Applied Statistics for FDA Process Validation

Course “Applied Statistics for FDA Process Validation” has been pre-approved by RAPS as eligible for up to 12 credits towards a participant’s RAC recertification upon full completion.

In Guidance for Industry Process Validation: General Principle and Practices, process validation is defined as, “”…the collection and evaluation of data, from the process design stage through commercial production..” The guidance further delineates the ‘process design stage through commercial production’ into three distinct stages of the product lifecycle:

Stage 1: Process Design: The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities.

Stage 2: Process Qualification: During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.

Stage 3: Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control.

The first stage of process validation is process design. The Process Validation guidance document states, “A successful validation program depends on information and knowledge from product and process development. This knowledge and understanding is the basis for establishing an approach to control of a manufacturing process that results in products with desired quality attributes:

Manufactures should:

• Understand the sources of variation
• Detect the presence and degree of variation
• Understand the impact of variation on the process and ultimately on product attributes
• Control the variation in a manner commensurate with the risk it represents to the process and product.”

The second stage of process validation is process qualification. Although stage 2 has two elements, this course will focus on recommendations for the second element, PPQ. PPQ “combines the actual facility, utilities, equipment (each now qualified), and the trained personnel with the commercial manufacturing process, control procedures, and components to produce commercial batches.” Additionally, the process validation guidance document that “Each manufacturer should judge whether it has gained sufficient understanding to provide a high degree of assurance in its manufacturing process to justify commercial distribution of the product. Focusing exclusively on qualification efforts without understanding the manufacturing process and associated variations may not lead to adequate assurance of quality.”

The third stage of process validation is continued process verification. The process validation guidance document defines the need for this stage: “After establishing and confirming the process, manufacturers must maintain the process in a state of control over the life of the process, even as materials, equipment, production environment, personnel, and manufacturing procedures change.” Manufacturers should use ongoing programs to collect and analyze product and process data to evaluate the state of control of the process. These programs may identify process or product problems or opportunities for process improvements that can be evaluated and implemented through some of the activities described in Stages 1 and 2.”

This course focuses on how to establish a systematic approach to implementing statistical methodologies into a process validation program consistent with the FDA guidance. It begins with a primer on statistics, focusing on methods that will be applied in each remaining chapter. Next, it teaches the application of statistics for setting specifications and assessing measurement systems (assays), two foundational requirements for process validation. Lastly, the course applies statistic through the three stages of process validation defined by requirements in the process validation regulatory guidance documents. Methods taught through all three stages are recommended by regulatory guidance documents; references to the specific citations in the guidance documents are provided.

Why you should attend:

The Food and Drug Administration (FDA) provided a guidance for industry in 2011 that has established a framework for process validation in the pharmaceutical industry. This guidance, titled “Process Validation: General Principles and Practices” consists of a three-stage process. The three stages are 1) Process Design, 2) Process Qualification, and 3) Continued Process Verification.

This course focuses on how to establish a systematic approach to implementing statistical methodologies into a process development and validation program consistent with the FDA guidance. This course teaches the application of statistics for setting specifications, assessing measurement systems (assays), using design of experiments (DOE), developing a control plan as part of a risk management strategy, and ensuring process control/capability. All concepts are taught within the three-stage product cycle framework defined by requirements in the process validation regulatory guidance documents.

Although established for the pharmaceutical industry, it also provides a useful framework for other industries.

Analyses in this course use the point-and-click interface of JMP software by SAS.

Areas Covered in the Session

• apply statistics to set specifications and validate measurement systems (assays)
• develop appropriate sample plans based on confidence and power
• implement suitable statistical methods into a process validation program for each of the three stages
• Stage 1, Process Design: utilize risk management tools to identify and prioritize potential critical process parameters; and define critical process parameters and operating spaces for the commercial manufacturing process using design of experiments (DOE)

• Stage 2, Process Qualification: assess scale effects while incorporating large (pilot and/or commercial) scale data; develop process performance qualification (PPQ) acceptance criteria by characterizing intra and inter-batch variability using process design data and batch homogeneity studies; and develop an appropriate sampling plan for PPQ
• Stage 3, Continued Process Verification: develop a control plan as part of a risk management strategy; collect and analyze product and process data; and ensure your process is in (statistical) control and capable.

