Tag: Regulatory Strategy

Leveraging Process Analytical Technology for CMC

 

Introduction

 

In the evolving field of pharmaceutical development, the implementation of Process Analytical Technology (PAT) for manufacturing is an essential competitive advantage. PAT offers widely accepted methods to safeguard quality assurance and the general safety of pharmaceutical products. The goal of this article is to provide a summary of PAT, best practices of principles and adoption of PAT, and how to leverage increased process knowledge in your regulatory submission.

 

Understanding Process Analytical Technology (PAT)

 

Efficient pharmaceutical manufacturing is a significant facet of the global healthcare system. The well-being of patients is contingent on the accessibility of safe and effective treatments. The U.S. Food and Drug Administration (FDA) framework for process analytical technology was originally established based on insights to facilitate quality improvement. It includes risk-based regulatory outcomes that have been validated by both life science manufacturers and FDA regulators.

 

The Agency framework is based on two primary drivers:

 

• Scientific principles and tools that support the development of innovation
• Regulatory strategies that accommodate innovation during the submission process

 

Principles of Process Analytical Technology

 

CMC (Chemistry, Manufacturing, and Controls) is one of the most influential facets of drug product development. Traditional drug development in pharmaceutical manufacturing is completed using batch processing and production sample lab testing to evaluate quality. This approach has been effective in delivering quality pharmaceuticals to patients in need.

 

However, modern technologies now offer life science employees the opportunity for improving pharmaceutical development. Specifically, PAT principles and technologies focus on increasing quality assurance during the product development process. This often involves the use of unique quality controls from different types of technologies.

 

Process Analytical Technology and CMC

 

The implementation of process analytical technology encourages drug manufacturers to create a team-based regulatory approach to chemistry, manufacturing and controls. Further, the review of current good manufacturing practices (cGMP) is also essential to the success of process analytical technology.

 

Finally, in-depth CMC training is important to achieve certification in process analytical technology. This is important considering the regulatory inspection review by Agency auditors for each new drug in development. The ability to demonstrate regulatory compliance is a foundational training strategy that supports the use of process analytical technology in manufacturing.

 

Implementing Process Analytical Technology

 

In the past, many manufacturing procedures have been considered static due to regulatory constraints. Proposed process changes are often considered for feedback by FDA early in the regulatory submission process. However, this can also lead to ambiguity of what types of technology will be authorized or declined by the Agency going forward. Life science manufacturers often stick with what is approved to stay in compliance and not raise red flags with FDA.

 

Recognizing the need to reduce this ambiguity for embracing innovation, FDA launched an initiative called Pharmaceutical CGMPs for the 21st Century: A Risk-Based Approach. The goal of this program is to ensure process analytical technology principles are known by life science companies and include:

 

• Modern concepts of risk management
• Quality system approaches are incorporated into pharmaceutical manufacturing while maintaining product quality
• Life science manufacturers are encouraged to use modern innovations in pharmaceutical manufacturing technology
• FDA’s submission review and inspection programs operate in a coordinated manner
• Regulations and manufacturing standards are applied consistently by FDA and the manufacturer

 

Benefits of Implementing Process Analytical Technology

 

FDA considers process analytical technology to be:

 

“a system for designing, analyzing, and controlling manufacturing through timely measurements of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality.”

 

The primary benefit of implementing process analytical technology is to enhance understanding and control of the manufacturing process. Consequently, the tools and principles of process analytical technology should increase the level of manufacturing process understanding in general.

 

Manufacturing Process

 

Further, meeting the regulatory requirement of validating the manufacturing process can only benefit from this understanding of what quality looks like. Five core ingredients of process analytical technology strategy that should help users boost their understanding include:

 

• Enhanced process understanding and knowledge
• Improved process control and efficiency
• Reduction in production costs and waste
• Faster and more efficient product development
• Enhanced regulatory compliance

 

Adoption of Process Analytical Technology

 

Equally important, for the manufacturing team’s adoption of new technologies to be successful, employees must recognize the importance of quality assurance and patient safety. Moreover, proposing innovative approaches to pharmaceutical development should not lead to a regulatory stalemate between FDA and the life science manufacturer.

 

FDA encourages manufacturers to use the process analytical technology framework in clinical documentation, so a stalemate doesn’t occur during the regulatory process. This can include clinical evidence that helps demonstrate:

 

• Process understanding and control strategy
• Real-time process monitoring
• Multivariate data analysis (MVDA)
• Process control and optimization
• Continuous manufacturing and quality by design (QbD)

 

Process Analytical Technology Manufacturing Examples

 

FDA has provided process analytical technology examples of the tools available that facilitate manufacturing process understanding. These converge at the intersection of scientific, risk-managed pharmaceutical development, manufacturing, and quality assurance.  

