Objectives
§Introduce current Good Manufacturing Practices
Definitions
• cGMP – current Good Manufacturing Practice
• GCLP - Good Control Laboratory Practice
• GAMP- Good Automated Manufacturing Practice
• GxP- Abstract term to cover good practices in general
within pharmaceutical environment
• GDSP- Good Distribution and Storage Practice
Risk Based approach
• The regulatory framework is based on a risk management
approach, designed to ensure public health and safety.
• At the same time the framework frees industr y from
unnecessary regulatory burden. However the framework
should not be seen as an alternative to compliance with
regulations.
Good Manufacturing Practice (GMP)
• The GMP rules have their origins in the US FDA laws that were passed in the USA in 1938.
These laws mandated that new drugs must be safe and that manufacturing methods,
facilities, and controls be “ adequate”
• The laws were introduced in response to the elixir sulfanilamide crisis that killed
107people, mostly children due to contamination of Glycerine with Di ethylene glycol
• The GMP rules were further strengthened after the Winthrop Chemical Company
produced sulfathiazole tablets contaminated with phenobarbital in 1940, which killed or
injured over 300 people
• The Clothier report in the UK in 1972, based upon the Evans medical due to sterilization
issues of a dextrose infusion that caused 5 deaths of children prompted the first UK
orange guide, which formed the basis of the current EU GMP (and PIC/s) regulations
The GMP rules are there to ensure that drugs and
medical devices are safe and effective.
(cGMP)
§Understand the Major Aspects of GMP
§Learn the 10 Golden Rules of GMP
Who Regulates the GMP Rules?
• The governments of different countries have formed regulatory authorities to
make GMP regulations about how pharmaceutical and life science products are
made. The International Council for Harmonization of Technical
Requirements for Pharmaceuticals for Human Use (ICH) brings together these
regulatory authorities and pharmaceutical industry to harmonize regulations
and enforcement. The Pharmaceutical Inspection Cooperation/Scheme (PIC/s)
organization leads the international development, implementation and
maintenance of harmonized GMP standards.
• The health regulatory authorities, like the FDA Philippines, performs audits of
manufacturing sites to check that GMP regulations are followed, i.e. PIC/S GMP
Guidelines for Medicinal Products.
• The regulatory authorities also provide a framework for the regulation of
medical goods to ensure the quality, safety and efficacy of medicines and
ensure the quality, safety and performance of medical devices.
What is GMP?
• The acronym GMP is used internationally to describe a set of principles
and procedures which, when followed by manufacturers of medical
goods, help ensure that the products manufactured will have the
required quality.
• GMP is the part of the quality management which ensures that
products are consistently produced and controlled to the quality
standards appropriate to their intended use and as required by the
marketing authorization clinical trial authorization or product
specification. GMP is concerned with both production and quality
control , plus product and process design.
• A basic tenet of GMP is that quality cannot be tested into a batch of
product but must be built into each batch of product during all stages of
the manufacturing process.
Overview of Quality Assurance
Quality by Design
• A system approach to development that begins with predefined
objectives and emphasizes product and process understanding and
and process control, based on sound science and quality risk
management.
• Products must be designed and developed with GMP and GCLP in
mind.
 Overview of Quality Assurance
Manufacturing
• Production and control operations should be clearly specified
• cGMP compliant procedures should be made for the manufacture,
supply, and use of the correct starting and packaging materials.
• All necessary controls on intermediate products, and any other in-
process controls and validations must be carried out.
Overview of Quality Assurance
Finished product
• The finished product should be correctly processed and checked,
according to the defined procedures.
• Products should not be sold or supplied before an authorized person
has certified that each production batch has appropriate quality
• Products should be stored, distributed and subsequently handled so
that quality is maintained throughout their shelf life.

Overview of Quality assurance Overview of Quality Assurance

Self-inspection Responsibilities

• There should be a procedure for self-inspection which • Managerial responsibilities should be clearly specified
regularly appraises the effectiveness and applicability and documented
of the quality assurance system.

What does Quality Control department do? Foundations of Quality Control

• Quality Control (QC) shall ensure that raw materials and manufactured
products are released after verification of documents as per internal • The foundations of QC is having :
release procedures and under proper authorization
• Adequate Facilities
• QC is responsible for sampling, specifications, testing, data reporting
and data integrity • Trained Personnel
• As well as the organization, documentation and release procedures
which ensure that the necessary and relevant tests are carried out
before product release.

