This document discusses process validation for various pharmaceutical dosage forms and operations. It begins by defining process validation and its importance. It then provides details on validating different steps for products like ampoules, ointments, and liquid orals. These include validating washing, filling, sealing, sterilization, inspection, packaging, sampling, testing, and monitoring critical process parameters. The document also discusses validation protocols, reports, and references. The overall purpose is to establish documented evidence that specific processes will consistently produce pharmaceutical products meeting quality standards.
In Process Quality Control Tests (IPQC) for Solid Dosage FromSagar Savale
IPQC is concerned with providing accurate, specific, & definite descriptions of the procedures to be employed, from, the receipt of raw materials to the release of the finished dosage forms.
Glass as a packaging material in pharmaceutical packagingShweta Shelke
This presentation gives a brief idea about the types of glasses used in pharmaceutical industry and its intended use. Different tests used for assuring its quality for intended use.
In Process Quality Control Tests (IPQC) for Solid Dosage FromSagar Savale
IPQC is concerned with providing accurate, specific, & definite descriptions of the procedures to be employed, from, the receipt of raw materials to the release of the finished dosage forms.
Glass as a packaging material in pharmaceutical packagingShweta Shelke
This presentation gives a brief idea about the types of glasses used in pharmaceutical industry and its intended use. Different tests used for assuring its quality for intended use.
IPQC Tests for capsules As per IP, BP & USPPramod Ramane
IPQC- In Process Quality Control Tests for Capsules are
1. Uniformity Of Content
2. Disintigration Test
3. Weight Variation Test
4. Dissolution Test
The tests are with Acceptance limits/Criteria as per Indian Pharmacopoeia (IP), British Pharmacopoeia (BP) & United States Pharmacopoeia (USP)
The presentation describes types advantages, disadvantages of parenteral preparations, route of administration, general requirement, evaluation, labeling & packaging, containers & their types etc
IPQC?
Its Need
In-Process Quality Control tests for Tablets
Hardness
Friability
Thickness
Disintegration Time
Weight variation
Content uniformity
Dissolution test
Leakage testing for strip and blister packaging
IPQC Tests for capsules As per IP, BP & USPPramod Ramane
IPQC- In Process Quality Control Tests for Capsules are
1. Uniformity Of Content
2. Disintigration Test
3. Weight Variation Test
4. Dissolution Test
The tests are with Acceptance limits/Criteria as per Indian Pharmacopoeia (IP), British Pharmacopoeia (BP) & United States Pharmacopoeia (USP)
The presentation describes types advantages, disadvantages of parenteral preparations, route of administration, general requirement, evaluation, labeling & packaging, containers & their types etc
IPQC?
Its Need
In-Process Quality Control tests for Tablets
Hardness
Friability
Thickness
Disintegration Time
Weight variation
Content uniformity
Dissolution test
Leakage testing for strip and blister packaging
Validation by Vilegave Kailash, Shivajirao S. Jondhle college of Pharmacy Asa...Kailash Vilegave
General aspects
Validation of parenterals
Validation of tablets
component of validation,function of different departments,reasons for validation,shivajirao s jondhle college of pharmacy asangaon,validation of parenterals,validation of tablets,validation priority,vilegave kailash
DIR Technologies | PAT for Packaging by Fabian SchapiroDIR Technologies
The need fpr PAT in packaging:
1) The primary package is an integral part of the drug.
2) The sealing process of the package must be validated and monitored.
3) In a PAT framework, 100% inspection of the seal integrity is the ideal approach.
Previously there was no process analytical technology for continuous process verification of the sealing process. Sampling was the best option available. Now there is a technological, 100% in-line, non-destructive, testing method.
Summary:
1) Sampling provides probabilistic monitoring and cannot provide a solid process analytical control.
2) Thermal imaging technology enables a PAT approach to the induction sealing process with 100% in-line testing and process monitoring => Continued Process Verification
3) Case studies from packaging lines reflect the potential impact of PAT for induction sealing.
