Maintaining a Validated State PV, PM and Statistics

associated with Current Regulation.

Date: Tuesday, July

14th, 2015 || Time: 01:00 PM EDT | 10:00 AM PST

Duration: 90 Minutes || Course Level: Beginner

'Live' Webinar by Jerry

Dalfors

Register Now

Overview
Validation is a continuous improvement journey; it is not a voyage of discovery or
successfully completing three conformance lots. Hence the means by which we identify
the elements that need to be validated are often missing a few steps in the operational,
cycle development and performance qualification that after we move into a normal
operation may require a re-assessment as per the current PV guideline (evaluating the
performance of the process identifies problems and determines whether action must be
taken to correct and re-validate, anticipate, and prevent problems so that the process
remains in control). This includes an on-going review of the originally defined Critical
Steps, Product Test Data, Change Control, and OOS, OOL and OOT incidents which all
have to be included in the Annual Product Review to demonstrate an acceptable
validated state of operation and process control.
Critical Steps, Parameters that Cause Variability, Critical Process Parameter Definition,
Target and Range, Product Test Data, Process Monitoring and Control, Change Control,
Critical and Support Utilities, Product Processes, Computer Systems, Controlled
Equipment and Facilities, Process and Laboratory Equipment, QC Laboratory Data,
Reportable Values, OOS, OOL and OOT Investigations, Control Charts,Method
Validation/Revalidation, Revalidation Process/Product Assessment, Process Monitoring
Tools and Control, Data Review, Trending and Analysis, Complaints and Adverse
Events, Deviation Investigations/Product Impact, Assessments, Annual Product Reviews.
Why Should You Attend
Process knowledge and understanding is the basis for establishing an approach to
process control for each unit of operation specific to equipment variables in order to
generate overall process control needed for validation. The current majority of serious
warning letters and consent decrees have been issued against companies with years of
experience but an overall miscomprehension of the validation expectations. Is a validated
process that has a significant number of OOS batches considered a validated process? A

system or systems for detecting unplanned departures from the process as initially
designed or currently operated is essential to accomplish this objective.
Educating the Experienced
How do we teach old dogs new tricks?
How do we teach new dogs new tricks?
We have to know what the objective is, what tools we have in our tool-box, know how
to use them and demonstrate the confidence to apply them
How to get more bang for your buck (validation is a cost savings program, but
validation is viewed by executives as serious expense that would like to be avoided)
Randomized Block Statistical Model for Effective Validation
Grouping to have the units in a block as uniform as possible so that observed
differences will be largely due to treatment and make root cause analysis simple and
accurate
Measure uniformity within a loaded sterilizer chamber and at the same time map the
chamber.in two runs we can tell as much about the performance of the sterilizer using
a randomized block experimental design as is normally with a dozen or so experimental
temperature distribution and heat penetration runs
Uses randomization, an expectation of uniformity, analysis of variance and an equally
likely chance for each location to have an independent lethality value of all other
locations in the chamber.
Areas covered in the webinar
Continued monitoring and/or sampling at the levels established during the development
and qualification stages until sufficient data is available to generate statistically significant
variability estimates. Once the variability is known, sampling and/or monitoring should be
adjusted to a statistically significant level. Variation is to be used to detect the potential
for defect complaints, OOS including OOT and OOL results, including deviation reports,
process yield variations, BPR deficiencies, incoming raw material variances, adverse
events and many other issues that may be found to enhance a validated (cost effective
with minimal patient risk) means of operation. Hence change control becomes a critical
component using SSR (sound scientific rationale) to manage an on-going validated state.
Appropriate Application of Simple Statistical Tools, the Scientific Methods, facts,
theories, proposals, functional requirements (FRS), acceptance criteria, and formation of
a hypothesis that is logical with sound scientific rationale by being scientifically based
making it defendable.
Objective Evaluation - To most scientists, statistics is logic or common sense with a
strong admixture of arithmetic procedures. The logic supplies the method by which data
are to be collected and determined how extensive they are to be. Critical thinking as
opposed to assumed awareness creates significant issues during the evaluation phase of
any process.
The arithmetic, together with certain numeric tables, yields the material on which to
base the inference and measure the level of uncertainty associated with the process
variables.The arithmetic is often routine, requiring no special mathematical training for
the user, however the choice of the statistical model requires significant comprehension

