Product Development

Pharmaceutical
536

PROCESS VALIDATION PHASES

classified into three phases (Agalloco
co, 1993,
100
Jatto
validation studies may be
relating to process
The activities
& Okhamafe, 2002):

Phase 1 (Process Capability Deslgn)

should evaluate all factors that aCc
a manufacturer
validation guidelines states that
FDA in its process validation study. Not all the parameterS are
and undertaking a process al
product quality when designing therefore elemental to identify critical parameta
characteristics and it is ters.
in order to defile the final product the number and relative importance c
of the studies to determine (1)
Process capability is the carrying out numerical values or ranges for each of
influence process output, and (2) the
critical process parameters that
the critical process parameters that result in acceptable process output (Nash, 1990).
the process should result into output of consistent attribtes
If the process capability is properly defined,
when operated within the defined limits of
critical process parameters.
tablet manufacture and respective in-process variables
Fig. 16.8 represents various processing steps of
that may have impact on tablet characteristics (in terms of dose uniformity and disintegration/dissolution
time). In order to find critical process parameters and their relative importance each process variable is varied
in a measured way within operating ranges, and its influence on final product attributes is measured (Ohm.
1997).The variables, which do not affect final product attributes, are considered non-critical while those
influence product attributes are taken as critical. Critical parameters further can be listed in order of their
relative importance by measuring the extent of change in product attributes with small variation in process
variables (Chow, 1997). Data to substantiate the ranges for critical process parameters generally should be
obtained from laboratory- or pilot-scale batches, unless a specific parameter can only be determined from a
production-scale batch (Nash, 1979).
Raw materials (active ingredients and excipients) must be clearly defined in terms of its critical quality
attributes. Among the attributes that should be considered
are:
Chemical purity,
Impurity profile (qualitative and quantitative),
Polymorphic forms,

| 1. Pre-blending of 3. Granulation
powders 5. Blending
Drying Add lubricant
(Vertical mixer) (Fluid Bed Dryer) (V-Blender)
Speed- Temp Speed-
Load
Size Load
Time- Time
Time-
Contentweight
Speed uniformity
Disintegration
Amount Time Rate
- Load
Speed- Force
Dissolution
Rate Screen - Speed

2. Blend 4. Sizing Granules

Granulation 6. Tablet Compression
(Comminutor) (Rotary Press)
Fia. 16.8.Schematic diagram processing sieps and
of
may influence final product attributes (dose unormny, respective in-process variables during tablet manutactu
hat
disintegration/dissolution Time)
 Chaptor 16
Pharmaceutical Validation 537

Physical characterization (particle sizc, bulk and tap density).

Moisture content, and
.Microbial quality (if the product is susceptible to nicrobial contamination).

Phase 2 (Process Valldatlon Phase or Process Quallfication Phase)

It is designed to verify that all cstablished limits of the critical process parameters valid and that
are
satisfactory
praducts can be produced even under the 'worst casc' conditions (Byers, 1982). It represents the actual
studies or trials conducted to show:
that all systems, subsystems or unit operations of a manufacturing process perform as
intended
that all eritical parameters operate within their assigned control
limits
that such studies and trials, which form the basis of process capability design and testing. are verifiable
and certifiable through proper documentation.

Phase 3 (Validation Maintenance Phase)

It requires frequent review of all process-related documents, including validation audit reports to assure that
there have ben no changes, deviations, failures, modifications to the production process, and that ali SOPs
have been followed, including change control procedures. At this stage the validation team also assures that
there have been no changes/ deviations that should have resulted in re-qualification and revalidation.
Fig. 16.9 schematically represents the validation life cycle with yes/no checks. The checks at each siep
facilitate in decision making to complete validation exercise effectively.
The product and process development usually involve following key activities:
Process and formulation optimization based on various preliminary formulations development and
designed characterization,
Laboratory batch preparation and conducting initial accelerated stability studies.
Pilot scale (a scale intermediate to small laboratory scale and large full manufacturing level production)
formulation development, if formulation is deemed stable.
Pilot scale is usually gradually moved from laboratory pilot batch (10 times of laboratory scale)
to manufacturing pilot production phase (usually 100 time of laboratory scale to l/10 of intended
manufacturing level).
Full manufacturing scale production
Process capability and qualification studies, involving process ranging. process characterisation
and process optimisation, are usually started at laboratory pilot batch and continue until prvess is
vzlidated in pilot production or manufacturing production phase. Usually 3 successiul completed
pilot production batches are required for validation phase.

