Top 2 FDA Citations to Avoid

Top 2 FDA Citations to Avoid

The consequences of FDA citations can be costly. In this blog article, we discuss the top two FDA citations for pharmaceuticals and how to avoid or prevent them. In the United States of America, pharmaceutical drugs and medical devices are controlled according to The Code of Federal Regulations, Title 21: Food and Drugs (21 CFR). The FDA publicly releases warning letters and citations. Therefore, the cost of addressing citations and warning letters is not limited to production, maintenance, upgrades, or supply chain but also public confidence in your product and company.

Responsibilities of the Quality Control Unit

The Quality Control Unit (QCU) of a company may be referred to as the Quality Assurance Department or a similar name. This division of a pharmaceutical company is responsible for the ultimate quality of the product. The 21 CFR part 211.22, subpart B, details the responsibilities of the quality control unit.

Applying Quality Risk Management (QRM) to C&Q Planning

§ 211.22 Responsibilities of the quality control unit.

(a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. The quality control unit shall be responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company.

(b) Adequate laboratory facilities for the testing and approval (or rejection) of components, drug product containers, closures, packaging materials, in-process materials, and drug products shall be available to the quality control unit.

(c) The quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product.

(d) The responsibilities and procedures applicable to the quality control unit shall be in writing; such written procedures shall be followed.

– Code of Federal Regulations Title 21 Section 211.22

The most frequent FDA citation in pharmaceuticals is 21 CFR part 221.22, subpart B, letter D: “The responsibilities and procedures applicable to the quality control unit shall be in writing; such written procedures shall be followed.” CFR §211.22(d) accounts for 27% of the observations recorded from 2016 to 2020. This part of the code seems logical, simple, and should be easy to follow. So, why is it the most cited part of the code? Obviously, the procedures are not entirely in writing or wholly followed.

Therefore, having the quality control procedure and the product review documented appropriately is absolutely critical to avoid this citation. We will discuss the second most cited part of 21 CFR before discussing ways to avoid or prevent both citations.

Production Record Review

The next most common citation is regarding production record review, precisely 21 CFR part 211, subpart J, 192. CFR §211.192 accounts for 31% of the observations made by the FDA from 2016 to 2020.

Reviewing documents 101

§ 211.192 Production record review.

All drug product production and control records, including those for packaging and labeling, shall be reviewed and approved by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed. Any unexplained discrepancy (including a percentage of theoretical yield exceeding the maximum or minimum percentages established in master production and control records) or the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated, whether or not the batch has already been distributed. The investigation shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy. A written record of the investigation shall be made and shall include the conclusions and followup.

– Code of Federal Regulations Title 21 Section 211.22

Examples of frequent observations for CFR §211.192:

    • There is a failure to thoroughly review any unexplained discrepancy, whether or not the batch has been already distributed.
    • Investigations of an unexplained discrepancy did not extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy.
    • No written record of investigation
    • The written record of the investigation is incomplete.
    • Quality control unit review of records – Drug product production and control records are not reviewed by the quality control unit to determine compliance with all established and approved written procedures before a batch is released or distributed.

Actions to avoid, prevent or reduce similar observations

a) Create and Implement Quality Systems
b) Create a QCU and establish adequate policies and procedures
c) Follow the six-system inspection model approach for a self-inspection program
d) Monitor the regulatory compliance activities through regular management reviews

a) Create and Implement Quality Systems
    • Quality – product quality
    • Quality by Design – pre-development, development, and launch
    • Quality Risk Management –
    • Corrective And Preventive Action (CAPA)
    • Change Control
    • Quality Unit
    • Six-system based inspection model (quality, production, facilities and equipment, laboratory controls, materials, and packaging and labeling.
b) Create a QCU and establish adequate policies and procedures
    • Procedures need to be clear and describe the responsibilities and authority of the QCU for:
      • approving regulatory and controlled documents,
      • approving or rejecting all components, drug products containers and closures, in-process materials, packaging materials, labeling, and drug products, including those manufactured, processed, packed, or held under control by another company
      • Reviewing batch records to ensure compliance with the requirements etc.
c) Follow the six-system inspection model approach for a self-inspection program
    • Quality, production, facilities and equipment, laboratory controls, materials, and packaging and labeling

Six-System Inspection Model is described according to four major factors:

i) Management responsibilities

ii) Resources

iii) Manufacturing operations

iv) Evaluation of activities

d) Monitor the regulatory compliance activities through regular management reviews on the following examples of Key Performance Indicators
    • Non-conformance and CAPAs
    • Customer Complaints
    • Field Alert Reports (FAR) and Medical Device Reporting under part 803
    • Recalls
    • Internal Audits
    • Training including GMP refresher training 

Summary

To prevent the top two FDA citations, 21 CFR §221.22 and §211.192, create and implement quality systems overseen by a QCU with written policies and procedures, and perform internal inspections and regular reviews. PSC Biotech® has quality professionals to help you evaluate gaps and conduct internal audits and inspections. Contact us today for a free consultation and quote to fit your budget and needs!

