The document discusses validation of critical utility systems used in pharmaceutical manufacturing facilities. It focuses on validation of HVAC, water, and steam systems. For HVAC validation, it provides details on DQ, IQ, OQ, and PQ protocols including objectives, responsibilities, tests performed. It discusses user requirements, specifications for HVAC control and monitoring. For water system validation, it discusses purification methods, grade of water, and protocols for IQ, OQ and PQ. It also discusses two types of steam systems - house steam and clean steam - and validation considerations for each.
It is process of “Establishing documentary evidence that provide a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”.
In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.
Validation is action of proving in accordance with the principles of good manufacturing practices, that any procedure, process, equipment, material, activity or system actually leads to expected results.
Cleaning validation is documented evidence with a high degree assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable limits.
The primary regulatory concern driving the need for cleaning validation is cross contamination of the desired drug substance either by other API from previous batch runs or by residues from the cleaning agents used.
The prime purpose of validating a cleaning process is to ensure compliance with federal and other standard regulations
1. Cross contamination with active ingredients
Contamination of one batch of product with significant levels of residual active ingredients from previous batch cannot be tolerated.
In addition to the obvious problems posed by subjecting consumers or patients to unintended contaminants, potential clinically significant synergistic interactions between pharmacologically active chemicals are a real concern.
2. Contamination with unintended materials or compounds
While inert ingredients used in drug products are generally recognized as safe for human consumption, the routine use, maintenance and cleaning of equipment's provide the potential contamination with such items as equipment parts, lubricants and chemical cleaning agents3. Microbiological contamination
Maintenance , cleaning and storage conditions may provide adventitious microorganisms with the opportunity to proliferate within the processing equipment.
In this slide contains introduction, qualification, preventive maintenance, requalification method.
Presented by: Malarvannan M (Department of pharmaceutical analysis).RIPER, anantapur
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with qualifications of HPLC which is the " High Performance Liquid Chromatography".
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
It is process of “Establishing documentary evidence that provide a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”.
In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.
Validation is action of proving in accordance with the principles of good manufacturing practices, that any procedure, process, equipment, material, activity or system actually leads to expected results.
Cleaning validation is documented evidence with a high degree assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable limits.
The primary regulatory concern driving the need for cleaning validation is cross contamination of the desired drug substance either by other API from previous batch runs or by residues from the cleaning agents used.
The prime purpose of validating a cleaning process is to ensure compliance with federal and other standard regulations
1. Cross contamination with active ingredients
Contamination of one batch of product with significant levels of residual active ingredients from previous batch cannot be tolerated.
In addition to the obvious problems posed by subjecting consumers or patients to unintended contaminants, potential clinically significant synergistic interactions between pharmacologically active chemicals are a real concern.
2. Contamination with unintended materials or compounds
While inert ingredients used in drug products are generally recognized as safe for human consumption, the routine use, maintenance and cleaning of equipment's provide the potential contamination with such items as equipment parts, lubricants and chemical cleaning agents3. Microbiological contamination
Maintenance , cleaning and storage conditions may provide adventitious microorganisms with the opportunity to proliferate within the processing equipment.
In this slide contains introduction, qualification, preventive maintenance, requalification method.
Presented by: Malarvannan M (Department of pharmaceutical analysis).RIPER, anantapur
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with qualifications of HPLC which is the " High Performance Liquid Chromatography".
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
In this slide contains details about Pharmaceutical validation of water system
Presented by: K VENKATSAI PRASAD (Department of pharmaceutical analysis and quality assurance).RIPER, anantapur
QUALIFICATION OF MANUFACTURING EQUIPMENTSANKUSH JADHAV
it gives the information about qualification of various manufacturing equipment which is used into the pharmaceutical labs. (only for information purpose)
Manufacturing Control Systems. J R Controls provides control systems for the manufacturing industry. A typical control system will monitor the progress of parts through the manufacturing and finishing process.
This presentation explains about qualifications of HPTLC, types of qualifications, design qualification , installation qualification ,operational qualification, performance qualification ,documentation of qualification .
Validation of utility system (water system)ShameerAbid
these slides talked about the validation of utility systems in pharmaceutical industries
with special emphasis on the water system
helpful for pharmaceutical student
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
In this slide contains details about Pharmaceutical validation of water system
Presented by: K VENKATSAI PRASAD (Department of pharmaceutical analysis and quality assurance).RIPER, anantapur
QUALIFICATION OF MANUFACTURING EQUIPMENTSANKUSH JADHAV
it gives the information about qualification of various manufacturing equipment which is used into the pharmaceutical labs. (only for information purpose)
Manufacturing Control Systems. J R Controls provides control systems for the manufacturing industry. A typical control system will monitor the progress of parts through the manufacturing and finishing process.
This presentation explains about qualifications of HPTLC, types of qualifications, design qualification , installation qualification ,operational qualification, performance qualification ,documentation of qualification .