TYPES OF VALIDATION
There are three basic types of process validations. Each iype represents a different pathway to concluding
that a manufacturing
process is in a state of control.
Prospective (pre-market) validation- Validation is completed prior to the manufacture of tinished produt
that is intended for sale.
Concurrent validation- When prospective validation is not possible, it may be nevesary to valale

process during the routine production.

Retrospective validation- Processes that have been in use for some time without any significant aung
may also be validated according to an
approved protocol.
 Deverupi
Pharmaceutical Product
538

Start

Optional
Define Process

Define
The System

System Meets No
Needs of Process?

Yes

Qualfy
The System

Redesign

No
System Meets
Requirements?

Yes
Qualify
Process

Continued
Validation

Fig. 16.9. Validation life

cycle
 There is one more type of validationapartfrom the three mentioned above. known as 'revalidation'. Revalidation
is repetition ofvalidation process or some specific portion of it. Revalidation of any process, equipment or facility may be
performed on a periodic basis or due to some change introduced in a system. Theoretically a validation exercise should
only need to be carried out once for a given process. Practically the processes rarely remain static. Changes occur in
components (raw materials, packaging materials); cquipment is modified and in such cases process environment cannot
be assumed to remain same as during initial validation. A documented program should exist to review the state of
validation and a commitment made of the need of revalidation.

Prospective Validation
Prospective validation is usually undertaken whenever a new formula, process, and/or facility need to be
validated before routine pharmaceutical production starts e.g. switching to new filter medium, leak testing of
lyophiliser. It is also usually employed when sufficient historical data is either unavailable or insufficient and
in-process and final product testing is inadequate to ensure high degree of confidence for product quality
characteristics and reproducibility, e.g. a sterile solution filled on new equipment should only be released
after a media fill validation. Recently, the FDA guidelines on pre-approval inspection, associated with NDA/

ANDA submission, added a new dimension to this of validation. FDA is seeking evidence that the
type
for sale. FDA favours
manufacturing process is validated before it allows a product to enter the market
minimal risk, as it ensures
prospective validation for obvious reason of higher degree of confidence and
manufacture or release of product. Nevertheless, higher
process to be under control and effective prior to
a due consideration must be
degree of confidence is also associated with higher cost of operation. Therefore, validation is
alternative type of possible).
given to FDA preference and cost to benefit analysis (when
Concurrent Validation
Concurrent validation is appropriate when:
is
i t is not validation programme before routine manufacturing starts and it
possible to complete a
transference of process to contract
known in advance that finished product will be for sale e.g. during
manufacturer;
due to well understanding of
it is appropriate to validate process during routine production
more
or strength;
process e.g. on change in tablet shape
characteristics of product with high
extensive testing and monitoring ensures the desired quality
are placed in the product throughout
degree of confidence e.g. if the sufficient number of thermocouples the
from chamber, at various intervals.
the load and representative samples of the products are collected
for a lyophilization
for moisture analysis then it may be appropriat: to validate secondary drying process
cycle.
validation guidelines and
FDA does not include the terminology 'concurrent validation' in its process
Extensive testing and monitoring during concurrent
expresses its concern on reproducibility and consistency.
validation may verify quality attributes of product of particular batch, but,
does not provide a high degree of
assurance that subsequent batches processed under same condition
and parameter will attain same quality
attributes.
is manufactured on one time
Nevertheless, FDA understands that in certain cases, e.g. where a product
include the concept of concurent
basis, prospective and retrospective validation have limited applicability and
FDA expecEs
validation under paragraph "Acceptability of Product Testing" in process validation guidelines.
validations.
evaluation of manufacturingdata and test results more extensively than the usual prospective

Retrospective Validation
undergone a formally doCumented
nere are many processes in use in many companies that have not to
validation process. Validation of these processes is possible provided sufficient historical data is available provide
 Pharmaceutical Product Development
540

stable and are doing what they are believed . to do.