4) Reliability of Induction Integrity Verification System tested and proved.
*presentation given at IFPAC 2015 session
PAT for packaging real time monitoring of pharmaceutical bottles’ induction s...PT Asia Limited
- The need for PAT Packaging
- Sealing integrity inspection methods
- What is thermal imaging?
- The induction sealing process
- Case studies
- Reliability test
- Summary
- About DIR Technologies
IPQC of Pharmaceutical Dosage Form at Pharmaceutical Industry mahbub tanim
This slides contents some details on In Process Quality Control (IPQC) of pharmaceutical dosage form (tablet, capsule, syrups, sterile etc.) at pharmaceuticals before sent them to Quality Control (QC) department.
Complete Information and knowledge about the selection criteria for packaging material and different test used for them .
All this material data is , Collected for seminar in QA SEM 2 , in the Subject of Pharmaceutical Manufacturing Technology .
Which also explain the How Quality control for Filling an pharmaceutical equipment is done.
Visual Inspection of Parentetal Drug Products in Pharmaceutical Quality testingKarishmaRK
This presentation aims to elaborate the regulatory & compendial requirements of Visual inspection in Pharmaceutical parenteral manufacturing and the methodology of carrying out the testing.
In Process Quality Control (IPQC) of pharmaceutical dosage form in Pharmaceut...Saad Ahmed Sami
A brief description of in process quality control (IPQC) definition, factors affecting the process and IPQC process in solid, liquid and sterile dosage form . IPQC cover the entire chain of operations from the receipt of raw material in the warehouse to the release of finished products from the warehouse for distribution and or sale. IPQC is a process where quality of a product is ensured that it meets the standard according to regulatory authority guideline.
IPQC For Parenterals - By Kaleem PetkarKaleem Petkar
IN PROCESS QUALITY CONTROL (IPQC) means controlling the procedures involved in manufacturing of the dosage forms starting from raw materials purchase to dispatch of the quality product in ideal packaging
IPQC cover the entire chain of operations from the receipt of raw material in the warehouse to the release of finished products from the warehouse for distribution and or sale. IPQC is a process where quality of a product is ensured that it meets the standard according to regulatory authority guidline.
Similar to PROCESS VALIDATION- AMPOULES, VIALS, ORAL PREPARATION (20)
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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. CONTENTS
DEFINITION
IMPORTANCE
AMPOULES/VIAL VALIDATION
i. WASHING
ii. FILLING
iii. SEALING
iv. STERILIZATION
v. INSPECTION
vi. PACKAGING
2
3. VALIDATION OF OINTMENT & CREAM
i. SAMPLING
ii. TESTING
iii. MOITORING
VALIDATION OF LIQUID ORALS
i. CLASSIFICATION
ii. TESTING
iii. SAMPLING
VALIDATION REPORT
REFERENCE
3
4. DEFINITION
› Process validation is establishing document evidence
which provide a high degree of assurance that are
specific process will consistently produce a product
meeting its predetermined specification and quality
characteristics.
› The concept was first proposed by Food and Drug
Administration(FDA) in 1970 in order to improve
quality of pharmaceuticals.
4
5. › The definition can be simplified and explained by
three main points:
› Documented evidence
› Assurance
› Consistent Quality
5
7. IMPORTANCE:
› Assurance of Quality
› Process Optimization
› Safety
› Reduction of Cost
› Compliance
› Time Bound
7
8. PROCESS
JUSTIFICATION
› To identify Critical Quality Attributes(CQA)and
Critical Process Parameters(CPP).
› To confirm that overall ampoule/vial filling process
consistently produces the quality finished products.
