The Enterey Blog

Where Do We Go From Here With Our Process Validation?

Posted by Tita Tavares on Fri, Apr 22, 2011 @ 01:00 PM

What are the next steps?

Having read our first 3 blogs to become familiar with the FDA’s recent Guidance for Industry Process Validation: General Principles and Practices (January 2011), you now need to start thinking about where you and your company go from here to align your organization and process validation activities with the new guidance.

Process Validation Success


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NEXT STEPS to help you: 


1. Build your knowledge base early. A successful validation program relies on information and knowledge obtained early from product and process development. This knowledge and understanding is the basis for establishing your approach to controlling the manufacturing process through continued process verification to produce products with desired quality attributes.

2. Understand the sources of your variation and the impact this variation has on your process and product. Detect the presence and degree of variation in your process. Control your variation proportionate to the risk it poses to your process and product.

3. Develop and implement a Risk Management program. Establish procedures, train personnel, and document and manage your risks in a risk management plan to reduce, eliminate, or accept process risks.

4. Use a Lifecycle Approach. Process validation activities occur over the lifecycle of the product and process from Process Design (Stage 1) to Process Qualification (Stage 2) to Continued Process Verification (Stage 3).  Science and process understanding will increase through the lifecycle.

5. Perform process monitoring to continually analyze your product and process data to ensure a state of control. This will eliminate the need for revalidation. Opportunities for process improvements can be identified, evaluated and implemented.

6. Use an integrated team approach to Process Validation. Include subject matter experts from various disciplines including process engineering, industrial pharmacy, analytical chemistry, microbiology, statistics, manufacturing, and quality assurance. Project plans with full support of senior leadership are important to success.

7. Plan and conduct all studies using sound science, appropriately documented, and approved per established procedures throughout the product and process lifecycle.

8. Develop an ongoing program to collect and analyze product and process data as required per 211.180(e). The data should include process trends and quality of incoming materials, in-process materials, and finished products, and be statistically trended and reviewed by trained personnel. A statistician or person trained in statistical process control is recommended.

9. Identify gaps in your existing process validation procedures and implement a plan to revise them appropriately to meet the expectations in the new guidance.

10. Prepare to address questions and show documented evidence to demonstrate that your manufacturing processes have been validated and are in a state of control though continued process monitoring.

Published by: Jim Anthony, Enterey| Director

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What Are the Differences in the New Process Validation Guidances?

Posted by Tita Tavares on Thu, Apr 14, 2011 @ 04:40 PM

  Enterey Process Validation Differences

 
What should you be doing differently?
  

There has been an FDA industry paradigm shift, with which you will need to align. Provided below is an easy reference table pointing out key elements of FDA’s Guidance for Industry Process Validation: General Principles and Practices (January 2011), some of the differences in the new guidance, and the areas of focus for FDA during their next inspection of your facility as it pertains to process validation.

Take a look at how these modifications could influence today’s current practices.

FDA Guidance for Industry
Process Validation: General Principles and Practices (2011)

Scope includes entire Product and Process Lifecycle

Decisions are based on Sound Science and Risk Management

3-Staged Approach to Process Validation:

1)       Process Design

2)       Process Qualification (PQ)

3)       Continued Process Verification

Emphasis on Process Design – Process design is dependent on process knowledge and understanding obtained; testing to failure is not required or expected; studies are conducted with sound scientific methods and principles, including good documentation practices

Process Qualification (PQ) differs from 1987 guidance - Process Performance Qualification (PPQ) is milestone in product lifecycle prior to commercial distribution; PPQ  is based on sound science, product and process understanding, and demonstrable control

Emphasis on Continued Process Verification and Process Control – Process knowledge and understanding is basis for approach to process control; ongoing program must be established to collect and analyze product and process data, trends, quality of incoming materials, in-process material, and finished products

Statistics – Statistician or person with adequate training in statistical process control to develop data collection plan for Continued Process Verification, statistical methods and procedures to measure and evaluate process capability, intra-batch and inter-batch variation is recommended

Revalidation and Retrospective Process Validation has been eliminated with Continued Process Verification

There is no magic number of required lots or runs in PPQ;  a documented justification and rationale that assurance is achieved and the process is in a state of control is stated in the PPQ Protocol Execution and Report

Level of PQ effort, documentation, testing, degree of control over attributes or parameters during Continued Process Verification, etc. are all commensurate to the level of risk to the process or product

Publishe by: Jim Anthony, Enterey | Director

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Key Points & Concepts: FDA’s New Guidance Docs for Process Validation

Posted by Tita Tavares on Mon, Apr 11, 2011 @ 11:00 AM

FDA: NEW Guidance for Industry Process Validation: General Principles and Practices - Issued January 2011

FDA’s new guidance aligns process validation with the product lifecycle concept and ICH Guidelines Q8 (R2) Pharmaceutical Development, Q9 (Quality Risk Management), and Q10 (Pharmaceutical Quality System).

The guidance encourages the implementation of modern development concepts of Quality by Design (QbD), such as design space, Quality Risk Management (QRM) and control strategy, throughout the product lifecycle.

The lifecycle concept links product and process development, qualification of commercial manufacturing process, and maintenance of the process in the state of control during commercial production.

Process Validation Key Points and Concepts

The guidance supports process improvement and innovation through sound science and knowledge management.

Effective process validation contributes significantly to assurance of drug quality and that the drug produced is fit for its intended use.

The guidance defines process validation as the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product.