documentary evidence that various processes are considerably
Retrospective validation is prefemed because ofcost effectiveness. Further, large historical data set available mav nruovide
from few trial runs in prospective validation. This tvn
higher confidence and better picture than data generatcd ype of
validation is acceptable only for well-established processes and where critical quality attributes and critical neorocess
and controls have been establishod
parameters have been identified and documented; appropriate in-process specifications
and documented; and there have not been excessive process/product failures attributable to causes other than operator
emor or equipment failure unrelated to equipment suitability. The number of batches to review will depend on the process
but. in general. data from 10 to 30 consecutive batches should be cxamined to assess process consistency. The review
should include any batches that failed to meet specifications. However, any discrepancies or failure in the historical data
may be excluded provided there is sufficient evidence that the failure was caused by isolated occurrences e.g. emplovee
emor. and were not result of process variations. The source of data for this validation may include batch documents.
control eharts. maintenance logbooks, records of personnel changes, process capability studies. finished product data
including trend cards, and storage stability results. Whenever test data are used to demonstrate conformance to
specifications. it is important that the test methodology be qualified to assure that test results are objective and accurate
(Agalloco, 1983).
Appropriate personnel should evaluate data obtained, and a final validation report summarizing the
results and appropriate conclusion should be prepared. This report should be reviewed and approved by the
organizational units that approved the original protocol. The validation protocol should include the batch
selection criteria and analytical data that will be evaluated to determine consistency of the process.

Change Control Revalidation

Revalidation is the repetition of the validation process or a specific part of it. It is either performed periodically
to ascertain the process or to incorporate changes in the procedure.
1. Changes to validated system
A system once validated, continues to remain validated as long as all conditions and control
parameters are
not changed. Therefore, a change control quality assurance system must be established, which
revalidation whenever there are changes in product characteristics or requires
conditions, which can impact on
product characteristics. Conditions requiring revalidation study and documentation are:
specifications (including formulation), test procedures, raw materials including changes to
closures). facilities/plant location or site, support systems, packaging system (container
materials.
equipment, processing steps, batch size, packaging
2. Periodic revalidation

Some manufacturers revalidate certain

systems at pre-established periodic intervals, even when no
believed to occur. The need for
periodic revalidation of non-sterile processes is considered of change is
than for sterile processes. In the case of limited usefulness
standard processes on conventional
similar to as in retrospective validation
may provide adequate assurance that
equipment a review of data
control. process cantinues under
3. Change-control classification
The change-control program should provide a classification scheme to
materials. manufacturing site/location, batch size, evaluate changes in raw/packaging
attributes (changes in formulation, unit size and manufacturing equipment, and
strength). This classification production processes. pro0u
determining what level of testing, validation, and documentation is procedure should be used
process. Changes should be categorized as minor or needed to justify changes to a valiaa
changes, and the effects these changes could impart he major depending on the nature and extent of
on product attributes. In all cases,
determine what additional testing and validation studies scientific
to justify a change in a validated ijudgmentAsno nor
are needed

process.
hange stNNIid e defunds Oe that woilkt kely sagnitcantly attectthe cntical quality attnbutes ot the prouct. Sucn
shanges shuldbejustitiodby aititimal testing. and if appropriate. evalidation
FDA inits sale up and post approval changes (SUPAC) guidance classifies the various levels of changes and
mwmends varius naunufiarturing. chemistry and evnumol test and final proaduct perfomance test to evaluate the impact
wtese changes (FDA, 100s). sUPAC guidane defines three levels ofchange
depending upon the impact of change o
quality and perfmmannr of pnadurt (Mentnup. 1997).
Level 1-changes that are unlikely to have any detetable impact on formmulation quality and performance. e.g.
ieetion or partial deletion ofcolorants or flavours or change in binder level below0.5 in solid dosage forms, change
o altemative equipent of the same design and operating principles of the same or of a different capacity.
technical
Level 2<hanges thatould haveasignificant impact om formulation quality and perfomance eg. change
in

in binder level between 0.5-1.0 in

grade excipients eg. change of Avicel PH 102 vs. Avicel PH200 or change
of
slid dasage fom. Change in cquipment to a diferent design and different operating principles.
Level 3-Level 3 changes are those that are likely to have a signiticant impact on
formulaton and
quality perfomance
used in the manufactur
eg. change in binderlevel beyond 1.0in
solid dosage fom, change in the type of process
of the product. such as a change fnn wet granulation to direct compression of dry powder