---

Who Will Benefit:

This seminar is designed for pharmaceutical and biopharmaceutical professionals who are involved with product and/or process design, validation, or manufacturing/control.

• Process Scientist/Engineer
• Design Engineer
• Product Development Engineer
• Regulatory/Compliance Professional
• Design Controls Engineer
• Six Sigma Green Belt
• Six Sigma Black Belt
• Continuous Improvement Manager

Day 1 Schedule

Lecture 1: Introduction to Statistics for Process Validation

• principles of process validation
• stages of process validation

Primer on Statistical Analysis

• basic statistics

Lecture 2: Primer on Statistical Analysis (cont.)

• statistical intervals and hypothesis testing

Lecture 3: Primer on Statistical Analysis (cont.)

• statistical intervals and hypothesis testing
• ANOVA

Lecture 4: Primer on Statistical Analysis (cont.)

• regression
• run charts

Day 2 Schedule

Lecture 1: Foundational Requirements for Process Validation

• setting specifications
• analytical methodology

Stage 1 – Process Design

• steps to DOE
• screening designs

Lecture 2: Stage 1 – Process Design

• response surface designs
• establishing a strategy for process qualification

Lecture 3: Stage 2 – Process Qualification

• introduction
• incorporation of large-scale data
• development of PPQ acceptance criteria
• development of sampling plans

Lecture 4: Stage 3 – Continued Process Verification

• statistical process control
• process capability

Heath Rushing

Co-founder and Principal, Adsurgo

Heath Rushing is the cofounder of Adsurgo and author of the book Design and Analysis of Experiments by Douglas Montgomery: A Supplement for using JMP. Previously, he was the JMP and Six Sigma training manager at SAS. He led a team of nine technical professionals designing and delivering applied statistics and quality continuing education courses. He created tailored courses, applications, and long-term training plans in quality and statistics across a variety of industries to include biotech, pharmaceutical, medical device, and chemical processing. Mr. Rushing has been an invited speaker on applicability of statistics for national and international conferences. As a Quality Engineer at Amgen, he championed statistical principles in every business unit. He designed and delivered a DOE course that immediately became the company standard required at multiple sites. Additionally, he developed and implemented numerous innovative statistical methods advancing corporate risk management, process capability, and validation acceptance criteria. He won the top teaching award out of 54 instructors in the Air Force Academy math department where he taught several semesters and sections of operations research and statistics. Additionally, he designs and delivers short courses in statistics, data mining, and simulation modeling for SAS.

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What are the FDA’s Process Validation requirements?

Process Validation (PV), according to the FDA, is collecting and assessing data right from the design stage till the production stage. PV is set out for all the stages of production for a product in the FDA-regulated industries. The core purpose of PV is to establish scientific proof that any process being employed has the capability of delivering quality products consistently.

The FDA’s process validation requirements are set out in its general principles of Process Validation. Starting from 1987, the FDA has been issuing guidelines at intervals to state, improve and strengthen the general principles of Process Validation. In almost a quarter century of the first guideline, the revision of January 2011 came into being. This guideline is considered a landmark and a guide for PV professionals since it reworked extensively and expanded the general principles on process validation. It is the current guideline from the FDA on Process Validation requirements.

These are what the FDA’s 2011 guideline on general principles on Process Validation propagate:

• Incorporation of the principles of sound science
• Taking steps to assess and mitigate risk
• Bringing about improvements in every stage of the process
• Adapting the science-based principles of contemporary manufacturing
• Fostering and encouraging innovation

The centrality of control to process validation

Process validation is tied to the product lifecycle approach by the FDA general principles on process validation of 2011. The central purpose of process validation is to ensure that the process is in a state of control at all stages of production.