› To assure that product is sterile after sterilization
8
9. VALIDATION
REQUIREMENTS
› Calibration of Equipments
› Cleaning Validation
› Equipment Qualification
› Raw Material Testing Methods
› Change Control
› Training of Operators
9
10. PROTOCOL› The protocol should include the critical specifications and operating
› parameters that were identified, such as the following:
› a. Purpose of validation
› b. Operation being validated
› c. Major equipment involved
› d. Components used
› e. Parameters and ranges
› f. Sampling and testing
› g. Acceptance/rejection criteria
› h. Deviations and corrections
› i. Review and approval
› j. Actions to be taken by failure
› k. Responsible personnel and their function
10
11. AMPOULES
› The primary packaging material for injectibles is the
ampoules.
› Ampoules may be clear or amber, manufactured
with type I glass, type C form (acc. to ISO 9187-2).
› Ampoules glass must comply with European
Pharmacopoea requirements for type I glass
containers and, if they are manufactured with amber
glass, it should also comply with light transmittance.
11
12. Ampoules Washing
› Ampoules’ washing is performed in a rotary washer
machine. This machines CPPs are:-
› Water Temperature– This parameter can influence
the efficiency of the washing;
› Water Pressure– this parameter will influence the
correct and efficient washing of the ampoules;
› Washer Velocity– this parameter can influence the
efficiency of the washing as well as the efficient
processing, as if the washer is too fast, more
ampoules can break on the process 12
13. VIAL WASHING
› Washed by series of water at high pressure and the
pressure should be maintained throughout the
process.
› Pressure less = improper washing.
› Pressure more = breakage.
› Compressed air is used for drying the washed vials
and are moved towards the tunnel.
13
14. Ampoules and vials
Depyrogenation
› After washing, the ampoules are continuously conveyed to the
tunnel, sterilized, depyrogenated and then cooled before
being transferred to the filling and sealing station. The key
parameters are:
› 1)Conveyor belt velocity– this parameter can influence the
stability of the ampoules in the tunnel and also the time that
they spend in the tunnel, affecting the exposure to the
sterilization temperature.
› 2)Chamber temperature– the temperature should be high
enough so that the ampoules are efficiently sterilized and
depyrogenated and the value of FH is sufficiently high to
assure the accomplishment of the process.
14
15. Filling
› After cooling, the ampoules are directed to the filling
and sealing line. The Filling process can be
influenced by:
› 1)Solution flow– the solution should flow properly in
order to be filled in the ampoules. Filling needles
depend on product flow.
› 2)Volume to fill– The correctness of the volume will
influence the intended use on the dosage form, as it
can influence the dosage uniformity
15
16. Sealing
› The sealing process can be influenced by:
› Flame Temperature – the flame will melt the glass
and seal the ampoule. If the flame temperature is
not adequate, the sealing may be compromised.
› Ampoules Height- it is determined by the height
of the flame and will influence the ease of opening.
16
17. Sterilization
› Ampoules are now placed in trays and, depending on the
product, may be sterilized in the autoclave by hot steam. This
step assures the use of the finished product.
› Time– This parameter determines the time that the product
remains under the 121ºC temperature. Together with the
temperature it will influence the Fo of the sterilization
process. According to European Pharmacopoeia (EP) the
process should take at least 15 minutes.
› Temperature– This parameter is the key to the sterilization
process, as high temperatures assure the absence of
microorganisms .According to EP it should be at least 121ºC,
unless the process is demonstrated to possess the same
lethality rate.
17
18. Visual Inspection
› Visual inspection is performed in an automated machine. The machine
contains a light-transmission double-check system for detecting particles
in ampoules.
18
1
•Static Division system
2
•Divides photo-detection system into individual parts,
detection is done from base of ampoule.
3
•Container is spin at specified speed.
4
•Liquid forms a vortex imparts movement of insoluble part
5
•Vial stops , vortex collapses image is projected with
variation in transmitted light is detected.
19. › This machine inspects the following defects: particles,
volume and cosmetic defects in the head of the ampoule.
The inspection process can be influenced by:
› Rotation Speed - this parameter is defined so that it can
optimize the particles to suspend.
› Brake Position -this parameter affects meniscus recovery
and the timing between the end of spin and the
inspection.
› Light Intensity – this parameter defines the intensity of
the light that will illuminate the solution.