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With the ever-changing mechanics of innovation in the manufacturing environment, work from home and federal regulation validation strategies need to evolve to accommodate the new space. This white paper provides the background, rationale, and strategy for innovating validation for cell and gene therapy manufacturing. We focus on adapting to the unique challenges that advanced cell and gene therapy manufacturing encounters. How do you overcome supply chain, cost, volume, and speed and sensitivity issues specific to advanced cell and gene therapy products? Read this whitepaper for the latest in innovative strategies.

Table of Contents

    • History
    • The Concept
    • Issues in Cell and Gene Therapy Manufacturing
    • Innovative Strategies Overview
    • PDCA Cycle
    • Productivity Tools
    • Paperless Validation
    • Real-time Monitoring
    • Cross-functional Teams
    • The Five Pillars
    • Strategies for Bringing Innovative Cell and Gene Therapies to Market
    • Summary
    • About Us
Innovation in Validation: Advancing Cell and Gene Therapies White Paper

Download the Innovations in Validation: Advancing Cell and Gene Therapies White Paper today!

PSC® can assist in bringing your new cell or gene therapy to clinic

PSC Software®

PSC Software® provides innovative technology options for validation data and team communication for regulatory compliance. PSC Software® provides industry-leading real-time quality management software to ensure regulatory compliance goals are met while reducing business costs. See PSCSoftware.com for more information on our adaptive compliance engine (ACE®) products and inspection management system, AUDITUTOPIA®.

PSC Biotech®

PSC Biotech® consultants act as a seamless extension of your company to assist you in accomplishing the projects required to produce the highest quality products. See Biotech.com for more information about the services that we provide. PSC Biotech® has served life science companies in 52 countries across the globe. Contact us for a free consultation on tailored and cost-efficient project assistance for all your quality, validation, systems, and regulatory needs!

We look forward to hearing about your needs in Cell and Gene Therapies and whether we can be of service. Please get started by emailing us at info@biotech.com or using our contact form online. We have options for professional services and software across a range of budgets and constraints.

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Maximize efficiency and effectiveness in your validation projects by utilizing multi-disciplinary teams. The term “Validation,” as used in this white paper, will be taken to mean either or both activities of Qualifying systems and facilities as fit-for-purpose (IQ/OQ/PQ) and the Process Validation of manufacturing processes and procedures (PQ or PV).

Lean project management strategies incorporate subject matter experts (SMEs) in cross-functional teams. For example, commissioning equipment with computerized functions needs to be validated by the computer systems validation SME and the commissioning and qualification validation SME. This white paper discusses some considerations for using a multi-disciplinary team approach to sitewide or corporate Validation project planning, oversight, execution, and approval.

Table of Contents

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    • Overview of Multi-Disciplinary Validation Teams

    • Establishing Validation Teams

      • Complexity and Scope

      • Novelty

      • Criticality and Risk

    • Availability of Required Personnel

    • Organizational Experience Level

    • Time and Project Length

    • Engineering/Technical Support

    • Summary

Multi-disciplinary teams for GxP

The establishment and management of multi-disciplinary validation teams are crucial to managing changes in the modern Pharmaceutical and Biopharmaceutical industries. These teams are typically responsible for the review, planning, and approval of changes (additions of or modifications) to equipment, facilities, systems, and processes with the potential to impact product quality. Project Management can significantly impact project quality, cost, and time through the decisions and mechanisms they choose to implement. Third-party resources and service firms can help with current developments in industry practices and standards and have the potential to more than pay for themselves in terms of money and time saved.

PSC Biotech® Project Management

PSC Biotech® project management experts have a strong track record of delivering projects and offering the best solutions for all kinds of projects in the life science industry. We follow current Good Practice regulations, the Project Management Institute’s Best Practices, and ISPE’s Good Practice Guides. Our Project Life Cycle services include project initiation, planning, execution, monitoring and controlling, and closure. Throughout the Life Cycle of a project, our primary focus is on delivering our project, on time, on budget, and to specifications.

Download the Multi-Disciplinary Validation Teams for GXP Projects White Paper today!

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Validation (IQ, OQ, and PQ) of the HVAC system Reconnection

PSC Biotech provided exceptional professionalism in project planning and time management, qualification document designing, and the executive power of completing qualification tests and solving qualification deviations. 

PSC Biotech® delivered a detailed service quotation including personnel, transportation, and accommodation to our client, a global biopharmaceuticals development and manufacturing company located in Taiwan.

