Validation: 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.
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.
Cleaning validation is one of the major and critical activity in pharmaceutical operations
The four basic requirement of cGmp are …
Identity
Safety*
Strength
Purity*
Validation: 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.
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.
Cleaning validation is one of the major and critical activity in pharmaceutical operations
The four basic requirement of cGmp are …
Identity
Safety*
Strength
Purity*
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”
CLEANING VALIDATION for M.pharm and industry personabhishek pandey
YOU CAN EASY WAY TO UNDERSTAND A PROCESS AND ANLYTICAL METHOD OF CLEANING VALIDATION
Cleaning validation is the methodology used to assure that a cleaning process removes residues of the active pharmaceutical ingredients of the product manufactured in a piece of equipment, the cleaning aids utilized in the cleaning process and the microbial attributes.[1] All residues are removed to predetermined levels to ensure the quality of the next product manufactured is not compromised by waste from the previous product and the quality of future products using the equipment, to prevent cross-contamination and as a GMP requirement.
The U.S. Food and Drug Administration (FDA) has strict regulation about the cleaning validation. For example, FDA requires firms to have written general procedures on how cleaning processes will be validated. Also, FDA expects the general validation procedures to address who is responsible for performing and approving the validation study, the acceptance criteria, and when revalidation will be required. FDA also require firms to conduct the validation studies in accordance with the protocols and to document the results of studies.The valuation of cleaning validation is also regulated strictly, which usually mainly covers the aspects of equipment design,cleaning process written, analytical methods and sampling. Each of these processes has their related strict rules and requirements. Regarding to the establishment of limits, FDA does not intend to set acceptance specifications or methods for determining whether a cleaning process is validated. But some limits that have been mentioned by industry include analytical detection levels such as 10 PPM, biological activity levels such as 1/1000 of the normal therapeutic dose and organoleptic levels.[2][3][4]
Cleaning Validation in the context of Active Pharmaceutical Ingredient manufacture may be defined as: "The process of providing documented evidence that the cleaning methods employed within a facility consistently controls potential carryover of product (including intermediates and impurities), cleaning agents and extraneous material into subsequent product to a level which is below predetermined levels".
In this presentation from CPhi 2014, Elise Gallais outlines the guidelines for cleaning validation: and focuses on analytical methods and their validation.
Fluidized Bed Dryer
Principle of FBD
Construction of FBD
Working of FBD
Steps of Fluidization
Qualification of FBD
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
References
In this presentation from IVT's 4th Annual Validation Week EU, Paul Pluta, discussed the differences between the traditional approach to cleaning validation and the lifecycle approach, applicable regulatory guidance, current industry trends, the necessary phases of the lifecycle approach (design and definition, cycle development, validation, and implementation), how to continously monitor the process, change control, and common obstacles to compliance.
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”
CLEANING VALIDATION for M.pharm and industry personabhishek pandey
YOU CAN EASY WAY TO UNDERSTAND A PROCESS AND ANLYTICAL METHOD OF CLEANING VALIDATION
Cleaning validation is the methodology used to assure that a cleaning process removes residues of the active pharmaceutical ingredients of the product manufactured in a piece of equipment, the cleaning aids utilized in the cleaning process and the microbial attributes.[1] All residues are removed to predetermined levels to ensure the quality of the next product manufactured is not compromised by waste from the previous product and the quality of future products using the equipment, to prevent cross-contamination and as a GMP requirement.