 

Process validation activities occur over the product and process lifecycle in 3 stages:

1 | Process Design: The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities. The goal of this stage is to design a process suitable for routine commercial manufacturing that can consistently deliver a product that meets its quality attributes.

Process knowledge and understanding are obtained and captured during this stage. Studies should be conducted with sound scientific methods and principles and documented. Design of Experiment (DOE) studies help develop process knowledge. Risk analysis can be used to screen variables to minimize number of experiments while maximizing knowledge gained. Process information from product development can be leveraged in the process design stage and used in process qualification and continued process verification stages when the process design is revised or the control strategy changed.

The process knowledge and understanding gained at this stage form the basis for establishing a process control strategy.

 

2 | Process Qualification: During the process qualification (PQ) stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.

PQ consists of 2 elements:
1) Facility design and qualification of equipment and utilities
2) Process performance qualification (PPQ).

Facility design and commissioning precede PPQ. CGMP procedures must be followed.

Completion of this stage is necessary prior to commercial distribution. If acceptable, products can be released for distribution.

The PPQ combines the actual facility, utilities, qualified equipment, and trained personnel with the commercial process under normal operating conditions.

A successful PPQ confirms process design and demonstrates commercial manufacturing process performs as expected. PPQ is based on sound science and manufacturer’s overall level of product and process understanding and demonstrable control. Higher level of sampling, additional testing, and greater scrutiny of process performance usually occurs during PPQ. The PPQ protocol is reviewed and approved by quality unit. The PPQ protocol execution and report, also reviewed and approved by all appropriate departments and quality unit, state a clear conclusion that the process is in a state of control.

 

3 | Continued Process Verification: During this stage, there is continual assurance that the process remains in a state of control (validated state) during commercial manufacture.

An on-going program to collect and analyze product and process data must be established. Data collected includes process trends and quality of incoming materials or components, in process materials, and finished products. Data should be statistically trended by trained personnel Production data is collected to evaluate process capability and stability. Continued process monitoring and sampling occurs at the level established during process qualification until sufficient data are available to generate significant variability estimates. Monitoring can then be adjusted to statistically appropriate and representative levels.

Knowledge and understanding gained is the basis for establishing an approach to control the process.

Manufactures should understand the sources of variation, be able to detect the variation, understand the impact of variation on the process and product, and control the variation commensurate with the level of risk to the process and product.

Controls can consist of material analysis and equipment monitoring at significant processing points.

Manufacturers of legacy products can benefit from knowledge gained from the original process development, qualification and experience. Legacy products and processes would likely begin with Stage 3 activities for continued process verification.

Homogeneity within a batch and consistency between batches are goals of process validation activities. 

 

Recommendations:

FDA recommends an integrated team approach to process validation with subject matter experts from process engineering, industrial pharmacy, analytical chemistry, microbiology, statistics, manufacturing, and quality assurance. Project plans and full support of senior management are necessary for success.

Published by: Jim Anthony, Enterey | Director

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Up Next: What is different about the new process validation guidance? What should we be doing differently?

 

Tags: Life Sciences Industry News, Life Sciences News & Hot Topics, FDA New Guidance for Industry, Process Validation, ICH Q8, ICH Q9, ICH Q10, QRM, Quality Risk Managment, Process Verification, Process Qualification, Facility Design, CGMP, DOE, Quality Assurance, Drug Manufacturers

3 Simple Steps for Successful Process Validation Gap Analysis

Posted by Tita Tavares on Wed, Mar 30, 2011 @ 11:43 AM

Process-Validation-Supplements

FDA: NEW Guidance for Industry
Process Validation: General Principles and Practices

FDA issued its final guidance on Process Validation (Revision 1) on January 24, 2011. This guidance replaces the 1993 guidance.

 

This guidance reflects FDA’s current thinking on the topic and outlines the general principles and approaches that FDA considers appropriate for process validation for the manufacture of human and animal drug and biological products, including finished products, APIs, and combination products, and collectively referred to as drugs or products in the guidance.

 

This guidance aligns process validation activities with the product lifecycle concept and with existing FDA guidance, including FDA / ICH guidances for industry Q8 (R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. Although this guidance does not repeat the concepts and principles explained in these guidances, FDA encourages the use of these development concepts, QRM, and QS at all stages of the product and manufacturing process lifecycle.

 

FDA has the authority and responsibility to inspect and evaluate process validation performed by manufacturers. Process validation for drugs is a legally enforceable requirement under section 501(a)(2)(B) of the Act (21 U.S.C. 351(a)(2)(B). CGMP regulations for validating pharmaceutical manufacturing can be found in 21 CFR Parts 210 and 211.

 

Although FDA guidance documents are recommendations, pharmaceutical manufacturers are already assessing the scope of the new guidance and performing a gap analysis to initiate corrective action and remediate the gaps in their current standard operating procedures to enhance and align their process validation activities with FDA recommendations.

 

Successful Process Validation in 3 Steps

Step 1: read the FDA guidance for industry documents.

Step 2: complete a gap assessment.

Step 3: determine an action plan via CAPA to correct the gaps and maintain the changes to your
process validation activities and Quality System.

Published by: Jim Anthony, Enterey | Director 

Follow these steps and you’re on your way!
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Tags: Corrective Action, FDA New Guidance for Industry, Process Validation, ICH Q8, ICH Q9, ICH Q10, Gap Analysis, Quality Risk Management, Pharmacautical Quality System, Steps to Successful Process Validation, CAPA