PROCESS VALIDATION: ORDER OF PRIORITY

what are the expertations of FDA. It is no always
It isimportant to know, what to validate, how much. and limitations (Gold.
of a company. simply because of resourres
pOSsible to validate entire range of products a list of product categories that
1996. Kieffer. 1998). It is suggested to draw up on the basis of risk potential.
are to be validated (Table 16.3).
be useful in determining whether or noa a praces
The model, schematically represented in Fig.16.10, may
should be validated. The decision tree flows like
this:
both the process parameters and the ourpu
. Each process should have a specification describing
desired. The manufacturer should consider whether
the output could be fully verifiad by inspeion
and/or test.
venitication alone
consideration should be made as to hether or not
2Ifthe answer is positive, then the
a cost etfective solution.
is sufficient to eliminate unacceptable risk an: is
should be apprapriately oontrollai.
3. Ifyes., the output should be venified and the process
is not verifiable then the
manufacturer should consider the nsk tothe
I f the output of the process
patient of the process or the final product.
5. Ifthe risk is high then the decision should be to validate the proves
an
m a y become apparent that the product or process should be mdesigned to niur vanatim
improve the product or process.
 Pharmaceutical
Product Development
542

3.
1.
Yes Yes Verify and
ls a process verification control the
output fully sufficient
process
verifiable? and cost
effective?

No No
7.
Accept risk;
verify and
4. LoW control thhe
What is level process
of risk to
patient?
8.
Validate for
High business
reasons.

5. 6
Validate to Redesign
control the product and/
risk. or process.

Fig. 16.10. Validation decision tree

7. Ifthe risk is low, then the manufacturcr may consider justifying not validating the process and accept those nsks
8. Also, if the risk is low, management may decide to validate a process even though the output of the process Is
verifiable. This may be because the cost of ensuring compliance with output requirements of a non-validateu
process is too high, or because the manufacturer may not be prepared to accept the
rnsk-to-patient of acveptabie
only, or for other reasons. Redesigning the product or process to a point where simple verification is anventicaion
decision may also reduce the risk or cost.
The Table 16.4 is a list of examples of processes which normally: (1) should be validated. (2) may oc
satisfactorily covered by verificalion, and (3) processes for which the ubove model may be useful in determins
the need for validation.

PREREQUISTES FOR sUCCESSFUL VALIDATION

The tool or clements required for conducting effective validations are (Neal, 2003):
 Tabie 6 . eral critIcality of validation for vari0us
pharmaceutical processes
Processes which should
be validated
(1)
Sterilization
Clean room ambient conditions

Aseptic filling
Sterile packaging sealing
Lyophilization
Heat treating
Plating
Plastic injection molding
(2) Processes which may besatisfactorily covered by verification
Manual cutting
Testing for color, turbidity, total pH for solutions
(3) Processes for which the above model may be useful in determining the need for validation
Cleaning
Filling

Understanding and communication

Given the fact that regulated drug manufacturers must perform validations. it is very important that this
understanding be shared throughout the organization. Apart from validation department only. thorough
understanding of the need of validation should be understood by each department personnel (Powell-Evans.
1998). Starting from validation department, good understanding should be disseminated throughout the
entire organization. Why can't the laboratory use a piece of equipment undergoing validation? Why are
validations so expensive? If the entire company is fairly educated on what validation entails. less time will be
required defending validation actions. The best way to improve environmental understanding is effective
communication. When is the validation of unit ABC scheduled to begin? How many resources will be
required? When do the protocols have to be approved? At what sites will sampling occur? These are the
typical questions that can be answered through communications like conversations. memos. periodic meeings
and training sessions.

Experience
A firm's validation team must have solid validation experience in order for the validation program to be
SUCCessful. The average person cannot be expected to perform open-heart surgery. Seasoned validation
the midst of completing the validation, encounters a failure that will necessitate validation to be
stat1, in
epeated completely. However, with proper coaching and consultation, some success can be realizei. A solid
validation requires solid background.

Cooperation and plan

Xecuion of a validation program is multidepartment activity such as process enginering. quality assuranc*
uaty control, accounting. project management, or regulatory. Each department has its own set of
partmental priorities and typically they may put validation back prionty. Cooperatinas
cal to realize department's and validation objectives, both. In order to get a team synergy
is cssential and
all departments
shall plan to get best of inputs and output.
 Pharmaceutical Product Development
544

Resources
resources in terms of
validation perSonnel, materials to
validation it is essential to allocate the proper
For a successful
laboratories to perform necessary analysis,
money to pay, and time in
validation, equipment to be validated,
conduct
which to perform validation.