The U.S. Food and Drug Administration (FDA) has strict regulation about the cleaning validation. For example, FDA requires firms to have written general procedures on how cleaning processes will be validated. Also, FDA expects the general validation procedures to address who is responsible for performing and approving the validation study, the acceptance criteria, and when revalidation will be required. FDA also require firms to conduct the validation studies in accordance with the protocols and to document the results of studies.The valuation of cleaning validation is also regulated strictly, which usually mainly covers the aspects of equipment design,cleaning process written, analytical methods and sampling. Each of these processes has their related strict rules and requirements. Regarding to the establishment of limits, FDA does not intend to set acceptance specifications or methods for determining whether a cleaning process is validated. But some limits that have been mentioned by industry include analytical detection levels such as 10 PPM, biological activity levels such as 1/1000 of the normal therapeutic dose and organoleptic levels.[2][3][4]
Cleaning Validation in the context of Active Pharmaceutical Ingredient manufacture may be defined as: "The process of providing documented evidence that the cleaning methods employed within a facility consistently controls potential carryover of product (including intermediates and impurities), cleaning agents and extraneous material into subsequent product to a level which is below predetermined levels".
In this presentation from CPhi 2014, Elise Gallais outlines the guidelines for cleaning validation: and focuses on analytical methods and their validation.
Fluidized Bed Dryer
Principle of FBD
Construction of FBD
Working of FBD
Steps of Fluidization
Qualification of FBD
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
References
In this presentation from IVT's 4th Annual Validation Week EU, Paul Pluta, discussed the differences between the traditional approach to cleaning validation and the lifecycle approach, applicable regulatory guidance, current industry trends, the necessary phases of the lifecycle approach (design and definition, cycle development, validation, and implementation), how to continously monitor the process, change control, and common obstacles to compliance.
The subject of cleaning validation in active pharmaceutical ingredient manufacturing plants has continued to receive a large amount of attention from regulators, companies and customers alike.
The integration of Cleaning Validation within an effective Quality System supported by Quality Risk Management Processes should give assurance that API Manufacturing Operations are performed in such a way that Risks to patients related to cleaning validation are understood, assessed for impact and are mitigated as necessary.
It is important that the requirements for the finished manufacturing companies are not transferred back in the process to active pharmaceutical ingredient manufacturers without consideration for the different processes that take place at this stage.
This presentation covers the requirements of Cleaning Validation for a Multipurpose API Manufactuirng Plant
Considerations to Extractables and Leachables Testing SGS
How to organize Extractables Assessments? FDA continues to issue Warning Letters to companies that fail to properly complete Design Verification, Design Validation, and Process Validation, and recently to include failures of manufacturers in Risk Management. The evaluation of extractables and leachables has become an increasingly important aspect in the Quality by Design (QbD) initiative of the FDA in the area of drug product design, including materials used in the drug product production process and container and closure systems used for product packaging. This presentation provides general approaches and practical aspects in E&L testing.
Cleaning validation is a procedure of establishing evidence that cleaning processes for
manufacturing equipment prevents product contamination. Cleaning validation should be
properly documented to demonstrate Current Good Manufacturing Practice (CGMP) for
finished pharmaceuticals.
◦ Cleaning procedures should normally be validated. In general, cleaning validation should be
directed to situations or process steps where contamination or carryover of materials poses the
greatest risk to API quality.
◦ For example, in early production it may be unnecessary to validate equipment cleaning
procedures where residues are removed by subsequent purification steps.
◦ Validation of cleaning procedures should reflect actual equipment usage patterns. If various
APIs or intermediates are manufactured in the same equipment and the equipment is cleaned
by the same process, a representative intermediate or API can be selected for cleaning
validation.
◦ This selection should be based on the solubility and difficulty of cleaning and the calculation
of residue limits based on potency, toxicity, and stability.
Types of Validation & its Aspects PPT.pptxdrsabaasif
Types of validation used in pharmaceutical industry. it will help people to understand and develop understanding regarding validations used in industry.
This presentation includes detail about cleaning levels,equipments for cleaning validation , steps for cleaning method validation and analytical method validation used for cleaning.