 

When used within an effective manufacturing system, process analytical technology can provide effective and efficient means for facilitating process understanding. Further, continuous improvement, and development of risk-mitigation strategies. In the PAT framework, PAT manufacturing examples can be categorized according to the following:  

 

• Multivariate tools for design, data acquisition, and analysis
• Process analyzers
• Process control tools
• Continuous improvement and knowledge management tools

 

Process Analytical Technology and Quality Assurance

 

Process analytical technology and quality assurance go hand in hand when it comes to manufacturing innovation. The above performance metrics for measuring quality focus on designing, analyzing, and controlling manufacturing through timely measurements of raw and in-process materials and processes.

 

For the same reason, process analytical technology commonly includes tools that can improve chemical, physical, microbiological, mathematical, and risk analysis. Simultaneously, these quality assurance tools that aid process understanding can also support meeting existing regulatory submission requirements to validate the manufacturing process.

 

Process Analytical Technology and Regulatory Approval

 

Achieving regulatory submission approval for a new product is rarely an easy process. The clinical evidence needed to support efficacy must include documentation of quality assurance delivered by the manufacturer.

 

Innovation in development, manufacturing and quality assurance that leverages process analytical technology should help answer these common regulatory questions from FDA experts:

 

• What are the mechanisms of degradation, drug release, and absorption?
• What are the effects of product components on quality?
• What sources of variability are critical?
• How does the process manage variability?

 

Regulatory Submission

 

Regulatory considerations that can help document quality assurance improvements from process analytical technology often are found in:

 

• Reducing production cycle times by using on-, in-, and/or at-line measurements and controls
• Preventing rejects, scrap, and re-processing
• Real time release
• Increasing automation to improve operator safety and reduce human errors
• Improving energy and material use and increasing capacity
• Facilitating continuous processing to improve efficiency and manage variability

 

Regulatory Documentation

 

Quality assurance improvements are centered around the manufacturing process and system processes involved. FDA considers a process to be well understood if regulatory documentation shows:

 

• Why sources of variability can be identified and explained
• When production variability can be managed by owners of the process
• How quality attributes can be accurately and reliably predicted

This type of regulatory documentation provides insights for FDA regulators into materials used, an understanding of process parameters, changes in manufacturing, and environmental conditions.

 

The ability to predict these three items can show a high degree of process understanding. The goal is for your regulatory application to demonstrate your team and company understand how to reproduce process capability data and maintain a consistent state of control.

 

Conclusion

 

Process analytical technology is used to improve the scientific basis for regulatory specifications and promoting continuous improvement. The ability to enhance manufacturing while retaining or improving product quality is essential to helping patients and population health in general. Life science manufacturers should document technology improvements to FDA and demonstrate the ability to quickly resolve production-related technical issues.  

 

About the Author

 

As Vice President of Regulatory Services for Regulatory Compliance Associates® (RCA), Erika Porcelli touches all aspects of the customer experience. RCA provides consulting services to life science organizations for the resolution of compliance and regulatory challenges. RCA is a global business unit of Sotera Health, a trusted partner to more than 5,800 customers in over 50 countries, including 40 of the top 50 medical device companies and 8 of the top 10 pharmaceutical companies.

 

About Regulatory Compliance Associates

 

Regulatory Compliance Associates^® (RCA) provides life science consultants & consulting services to the following industries for resolution of compliance and regulatory challenges:

 

• Pharmaceutical
• Biologic & Biotechnology
• Sterile compounding
• Medical device
• Lab Testing

 

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. Our life science consultants are used to working on the front lines and thriving in the scrutiny of FDA, Health Canada, MHRA, and globally regulated companies.

 

As your partners, we can negotiate the potential minefield of regulatory compliance and regulatory due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

• Founded in 2000
• Expertise backed by over 500 industry subject matter experts
• Acquired by Sotera Health in 2021

 

About Sotera Health

The name Sotera Health^® was inspired by Soteria, the Greek goddess of safety, and reflects the Company’s unwavering commitment to its mission, Safeguarding Global Health^®.