The following points illustrate the reason for which the FDA expects its PV requirements to be met:

• Being a process that is ongoing and continuous, PV begins at the earliest stages of production and goes on till the product’s lifecycle is completed
• Those in charge of commercial production should have deep and intimate knowledge of the workings of PV principles
• Only this knowledge helps PV professional locate the sources of variability and address them
• Only PV into which risk management is built frees errors from the product

The three stages of PV

The FDA stipulates three layers or stages on which its general principles of Process Validation are built:

• Process design: The stage in which the knowledge gained helps the commercial process define the process development activities
• Process qualification: The stage where PV guarantees that the process design has the capability for being reproduced at industrial level
• Continued Process Validation: The most important stage PV in that this is where the element of control into the routine production process is introduced and built; Continued Process Validation takes under its ambit all activities such as continuous verification, maintenance, and process improvement. Information is collected and monitored during commercialization to assess the Continued Process Validation stage.

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Seminar

Applied Statistics for FDA Process Validation

Course “Applied Statistics for FDA Process Validation” has been pre-approved by RAPS as eligible for up to 12 credits towards a participant’s RAC recertification upon full completion.

In Guidance for Industry Process Validation: General Principle and Practices, process validation is defined as, “”…the collection and evaluation of data, from the process design stage through commercial production..” The guidance further delineates the ‘process design stage through commercial production’ into three distinct stages of the product lifecycle:

Stage 1: Process Design: The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities.

Stage 2: Process Qualification: During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.

Stage 3: Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control.

The first stage of process validation is process design. The Process Validation guidance document states, “A successful validation program depends on information and knowledge from product and process development. This knowledge and understanding is the basis for establishing an approach to control of a manufacturing process that results in products with desired quality attributes:

Manufactures should:

• Understand the sources of variation
• Detect the presence and degree of variation
• Understand the impact of variation on the process and ultimately on product attributes
• Control the variation in a manner commensurate with the risk it represents to the process and product.”

The second stage of process validation is process qualification. Although stage 2 has two elements, this course will focus on recommendations for the second element, PPQ. PPQ “combines the actual facility, utilities, equipment (each now qualified), and the trained personnel with the commercial manufacturing process, control procedures, and components to produce commercial batches.” Additionally, the process validation guidance document that “Each manufacturer should judge whether it has gained sufficient understanding to provide a high degree of assurance in its manufacturing process to justify commercial distribution of the product. Focusing exclusively on qualification efforts without understanding the manufacturing process and associated variations may not lead to adequate assurance of quality.”

The third stage of process validation is continued process verification. The process validation guidance document defines the need for this stage: “After establishing and confirming the process, manufacturers must maintain the process in a state of control over the life of the process, even as materials, equipment, production environment, personnel, and manufacturing procedures change.” Manufacturers should use ongoing programs to collect and analyze product and process data to evaluate the state of control of the process. These programs may identify process or product problems or opportunities for process improvements that can be evaluated and implemented through some of the activities described in Stages 1 and 2.”

This course focuses on how to establish a systematic approach to implementing statistical methodologies into a process validation program consistent with the FDA guidance. It begins with a primer on statistics, focusing on methods that will be applied in each remaining chapter. Next, it teaches the application of statistics for setting specifications and assessing measurement systems (assays), two foundational requirements for process validation. Lastly, the course applies statistic through the three stages of process validation defined by requirements in the process validation regulatory guidance documents. Methods taught through all three stages are recommended by regulatory guidance documents; references to the specific citations in the guidance documents are provided.

---

Why you should attend:

The Food and Drug Administration (FDA) provided a guidance for industry in 2011 that has established a framework for process validation in the pharmaceutical industry. This guidance, titled “Process Validation: General Principles and Practices” consists of a three-stage process. The three stages are 1) Process Design, 2) Process Qualification, and 3) Continued Process Verification.

This course focuses on how to establish a systematic approach to implementing statistical methodologies into a process development and validation program consistent with the FDA guidance. This course teaches the application of statistics for setting specifications, assessing measurement systems (assays), using design of experiments (DOE), developing a control plan as part of a risk management strategy, and ensuring process control/capability. All concepts are taught within the three-stage product cycle framework defined by requirements in the process validation regulatory guidance documents.

Although established for the pharmaceutical industry, it also provides a useful framework for other industries.

Analyses in this course use the point-and-click interface of JMP software by SAS.