Validation of utility system (water system)ShameerAbid
these slides talked about the validation of utility systems in pharmaceutical industries
with special emphasis on the water system
helpful for pharmaceutical student
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
Validation of HVAC pharma geeta TUBE (Utility Systems)Saikat Bagchi
Validation Of HVAC, Heating, Ventilation, Air Conditioning; Utility Systems, Validation Parameters, Air Handling Unit, Work Flow Animation Diagram, Validation Process Tests & Parameters.
Validation is a documented program that provides high degree of assurance that a specific process, method or system consistently produces a result meeting pre-determined acceptance criteria.
Qualification of Dissolution Test Apparatus and Validation of Utility System this presentation will help to enhance your knowledge in validation and qualification area.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
2. Validation Of Utility System
• The use of critical utility systems in the pharmaceutical
industry is very important to final product quality.
• Critical utilities found in pharmaceutical, medical device,
and biotechnology production facilities usually support
various equipment and processes.
• These utilities must meet both quantitative and qualitative
specifications.
• These utilities must meet both quantitative and qualitative
specifications.
• The critical utilities that been used:
1. Water systems
2. Clean steam system
3. Heating Ventilation and Air Conditioning (HVAC) systems
4. Process gases
3. Why is Utility System Quality
Important in Pharmaceuticals?
• All pharmaceutical manufacturing facilities
need to adhere strictly to FDA-approved
regulations
• CGMP requirements can be useful in ensuring
the efficacy, quality and safety of product,
.
4. VALIDATION OF HVAC SYSTEM
• Heating, ventilation and air conditioning system are used
in the pharmaceutical plant to prevent contamination and
to provide comfortable working conditioning.
• Environmental parameter like conc. of airborne nonviable
and viable particulate matter, chemical and gaseous
material can affect the quality of finished product.
• The product quality can also be affected although to a
lesser extent by vibration, lighting and other radiation.
• Ambient air may have different contaminant the most
common being the dust. Dust can be roughly classify by
size:
• a) Coarse dust(particle size 50-500µ)
• b) Fine dust(particle size 1-50µ)
• c) Ultra fine dust (particle size 0.5-1.0µ)
5. HVAC Control and monitoring system
The validation team should prepare a validation
protocol first. The protocol should include DQ, IQ, OQ, &
PQ.
User required specification
1. Room name.
2. Pressure gradient.
3. Temperature, Relative humidity.
4. Filter to be used.
5. Machine horse power.
6. Minimum air changes per hour.
7. Class of air to be maintained.
8. Room dimension in meters
6. DQ protocol
• Scope: to demonstrate that functional requirement have been
incorporate into the HVAC design specification and equipement
selection.
• Objective: the element will provide for the verification of the
conformance of the selected components design specification with
their intended operational and performance specification.
• Responsibility: the element define the responsibility.
• System Description: this element give description of the system
specify:
1) Class of cleanliness
2) Category of product to be manufactured
3) Room design criteria
4) Design and guideline for equipement and material selection
5) Reference to regulatory requirement
6) Testing and qualification requirement
7. IQ protocol:
Scope: to verify that all component of HVAC system have
been installed in accordance with their approved
design and engineering specification.
Responsibility: name and designation of person
responsible for approving and executive of the protocol
Manufacturing equipment and workmanship
verification:
this element should provide an inventory of
the equipment installed vis-a-vis approved
specification. It should also provide the means to verify
the proper installation of system.
8. • Calibration verification:
under this element a list of instrument which require
calibration should be prepared and calibration should be carried out
calibration certificate should form a part of the documentation.
• SOP verification:
under this element a list of SOP and manual should be
prepared.
• Utilities connection verification:
under this element utilities connection supporting
HVAC system should be verified to ensure that the same have been
installed properly and are in accordance with specification and
drawing.
• Change parts and replacement parts verification:
under this element a list of replacement and change
part should be prepared.
9. • Maintenance procedure verification:
under this element it should be ensure
that a maintenance program exist as
recommended by the manufacturer.
• Lubricant verification:
under this element it should be ensure
that only approved lubricant have been used and
these do not come in contact with supply air.
• As built drawing listing & verification:
many time there are difference
between original drawing and as built drawing .
As built drawing is the drawing which has been
physically verified through inspection, signed and
dated by the person performing inspection
10. OQ protocol
• Objective: to verify that given component of
HVAC system operate as specified and are in
agreement with acceptance criteria fixed for the
system parameter.
• Responsibility: names and designation of person
who are responsible for approval and execution
of protocol.
• System description: under this element a brief
description of how the system operates and
sequence of control should be given.
11. • Instrumental calibration: under this element it should
be verified that all the instrumentation specified have
been installed and are in calibrated system.
• equipment calibration verification: certain instrument
might be required to verify operation of the system.
• SOP verification: under this element verification of all
SOP required operation system should be verified. If
SOP is under draft stage, it should be finalized.
• OQ test: these include a series of tests designed to
prove proper operation of HVAC system;
1) Air system balancing
2) HEPA filter integrity system
3) Pressure differential stress test.
4) Airflow velocity and uniformity system
12. PQ protocol
• The PQ protocol is similar to OQ protocol. In the PQ the
HVAC system is assessed for its performance with in
the area it serving.
• Data is collecting under static conditions as well as
under dynamic condition by stimulating the process or
actually carrying the process.
