It is rare when a journalist reports on the GMP side of the industry. Most reporting tends to be pretty shallow, and only when a major crisis happens, such as the baby food manufacturing failures. So I love it when a journalist takes the time to understand our field and write a detailed piece. Katherine Eban, who wrote the insightful Bottle of Lies, which I am known to gift copies of, being a great example of a journalist can creditably speak our language and than translate it to the general public.
The article stresses the ongoing crisis in that the FDA does not have enough inspectors, a crisis that keeps getting worse under the current administration.
The Form 483 that is linked should frighten anyone, as it has 3 pages of redacted batches that were shipped to the US.
I share the frustration and concern that Form 483s are not transparent, and that the FDA does not follow the same principle of the average health inspector for local restaurants where I see the grade when I walk in. It is pretty difficult to figure out where a medicine is made, and failing access to some expensive services, can be a real pain to figure out the status of any given manufacturing site.
The Form 483 for Glenmark is, unfortunately, all too common for an Indian generics manufacturing site. Poor validation, no real cleaning, lack of investigations – these are all very serious, and unfortunately recurring.
I am very concerned that the woes of Indian manufacturing sites (and Chinese) will just get worse as the FDA is torn apart by a bunch of authoritarian ideologues who think sunshine and bleach are cure-alls.
The Establishment Inspection Report (EIR) is a comprehensive document generated after FDA investigators inspect facilities involved in manufacturing, processing, or distributing FDA-regulated goods. This report not only details compliance with regulatory standards but also serves as a vital tool for both the FDA and inspected entities to address potential risks and improve operational practices.
Regulatory Framework Governing EIRs
The EIR is rooted in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and associated regulations under 21 CFR Parts 210–211 (Current Good Manufacturing Practices) and 21 CFR Part 820 (Quality System Regulation for medical devices). These regulations empower the FDA to conduct inspections and enforce compliance through documentation like the EIR. Key policies include:
Field Management Directive (FMD) 145: This directive mandates the release of the EIR’s narrative portion to inspected entities once an inspection is deemed “closed” under 21 CFR § 20.64(d)(3). This policy ensures transparency by providing firms with insights into inspection findings before public disclosure via the Freedom of Information Act (FOIA).
Inspectional Conclusions: EIRs classify inspections into three outcomes:
No Action Indicated (NAI): No significant violations found.
Voluntary Action Indicated (VAI): Violations identified but not severe enough to warrant immediate regulatory action.
Official Action Indicated (OAI): Serious violations requiring FDA enforcement, such as warning letters or product seizures.
Anatomy of an EIR
An EIR is a meticulous record of an inspection’s scope, findings, and contextual details. Key components include:
1. Inspection Scope and Context
The EIR outlines the facilities, processes, and documents reviewed, providing clarity on the FDA’s focus areas. This section often references the Form FDA 483, which lists observed violations disclosed at the inspection’s conclusion.
2. Documents Reviewed or Collected
Investigators catalog documents such as batch records, standard operating procedures (SOPs), and corrective action plans. This inventory helps firms identify gaps in record-keeping and align future practices with FDA expectations.
3. Inspectional Observations
Beyond the Form FDA 483, the EIR elaborates on objectionable conditions, including deviations from GMPs or inadequate validation processes.
4. Samples and Evidence
If product samples or raw materials are collected, the EIR explains their significance. Extensive sampling often signals concerns about product safety, such as microbial contamination in a drug substance.
5. Enforcement Recommendations
The EIR concludes with the FDA’s recommended actions, such as re-inspections, warning letters, or import alerts. These recommendations are reviewed by compliance officers before finalizing regulatory decisions.
How the EIR Informs Regulatory and Corporate Actions For the FDA
Risk Assessment: EIRs guide the FDA in prioritizing enforcement based on the severity of violations. For example, an OAI classification triggers immediate compliance reviews, while VAI findings may lead to routine follow-ups.
Trend Analysis: Aggregated EIR data help identify industry-wide risks, such as recurring issues in sterile manufacturing, informing future inspection strategies.
Global Collaboration: EIR findings are shared with international regulators under confidentiality agreements, fostering alignment in standards.
For Inspected Entities
Compliance Roadmaps: Firms use EIRs to address deficiencies before they escalate.
Inspection Readiness: By analyzing EIRs from peer organizations, companies anticipate FDA focus areas. For example, recent emphasis on data integrity has led firms to bolster electronic record-keeping systems.