Foundations of Quality Control Foundations of Quality Control

Procedures Testing
Ensure approved procedures are available for:
• Sampling of raw materials Test methods must be available and validated.
• Self-inspection of at least personnel premises including:
1) personnel, 2) facilities and maintenance of buildings and
equipment, 3) storage of stating materials, and finished products,
4) equipment, 5) production and in-process controls,6) QC,
7) documentation, 8) sanitation and hygiene, 9) validation and
revalidation programs, 10) calibration of instruments or
measurement systems, 11) recall procedures and complaints
management,12) labels control, results of previous self-
inspections and any corrective steps taken
• Testing starting materials
• Testing of packaging materials
• Testing intermediate, bulk and finished products and,
where appropriate
• Monitoring environmental conditions
 Foundations of Quality Control Foundations of Quality Control
Starting materials Records

Samples of starting materials, packaging materials, intermediate • Records should be maintained which demonstrate that all
products, bulk and finished products should be drawn and tested by required sampling, inspections and testing procedures have
quality control. been performed.
• Ensure you record and investigate any deviations.

Foundations of Quality Control Foundations of Quality Control

Finished Product Release
• The finished product should contain active ingredients complying No batch of product can be released for sale or supply prior to
with the qualitative composition of the marketing authorization
certification by an authorized person that it is in accordance
• Finished product should be of the purity required and enclosed within with the requirements of the license.
their proper container and correctly labeled
• Records should be made of the results of inspection and that testing
of materials, intermediate, bulk, and finished products was formally
assessed against specifications
• Product assessment should include a review and evaluation of
relevant production documentation and assessment of any deviations
from specified procedures.

Foundations of Quality Control

Sampling GMP and the law
• Regulatory authorities have the power to :
• Sufficient samples of starting materials and products should • Stop manufacturers from producing
be retained to permit full release testing twice, with the
exception of sterility testing. • Stop the sale of products
• Close down the plant and facilities
• Suspend or revoke manufacturing licenses
• Prevent products from entering a country
• Bring charges which could result in fines and/or jail
sentences