Training being studied should be

studies and those running the process
Both the personnel conducting the
and should be suitable and competent
to perform the task assigned to
appropriately trained and qualified
them bodies require the proper
beyond the act of mere teaching. The regulating
Requirement of training goes
Proper documentation
r e s o u r c e s have undergone required training.
documentation that proves that key
and the date on which
should minimally include employee
identification, a description of training course,
training occurred.

sOPs, instruments and methodologies

must be finalized, approved, trained
Before process validation starts the entire SOP related to equipment
calibrated and all validation
routine use. All analytical instruments must be
upon and implemented for
methodologies must be validated.
Realistic completion dates
for validation should be
Validation is expensive affair both in terms of money and time. The time required
will result when the
realistic in terms of completion of activity. If it is overly constrained, disappointment
based upon projected completion
completion date is not met. Oftentimes, commercial campaigns are planned,
date. These campaigns may involve contractual commitments. If the dates are not met, financial losses may

reputation. If the time is too pessimistic chances are, environment will not be
occur or company may loose its
ready to react when validation is completed well before the projected date. In this case, campaigns may not be
therefore
and opportunity will be lost. Either
to earn money of these one
persuaded in a timely manner,
extremes causes some degree of disarray.

VALIDATION MASTER PLAN

Validation, in general requires a meticulous preparation and careful planning of the various steps in the
process. Validation is a costly affair, which requires multidisciplinary team cooperation; therefore, all such
work should be carried out in a structured way. As a prerequisite, all studies should be conducted in accordance
with detailed pre-established protocol, which in turn are subject to a formal change control procedure.
Protocols in context of validation is a document that gives detail of the critical parts of the manufacturing
process, the parameters that should be measured, their allowable range of variability and the manner in which
the system will be tested.
For example, validation of solid dosage form product protocol should include items such as:
Acceptable limits for equipment operating parameters (e.g. feed rate in milling, blender shell and
intensifier bar rpm for blending)
Sampling procedure for granulations
Specification for testing the active ingredients, particle size and bulk density (if applicable)
The results of recorded parameters should be compared with the acceptance criteria set down in tne
testing protocol. If necessary, equipment, manutacturing procedure, and measurement methodologies may
be altered to suit the intended purpose, and the reasoning behind the
change must be documented.
A validation master plan is a document, which presents overview of the
entire validation operation.
Chapter 16
Pharmaceutical Validation 545
niyational structure. content and planning (Ramamurthy &
orga
should contain data on following chapters (Maynard, 1993) Saravanakumar, 1997). A validation master
plan (VMP)
.Validation policy of company, general description of the scope of those
location and schedule: operations covered by VMP,
Organization and structure of validation
activities. personnel responsibility for each
VMP itself, protocols of individual projects, validation activity such as
work, report and document
their control, approval of validation protocols and preparation and
reports in all stages of validation processes,
system for review, training needs in support of validation, tracking
.Rationale behind any challenge or 'worst case' situation,
Specific requirement of the plantprocesses etc. that need extra attention may be briefly outined,
List of products, processes and systems to be validated,
Installation and qualification requirement for new equipment,
Key acceptance criteria,
Documentation format to be used for
protocols and reports,
Planning andscheduling i.e. estimate of staffing (including training needs), equipment and specific
requirements complete the validation, time plan of project with detailed planning of subprojects.
to

Change control- a statement of company's commitment to controlling critical changes to materials,

facilities. equipment or processes, analytical methods.
The VMP should be a summary document and should therefore be brief, concise and clear. It should not
repeat infomation documented elsewhere. The core of VMP is the list/inventory of items to be validated and
the planning schedule (Auterhoff, 1996). A VMP helps:
Management- to know what validation programme involves with respect to time, people and money
and to understand the necessity for the programme.
Members of validation team- to know their tasks and responsibilities,
GMP inspectors- to understand company's approaches to validation and the setup an organization of
all validation activities.

Data Analysis
It is the evaluation of the entire study against the protocol requirements as outined above
It should be prepared and the conclusion drawn at each stage stated.
The final conclusions should reflect whether protocol irements wer met.

The evaluation should include an assessment of the planned calibration and maintenance programs
for the equipment and instrument to maintain the validated conditions.
All process monitoring and control procedures, required to routinely ensure the validated conditions
are maintained, should be reported.
The analysis should be signed by authorized officer of organization who were members of team establishing the
protocol and who have appropriate expertise in the area assigned to them
Overall approval of the study should be authorized by the head of quality control department and
head of validation team.

The Validation Report

A writen report should be available after completion of the validation. If found acceptable, it should be
approved and authorized (signed and dated). The report should include at least the following:
 546 Pharmaceutical Product Development

Title and objective of study.