Reputational Management: A clean EIR (NAI) enhances stakeholder confidence, while recurrent OAI classifications may deter investors or partners.
Challenges and Evolving Practices
Timeliness: Delays in EIR release hinder firms’ ability to implement timely corrections. The FDA has pledged to streamline review processes but continued workforce issues will exacerbate the problem..
Digital Transformation: The FDA’s adoption of AI-driven analytics aims to accelerate EIR generation and enhance consistency in inspection classification. Hopefully this will increase transparency.
Global Harmonization: Joint FDA-EMA inspections, though rare, highlight efforts to reduce redundant audits and align regulatory expectations.
Conclusion
The FDA Establishment Inspection Report is more than a regulatory artifact—it is a dynamic instrument for continuous improvement in public health protection. By demystifying its structure, regulations, and applications, firms can transform EIRs from compliance checklists into strategic assets. As the FDA evolves its inspectional approaches, staying abreast of EIR trends and best practices will remain pivotal for navigating the complex regulatory compliance landscape.
Proactively engaging with EIR findings for organizations subject to FDA oversight mitigates enforcement risks. It fosters a quality culture that aligns with the FDA’s mandate to protect and promote public health.
Through the skilled work of a very helpful FOIA officer at the FDA I have been reviewing the 2020 483 and EIR for the pre-approval inspection at the Sanofi Framingham, MA site that recently received a Warning Letter:
The 2020 pre-approval inspection (PAI) of Sanofi’s facility in Framingham, MA, uncovered critical deviations that exposed systemic weaknesses in contamination controls, equipment maintenance, and quality oversight. These deficiencies, documented in FDA Form 483 (FEI 1220423), violated 21 CFR 211 regulations and FDA Compliance Program 7346.832 requirements for PAIs. The facility’s failure to address these issues and to make systeatic changes over time (and perhaps backslide, but that is conjecture) contributed to subsequent regulatory actions, including a 2022 Form 483 and the 2024 FDA warning letter citing persistent CGMP violations. This analysis traces the 2020 findings to their regulatory origins, examines their operational consequences, and identifies lessons for PAI preparedness in high-risk API manufacturing.
Regulatory Foundations of Pre-Approval Inspections
The FDA’s PAI program operates under Compliance Program 7346.832, which mandates rigorous evaluation of facilities named in NDAs, ANDAs, or BLAs. Three pillars govern these inspections:
Commercial Manufacturing Readiness: PAIs assess whether facilities can reliably execute commercial-scale processes while maintaining CGMP compliance. This includes verification of validated equipment cleaning procedures, environmental monitoring systems, and preventive maintenance programs. The FDA prioritizes sites handling novel APIs, narrow therapeutic index drugs, or first-time applications—criteria met by Sanofi’s production of drug substances.
Application Conformance: Inspectors cross-validate submission data against actual operations, focusing on batch records, process parameters, and analytical methods. Discrepancies between filed documentation and observed practices constitute major compliance risks, particularly for facilities like Sanofi that utilize complex biologics manufacturing processes.
Data Integrity Assurance Per 21 CFR 211.194, PAIs include forensic reviews of raw data, equipment logs, and stability studies. The 2020 inspection identified multiple QC laboratory lapses at Sanofi that undermined data reliability—a red flag under FDA’s heightened focus on data governance in PAIs.
Facility Maintenance Deficiencies
Sterilization Equipment Contamination On September 2, 2020, FDA investigators documented (b)(4) residue on FB-2880-001 sterilization equipment and its transport cart—critical infrastructure for bioreactor probe sterilization. The absence of cleaning procedures or routine inspections violated 21 CFR 211.67(a), which mandates written equipment maintenance protocols. This lapse created cross-contamination risks for (b)(4) drug substances, directly contradicting the application’s sterility claims.
The unvalidated cleaning process for those chambers further breached 21 CFR 211.63, requiring equipment design that prevents adulteration. Historical data from 2008–2009 FDA inspections revealed similar sterilization issues at Allston facility, suggesting systemic quality control failures which suggests that these issues never were really dealt with systematically across all sites under the consent decree.