The nine sections of the GMP guidelines Quality Management System (QMS)
• Experience has taught regulators that it is not just the steps involved in • QMS is the responsibility of senior management, but it requires the
product manufacture that are important. GMP must be a holistic process
that controls everything that can impact product quality. participation and commitment of all staff
• There are 9 key aspects that need to be controlled in order for GMP to be • International standards:
in place: • Regulatory guidance on quality management comes from ICH Q10
1. Quality management system Pharmaceutical Quality System that has been harmonized and accepted by all
2. Personnel the major authorities worldwide
3. Premises and equipment
4. Documentation • Governance
5. Production • QMS is the high level governance of quality by a company. It envelopes GMP,
6. Quality control quality assurance , quality control, produce quality review and quality risk
7. Contract manufacturing and analysis management (QRM)
8. Complaints, returns and product recalls
9. Self-inspection
 Product Quality Review
• Product quality reviews are regular periodic or rolling review of all
licensed medicinal products, including export only products.
Regulatory authorities require annual product reviews (APRs) as
formal reports for each licensed product, each year.
• They are conducted with the objective of:
• Verifying the consistency of the existing process
• The appropriateness of current specifications for both starting materials and
finished product
• Highlight any trends; and
• Identify product and process improvements
Personnel
• A systems and adherence to GMP guidelines relies
exclusively on people.
• Having the right number of personnel:
• The GMP guidelines recognize how critical people are
ensuring product quality.
• To meet the GMP requirements, it’s essential to have :
• The right number if people, and
• That they have the right qualifications and experience to do
the job
To meet these requirements it is essential that what “ right”
means has been identified for every functions and process.
Personnel
GMP essentials
Because personnel are such a critical part of GMP, the GMP guideline specify
that :
• All staff must have the education, experience and training to perform their
duties
• Documentary evidence of this must be maintained, including resumes,
professional qualifications, and training records
• An organizational chart is mandatory (and can be subject to auditing)
• The responsibilities of each position must be defined and documented
• The head of production and quality control must be independent from
each other
• Good personal hygiene is critical- staff must be trained and equipped to
ensure good personal hygiene
Premises and Equipment
§ Ensure manufacturing equipment :
§ Is designed, located, and maintained to suit its intended use
§ Is designed so that it can be easily and thoroughly cleaned
§ Has procedures for how and when to clean each place of
equipment that can impact product quality
§ Has procedures that clearly state who is responsible for the
cleaning and have cleaning records
Quality Risk Management
• Quality risk management is a systematic process for the assessment,
control, communication and review of risks to the quality of the
product.
• Risk must be assessed based on scientific knowledge and impact on
patient safety.
• Level of effort of risk management needs to be commensurate with
the level of risk.
Personnel (continue)
Personnel Training in GMP guidelines is recognized verify important. During an audit, an
auditor might ask to see:
• Competency matrices – identifying the skills and training required for each role in the
organizations
• Training records to show when someone was trained and what they were trained on
These records must be kept for everyone who works in a GMP area, including :
qContractors – such as sales people and cleaners, are a common source of non-
compliance. It is critical that contracting companies supply only GMP trained personnel
to work in production areas. Untrained staff, filling in for someone who is away, will not
understand how much they can impact product quality.
EX: a piping contractor, installing a filler housing unknowingly left the waste materials in
the water systems. The system supplied sterile water for the manufacture of injectable
drugs. However, the water system would contain an on-line Total Organic Carbon (TOC) or a
conductivity meter to detect and dump un-sterile water before it gets into the distribution
loop. Also, QC tests on the water would detect such a problem before any drugs were
released.
qCleaners
qSupplier’s representatives who visit frequently such as equipment service engineers
Personnel
Good Hygiene
• It is critical that staff reduce the risk of introducing infections and bacteria
into the area where products are being made. This includes:
• Reporting open sores of any illness to their supervisor
• Appropriate washing of their hands
• No eating drinking, chewing or smoking and no storage of food, drink,
smoking materials or personal medication in production and storage areas
• All personnel entering the manufacturing areas should wear clothing
appropriate for the area and the operations to eb carried out
• Unhygienic practices with the manufacturing areas or other areas where
product may be adversely affected should be forbidden
Premises and Equipment
Design
The GMP guidelines that manufacturing facilities are designed to
minimize product contamination and mix-ups.
qUsing covered ceilings, floor and corners within manufacturing areas
minimizes debris and thus bacterial accumulation
qMachines should be located to allow easy access for regular
maintenance
qDedicated lines and facilities i.e. physical separation, should be used
when manufacturing products that have high cross-contamination
potential
Premises and equipment
Equipment placement
Example
• In one company, the maintenance schedule for a piece of production
equipment required the oil to be changed and 55 sensor points to be
checked every three months.
• During an audit, the auditor discovered that this was only being done
during the annual shutdown period. Why?
• The machine has been installed very close to the wall. The
maintenance could not access the back of the machine when it was
moved away from the wall, This could only be done during annual
shutdown, when a mobile crane was available to lift the machine.
Premises and Equipment
Facilities
• The facilities should be designed and equipped to prevent entry of
pests or animals.
• Steps should be taken to prevent entry of unauthorized personnel
• Where special storage conditions are required (e.g. temperature,
humidity) these conditions should be provided , checked and
monitored and also validated (e.g. temperature mapping) on a
periodic basis.
Premises and Equipment
Data Collecting equipment
• The GMP guidelines require equipment to be fit for purpose. If the
weighing step is critical to product quality, then equipment should be used
that will ensure an appropriate level of accuracy.
• A good practice is to display the usable range on all scales. A s a rule of
thumb, the minimum weight that the scale can introduce should be less