› Sensitivity – this parameter defines the threshold of
particle detection, differentiating the signal from the
noise.
19
20. Integrity Inspection
› Integrity inspection is performed in an automated
machine by High Voltage Leak Detection (HVLD).
20
High voltage is applied to the container.
If crack is present then current will flow through and
detected by the detector.
Difference in the conductivity is measured.
21. Labelling
› Labelling is performed in an automated machine that imprints
the batch number and expiry date on the label, as well as
possesses a sensor that detects the ring code colour and label
presence.
› The parameters that can influence the labelling process are:
› -Label – The correctness of the label placement is essential to
the identification of the product, influencing its quality.
› -Ring quality & quantity – The correctness of the ring colour
code is essential to the identification of the product to be
labelled, as the colour code is exclusive to one product.
21
22. › Bar code – The correctness of the bar code is essential
to the correctness of the label that will identify the
product.
› -Batch &Expiry date printing – The correctness of the
printing will allow the correct traceability of the batch.
22
23. Packaging
› Packaging is performed in an automated machine that
forms the blister tray, presses the ampoules in the
blister tray and places the trays in the carton box with
the leaflet.
› The parameters that can influence the labelling
process are:
› Leaflet - The correctness of the leaflet (detected by
bar code sensor) and its placement is essential to the
completeness of the packaging.
23
24. › Carton Box -The correctness of the carton box
(detected by bar code sensor) and its correct
formation is essential to the correctness of the
packaging.
› Batch & Expiry date printing – The correctness of the
printing will allow the correct traceability of the batch.
24
25. To achieve the QTTP, the Finished
Product CQAs should be:
› -Assay;
› - Impurities;
› -Particulate Contamination;
› -Endotoxins;
› -Sterility;
› -Correct identification of product and batch number.
25
28. PROCESS VALIDATION OF
OINTMENT/CREAM FORMULATION
› Why need of process validation for ointment/cream?
› Product bio burden high?
› Multiple component?
› More adequate preservative system?
› All have Newtonian flow behavior?
› History: Zinc oxide rash cream that was heated to a
relatively high temperature solely by the action of rotating
mixing plate.
28
30. Processes must be validated in
pharmaceutical manufacturing are:
› Cleaning
› Sanitization
› Depyrogenation
› Sterilization
› Sterile filling
› Purification
› Filling, capping, sealing
› Lyophilization 30
31. Validation Protocol
› Written plan describing the process to be validated,
including production equipment.
i. How validation will be conducted
ii. Objective test parameter
iii. Product characteristics
iv. Predetermine specification
v. Factors affecting acceptable result
31
32. Components Included in cGMP
Process Validation
› All should be validated.
› Facility
› Environment
› People
› Analytical laboratory
› Raw materials
› Equipment
› Procedures
› Process
32
35. Unit Operation for semisolid
System
› Five unit operation
› Mixing of liquid
› Mixing of solid
› Mixing of semisolid
› Dispersing
› Milling and size reduction of solid and semisolid
35
36. Filling and Packaging
Operation
› The following critical aspects must be evaluated and
controlled during large-scale validation and manufacturing
runs
› Proper control of product temperature to aid product flow
and maintain product consistency before and during filling and
packaging operations
› Proper agitation in holding tanks and filling heads in order to
main product uniformity and homogeneity during filling and
packaging operation
› The use of air pressure and inert atmosphere to achieve
product performance and stability in the primary container.
36
37. Product testing
› Validation testing of bulk and finished product must
be based on testing standard release criteria and in
process testing criteria
› Routine QC release testing should be performed on a
routine sample.
› These samples should be taken separately from the
validation samples.
› Validation sampling and testing typically is 3 to 6 time
the usual QC sampling.
37
38. Bulk Sampling
› Take 10 sample from the mixture, tank, or during
product transfer to the storage/filling vessel.
› The samples must represent the top, middle and
bottom of the vessel
› If sampling from the mixture/tank using an specific
equipment, samples should be taken immediately adjacent to
blades, baffles, and shafts where product movement during
mixing may restricted.
