Categories

Search This Blog

ANALYTICAL METHOD AND ITS SUITABILITY


Analytical method or procedure: 

The analytical procedure refers to the procedure or steps necessary to perform each analytical test. 

This may include but is not limited to: the method & instrument parameters, the sample/ reference standard & the reagents preparations, use of the apparatus, dilutions required, generation of the calibration curve, use of the formulae for the calculation, etc. 


In-house developed Analytical Method: 

The analytical method that was not listed in any of the pharmacopeias like USP, EP, IP, and JP and developed as per the internal requirements. 

All the in-house developed analytical methods should be validated and transferred to the laboratories where commercial batch analysis shall be performed. 


Compendial or Pharmacopoeial Analytical Method: 
The analytical method that was listed in any of the pharmacopeias like USP, EP, IP, and JP…etc. 

All the compendial or pharmacopoeial methods considered to be validated and only verification to be performed to demonstrate that the procedure is suitable for the intended purpose. 

If a method is listed in pharmacopeias like USP, EP, IP, and JP…etc, but you want to use the same method with modification or completely different methods then you should show method equivalency between your method & the method listed in monographs. 


Analytical method Validation: 
Analytical method validation is the process of demonstrating that the analytical procedure is suitable for its intended purpose. 

The following characteristics shall be considered for the demonstration of method suitability for its intended purpose. 

Method Validation Parameter
Purpose
Procedure

Specificity

Interference Study. To verify whether the interested peak is spectrally pure or not?

i.e. peak response is due to a single component only and no co-elutions exist.

Specificity of the method shall be demonstrated by analyzing the sample spiked with all known impurities at specification level and showing that no interference of impurities at the retention time of main peaks.

Precision

To verify the degree of repeatability of the analytical method under normal conditions. Usually expressed as a standard deviation. Minimum of six determinations at 100% of the test or target concentration

Repeatability

Repeatability is the results of the method operating over a short time interval under the same conditions

Reproducibility

Reproducibility expresses the precision between laboratories (collaborative studies, usually applied to standardization of methodology).

Intermediate Precision

Intermediate precision is the result from within lab variations due to random events such as different days, analysts, equipment, etc. If reproducibility is performed then intermediate precision not required.

Accuracy

To verify the exactness of the analytical method or closeness of the accepted reference value and actual value found from the experiment.

Collecting data from a minimum of nine determinations over a minimum of three concentration levels covering the specified range (for example, three concentrations, and three replicates each).
 The data should be reported as the percent recovery of the known, added amount, or as the difference between the mean and true value with confidence intervals.

Limit of Detection

The lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value.

S/N ratio is determined by comparing  signals from the analyte of known low concentrations samples with blank samples and determining the minimum concentration at which the analyte can be consistently detected. 

S/N ratio between 3:1 or 2:1 is considered as acceptable for estimating the detection limit. The detection limit (DL) can be expressed as DL = 3.3 σ/S where
σ is the standard deviation of the peak response
S is the slope of the calibration curve formed concentration vs response

Limit of Quantitation

The lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. And is used particularly for the determination of impurities and/or degradation products

Determination of the S/N ratio is done by comparing measured signals from known low concentrations samples of an analyte with those of blank samples and by establishing the minimum concentration at which the analyte can be consistently quantified. 

A typical S/N ratio is 10:1 The quantitation limit (QL) may be expressed as: QL = 10 σ/S where
σ is the standard deviation of the peak response
S is the slope of the calibration curve formed concentration vs response

Linearity

Ability to get test results within the given range  that are proportional to the concentration (amount) of the analyte in the sample

Guidelines specify a minimum of five concentration levels, along with certain minimum specified ranges. 

For the assay, the minimum specified range is from 80-120% of the target concentration. 

For an impurity test, the minimum range is from the reporting level of each impurity, to 120% of the specification. (For toxic or more potent impurities, the range should be commensurate with the controlled level.)
 For content uniformity testing, the minimum range is from 70-130% of the test or target concentration, and for dissolution testing, +/- 20% over the specified range of the test.