than 0.5% error.
• This means if a scale can weigh up to 1000g and the scale interval is to 0.1g,
then the minimum 20g may be weighed on that scale.
• If the scale rounded to say 0.5g intervals then the minimum permissible
weight should be 100g
• The above is only a rule of thumb – all scales should be validated for
their intended purpose.
Solution
• She should have requested a scale that had a
range from 0-1kg and displayed x.xg
Premises and Equipment
Premises Design
• Modern warehouses at commercial manufacturing sites are today
automated and their status and location are controlled by an
enterprise management system. A modern warehouse is divided into
a receiving area and a storage area in which there are specific areas to
store rejected recalled or returned materials or products. Optimally,
rejected product would be kept in a caged area.
• Again the aim is to prevent contamination and mix-ups. It would ne
very easy for a batch of recalled products to be accidentally shipped
out to customers if the recalled products were not kept physically
separate from the final products in the warehouse,
• QC labs are separate from production areas.
Premises and Equipment
• Qualification and validation should establish and provide documentary
evidence that:
• The premises, supporting utilities, equipment and processes have been designed in
accordance with the requirements for GMP (design qualification or DQ)
• The premises supporting utilities and equipment have been built and installed in
compliance with their design specifications (operational qualification or OQ)
• A specific process will consistently produce a product that meets its predetermined
specifications and quality attributes (process validation or PV, also called performance
qualifications or PQ)
Any aspect of operation including significant changes to the premises, facilities,
equipment or processes which may affect the quality of the product , directly or
indirectly should be qualified and validated.
Particular attention should be paid to the validation of analytical test methods,
automated systems and cleaning procedures.
The responsibility for performing validation should be defined.
Scenario
• Dana was required to weigh completed products to ensure
that they met specifications. They were supposed to weigh
500g +/-2g
• She first weighed herself on the large scales in the
warehouse. These scales were used to weigh packaged goods
to determine shipping costs.
• Dana then held a product and weighed herself again.
• She calculated the weight of the product by subtracting the
second from the first.
Documentation
Documentation is an essential part of manufacturing a product. It performs
several functions:
• It held the people who make the product by providing them with
instructions on the steps to follow so that nothing is left to memory
• It shows auditors what the proven process for manufacturing a particular
product is and that the recess was followed.
• It provides data for any investigation if there is a problem with a batch of
product
• It makes sure that everyone, internal and external to the company, knows
how a particular product is made and the quality checks that must be
performed during ,manufacture to ensure everything is working as it
should
• It is used to assess the quality of the product manufactured for release
Documentation
• Documents can be hard copy, electronic or a hybrid of the two forms. In a
manufacturing environment you will typically need the following types of
documents.
• This may vary according to the type of products manufactured:
• Specifications, both for raw materials and for the finished product
• Manufacturing formulae and instructions
• Processing and packaging instructions
• Procedures an work instructions
• Records
• Site Master file
Any of these documents maybe reviewed during an audit.
Document Control
• It is a GMP requirement that the document that
controls the manufacture of products must be
controlled themselves. This prevent mistakes in
documents that could impact product quality.
• Controlled documents must be prepared ,
reviewed, distributed and changed using a
documented process.
Documentation essentials
• The GMP guidelines for documentation state that documents must
• Be approved, dated, and signed by authorized staff
• Be designed, prepared, reviewed, approved, and distributed using
controlled processes
• Be unambiguous
• Be regularly reviewed and kept up to date (typically every 2-3 years)
• Not have hand-written notes attached
• Be retained for a predetermined period
• Have an inventory of current documents in use
Production
•GMP is that part of quality assurance which
ensures that products are consistently produced
and controlled t the quality standards
appropriate to their intended use as required by
the license or marketing authorization.
Documentation
• The GMP guidance requires log books to be kept for major or critical
equipment.
• The following must be recorded in the log books:
• Equipment usage
• Validation activities
• Calibrations
• Planned and unplanned maintenance
• Cleaning
Each entry must be dated and signed by the person who performed the task.
Documentation
Things that go wrong with documents
• Here are some examples of things that can go wrong if documents are
not controlled-you have probably experienced some of them.
• If different versions of a document are not identified using a common
process then several different versions of the same document may be
in circulation. No one knows which is the “right” one.
• If the review process is not formalized then simple mistakes such as
the required temperature for a process may b e listed as different
values in different documents e.g. 44 °C in a procedure and 44 °C on a
for the process. Or the temperature is stated as °C but the
temperature measurement is °F. In pharmaceutical manufacturing
temperatures should always be stated and recorded in °C.
Production
The critical aspects of production in GMP environment are:
• The prevention of cross-contamination in production areas
• Validation-so processes are understood and controlled
• Starting materials
• Processing operations, both intermediate and bulk products
• Packaging materials and operations
• Finished products
• Rejected, recovered, and returned materials
Production
Containment and Cross-contamination
• Within the production areas of a company, the GMP
guidelines focus on preventing contamination, cross
contamination and mix-ups.
• GMP guidelines require that you should understand
and control all production processes so that you can
be sure of the outcomes of those processes.
Production Production
• People are a major source of a product contamination
• Process operations follow clearly defined and • Access to production areas must be restricted to authorized
proven procedures. personnel.
• Production personnel must be trained in appropriate personnel
• Procedures must comply with GMP principles in hygiene and clothing procedures e.g. wearing hair nets and shoe
order to manufacture products of the required covers
quality. • Technical systems such as swipe card access to areas, air locks and
pressure differentials should also be used to prevent cross
contamination