• The test that may be carried out during the PQ include;
1. Temperature-humidity control test.
2. Air cleanliness test.
3. Airborne bio-burden test.
4. Surface bio-burden test.
13. • PQ include various test:
1. Air system balancing and pressure differential test:
2. Air volume for non-unidirectional airflow terminal airflow
filter test:
3. HEPA filter integrity system(DOP test):
4. Pressure differential stress test:
5. Start up and shut down test:
6. Control and monitoring device test
7. Power fail and recovery test:
8. Airflow velocity:
9. Airflow parallelism test:
10. Temperature-humidity test:
11. Air cleanliness test:
12. Air borne bio-burden test:
13. Surface bio-burden test:
14. Validation of water system
The Indian GMP text state that:
There shall be validated system for treatment for
water drawn from own or any other source to render it
potable in accordance with standard specified by the
Bureau of Indian standard or local municipality.
Grade of water:
1. Drinking water
2. Purified water
3. water for injection.
water purification method:
1) Reverse osmosis
2) Chlorination
3) Distillation
15. User required specification
The first step in designing a water system is to
define the system’s intended use.
Type of water
Temperature
Purification method.
Conductivity.
Flow of water
Grade of water
Source of water
16. IQ PROTOCOL
• A careful check is made to ensure piece of the
equipment ordered has been received and is according
to the system design.
• It will be the beneficial to make a check before the
equipment is shipped by the vendor.
• At this stage issue related to support system like
instrument calibration system, prevention &
maintenance procedure and operation sop are
addressed
• IQ also involved the following activities:
1. Review of steel passivation
2. Verification of material of instrumentation
3. Absence of leaks
4. Review of documentation
17. OQ protocol:
• OQ verifies the capability of the processing until that they
perform satisfactory within the operation limit
• The focus of the OQ is to define the critical item and practices e.g.
alarm conditions for utilities such as low stem pressure, differential
pressure limit, conductivity limit.
• calibration need are assesed and calibration are carried out
• Documented procedure are also developed fir the maintainance,
adjustments, monitoring and control of the equipement involved.
.
• Limites within which the plant will operate should be specified.
• The OQ protocol provide a functional testing of the system
component.
18. • PQ protocol:
Phase 1:
During the phase a test period of 2-4 weeks
should be spent monitoring the system. The system
should operate contineously without failure or
performance deviation. T include;
1. Sampling of the incoming feed water daily to verify its
quality.
2. 2. Sampling after each step in psurification process
daily.
3. 3. Finalization of operating ranges.
4. 4. Verification of provisional alert.
5. 5. Finalization of operation, sanitization, cleaning and
maintainance procedure.
6. 6. Testing of water for each microbiological and
chemical testing as per plan.
19. • Phase 2:
• After complition of phase1 a further period of 2-4 week should be
spent on monitoring the water system. the sampling system might
remain the same as in the phase1.
• This approach should demonstrate the following:
1. The water system operate consistency.
2. The water system produce and delivared constantly the require
quality of water in require quality.
• Phase 3:
• Usually run of 1 year after the succesfull complition of phase 2.
water can be used for manufacturing purpose during the phase.
• The phase has the following objective:
1. To demonstrate reliable performing in long run .
2. To evaluate seasonal variation in feed water.
3. To reduce sample location.
20. VALIDATION STEAM SYSTEM
There are 2 type of steam system in pharmaceutical industry.
The system which is called house steam. Consist of steam generator and
distribustion system made up of iron or steel.
The second type of system called as clean steam estabilished when steam is
used for directly treating the product or product contact surface.
Distribution line in both plant and clean steam are insulted to reduce heat
and to provide safety.
Approach of steam system validation include the following step:
1. Make a process diagram and identify major step.
2. Define major equipment process.
3. Carry out IQ & OQ.
4. Carry out PQ
21. • IQ protocol:
• Clean steam generator:
1. Conform the checklist according to purchase
specification
2. Connect the generator to the required utilities.
3. Tighten flanges or other fiting clean generator
chemically and passivate generator after
installation.
4. Carry out pressure testing and result record.
5. Check and calibrate all critical process intrument. If
calibration of any instrument can not be done by
internal staff, engage an external agency.
22. Distribuion system:
1. Conform that material of construction of
distribution system is as per the specification
of the company.
2. Compare the design drawing and the as built
drawing and make note of modification
carried out in the design drawing at the time
of construction.
3. Clean the distribution system efoe start up
and record it.
4. Carry out the pressure test and record the
result
23. • OQ protocol:
• Test all the point of the system for adequate
supply of the steam under maximum load or
other production conditions. If there is limitation
of use of only a few use point at time these
conditions should be tested as worst case
condition.
• Quality of steam should be tested ay all the use
point.
• Use point should be tested to find out that excess
condensate is not present under operation
condition
• If it is found excess condensate is present, it
should be removed by additional traps or other
suitable means.
24. • PQ protocol
• The PQ consist of the required testing
specified in protocol.
• A typical protocol would include several test
under defined load conditions.
• testing consist of conditioning steam at
various use point and subject condensate to
testing for WFI.