References to protocols.
Details of materials.
Equipments.
Programme and cycles used.
Details of procedures and test methods.
Results (compared with acceptance criteria), and
Recommendation on the limit and criteria to be applied on future basis.

cONCLUSION
Phamaceutical validation which includes assay validation, cleaning validation, cquipment validation as well asoveral
process validation is crucial in stability analysis, animal studies and carly phasesof clinicaldevelopment such as bioavailability
and bioequivelence studies. After the drug is approved, phamaceutical validation and process controls are necessary to
ensure that the drug product will meet phamnaceutical standards for identity, strength. quality. purity, stability evaluation.
safety and efficacy.

Table 16.5 Internet links of regulatory agencies of various countries

Country and Regulatory Web Page Web page Validation/GMP
on
regulations/guidelines
Agency
Australia. Therapeutic http://www.tga.gov.au
Goods Administration
http://www.tga.gov.au/manuf/index.htm#gmp
(TGA)
Canada. Health Products
and Food Branch
http://www.hc-sc.gc.c hitp://www.hc-sc.gc.ca/hpfb
Inspectorate -dgpsa/inspectorate/gmp_guidelines 2002_tc_e.html
Europe, European http://www.emea.eu.int/
Medicines Agency (EMEA) http://www.emea.cu.int/Inspections/GMPhome.html
india. Ministry of Health
and Family Welfare
http://www.mohfw.nic.in Schedule 'M on Good Manufacturing Practices under
Drugs
and Cosmetics Rules. 1945.
Amendment notification (GSR 894(E) dated 11.12001)
pending for final implementation and publication in Gazett
of India is available
South Africa, Medicines
at
http://mohfw.nic.in/grS94e.hum
Control Council (MCC)
http://www.mccza.com/ htup://www.mccza.com/
showdocument.asp?Cat=21&Dese=GuidelinesT0
United Kingdom (UK).
%20Good%20Manufacturing%20Practices
Medicines and Healthcare
http://www.mca.gov.uk/ http://medicines.mhra.gov.uk/ourwork/ensurequalmed
http://www.mhra.gov.uk gmpandgdp.htm
products Regulatory
Agency (MHRA)
United State (US), Food
and Drug Administration
http://www.fdu.gov hup://www.fdu.gov/eder/guidaneel
(FDA).
World Health Organisation http://www, who.int
(WHO) hup://www.who.in/medicines/organization/qsnv/activities
qualityassurance/gmp/gnmpcover.htmlhtup://www.who.inu
nedicines/orgunization/qsm/aetivities/qualityassurance/gmp/
International Conference
gmp-sup/suptrainingmodulesgmp.hum
hltp://www.ich.org hup://www.ich.org/
on Harmonisation (1CH)
UrlGrpServer.jser?@_ID=2768&@ TEMPLATE=254
 VALIDATION MASTER PLAN
Validation Protocol
Purpose of study
Responsibility of personnel
Process-crtical steps-defined
Crtical paremeters specified
Sampling Plan
Testing Plan
Acceptence crteria

Sampling Plan- softgelatin

capsules
Semisolid deaeration-physical test only
Final Mix-content uniformity
Fill and shell weight-
monograph testing
Capsule nonograph testing
Testing Plan
In process inished Blend
Content uniformity and assay Hardness
(Final blend) Average weight
Average fill weight Assay (capsuie)
Disintegration Content Uniformty
Fill moisture Dissolution profie

Validation Report
Aim and purpose of study Acceptance criteria evaluation
List of ravw materials used Analysis of results
List of equipment used Validation statement of purpose
Critical Process steps studied Validation recommendations
Resuts of data collected Attachments (Batch records)

validation master plan.

Fig. 16.11. Pictorial representation of the various elements of

what and how some tha

validation is 'documented common sense' i.e. documenting
Conclusion, therefore. requres
done. Validation of a system.
would be done and documenting how the same thing was which is a written plan stating ho
including a validation protocol,
Set of documents, typically be included
that states what documents will
Validation will be conducted; a documentation plan
S
how tD e approved; functional requirements and specifications that cover the technical aspects ofthe systenm
executed installauon. oPEe
sIS, which considers inherent risks ofthe process and potential contingency plans;
validation summaryrepoto
to the functional requirements; signitying that
Omance qualification protocols, traceable results of validation testing and
whether the system is fit to manufacture the product by summarizing controis prds
Syslemi pharmaceutical validation and process
have been obtained. In general,
CertaiPPIOval signatures manuractured.
dassurance of batch uniformity and integrityofthe product it is a need of the nour

in an era of rapid change. Therefore

C pnanaceutical companies definitely live