Production Production
Labeling Process
The process should :
All materials , bulk containers, supplies and major items
of equipment used should be labeled with: • Be clearly defined;
• Clearly defined materials, equipment use and
• The product or material name personnel involved and timing of activities must be
• Its strength fully traceable;
• The batch number • Have the activities documented in real time by the
person performing the tasks;
• The stage production
• Have secondary verification of critical steps in the
process.

Quality Control QC is not confined to a lab

The quality control (QC) aspect of a quality management system is • Quality control should be involved in all decisions which may impact
concerned with: product quality.
• Protocol sampling • The independence of a quality control from production is considered
• Testing raw materials and final produces against specification a fundamental GMP requirement.
• Organization • During the investigation of the Pan Pharmaceuticals case, auditors
• Documentation found that the managing director was signing off QC tests and
• Product release procedures releasing product from production. The concentration of the active
pharmaceutical ingredients in the products varied from 0.1% to 70.0%
• On-going stability program
of the required concentration. The company was closed down by the
QC ensures that the necessary and relevant tests are carried out, and test TGA.
materials and products are not released for use, sale or supply, until their
quality has been judged satisfactory.

QC is at the core of every process QC from start to finish

• All quality control procedures should be established
validated and implemented.
• Reference samples of materials and products must be kept.
• Monitoring product stability is a fundamental responsibility
of QC,
• QC must participate in the investigation of complaints related
to the quality of the product.
• Quality control runs through manufacturing from start to finish (S2F),
it continues after the product has been manufactured.
• Reference samples of materials and products must be of a size
sufficient to permit full release testing to be performed twice with the
exception of sterility testing.
Note:
The EU also requires that the analytical materials and equipment be available to
carry our full testing one year past expiry.

• Testing methods should be validated.