Range

lower and upper concentration (amounts) interval of analyte in the sample (including lower & upper concentrations) for which it has been proven that the analytical the procedure has a suitable level of precision, accuracy, and linearity.

Robustness

The measure of analytical method capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage.

The robustness of an analytical  method is assessed by deliberately varying method parameters such as temperature, ionic strength, pH & % organic etc., and evaluating the effect (if any) on the results of the analytical method.

Ruggedness

The degree of reproducibility of the results obtained under a variety of conditions, expressed as %RSD.

These conditions include different laboratories, analysts, instruments, reagents, days, etc.
  

Solution Stability

To establish the stability of the sample and standard solutions

Sample & Standard solutions to be analyzed at periodic times.

System Suitability

To verify the system suitability parameters

All system suitability parameter to be verified as per respective testing procedure.

Analytical method Transfer: 

Analytical method transfer is a documented process that qualifies a laboratory to use an analytical test procedure that originated in another laboratory thus ensuring that the laboratory has the procedural knowledge and ability to perform the test. 

If the receiving laboratory participated in the collaborative study (Reproducibility as part of the precision study) during the validation of the analytical method, then the same shall be reported as Co-Validation and the laboratory can be considered as qualified for use of analytical test method. 

If the receiving laboratory has not participated in the Validation study then method transfer activity shall be performed as follows to qualify a lab to use the test method. 

In-direct method Transfer (Inter Lab): 
Analysis of the same samples (Single batch), six times at both the transferring unit & receiving unit by using the same analytical method. However, the transferring unit can consider data from the method validation study. 

Direct method Transfer (Inter Lab): 
Analysis of the same samples (Single batch), six times by both the analyst of the transferring unit & receiving unit by using the same analytical method at the receiving laboratory. 

Analytical method Verification: 

Users should have the appropriate experience, knowledge, and training to understand and be able to perform the compendial procedures as written. 

Verification should be conducted for all compendial procedures in a way such that the verification results will provide assurance that the procedure will perform consistently as intended. 

Verification requirements should be based on an assessment of the complexity of both the procedure and the material to which the procedure is applied. 

Although complete revalidation of a compendial method is not required to verify the suitability of the method under actual conditions of use, some of the analytical performance characteristics listed at the analytical method validation section may be used for the verification process. 

Only those characteristics that are considered to be appropriate for the verification of the particular method need to be evaluated. The degree and extent of the verification process may depend on the level of training and experience of the user, on the type of procedure and its associated equipment or instrumentation, on the specific procedural steps, and on which article(s) are being tested. 

Routinely performed basic compendial test procedures do not require verification unless there is an indication that the procedure is not appropriate for the article under test. Examples include, but are not limited to, residue on ignition, loss on drying, several wet analysis procedures such as simple instrumental methods such as pH measurements & acid value. However, for the application of already established routine procedures to compendial articles tested for the first time, it is recommended that consideration be given to any new or different sample handling or solution preparation requirements. 

Analytical method Equivalency: 
Equivalency demonstrates the sameness of two analytical methods. 

Method equivalency comes in to picture whenever you want to use different methods against to monograph method and/or already filed methods during product registrations. 

The goal of method equivalency is to demonstrate acceptable method performance by comparison of a specific set of results (e.g., an assay). I.e. the method proposed is equally capable as a monograph / already filed method to analyze the interesting samples.

No comments:
Labels:

OTHERS

No comments:
Labels:

JUMBO JOBS - A JOB SCAMMER - BE CAREFUL

As you all know, every day a new job scam come in to picture and lots of people caught up with these job scams and loss so much money due to unawareness whether the offerings was of a scam or really good opportunity

As an example, in January 2019 a big job scam of www.wisdomjobs.com was blasted out that has cheated more than one lakh people (Approximately 70 cores) and the wisdom management was got arrested.