Bioburden Validation Strategy for Cleaning Validationangelsalaman
This presentation is based on the article published by Pharmaceutical Technology (USA) entitled “BIOBURDEN METHOD SUITABILITY FOR CLEANING AND SANITATION MONITORING: HOW FAR WE HAVE TO GO?”, Aug 2010. by Angel L. Salaman-Byron
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Paper presented at SYNERGY workshop at AVI 2024, Genoa, Italy. 3rd June 2024
https://alandix.com/academic/papers/synergy2024-epistemic/
As machine learning integrates deeper into human-computer interactions, the concept of epistemic interaction emerges, aiming to refine these interactions to enhance system adaptability. This approach encourages minor, intentional adjustments in user behaviour to enrich the data available for system learning. This paper introduces epistemic interaction within the context of human-system communication, illustrating how deliberate interaction design can improve system understanding and adaptation. Through concrete examples, we demonstrate the potential of epistemic interaction to significantly advance human-computer interaction by leveraging intuitive human communication strategies to inform system design and functionality, offering a novel pathway for enriching user-system engagements.
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Welcome to UiPath Test Automation using UiPath Test Suite series part 4. In this session, we will cover Test Manager overview along with SAP heatmap.
The UiPath Test Manager overview with SAP heatmap webinar offers a concise yet comprehensive exploration of the role of a Test Manager within SAP environments, coupled with the utilization of heatmaps for effective testing strategies.
Participants will gain insights into the responsibilities, challenges, and best practices associated with test management in SAP projects. Additionally, the webinar delves into the significance of heatmaps as a visual aid for identifying testing priorities, areas of risk, and resource allocation within SAP landscapes. Through this session, attendees can expect to enhance their understanding of test management principles while learning practical approaches to optimize testing processes in SAP environments using heatmap visualization techniques
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1. Insights into SAP testing best practices
2. Heatmap utilization for testing
3. Optimization of testing processes
4. Demo
Topics covered:
Execution from the test manager
Orchestrator execution result
Defect reporting
SAP heatmap example with demo
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Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
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All of this illustrated with link prediction over knowledge graphs, but the argument is general.
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Don’t miss this opportunity to elevate your FME expertise and drive your projects to new heights of efficiency.
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2. 2
What is Cleaning validation
Purpose of the Cleaning validation
How to do Cleaning validation
Compliance with GMP & other Regulatory requirements
CLEANING VALIDATION
3. 3
What is Cleaning validation
The process of providing “Documented evidence that the cleaning methods
employed within a facility consistently controls potential carryover of product,
cleaning agents and extraneous material into subsequent product to a level
which is below predetermined acceptance criteria”.
IMPORTANCE :
Heart of pharmaceutical activity
Related to safety and purity of the products
4. 4
Purpose of Cleaning validation
It is necessary to Validate Cleaning procedures for the following
reasons:
a. It is a customer requirement - it ensures the safety and purity
of the product.
b. It is a regulatory requirement in Active Pharmaceutical
Ingredient & formulation product manufacture.
c. It also assures from an internal control and compliance point
of view the quality of the process.
5. 5
How to do Cleaning validation
Cleaning Validation - Requirements
• Development of Cleaning Process
• Assessment for selection of Marker compound
• Determination of Acceptance Criteria
• Validated Analytical methods for detection of marker
compound
• Cleaning Validation Protocol
• Sampling Procedure
• Cleaning Validation Report
7. Possible contaminants
Product residues
Cleaning agent residues and breakdown
Airborne matter
Lubricants, ancillary material
Decomposition residues
Bacteria, mould and pyrogens
Development of cleaning Process
8. 8
Development of cleaning Process
Cleaning Process
Aqueous
cleaning
Solvent
cleaning
Manual cleaning
Ultrasonic
cleaning
Vapour
degreasing
Ultrasonic
cleaning
10. 10
Ultrasonic cleaning
An ultrasonic cleaning is a process that)
uses Ultrasound (usually from 20–
400 kHz) and an appropriate cleaning
solvent (sometimes ordinary tap water)
to clean items. The ultrasound can be
used with just water, but use of a solvent
appropriate for the item to be cleaned
along with the soiling enhances the
effect.
Ultrasound creates waves of
compression and expansion in the liquid.