---

Areas Covered in the Session

• apply statistics to set specifications and validate measurement systems (assays)
• develop appropriate sample plans based on confidence and power
• implement suitable statistical methods into a process validation program for each of the three stages
• Stage 1, Process Design: utilize risk management tools to identify and prioritize potential critical process parameters; and define critical process parameters and operating spaces for the commercial manufacturing process using design of experiments (DOE)
• Stage 2, Process Qualification: assess scale effects while incorporating large (pilot and/or commercial) scale data; develop process performance qualification (PPQ) acceptance criteria by characterizing intra and inter-batch variability using process design data and batch homogeneity studies; and develop an appropriate sampling plan for PPQ
• Stage 3, Continued Process Verification: develop a control plan as part of a risk management strategy; collect and analyze product and process data; and ensure your process is in (statistical) control and capable.

---

Who Will Benefit:

This seminar is designed for pharmaceutical and biopharmaceutical professionals who are involved with product and/or process design, validation, or manufacturing/control.

• Process Scientist/Engineer
• Design Engineer
• Product Development Engineer
• Regulatory/Compliance Professional
• Design Controls Engineer
• Six Sigma Green Belt
• Six Sigma Black Belt
• Continuous Improvement Manager

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Tougher Import Rules for FDA Imports in 2019

 

Course “Tougher Import Rules for FDA Imports in 2019” has been pre-approved by RAPS as eligible for up to 12 credits towards a participant’s RAC recertification upon full completion.

Description:

FDA and the Customs and Border Patrol Service (CBP) have become increasingly sophisticated and equally demanding in the submission of import information and adherence to government procedures. Firms that fail to understand and properly execute an import and export program find their shipments delayed, detained or refused. As of December 2016, FDA and CBP officially implemented the Automated Commercial Environment (ACE) entry filing system. You either meet ACE requirements or face entry refusals and monetary penalties of up to $10,000 per offense. Other factors can derail the expectation of a seamless import entry process. The course covers detailed information about the roles and responsibilities of the various parties involved with an import operation and how to correct the weakest link(s) in the commercial chain. The course will include tips on how to understand FDA’s thinking, negotiate with the FDA and offer anecdotal examples of FDA’s import program curiosities.

Why you should attend:

What happens when your product is detained? FDA will begin a legal process that can become an expensive business debacle. You must respond fully within short timeframes. This is not the time for you to be on a learning curve. You need to have a plan in place and know what you are doing.

The FDA is steadily increasing the legal and prior notice information requirements. If you do not know what those requirements are and you initiate a shipment, your product is figuratively dead in the water. You must be accurate with the import coding information and understand the automated and human review process. If not, you can expect detained shipments. CBP is implemented a new “Automated Commercial Environment” computer program that changes import logistics and information reporting for FDA regulated products. Your shipment may be stopped before it is even loaded at the foreign port.

Who Will Benefit:

• Domestic importers
• Foreign exporter
• Initial importers
• International trade executives
• Venture Capitalists
• Marine insurance underwriters

Agenda:

Day 1 Schedule

Lecture 1:

FDA Legal Authority Customs and Border Control (CBP) Import Process FDA Import Process Registration and documentation

Lecture 2:

FDA Import Process (continued)

• Import Brokers
• Prior Notice Information
• CBP and FDA computer programs
• Import Codes
• Bonds and Bonded Warehouses
• FDA “Notice of Action”

Lecture 3:

Import Delays Import Alerts Detention Refusals

Day 2 Schedule

Lecture 1:

Foreign Inspections FDA 483 – Inspectional Observations

Lecture 2:

FDA Warning Letters and Automatic detention

Lecture 3:

Import Hypothetical FDA Import for Export Program FDA Export Program Export Hypothetical

Lecture 4:

FDA Export Program Special Import Issues

• Trade Shows
• Personal Use
• Compassionate Use

 

Speaker:

Casper Uldriks

ex-FDA Expert and former Associate Center Director of CDRH

Casper (Cap) Uldriks owns Encore Insight LLC, which provides consulting services on FDA Law. He brings over 32 years of experience from the FDA. He specialized in the FDA’s medical device program as a field investigator, served as a senior manager in the Office of Compliance and as an Associate Center Director for the Center for Devices and Radiological Health. He developed enforcement actions and participated in the implementation of new statutory requirements. He is recognized as an exceptional and energetic speaker. His comments are candid, straightforward and of practical value. He understands how FDA thinks, operates and where it is headed.