of the process in order to select the appropriate statistical model, then make sure the
sampling fits the model so the arithmetic can be done to determine how the ANOVA
results can be interpreted to demonstrate a maintained validated state.
Process observations and data retrieval are the raw materials with which quality and
statistical workers deal which means the results need to be in the form of numbers
(objective evidence) as result of a measurement, not subjective results from check
boxes. Tracking the pass/fail results is only an appetizer to the next phase of the
assessment of the validated process including equipment and operator
performance.Numbers are what we use to constitute and address the situation to
determine if the data is a variability or variation.
Examples of Objective Data: Yield, pressure, pH, flow rate, time and lapse time,
amounts, number of defects, length, duration, and many, many more depending on the
validated equipment and associated process.
Our Responsibility: We are to manage the collection based on the statistical model.
Presentation, characterization and, summarization of data including potential elements
such as the results from the regression analysis, z-score, randomized block and a
multitude of other means of assessing the consistency and identified variables of the
validated process.
ANOVA - Analysis of Variance
Not used to test hypotheses about variances used to test hypotheses about means (bar
x and double bar x). Lifetimes of two different types of light bulbs. Effectiveness of two
different toothpastes.Now we calculate the sum of squares and variances to measure
variation between and within groups. Why? - Because we are trying to test a hypothesis
about the equality of the datas average or datas mean.Sum of squares sum of the
variance (an individual value minus the average squared). Null Hypothesis we test to
demonstrate that the difference between the means is null (not 0) or insignificant.Linear
Regression and Correlation. Used to Predict unknown values within a bracket (minimum
and maximum operating ranges outside a bracket future (be careful). Line of Best Fit
(Regression Line), the slope and the Y intercept define the regression line, the idea
behind finding a regression line (line of best fit) is based on the assumption that the data
is scattered randomly about a single straight line.
Correation Coefficient 1 is perfect either positive or negative 0 indicates the data
have no correlation. Correlation is the term used to indicate how close to the single line
the data fall.
Experimental Design - By now we should begin to understand the need to be able
know how we want to analyze the data before we begin to collect individual observations.
Learning objective
Statistical Applications Use of a statistician or person with adequate statistical training
(not just 6 Sigma) to develop the experimental design and the statistical methods/models
needed to measure and evaluate process capability, uniformity and on-going stability.
Generate A Sense of Control Process design and development, when assessed by the
statistician, should anticipate significant sources of variability and establish statistically

significant means of detection, control and mitigation strategies as well as initially finding
a means of defining the alert limits and action limits that will most likely change as the
process moves into a routine operation and now provides SQC and 6 Sigma
opportunities. Too often, as sited in a variety of 483s, 6 Sigma was used to establish
limits during development which is a significant statistical error.
Create Consistency
Enhance Process Understanding
Meet Industry Regulations
Who will benefit
This webinar will be highly beneficial for those within the pharmaceutical, medical device
and solid dosage industries, such as:
Statisticians
Quality Professionals
Engineering Professionals
Validation Personnel
Documentation Personnel
Speaker profile
Jerry Dalfors has extensive (40+ years) of business administration,
consultative, technical and managerial experience in the development and
manufacture of highly regulated biopharmaceutical products including
injectables, biologics, medical devices and oral dosages. He has held permanent
employee, temporary employee and company representative management positions with
a multitude of the major pharmaceutical and biotechnology companies in the US. He has
worked with or assisted more than two dozen companies with the establishment of
controlled document/quality systems, FDA briefing and submittal documents, project
management of several multimillion dollar projects including design, start-up and
validation to assure fast track FDA approval by maintaining strict regulatory compliance
during all phases of engineering, construction, commissioning and validation, and has
written numerous submission documents for product, process and facility
approval/licensing which also required the development of quality systems which
included customer complaint management, deviation management, CAPA and
associated site wide employee training. Each of his projects have been received and
accepted by the FDA and other regulatory agencies. Jerry is considered an expert in
most all aspects of the biopharmaceutical and medical device industry and has trained
many FDA field inspectors on a variety of topics. None of his work has ever received a
483 but has corrected and prevented many along with Warning Letter remediation