 

Sotera Health Company, along with its three best-in-class businesses – Sterigenics^®, Nordion^® and Nelson Labs^®, is a leading global provider of mission-critical end-to-end sterilization solutions and lab testing and advisory services for the healthcare industry. With a combined tenure across our businesses of nearly 200 years and our industry-recognized scientific and technological expertise, we help to ensure the safety of over 190 million patients and healthcare practitioners around the world every year.

 

We are a trusted partner to more than 5,800 customers in over 50 countries, including 40 of the top 50 medical device companies and 8 of the top 10 pharmaceutical companies.

 

RCA’s Pharmaceutical Services

 

Regulatory Compliance Associates (RCA) has helped thousands of pharmaceutical companies meet regulatory, compliance, quality assurance, and remediation challenges. With more than 20 years of experience with FDA, Health Canada, EU and global regulatory agencies worldwide, RCA offers leading pharmaceutical consultants that can help you navigate through the challenges associated with evolving industry regulations.

 

Our team of over 500 seasoned FDA, Health Canada and EU compliance consultants and regulatory affairs experts can understand the complexities surrounding the pharmaceutical industry and the unique inner workings of the regulatory process. 

 

Client Solutions

 

Whether you’re in the product planning, development or pharmaceutical lifecycle management stage or need a remediation strategy for a compliance crisis, RCA^® will guide you through every step of the regulatory process and create a customized approach depending on your product and your pharma company’s individual needs. Our clients include:

 

• Companies new to FDA, Health Canada or EU regulations and the pharmaceutical industry
• Start-up organizations with novel submissions to 510(k) submissions from multi-national corporations
• Investment firms seeking private equity due diligence for pre-acquisition and post-deal research
• Law firms seeking expertise in the remediation of warning letters, consent decrees, 483’s or import bans

 

Regulatory Affairs

 

Regulatory affairs is Regulatory Compliance Associates^®’s backbone and we fully understand the complexities of the pharmaceutical and biopharmaceutical industries. Our expertise spans all facets and levels of Regulatory Affairs, from Regulatory Support for New Products to Life Cycle Management, to other services like Outsourced Regulatory Affairs, Submissions, Training, and more.

 

As your partner, we can negotiate the potential assessment minefield of pharmaceuticals with insight, hindsight, and the clear advantage of our breadth and depth of knowledge and experience. We offer the following four regulatory affairs services for pharmaceutical companies.

 

• New Product Support
• Product Lifecycle
• Other Regulatory Services

 

Compliance Assurance

 

The regulations process surrounding pharmaceutical companies can be tricky for even the most experienced industry veteran to understand, and just one misstep could mean significant and lasting consequences for your business. At RCA^®, we offer the experience and resources necessary to guide you in quality compliance.

 

• Assessments
• Audits
• Regulatory Agency Response
• Preparation and Training
• Inspection Readiness

 

Quality Assurance

 

Regulatory Compliance Associates^® Quality Assurance services include assessments, strategy, implementations, staff augmentations, and identification of quality metrics to ensure continuous improvement, aligning with your business needs and goals. Our consultants are quality life science consultants with experience spanning major corporations and start-ups. We know firsthand how to achieve, maintain, and improve quality, and we excel in transferring this knowledge to your organization.

 

• 21 CFR Part 11
• Data Integrity
• Manufacturing Support
• Facility Support

 

Remediation 

 

Regulatory Compliance Associates^® has significant experience and a proven approach to managing FDA Warning Letters, Consent Decrees, Remediation and other serious regulatory situations. We know how to partner with executive, legal, and communication teams, and will assist management with a response that will be accepted by the regulatory agency and be realistic to execute.

 

We can develop a comprehensive proof book of documented objective evidence demonstrating the corrective actions taken to remediate non-compliant issues. In addition, RCA^® can help prepare a comprehensive strategy to assist in your remediation efforts, drive continuous improvement, and maintain compliance with the regulations.

 

• Regulatory Action
• Warning Letter
• 483 Observation
• Oversight Services

 

RCA’s Medical Device Services

 

The regulatory process surrounding the medical device industry involves a strict adherence to pre/post market compliance throughout a device’s life-cycle. Even a single compliance issue you have can turn into a significant effect on your business. RCA^®‘s medical device consultants can help guide you through any stage of this strategic process, with capabilities during product development through the regulatory clearance/approval of your product.