Contract Manufacture
• Contract manufacture and analysis must be correctly and
completely defined, agreed and controlled to a void
misunderstandings that could result in a product or work of
unsatisfactory quality.
• A written contract must exist that establishes the duties of
each party.
• Specific responsibilities for product personnel must be
considered and documented.
Responsibilities –Contract Acceptor
• The contract acceptor must have adequate premises and equipment,
knowledge and experience, and competent personnel to carry out
satisfactory the work ordered by the contract giver.
• The contract acceptor must ensure that all products or materials
delivered are suitable for their intended purpose.
• The contract acceptor must not pass to a third party any of the work
entrusted under the contract without the contract giver’s prior
evaluation and approval of the arrangements.
Investigation
• If a product defect is discovered or suspected in batch, other batches
must be checked in order to determine whether they were also
affected.
• In particular, other batches which may contain reworks of a defective
batch must be investigated.
• RECORD KEEPING
• You must record all the decision and measures taken as a result of a
complaint and reference the corresponding batch records.
• You must review complaint records regularly for any indication of
specific or recurring problems requiring attention and possible recall.
Self-inspection
• The following should be evaluated for conformity to QA and GMP principles:
• Personnel matters, for example the training system
• Premises
• Equipment , calibration records and procedures
• Documentation
• Production
• Quality control
• Distribution
• Complaints and recalls-is the distribution list current
• And even the self-inspection process!
All self inspections must be records. The quality system itself should also be part of the self-
inspection program, including deviation investigations, the CAPA system, training document
control and archives, quality metric, etc. Reports must contain all the observations made
during the inspections and, where applicable, proposals for corrective measures
A complete follow-up action plan must be adhered to. Progress of the action plan should be
regularly monitored to ensure agreed actions are completed.
Responsibilities – Contract Giver
• The GMP guidelines apply the following responsibilities to the
contract giver:
• The contract giver is responsible for assessing the competence of
the contract acceptor to successfully carry out work required and
ensuring that GMP is followed.
• The contract giver must ensure that all products and materials
delivered to them by the contract acceptor comply with their
specifications and that the products have been released by an
authorized person.
The key point is that it’s the contract giver (i.e. the customer) who has
the responsibility to ensure that products are manufactured and
released according to GMP guidelines. The responsibility cannot be
delegated to the contract manufacturer.
Complaints and Product recall
• Responsibilities
• There must be a designed person responsible for handling the
complaints and deciding the measures to be taken.
• What must happen?
• Ensure written procedures are available describing the action to be
taken including the need to consider a recall in the case of a
complaints concerning a possible product defect.
• Record all complaints and investigate thoroughly. The investigation
details and results, including risk assessment, root cause analysis
and remedial, corrective and preventive actions(s), must be
recorded, reviewed and approved by the responsible designated
quality staff.
Complaints and Product Recalls
Traceability
• Distribution records must:
• Be readily available
• Contain sufficient information on wholesalers and directly
supplied customers, including those for exported products and
medical samples
• Product reconciliation after a recall
• A reconsolidation of affected products must be performed to ensure
all recalled products have actually been received
• Regular audits of the recall process must also occur to evaluate the
effectiveness of the process.
The 10 Golden Rules of GMP
• Golden Rule 1: Facility Design
• Ensure that productivity considerations, product quality, and the
safety of products and employees are incorporated in the design and
construction of all processes, facilities and equipment
• Layout of design need to minimize the risk of error, permit
effective cleaning and maintenance such that there is no adverse
effect on product quality. Facilities should also be designed to
prevent mix-ups and cross contamination
• The key point is that is s essential to get the design of the plant
right from the start.
Golden Rule 2- Validation
• Ensure that systems achieve what they are designed
to do by validating processes and testing
methods and qualifying facilities and
equipment
Golden Rule 4 – Training and Development
• A common problem is that the procedures are
written but no one follows them.
• Ensure people are appropriately trained in the task
they are to perform.
Golden Rule 6 - Responsibilities
• Create clearly defined responsibilities and ensure the
development and demonstration of job competence.
• The Key point here is that everyone must know
who is responsible for what.
Golden Rule 8:Maintenance
• Ensure that all facilities and equipment are
properly maintained and recorded.
Golden Rule 3 - Procedures
• Prepare detailed procedures that provide a
step-by-step road map to controlling and
maintain consistent performance.
Golden Rule 5 – Good Record Keeping
• Accurately record process events in real time for
compliance and traceabilty.
• From an auditor’s perspective, if it isn’t written
down then it did not happen.
Golden Rule 7: Hygiene
Golden Rule 9: Quality
• Build quality into products by controlling product
components and product-related processes, such as
marketing, manufacturing , testing, packing, labeling
and product distribution.
• Also build quality into the design of the product and
of the processes
Golden Rule 10: AUDITS
• Plan regular self-inspection audits to ensure
compliance and performance.
Things go wrong! Case 2
• Fire alarm in factory!
• Clean room operators evaluate and assemble in parking lot
• Return to clean room but do not change gowns!
• Procedures requires daily change of gowns
• Does not cover fire evacuation
• High levels of microbial contamination in clean room
• Lack of awareness!
Lesson learned:
Awareness of concepts is as important as “how to” training
How was this resolved?
• Automated system should prevent this error
• BUT-automated process overridden by operator
• Root cause-operator error-operator counseled and re-trained
• Problem occurred again – different operator but the same root cause!
• Automation fix sufficient? What if both operators make the same
mistake?
Case Study-Hygiene and Cleaning
• Contamination in a clean room by an organism normally found in
water and soil (dirt):
• Operators walking out of clean room wearing dedicated shoes!
• Failure to clean frequent spillages
• Condensate from heat exchanger dripping on to a clean room floor
Lessons learned:
Dedicated shoes are dedicated to a specific clean room suite and to a
specific operator
Spillage and leakage must be dealt with immediately!
Case Example 3
• Semi-automated process for protein capture
• Cell culture –harvest (centrifuge, cell lysis and capture
chromatography column) – protein eluted to eluate tank – clean
column with NaOH solution
• NaOH accidentally run into eluate tank
• Batch was lost
• Problem occurred twice with a different operator each time
Lessons learned
• Operators may try to take short cuts to save time, but may lack an
understanding of why they shouldn’t!
• The automation is used to minimize the impact of operator error, but
the if the software can be overridden by the operators
• Operators should not be allowed to override the automated process
• Override should be done by supervisor or system administrator as
approved change or planned deviation