Now, similarly Jumbo jobs is doing the same again and cheated and trying to cheat so many people just by offering fake jobs and collecting money from the victims.

Refer following as few examples.

I personally had experience with this Jumbo jobs. One day ‘Geetha’ from Jumbo jobs called me and told that they looking for good candidates for position that exactly matches my current job profile. 

Later i verified in the web and found it is scam and same was discussed during call from jumbo jobs and immediately they said its ok... its ok and disconnected the call.

Refer below communication . Please be careful

Dear Mr. Kiranreddy Munnangi,
Greetings from Jumbo-Jobs,
Jumbo-Jobs based in India is a global leader in successfully connecting job opportunities and people. Jumbo-Jobs main Purpose is to improve the efficiency of recruitment. The recruitment process has four stages such as sourcing, engaging, selecting, and hiring. We’ll look at the market for recruitment tools from the point of view of recruitment stages We use the world's most advanced technology to help people in finding better job opportunities via digital, social and mobile solutions including Info@jumbo-jobs.com

Our primary business focuses Recruitment & Job Enhancement in 7 countries (Gulf, India, Canada, Australia, USA, Singapore, Malaysia).

Jumbo jobs is the India’s latest online search engine with new technologies which provides relevant profiles to employers and relevant jobs to job seekers across industry verticals, experience levels and geographies. Our international reach helps in dealing global employment services at domestic as well as at international level. We serve our clients keeping all their requirements and parameters into consideration and help them in getting relevant yet best responses in required time.

There is a position available for (Sr.Manager - QA/ Senior Level Position) in one of the leading (Pharma / Biotech / Clinical Research) industry based in (United Arab Emirates, Qatar) which suits your qualifications and experience as demonstrated by your resume on one of the job boards.

We have short-listed your resume to the above mentioned requirement directly with our client. If your are open for a change, we will forward your resume to prospective clients in above mentioned location.

Below are the details of Salary & Benefits:

Date Posted
15th  Oct 2019
Position Type
Permanent
Designation
Sr.Manager - QA
Nationality  
Any English Speaking
Industry
Pharma / Biotech / Clinical Research
Years of Experience
(13) Years+
Functional Area
Quality / Testing / QA / QC / Inspector
Availability To Join
90 days or less 
Number of Vacancies
2
Salary Range
USD  (5500 to 6500) Basic Negotiable + Benefits.
Work Location
United Arab Emirates, Qatar


Additional Benefits
Housing Allowaces
Subsidized Healthcare Package For You And Your Family
Medical & Life Insurance (As per Country’s Law)
Transport Benefits
Education Allowance For Children
Excellent Bonus Schemes
Paid Annual Leave (30 - 45 Days)
Round Trip – Annual Leave Family Air Tickets Per Year To Your Point Of Hire

Organization Type

MNC































T& C:-

1. The total cost of the services and the entire recruitment process including the registration charges is USD 600 out of which you have to pay 50% upfront which is USD 300 for the registration process, and remaining USD 300 you have to pay from your 1st month of salary after joining the client.
2. If Jumbo-Jobs fails in providing the relevant job opportunities in 90 days, the whole amount which you have paid for the services will be refunded.
3. The Client details will be disclosed only after registration process.


Awaiting for your immediate Response.


Thanks & Regards,
Geetha HR Manager
Contact number :+917093712674

Jumbo-Jobs - Agreement Form

SERVICE TERMS &CONDITIONS
Agreement (“Agreement”) is made by and between Jumbo-Jobs (“Recruitment Consultant”) and Mr. Kiranreddy Munnangi with its affiliates and subsidiaries.
First Party: Jumbo-Jobs
And
Second Party: Mr. Kiranreddy Munnangi
IT IS HEREBY AGREED AS FOLLOWS:

This Agreement shall commence on 16thOct 2019 (the “Start Date”) and Jumbo-Jobs shall provide the services detailed below for a period of 90 days from the Start Date i.e. 16-10-2019 till 15-01-2019.