Location:  Washington, DC Date: April 4th & 5th, 2019 and Time: 9:00 AM to 6:00 PM

Venue:  WILL BE ANNOUNCED SOON

 

Price:

1 ATTENDEE $2,000, Register for 1 attendee

5 ATTENDEES $10,000, Register for 5 attendees

10 ATTENDEES $20,000, Register for 10 attendees

Until March 10, Early Bird Price: $2,000.00
From March 11 to April 02, Regular Price: $2,200.00

 

Sponsorship Program benefits for seminar

For More Information– 

 

 

Contact us today!

NetZealous LLC DBA GlobalCompliancePanel

john.robinson@globalcompliancepanel.com

Toll free: +1-800-447-9407

Phone: +1-510-584-9661

Website: 

 

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What Happens When Your Product Is Detained by the FDA?

What happens when your product is detained by the FDA? In short and simple words, a nightmare. If you thought that the FDA Compliance had always been strict in its enforcement of import rules, you would think again if you heard about what it has worked out lately.

The FDA has partnered with the Customs and Border Patrol Service (CBP) to put in place a sophisticated and agile method by which it can monitor the information it requires from importing firms, and also ensure their adherence to government procedures. The CBP has created a novel mechanism to intensify vigilance of imports, called the Automated Commercial Environment (ACE). This computer program has brought in many changes into import logistics and the method by which importing firms have to report information pertaining to FDA-regulated products.

So, what powers do the FDA and the CBP have by implementing the ACE? They have powers of delaying, detaining or refusing shipments of firms that fail to put in place a thoroughly executed import and export program. Importing firms that believe they can take this mechanism easily could not be more mistaken: noncompliance with the requirements set out by the ACE program empowers the FDA and the CBP to stop a shipment before it is even loaded at the point of origin, even if it is a foreign port. A ship that wants to be precluded from the ACE program attracts a fine of up to $10,000 for every offense. Alternately, if the FDA detains a product or products from such a company; it will start a long drawn out and costly legal process.

Since the agency expects companies to have the import coding information accurate and up-to-date; companies that do not have a clear understanding of the automated and human review process are very likely to have their shipments detained.

Another scenario

What happens to an importer whose product is deemed fit for release and to be brought back to the port of entry by the FDA, but the importer cannot locate the product that is already sold? On such companies, the FDA slaps a fine whose value is treble that of the shipment! And this is not all. This in no way waives the other usual legal actions that the FDA will initiate anyway.

Not everything is bleak

All this should not intimidate and put importers off. Alongside the ACE program, the FDA has also put in place a redressal mechanism under its Food Safety and Modernization Act. Called the Voluntary Qualification Importer Program, this FDA-monitored program is aimed at smoothening the review and import of food items from importers who can show the agency that they are serious about implementing a higher degree of control over the safety and supply chain elements of the food items they are importing. Those Importers who are serious about the quality of food they import.

The FDA also offers export certificates, which could give an importer a level of advantage in foreign markets. Also available for a fee, albeit a small one, an FDA export certificate is a shot in the arm for importers, because this certificate is required in some markets.

Familiarize yourself with all parts of FDA import rules for 2018

GlobalCompliancePanel, a leading provider of professional trainings for all the areas of regulatory compliance, will be offering complete learning on all aspects of the FDA import rules for 2018 at a two-day seminar. The Director of this seminar on FDA import rules for 2018 is Casper Uldriks, an ex-FDA Expert and former Associate Center Director of CDRH, Olsson, who has served as a senior manager in the Office of Compliance and an Associate Center Director for the Center for Devices and Radiological Health. This course has been pre-approved by RAPS as eligible for up to 12 credits towards a participant’s RAC recertification upon full completion.

The full expanse of Casper’s many years of experience will be exhibited at this valuable seminar. He will show how to steer clear of the many common potholes and constraints that importers who don’t have a sound strategy run into. Participants will be offered tips on how importers need to put in place an established and effective business plan.

This course is of immense value to domestic importers, foreign exporters, initial importers, international trade executives, Venture Capitalists, marine insurance underwriters, import brokers, Regulatory Affairs managers, import/export consultants, in-house counsel, contract specialists, logistics managers, third party establishment inspection entities, sales managers, and investors.

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