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Temperature Controlled Chamber Qualification

PSC consultants performed qualification protocol and summary generation, and qualification execution.

PSC Biotech provided CQV and Metrology services for this project. Client required rapid use of refrigerated storage trailers to handle warehouse overload. Each trailer required sensor calibration, engineering study for temperature profile, installation qualification, and operational qualification with temperature mapping. PSC consultants performed the calibration, ran engineering studies, wrote and executed qualification protocols, resolved deviations, and closed out reports. 

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Engineering

We continually have positions available for engineers. What type of engineers? All sorts! We employ Commissioning and Qualification Engineers, Manufacturing Systems Engineers, Computer Systems Engineers, Validation Engineers, Quality Engineers, and more. If you have a degree in industrial engineering, mechanical engineering, chemical engineering, or electrical engineering, we may have a job for you! If we don’t have an opportunity right now, stay tuned! As PSC Biotech® is continually expanding, we are hiring engineers. We have opportunities across the career span – ranging from interns to regional managers.

Engineers

Project Management

PSC Biotech® assigns a Project Manager to each project. The Project Manager utilizes our exclusively developed Project Tracker (PT) software to maintain an accurate and up-to-date deliverable document status. PSC Biotech® provides project management training to its employees. Managers are needed across the board – in our metrology lab, purchasing, business development, and more.

Life Sciences

Quality assurance consultants come from various backgrounds, including the life sciences. For example, microbiologists are needed for environmental monitoring in pharmaceutical manufacturing. Biochemistry and molecular biology graduates are needed to do testing in laboratories and provide support for standard operating procedure development.

Supporting Staff

With talent acquisition specialists, we continue to hire new employees. For efficient and effective consulting, we need support staff such as maintenance specialists, writers, administrators, coordinators, and more.

 

Why join PSC Biotech®

Upward mobility, flexible hours, training opportunities, a benefits package, and good pay are hard to turn down. PSC Biotech® is a great company to start as a consultant with a supportive environment for young and experienced consultants. Offering a full suite of benefits, PSC Biotech® is firmly focused on diligently investing in our employees who enable our company to fulfill our mission and achieve success. We want to promote balance to enjoy your work and have the time and resources to live happily and healthy! We offer medical, vision, dental, and supplemental insurance options. Additional benefits include pet insurance discounts, education assistance, gym discount rate, and 401K options. Plus, we give generous PTO!

Find out more today!

 

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Risk assessment is a crucial competency for modern pharmaceutical and biomedical manufacturing organizations. The objective of any risk assessment is to identify, analyze and evaluate potential risk. The ICH Q9 “Quality Risk Management” guideline defines the risk assessment principle as, “The evaluation of the risk to quality should be based on scientific knowledge and ultimately linked to the protection of the patient”. This PSC Biotech® post lists the standard formal risk assessment methods and their appropriate use. 

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C&Q in Process Validation

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Applications for Quality Risk Management in Facility Operations

In the final installment of this series, we detail how to apply these principles and best practices on the floor and at the bench. This White Paper applies QRM principles to facility operations in the pharmaceutical industry. Update your Commissioning, Qualification and Validation principles to a science- and risk-based management. Download this whitepaper today!

Table of Contents

    • Introduction
    • QRM: Beyond Qualification and Validation
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    • Change Control According to Quality Impact
    • Calibration of Instruments
    • Preventative Maintenance
    • Periodic Review and Requalification of Legacy Systems
    • Summary
    • About the Author
    • CQV Outsourcing
FDA

PSC Biotech® provides engineering support and CQV services. 

PSC Biotech® is one of the largest providers for Commissioning, Qualification, and Validation services for the life science industry, with emphasis on Quality Risk Management. Our team consists of seasoned experts in the validation of facilities, utilities, equipment, computer systems, processes, cleaning, and test methods. We provide end to end solutions with expertise in Project Planning, CQV Master Planning, Requirement Specifications, Risk Assessments, Commissioning, Decommissioning, FATs, SATs, Installation Qualifications, Operational Qualifications, Performance Qualifications, Summary Reports, Traceability Matrixes, Calibration, Temperature/Humidity Mapping Services and more.

We look forward to hearing about your needs in Quality Risk Management and whether we can be of service. Please get started by emailing us at info@biotech.com or using our contact form online.

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Validation (IQ, OQ, and PQ) of the HVAC system Reconnection    Requalification of the HVAC system  Area: Zhubei, Hsinchu County, Taiwan Project Type: Qualification About this Project OBJECTIVE Qualification protocol and summary generation, and qualification...

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A cGMP Program Compliance and Gap AnalysisPerform cGMP compliance and Gap analysis Area: Saskatchewan – Saskatoon, Regina Project Type: Auditing About this Project OBJECTIVE Assess that client's quality systems are in compliance with current Good Manufacturing...

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