Jumbo-Jobs will provide the candidate with the name of the client they have already approached and will also provide details of any other clients who are interested in the resume for the duration of 90 Days.

Terms and Conditions
Jumbo-Jobs select and apply on behalf of candidates for either permanent/temporary employment on the following terms and conditions:
It is client who acknowledges and agrees that they are solely responsible for the recruitment decision they make. It is important that the client is entirely satisfied with a candidate before engagement.
Jumbo-Jobs will spot current job openings from various sources and we share job opportunities with the candidate with his/her accord. The details of the job roles and responsibilities along with a brief depiction about the prospective companies will be shared.

CONFIDENTIALITY
Any information supplied to a client by Jumbo-Jobs regarding a candidate is done so on a strictly confidential basis to enable the client to assess a candidate’s suitability for the position and except where authorized or required by law shall not be disclosed to any third party without the express written consent of the candidate.
Jumbo-Jobs endeavors to obtain accurate details on all candidates including their qualifications and experience. Jumbo-Jobs is however reliant on the integrity of information supplied to it by potential candidates placed by Jumbo-Jobs.• The total cost of the services and the entire recruitment process including the registration charges is USD 600 out of which you pay only USD 300 upfront, remaining USD 300 will be charged after you complete your probation period in the company.
The client shall be solely responsible for any failure in the interview. No liability is accepted by Jumbo-Jobs for any errors, expenses, loss and damage.

Jumbo-Jobs will ensures further and will arrange an alternate opportunity without any additional charges.• If Jumbo-Jobs fail in providing job Opportunities within 90 days, total amount which the Job Seeker has paid in advance for the services will be refunded.
We see our company as a bridge between jobseekers and employers adding value, productivity and a happy environment and career for all involved. We also help promote your profile to a wide range of people who know the value of your profile.

Jumbo-Jobs Date: 16th Oct 2019

No comments:
Labels:

PROCESS VALIDATION

Validation:
Validation is the action of proving or declaring something (Procedure, process & equipment etc) that actually capable to deliver expected results and is officially valid.

Process Validation:
Process validation is the action of proving or declaring that the established process is capable to deliver expected results and is officially valid.

Objective of process Validation
To generate a documented evidence, from the evaluation of data from process design stage through commercial production, that provides a high degree of assurance that a specific process will consistently results in a product that meets predetermined specification and quality characteristics.




Process validation should not be viewed as a one-off event. Process validation incorporates a life cycle approach linking product and process development, validation of the commercial manufacturing process and maintenance of the process in a state of control during routine commercial production.

The objective of process validation consists of following major steps. 

  • The process design is evaluated to show that it is reproducible,
  • The commercial manufacturing process is defined and controlled,
  • Ongoing assurance is gained to show that the process remains in a state of control.

Types of Process Validation:

Process validation mainly divided in to following four types.

a) Prospective Validation (Premarket Validation)
b) Concurrent Validation
c) Retrospective Validation
d) Re-validation


A) Prospective Validation (Premarket Validation) 

This approach to validation is normally undertaken during development stage by means of a risk analysis of the process, generally whenever the process for a new formula (or within a new facility) must be validated before routine pharmaceutical production commences. 

In fact, validation of a process by this approach often leads to transfer of the manufacturing process from the development function to production.

Prospective validation should be completed before commercial distribution.

B) Concurrent Validation: 

Concurrent validation is carried out during normal production. 

This method is effective only if the development stage has resulted in a proper understanding of the fundamentals of the process.

The first three production-scale batches must be monitored as comprehensively as possible. The nature and specifications of subsequent in-process and final tests are based on the evaluation of the results of such monitoring.

This validation generally used for batches produced infrequently and/or batches are produced by a validated process that has been modified.

Prior to the completion of concurrent validation, batches can be released.


C) Retrospective Validation: (Regulatory not considering this as on date) 

Retrospective validation is used for facilities, processes, and process controls in operation use that have not undergone a formally documented validation process.