In the expansion phase, the molecules
are pulled apart rapidly, causing the
formation of microscopic vapor bubbles.
Subsequently, these cavitation bubbles
implodes releasing tremendous energy.
Extreme temperature combined with
high velocity jets provides the cleaning
action.
11. Levels of cleaning (Ref APIC guidline)
The degree or level of cleaning and validation required for
cleaning processes in Active Pharmaceutical Ingredient
(API) & Formulation manufacturing depends largely on:
The equipment usage (i.e. dedicated equipment or not)
The stage of manufacture (early, intermediate or final
step)
The nature of the potential contaminants (toxicity,
solubility etc.)
Development of cleaning Process
12. LEVELS ATTRIBUTES CLEANING VALIDATION
LEVEL - 0 Batch to batch cleaning in an identical
process (same API). Change in the early
stage of another process
Not required
LEVEL - 1 Changeover between intermediate of one
product to final intermediate of another
product. Changes in early steps to
intermediate of another product
( API to intermediate )
Required
LEVEL - 2 Changeover from one API to another API.
Changeover from early step to final step of
same product
Essential
13. Level of cleaning differ from each other in the following
aspects
Level – 0 Level – 1 Level – 2
RISK Lowest Moderate Highest
ACCEPTANCE
LIMIT
Highest Moderate Lowest
VERIFICATION
OF CLEANING
Visual inspection Not required Analytical testing
required
14. When the cleaning process is considered
and developed?
Development of cleaning Process
15. Cleaning Process shall be considered during design
qualification of processing equipment to ensure the
implementation of effective and efficient cleaning
processes of equipment
Document the following requirements:
Cleaning cycle requirements: including the different types of
utilities (e.g. cold water, WFI, compressed air), selected
cleaning agent including concentrations, operating
temperatures and pressures (flow) of utilities, maximum
duration of the cleaning cycle etc.
Sampling requirements for qualification and validation
activities.
Development of cleaning Process
17. Assessment for selection of Marker compound
Marker compound:
It is a high contamination risk compound for patient safety
which is identified based on worst case scenario of the products
and governs the cleaning validation activity.
The risk assessment for prioritization and selection of marker
compound for the cleaning validation activity is documented
based on the following criteria:
Toxicity of active materials
Solubility of active materials
Colouring agents
‘Difficult to clean’ active materials
18. Toxicity of Active Materials (Criteria-1):
Active materials with the lowest recommended therapeutic dose and with the
highest toxicity effects, based on Pharmacopeial recommendations are likely to
have high contamination risk to patient safety.
Table: Toxicology Data -Lethal Dose (mg/kg)
S No. Included descriptive terms
Probable oral lethal dose
(mg/kg)
1 Practically nontoxic Slightly toxic >15 000
5 000 - 15 000
2 Moderately toxic 500 - 5 000
3 Very toxic 50 - 500
4 Extremely toxic 5 - 50
5 Supertoxic <5
Assessment for selection of Marker compound
19. Solubility of Active Materials (Criteria-2):
A solubility-rating is performed based on the solubilities of the API substances in
water used for cleaning. The United States Pharmacopeia (USP) describes the solubility of
drugs as parts of water required for one part solute. The solubility criteria for materials
soluble in water is listed in below Table
Table-Solubility criteria with respect to water (As per USP-29 NF 24)
Description form
(Solubility definition)
Parts of water required for one
part of solute
Solubility range
(mg/mL)
Very soluble (VS) < 1 > 1000
Freely soluble (FS) from 1 to 10 100 – 1000
Soluble from 10 to 30 33 – 100
Sparingly soluble (SPS) from 30 to 100 10 – 33
Slightly soluble (SS) from 100 to 1000 1 – 10
Very slightly soluble (VSS) from 1000 to 10000 0.1 – 1
Practically insoluble(PI) > 10000 < 0.1
Assessment for selection of Marker compound
20. Assessment for selection of Marker compound
Colouring agents (Criteria-3):
Risk of colouring agents should be assessed based on the
flavour ingredient concentration and colouring
characteristics for darkness, during visual inspection
of product contact parts by using lint free cloth.
