogen test
The presence of pyrogenic substance in parental's is determined by a qualitative
biologic test based on the fever response of the rabbits. Rabbits are used as test
animal because they show a physiologic response to pyrogens similar to that of
human beings. If a pyrogenic substance is injected into the vein of a rabbit, an
elevation of temperature occurs in a period of three hours.
Sterility test
All products labelled “sterile” must pass through sterility test, having been
subjected to an effective process of sterilization. The traditional concept of
sterilization is the absolute condition of total elimination of all the
microorganisms. With a terminal method of sterilization of a parenteral product,
particularly steam under pressure, a probability of no more than one sterile unit
in a million is readily achievable. The term aseptic indicates a controlled process
in which the level of microbial contamination is reduced to the degree that
microorganisms can be excluded from a product during processing. It des cribes
apparently sterile state.
Leaking test
Ampules are intended to provide hermetically sealed container for a single dose
of a product, thereby completely barring any interchange between the contents of
the sealed ampule and its environment. Should capillary pores or tiny cracks be
present, microorganisms or other dangerous contaminants may enter the ampule
or the contents may lead to the outside and spoil the appearance of the package.
Changes in temperature during storage cause expansion and contraction of the
ampule and contents, thereby accentuating interchange if an opening exists.
Leakers usually detected by producing a negative pressure with an incompletely
sealed ampule, usually in a vacuum chamber, while the ampule is entirely
submerged in a deeply coloured dye solution, usually 0.5 to 0.1% methylene blue.
Subsequent atmospheric pressure then causes dye to penetrate an opening, being
visible after the ampule has been washed externally to clear it of dye. The vacuum
(27 inches Hg or more) should be sharply released after30 min. Only a tiny drop
of dye may penetrate a small opening.
Vials and bottles are not subjected to such a leaker test because the rubber closure
is not rigid; however, bottles are often sealed while a vacuum is being pulled so
that the bottle remains evacuated during its shelf life.

Clarity test
Clarity is the relative term, the meaning of which is markedly affected by the
subjective evaluation of the observer. Question a clean solution having a high
polish conveys to the observer that the product is of exceptional quality and
purity. It is practically impossible, however, to prepare a lot of a sterile product
so that every unit of that lot is perfectly free from visible particulate matter, that
is, from particles that are 30 to 40 micrometre and larger in size.
Consequently, it is the responsibility of the quality control department to detect
and discard individual containers of a product that the ultimate user would
consider to be unclean.
This clarity test is performed in industry by visual inspection machine by the light
baffles against reflection into the eyes, and views against a black and white
background, with the contents set in motion with a swirling action

Stability
To enhance the assurance of successful manufacturing operations, all process
steps must be carefully reduced to writing after being shown to be effective. These
process steps are often called standard operating procedures (SOPs). No
extemporaneous changes are permitted to be made in these procedures; any
change must go through the same approval steps as the original written SOP.
Further external records must be kept to give assurance at the end of the
production process that all steps have been performed as prescribed. Such in -
process control is essential to assuring the quality of the product, sin ce these
assurances are even more significant than those from product release testing.
QUALITY CONTROL AND QUALITY ASSURANCE
INTER RELATIONSHIP
 CONCLUSION

Monitoring chemical processes for the formation of an API is the first step to
ensuring quality in pharmaceutical manufacturing. Having reliable and
reproducible methods will enable the production plant to guarantee the
consistency of drugs batch after batch. Furthermore, it may simplify the
characterization of such processes and their chemical profile. Through the years,
vast publications and general information have been presented to pharmaceutical
industry specialists about the validation of analytical methods. Federal and
international regulatory groups have published various guidelines to shed light on
analytical method validation. No such emphasis has been given, or guidelines
described, however, the validation of in- process control methods. This article
intends to establish a starting point for discussions about the validation of in -
process methods. So, in this, in- process methods quality control and validation
are dealer with several of criteria that are discussed in this report.
 REFERENCES

1. Chow S. Pharmaceutical Validation and Process Controls in Drug

Development. Drug
2. Committee on Specifications for Pharmaceutical Preparations. Good
Manufacturing Practices for Pharmaceutical Products. WHO Technical Report
Series no.82. Geneva: World Health
3. Celik, M. (1922) overview of compaction data analysis techniques. Drug
Devein. Pharm,
4. Hiestand, E.N.,Wells,j.e.,Poetic. and Ochs, J.F(1977) Physical processes of
tabletting, Pharmascience.
5. Dureli.A.J.Lin,Y.H(1986) stress and displacements on boundaries of circular
rings
6. Podsakoff and Newton. (2003) The implications of the determinations of the
mechanical strength of powder compacts containing a pre-formed hole. Powder
Technol.
7. Sietsma. And EIsland, G.M. (1965) Evaluation of physical properties of
compressed tablets,1: tablets hardness and friability Pharm.Science.
8. Upadrashta, S.M., Katikaneni, P.m. and Nussela, N.O. (1922) Chitosan as a
tablet.
9. Fell,J.T.and Newton (1970) Determination of the tablet strength by diametrical.
10. Okunola and Otaola O.A(2003) Evaluation of the effects of khaya gum on the
mechanical. And release properties of paracetamol tablet formulation. Drug
Dev.Ind.Pharm.
11. Chapman GM, Amer G, Boyce C, Brower G, Green, Hall WE, Harpaz D,
Mullendore B. Proposed Validation Standard VS1: Non-aseptic Pharmaceutical
Processes. J Val Technol
12. Le Blane DA. Establishing scientifically justified acceptance criteria for
cleaning validation of finished drug product.