Retrospective validation is obviously not a quality assurance measure in itself, and should never be applied to new processes or products. It may be considered in special circumstances only, e.g. when validation requirements are first introduced in a company. 

Retrospective validation may then be useful in establishing the priorities for the validation programme. If the results of a retrospective validation are positive, this indicates that the process is not in need of immediate attention and may be validated in accordance with the normal schedule.

Batches selected for retrospective validation should be representative of all batches made during the review period, including any batches that failed to meet specifications, and should be sufficient in number to demonstrate process consistency. Retained samples can be tested to obtain data to retrospectively validate the process.

D) Re-Validation: 

Re-validation means repeating the original validation effort or any part of it, and includes investigative review of existing performance data.

Re validation is needed to ensure that changes in the process and/or in the process environment, whether intentional or unintentional, do not adversely affect process characteristics and product quality.

Possible reasons for re-validation:
a) Periodic re-validation
b) Re-validation after change in the starting material
c) Re-validation after change in the packing material
d) Re-validation after change in the process
e) Re-validation after change in the equipment or measuring instrument
f) Re-validation after change in the production area or supporting system.
g) Re-validation after significant change in the batch size

Traditional Approach of Process Validation:
Traditionally process validation was focused on testing, instrument qualification, and process robustness and repeatability.

Traditional approach includes following four elements

Design Qualification (DQ)
Installation Qualification (IQ)
Operational Qualification (OQ)
Process Validation (PV)

In this approach the manufacturer performs a minimum of 3 commercial batches for validation and if successful, the validation effort is considered complete, and manufacturer could then routinely use the process to produce the product, without further process validation and there was no requirement to perform any further ongoing life cycle validation efforts.


Modern Approach of Process Validation (Life Cycle Approach):

Against to traditional approach, the current enhanced process validation approach consists three phase continuous process with ongoing effort for the entire life cycle of the product called as life cycle approach.

Phase I. Process design

Phase II. Qualification and process verification

Phase IIA. Qualification

Phase IIB. Continuous process performance verification

Phase III. Continued process verification



Phase I. Process design:

The goal of this stage is to design a process suitable for routine commercial manufacturing process that can consistently deliver a product that meets its quality attributes. 
Process design should normally cover design of experiments, product & process development, and the manufacture of products for use in clinical trials, pilot-scale batches and technology transfer. 
Process design should cover aspects for the selection of materials, expected production variation, selection of production technology/process and qualification of the unitary processes that form the manufacturing process as a whole, selection of in-process controls, tests, inspection and its suitability for the control strategy. 


Product & Process development: 
The aim of pharmaceutical development is to design a quality product and its manufacturing process to consistently deliver the intended performance of the product. 
It is important to recognize that quality cannot be tested into products; i.e., quality should be built in by design. 
At the completion of this stage technology transfer package containing information sufficient to plan and manufacture scale up & exhibit batches shall be made available. 
A development report and/or a technology transfer document, formally reviewed and approved by research and development personnel, and formally accepted by manufacturing, engineering and quality personnel, should be prepared. 
Such a document may include information, desired clinical performance, bills of materials, approved suppliers, finished product specifications and test methods, in-process testing specifications, equipment recommendations, master batch production records, master batch packaging records, stability reports, critical quality attributes, critical process parameters, batch comparisons, data on formulation batches, stability batches, clinical/ bio batches and scale-up batches. These documents should be readily available to the manufacturing site. 