21. Difficult To Clean Active Materials (Criteria-4):
One criterion which can be used is the ability to clean a substance
due to its solubility in water . Based on the solubility, Difficult-
to-clean substances are identified and the difficulty of cleaning
could be rated according to the three categories suggested below,
Category:
Easy
Medium
Difficult
Assessment for selection of Marker compound
23. Determination of Acceptance criteria
Acceptance Criteria for chemical residue can be determined in
the following ways :
Visual Inspection (Visually clean)
MACO limit Based on Therapeutic Daily Dose, NMT 0.1 % of
therapeutic dose
MACO limit Based on toxicology Data,
General Limit (10 ppm) criteria
24. Visually Inspection:
A visual check for cleanliness is an important part of the
acceptance criteria for cleaning validation.
A lint-free cloth will be used to wipe the equipment parts for
visual inspection to verify the effectiveness of the cleaning
process. This will be done after the machine parts have been
cleaned and oven-dried. The visual inspection should not be
done before the machine parts have completely dried as
sometimes a thin layer of water remaining on the surfaces of
the equipment parts might make residues difficult to detect.
Determination of Acceptance criteria
25. MACO limit Based on Therapeutic Daily Dose:
The principle for the requirement is that the standard Therapeutic Daily Dose (TDD) of the
following substance (contaminated. substance, in this case called "next") may be
contaminated by no more than a certain proportion (usually 1/1000 part) of the TDD of the
substance investigated in the cleaning validation (contaminating substance, in this case called
"previous").
Procedure
Establish the limit for Maximum Allowable Carryover (MACO) according to the following
equation.
Min TDDprevious x MBS
MACO = ------------------------------
SF x Max TDDnext
MACO Maximum Allowable Carryover: acceptable transferred amount from the contaminant product ("previous")
TDD previous Standard therapeutic dose of the contaminant product (in the same dosage form as TDDnext)
TDD next Standard therapeutic dose of the daily dose for the next product
MBS Minimum batch size for the next product(s) (where MACO can end up)
SF Safety factor (normally 1000 is used in calculations based on TDD)
Determination of Acceptance criteria
26. Determination of Acceptance criteria
Example: MACO based on therapeutic dose
Product A will be cleaned out. The product has a standard daily dose of 10 mg and
the batch size is 200 kg. The next product B has standard a daily dose of 250 mg and
the batch size is 50 kg. Both A and B are administrated orally and SF is set to 1000.
Calculate the MACO for A in B!
10 (mg) x 50 000 000 (mg)
MACO = ------------------------------------ = 2 000 (mg)
1000 x 250 (mg)
Result: MACO is 2 g (2000 mg), i.e 2 g of Product A is allolable to carryover into
product B
27. Determination of Acceptance criteria
MACO Limit Based on Toxicological Data:
In cases in which a therapeutic dose is not known (e.g. for intermediates and detergents), toxicity data may
be used for calculating MACO.
Procedure
Calculate the so called NOEL number (No Observable Effect Level) according to the following equation and
use the result for the establishment of MACO.
LD50 (g/kg) x 70 (kg a person)
NOEL = -----------------------------------------
2000
From the NOEL number a MACO can then be calculated according to:
NOEL x MBS
MACO = ------------------------------
SF x TDDnext
MACO Maximum Allowable Carryover: acceptable transferred amount from theinvestigated product ("previous")
NOEL No Observed Effect Level
LD50 Lethal Dose 50 in g/kg animal. The identification of the animal (mouse,rat etc.) and the way of entry (IV, oral etc.) is
important.
70 kg is the weight of an average adult
2000 is an empirical constant
TDD next Largest normal daily dose for the next product
MBS Minimum batch size for the next product(s) (where MACO can end up)
SF Safety factor
28. Determination of Acceptance criteria
General Limit (10 ppm) criteria:
A general upper limit for the maximum concentration of a contaminating
substance in a subsequent batch (MAXCONC) is often set to 10 ppm and 10
ppm in APIs is very frequent
Establish MACOppm, based on a general limit, using the following equations.