› The bottom of the tank and any potential dead spots
should be sampled and examined for unmixed material, if
possible
38
39. Monitoring Output
› Particle size Consideration- Particle size distribution
for most disperse system should be in the range of 0.2-
20 microns
› Viscosity- The Viscometer- Calibrated to measure the
apparent viscosity of the disperse system at
equilibrium at a given temperature to establish system
reproducibility.
› Content Uniformity-In ointment/cream formulation
are more dependent on particle size, shear rate, and
mixing efficiency in order to attain and maintain
uniformity of the active drug component 39
40. › The average result of 10 individual results must meet the release
limit for assay.
› The usual sample size for testing ranges between 0.5 and 1.5 g per
sample assay.
› Preservative effectiveness-Incorporating a USP antimicrobial
preservative testing procedure or microbial limit test into formal
validation of aqueous dispersion.
› Dissolution Testing- It is primary used as a quality control
procedure to determine product uniformity.
› secondary as a means of assessing the in vivo absorption of the
drug in terms of a possible in vitro/vivo correlation.
› For cream/ointments, the Franz in vitro flow through
diffusion cell has been modified by using silicon rubber
membrane barrier to stimulate percutaneous dissolution unit for
testing purpose
40
41. Validation Report
• STANDARD FORMAT
1. Executive summary
2. Discussion
3. Conclusions & recommendation
4. List of attachment
Topic should be presented in the order in which they appear in
the protocol.
Protocol deviation are fully explained & justified.
The report is signed & dated by designated representatives of
each unit involved in water system validation
41
42. Liquid orals
› Oral liquids are homogeneous or heterogeneous
liquid preparation.
› Consisting of solution, emulsion or suspension .
› In which one or more medicaments are been
dispersed in suitable vehicle.
42
46. Process Description
› The information given below provides a general description of
the process. Detailed information for the manufacturing will
be supplied separately in the batch manufacturing record.
› DISPENSING OF MATERIAL
› SUGAR SYRUP PREPARATION
› BULK MANUFACTURING
› PH ADJUSTMENT
› VOLUME MAKE UP
› FILTRATION
› WASHING, FILLING AND SEALING
46
51. oTest parameters specific for emulsion
Dilution test
Conductivity test
Dye solubility test
COCL2 filter paper test
Fluorescence test
oTest for filling and packaging
Leakage test for filled bottle
Cap seal test
Fill volume
Water vapour permeability test
51
53. › Sampling site: - Top (A), Middle (B), Bottom(C) position; use
the sample tube for A&B and bottom valve for
Position C
› Sampling Qty.: -About 100 ml from each sample site
› Sampling Time: - While mixing is on: - After ____ minutes,
after ____ minutes, After _____ minutes.
53
55. References
› Lieberman H. A. , Rieger M. M. and Banker G. S.
“Pharmaceutical Dosage Forms: Disperse System”
,vol.3; Second Edition,473-511
› R. A. Nash and A. H. Wachter “Pharmaceutical process
validation”; Third edition
› Agalloco James, Carleton J. Fredric “Validation of
Pharmaceutical Processes”; Third edition,417-428
55
56. › Ana Rita Correia Cabaço, A Validation Master Plan for Small
Volume Parenterals, Pg. No. 1-89
› Ronald P. Anjard, SPC chart selection process, Microelectron.
Reliab., Vol. 35, No. II, pp. 1445 1447, 1995 28
› PQRI, Process Robustness – A PQRI White Paper, The official
manazine of ISPE, November/December 2006, Vol.26, No.6 29
› Chien-Wei Wu et al, An overview of theory and practice on
process capability indices for quality assurance, Int.Journ of
Production Economics Volume 117, Issue 2, February 2009,
Pages 338–359 30
› Susan Haigney , QbD in Sterile Manufacturing, Pharmaceutical
Technology Europe, Dec.2013 vol 25 no.12 pp 32
56