Scale up activities: 
The aim of scale up activities is to assess the impact of scaling up of manufacturing process on the performance of manufacturing process and product quality. 
At the completion of this stage, control strategy of for manufacturing process for validation batches should be made available. 
A scale up report, formally reviewed and approved by research and development personnel, manufacturing and quality personnel, should be prepared. 
Such a document may include information related to Product, Manufacturing process, process evaluation and recommended control strategy with conclusion as a minimum criteria. 
— As part of the process validation life cycle some process validation studies may be conducted on pilot-scale batches (corresponding to at least 10% or 100 000 units, whichever is the greater) of the production scale. Where the batch size is smaller and/or where the process is tailored to the geometry and capacity of specific equipment, it may be necessary to provide production-scale validation data.
— The number of batches included in the process design stage of validation should be appropriate and sufficient to include (but not be limited to) the expected variations in starting materials, and confirm the suitability of the equipment and manufacturing technology
— Manufacturers should define the stage at which the product is considered to be validated and the basis on which that decision was made. It should include a justification for the number of batches used based on the complexity and expected variability of the process.


Phase II. Qualification and process verification:






This phase consist of following sub-phases.






Phase IIa: Qualification of personnel, premises, utilities, and equipment’s where commercial scale batches will be manufactured.
Phase IIb: Continuous process performance verification.






Phase IIa: 
Personnel Premises, utilities, support systems and equipment should be appropriately qualified before process performance verification (as part of validation) is started. 
In a traditional approach, stages of qualification may include design, installation, operational and performance qualification. 
In some cases process validation may be conducted concurrently with performance qualification. 


Phase IIb: 
After completion of qualification, commercial batches should be subjected to continuous process performance verification as part of process validation. It should confirm that scale up in batch size do not adversely affect the characteristics of a product. 
Demonstrates that a process that operates within the predefined specified parameters consistently produces a product which meets all its critical quality attributes (CQAs) and control strategy requirements 
The process should be verified on commercial-scale batches prior to marketing of the product. 
Extensive in-line or at-line controls should be used to monitor process performance and product quality in a timely manner. In most cases, PPQ will have a higher level of sampling, additional testing, and greater scrutiny of process performance than would be typical of routine commercial production. 
Manufacturers should describe the appropriateness and feasibility of the CPV strategy including the process parameters and material attributes that will be monitored as well as the analytical methods that will be employed. 
It is expected that additional monitoring for the first commercial batches should be done where continuous process verification is implemented. 


Phase III. Continued process verification: 
Manufacturers should monitor product quality of commercial batches after completion of Phase I and Phase II of process validation. This will provide evidence that a state of control is maintained throughout the product life-cycle 
Periods of enhanced sampling and monitoring may help to increase process understanding as part of continuous improvement. 
Process trends such as the quality of incoming materials or components, in-process and finished product results and non-conformances should be collected and assessed in order to verify the validity of the original process validation or to identify required changes to the control strategy. 
The extent and frequency of ongoing process validation should be reviewed periodically and modified if appropriate throughout the product life-cycle. 

Traditionally process validation was focused on testing, instrument qualification, and process robustness and repeatability.
Traditional approach includes following four elements
Design Qualification (DQ)
Installation Qualification (IQ)
Operational Qualification (OQ)
Process Validation (PV)

In this approach the manufacturer performs a minimum of 3 commercial batches for validation and if successful, the validation effort is considered complete, and manufacturer could then routinely use the process to produce the product, without further process validation and there was no requirement to perform any further ongoing life cycle validation efforts.

Modern Approach of Process Validation (Life Cycle Approach):
Against to traditional approach, the current enhanced process validation approach consists three phase continuous process with ongoing effort for the entire life cycle of the product called as life cycle approach.

Phase I. Process design

Phase II. Qualification and process verification

Phase IIA. Qualification

Phase IIB. Continuous process performance verification

Phase III. Continued process verification


Phase I. Process design:

The goal of this stage is to design a process suitable for routine commercial manufacturing process that can consistently deliver a product that meets its quality attributes.
Process design should normally cover design of experiments, product & process development, and the manufacture of products for use in clinical trials, pilot-scale batches and technology transfer.
Process design should cover aspects for the selection of materials, expected production variation, selection of production technology/process and qualification of the unitary processes that form the manufacturing process as a whole, selection of in-process controls, tests, inspection and its suitability for the control strategy.