MACOppm = MAXCONC x MBS
E.g. For a general limit of 10 ppm: MACO = 0.001% of the minimum batch
size (MBS).
29. Swab & Rinse Limits
Swab Limit per surface:
Limit per Surface (LS) = MACO x swab surface area
--------------------------------------- mg/swab
TSS x swab recovery rate
Rinse Limit for rinse Sample for an equipment
Limit per Rinse Sample (LRS) =
MACO x Surface of the equipment
---------------------------------------------- mg/ml
TSS x Final rinse volume
31. Analytical method Validation
Validate analytical method
The validation of an analytical method should occur in compliance with pre
established acceptance criteria.
Must be sensitive assay procedure
HPLC, GC, HPTLC
TOC
pH
conductivity
UV
Parameters evaluated as apart of acceptance criteria for
analytical method validation are given in the below table:
34. Cleaning validation protocol
Should include :
Objective of the validation and identification of the process
Responsibility for performing and approving validation study
Description of equipment to be used
Status of equipment (qualified, calibrated according to the
maintenance program etc.) used in the process to be validated
Status of utilities (water, gases etc.) needed during the validation
Responsibilities of personnel in the validation process
Training of personnel responsible for the process and personnel
operating with the process
Status of the SOPs concerning the cleaning and other related
activities
35. Cleaning Validation Protocol
Should include :
Dirty hold Time & Clean Hold Time (DHT & CHT) Interval between end of
production and cleaning, and commencement of cleaning procedure
Cleaning procedures to be used
Any routine monitoring equipment used
Number of cleaning cycles performed consecutively
Sampling procedures used and rationale
Sampling locations (clearly defined) and the defined area size
Data on recovery studies
Validated Analytical methods
Acceptance criteria and rationale
When revalidation will be required
37. Sampling Procedure
How to sample
Swab
Rinse fluid
The sample transport and storage conditions
should be defined
38. Sampling Procedure
Swab samples
Direct sampling method
Document swab locations
The swab are added with dilution solvent and these solvent were analysed
by suitable analytical instruments for the presence of residue of previous
products
Disadvantages
inability to access some areas
assumes uniformity of contamination surface
must extrapolate sample area to whole surface
39. Sampling Procedure
Rinse samples
Basic principle: to be used only to support other sampling methods, however may
be used in …
Indirect method
Combine with swabs
Sample very large surface areas
Usually use for rising an entire piece of equipment
A measured area of a cleaned surface is rinsed or solvent washed and solvent is
collect and test for traces of contaminants
41. Cleaning validation Report
Results and reports
Cleaning record signed by operator, checked by production and reviewed
by QA
Analysis results for chemical and Microbial testing
Final Validation Reports, including conclusions
Statement if there were any changes to the validation protocol
Clear statement if the validation results meet the criteria stated in the validation
protocol
Approval/rejection as described in SOP and/or validation protocol
43. Cleaning Validation is Extremely important, specific and are the requirements
established by regulatory agencies such as the US Food and Drug
Administration (FDA), the European Medicinal Evaluation Agency (EMEA),
Australia's Therapeutic Goods Administration (TGA), etc. For example, the
2004 Code of Federal Regulations (CFR) Title 21, Volume 4, Section 211.67,
states:
21 CFR 211.67 Equipment cleaning and maintenance
Equipment and utensils shall be cleaned, maintained and sanitized at
appropriate intervals to prevent contamination that would alter the safety,
identity, strength, quality or purity of the drug product.
ICH Q7, cGMP, Section 12.7, Cleaning Validation
Cleaning procedures should normally be validated. In general, cleaning
validation should be directed to situations or process steps where
contamination or carryover of materials poses the greatest risk to API quality.