 

Our team of over 500 life science consultants — including former FDA officials and other leaders in the field of medical device regulation — will work with your company to create a quality assurance and regulatory compliance approach tailored to your products and regulatory needs. RCA works with both international Fortune 100 companies and small local start-ups, as well as law firms requesting remediation for warning letters, 483’s, import bans or consent decrees. We offer expertise in a variety of medical fields, such

 

Cybersecurity

 

For medical device manufacturers, technology can be a double-edged sword. The innovative technologies that elevate the quality of life for patients can also be used to potentially undermine the organization using the device. The consequences can affect the device itself if we do not implement good IoT cybersecurity and FDA cybersecurity protocols. At Regulatory Compliance Associates^®, we offer a wide variety of services for medical device security to help ensure that your product is protected from cyber-attacks.

 

With a well-planned design, along with full visibility of product development and the supply chain, RCA can help strengthen your device’s cybersecurity posture throughout. We partner with medical device companies for the entire life cycle, including from the development of your product to the regulatory submission to your notified body.

 

Regulatory Affairs

 

Regulatory affairs is Regulatory Compliance Associates’s backbone, and we handle more submissions in a month than many manufacturers do in a lifetime. We have experience working with the FDA, global regulatory bodies and/or agencies, and notified bodies worldwide. Therefore, you can count on us for in-depth and up-to-date insights which increase speed-to-market.

 

As a trusted regulatory affairs consultant, our FDA veterans and industry experts are here to help you navigate the difficulties associated with new product submissions. They have expertise in both the approval process and post-approval support. 

 

• New Product Approval
• Post-Approval Support
• Outsourced Staffing
• EU MDR

 

Compliance Assurance

 

Increasingly, life science companies are feeling the pressure of greater scrutiny by regulators, and responding by developing sustainable compliance strategies. Whether it’s preparing for an audit, developing a response to an FDA finding, or remediation to an adverse event, Regulatory Compliance Associates^® Inc. can help.

 

Our network of over 500 FDA, Health Canada & MHRA veterans and industry professionals offers a unique blend of expertise that allows us to handle both simple and complex regulatory compliance challenges within the medical device industry.

 

• Gap Assessments
• Internal Audits
• Employee Training
• Notified Body Response

 

Quality Assurance

 

Regulatory Compliance Associates Quality Assurance services include quality system assessments, strategy, implementations, and identification of quality metrics to ensure continuous improvement, aligning with your business needs and goals. Our life science consultants are quality experts with experience spanning major corporations and start-ups. We know firsthand how to achieve, maintain, and improve quality, and we excel in transferring this knowledge to your organization.

 

In the medical devices field, quality assurance (QA) is more than merely ensuring the quality of a finished product. You need the tools to monitor and regulate every process from the design of a new product to continued quality compliance as the device is sent to market. At RCA^®, we offer you the assistance you need to monitor these processes and ensure quality compliance every step of the way.

 

With more than 20 years of experience as a trusted medical device quality assurance consultant, our team of over 500 industry Experts are fully equipped to handle your unique QA needs.

 

• ISO13485 
• 21 CFR 210
• 21 CFR 211
• Outsourced Staffing
• MDSAP
• Facility Validation
• Equipment Validation

 

Remediation Support

 

Regulatory Compliance Associates is widely recognized within the life science industry and global regulatory agencies for its ability to help companies successfully resolve complex regulatory challenges, including remediation. With a proven track record of success, we have significant experience with the development of responses to 483 Observations, Warning Letters, Untitled Letters and Consent Decrees.

 

Our value goes beyond the initial response by helping companies successfully execute their action plans, develop an improved compliance culture tailored to the needs of their business, and ultimately move beyond the regulatory action to emerge as a stronger business. We negotiate difficult demands of remediation with insight and the clear advantage of our unique expertise and experience that makes partnering with RCA^® Inc. a competitive differentiator in the remediation space.

 

• Quality System
• Technical File
• Design History File
• Data Integrity
• cGMP 

 

Strategic Consulting

 

Whether it’s a strategy, a technical plan, or project, Regulatory Compliance Associates life science consultants can help ensure a successful mix of people and product so your project is on time, on budget, and you’re never embroiled in a costly mistake.

 

Our 500 industry Experts are here to provide the unique insight you need before an M&A deal, through a staffing crisis and in every area of your product’s development and life cycle. As the trusted medical device manufacturing consultants of thousands of companies around the world, we have the knowledge and expertise needed to deliver exceptional results to your business — no matter your size or unique needs.

 

• Manufacturing Optimization
• Product Lifecycle Management
• Mergers & Acquisitions (M&A)
• Due Diligence
• Device Vigilance
• Product Complaints
• Medical Information

 

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