Product & Process development:
The aim of pharmaceutical development is to design a quality product and its manufacturing process to consistently deliver the intended performance of the product.
It is important to recognize that quality cannot be tested into products; i.e., quality should be built in by design.
At the completion of this stage technology transfer package containing information sufficient to plan and manufacture scale up & exhibit batches shall be made available.
A development report and/or a technology transfer document, formally reviewed and approved by research and development personnel, and formally accepted by manufacturing, engineering and quality personnel, should be prepared.
Such a document may include information, desired clinical performance, bills of materials, approved suppliers, finished product specifications and test methods, in-process testing specifications, equipment recommendations, master batch production records, master batch packaging records, stability reports, critical quality attributes, critical process parameters, batch comparisons, data on formulation batches, stability batches, clinical/ bio batches and scale-up batches. These documents should be readily available to the manufacturing site.


Scale up activities:
The aim of scale up activities is to assess the impact of scaling up of manufacturing process on the performance of manufacturing process and product quality.
At the completion of this stage, control strategy of for manufacturing process for validation batches should be made available.
A scale up report, formally reviewed and approved by research and development personnel, manufacturing and quality personnel, should be prepared.
Such a document may include information related to Product, Manufacturing process, process evaluation and recommended control strategy with conclusion as a minimum criteria.
 — As part of the process validation life cycle some process validation studies may be conducted on pilot-scale batches (corresponding to at least 10% or 100 000 units, whichever is the greater) of the production scale. Where the batch size is smaller and/or where the process is tailored to the geometry and capacity of specific equipment, it may be necessary to provide production-scale validation data. — The number of batches included in the process design stage of validation should be appropriate and sufficient to include (but not be limited to) the expected variations in starting materials, and confirm the suitability of the equipment and manufacturing technology — Manufacturers should define the stage at which the product is considered to be validated and the basis on which that decision was made. It should include a justification for the number of batches used based on the complexity and expected variability of the process.

Phase II. Qualification and process verification:





This phase consist of following sub-phases.





Phase IIa: Qualification of personnel, premises, utilities, and equipment’s where commercial scale batches will be manufactured. Phase IIb: Continuous process performance verification.





Phase IIa:
Personnel Premises, utilities, support systems and equipment should be appropriately qualified before process performance verification (as part of validation) is started.
In a traditional approach, stages of qualification may include design, installation, operational and performance qualification.
In some cases process validation may be conducted concurrently with performance qualification.


Phase IIb:
After completion of qualification, commercial batches should be subjected to continuous process performance verification as part of process validation. It should confirm that scale up in batch size do not adversely affect the characteristics of a product.
Demonstrates that a process that operates within the predefined specified parameters consistently produces a product which meets all its critical quality attributes (CQAs) and control strategy requirements
The process should be verified on commercial-scale batches prior to marketing of the product.
Extensive in-line or at-line controls should be used to monitor process performance and product quality in a timely manner. In most cases, PPQ will have a higher level of sampling, additional testing, and greater scrutiny of process performance than would be typical of routine commercial production.
Manufacturers should describe the appropriateness and feasibility of the CPV strategy including the process parameters and material attributes that will be monitored as well as the analytical methods that will be employed.
It is expected that additional monitoring for the first commercial batches should be done where continuous process verification is implemented.


Phase III. Continued process verification:
Manufacturers should monitor product quality of commercial batches after completion of Phase I and Phase II of process validation. This will provide evidence that a state of control is maintained throughout the product life-cycle
Periods of enhanced sampling and monitoring may help to increase process understanding as part of continuous improvement.
Process trends such as the quality of incoming materials or components, in-process and finished product results and non-conformances should be collected and assessed in order to verify the validity of the original process validation or to identify required changes to the control strategy.
The extent and frequency of ongoing process validation should be reviewed periodically and modified if appropriate throughout the product life-cycle.

No comments:
Labels:
Subscribe to: Posts (Atom)