Environmental Control Breakdowns The August 26, 2020 finding of unsecured pre-filters in Downflow Booth —a critical area for raw material weighing—exposed multiple CGMP violations:
21 CFR 211.46(b): Failure to maintain HEPA filter integrity in controlled environments
FDA Aseptic Processing Guidance: Loose filters compromise ISO 5 unidirectional airflow
21 CFR 211.42(c): Inadequate facility design for preventing material contamination
Ceiling diffuser screens in Suite CNC space with unsecured fasteners exacerbated particulate contamination risks. The cumulative effect violated PAI Objective 1 by demonstrating poor facility control—a key factor in the 2024 warning letter’s citation of “unsuitable equipment for microbiologically controlled environments”.
Quality Control Laboratory Failures
Analytical Balance Non-Compliance The QC microbiology laboratory’s use of an unqualified balance breached multiple standards:
21 CFR 211.68(a): Lack of calibration for automated equipment
USP <41> Guidelines: Failure to establish minimum weigh limits
FDA Data Integrity Guidance (2018): Unguaranteed accuracy of microbiological test results
This deficiency directly impacted the reliability of bioburden testing data submitted in the application, contravening PAI Objective 3’s data authenticity requirements.
Delayed Logbook Reviews Three QC logbooks exceeded the review window specified in the site’s procedure:
Temperature logs for water baths
Dry state storage checklists
The delays violated 21 CFR 211.188(b)(11), which requires contemporaneous review of batch records. More critically, they reflected inadequate quality unit oversight—a recurring theme in Sanofi’s 2024 warning letter citing “lackluster quality control”.
And if they found 3 logbooks, chances are there were many more in an equal state.
Leak Investigations – A Leading Indicator
there are two pages in the EIR around leak deviation investigations, including the infamous bags, and in hindsight, I think this is an incredibly important inflection point from improvement that was missed.
The inspector took the time to evaluate quite a few deviations and overall control strategy for leaks and gave Sanofi a clean-bill of health. So we have to wonder if there was not enough problems to go deep enough to see a trend or if a sense of complacency allowed Sanofi to lower their guard around this critical aspect of single use, functionally closed systems.
The FDA’s July 2022 reinspection of Sanofi’s Framingham facility revealed persistent deficiencies despite corrective actions taken after the 2020 PAI. The inspection, conducted under Compliance Program 7356.002M, identified critical gaps in data governance and facility maintenance, resulting in a 2-item Form FDA 483 and an Official Action Indicated (OAI) classification – a significant escalation from the 2020 Voluntary Action Indicated (VAI) status.
Computerized System Control Failures
The FDA identified systemic weaknesses in data integrity controls for testers used to validate filter integrity during drug substance manufacturing. These testers generated electronic logs documenting failed and canceled tests that were never reviewed or documented in manufacturing records. For example:
On June 9, 2022, a filter underwent three consecutive tests for clarification operations: two failures and one cancellation due to operator error (audible “hissing” during testing). Only the final passing result was recorded in logbooks.
Between 2020–2022, operators canceled 14% of tests across testers without documented justification, violating 21 CFR 211.68(b) requirements for automated equipment review.
The firm had improperly classified these testers as “legacy electronic equipment,” bypassing mandatory audit trail reviews under their site procedure. I am not even sure what legacy electronic equipment means, but this failure contravened FDA’s Data Integrity Guidance (2018), which requires full traceability of GxP decisions.
Biological Safety Cabinet: Rust particles and brown residue contaminated interior surfaces used for drug substance handling in April 20223. The material was later identified as iron oxide from deteriorating cabinet components.
HVAC System Leaks: A pH probe in the water system leaked into grade-D areas, with standing water observed near active bioreactors3.
Structural Integrity Issues
Chipped epoxy floors in grade-C rooms created particulate generation risks during cell culture operations.
Improperly sloped flooring allowed pooling of rinse water adjacent to purification equipment.
These conditions violated 21 CFR 211.42(c), requiring facilities to prevent contamination through proper design, and demonstrated backsliding from 2020 corrective actions targeting environmental controls.
Regulatory Reckoning
These cultural failures crystallized in FDA’s 2024 citation of “systemic indifference to quality stewardship”. While some technological upgrades provided tactical fixes, the delayed recognition of cultural rot as root cause transformed manageable equipment issues into existential compliance threats—a cautionary tale for pharmaceutical manufacturers navigating dual challenges of technological modernization and workforce transition.
Conclusion: A Compliance Crisis Decade
The Sanofi case (2020–2024) exemplifies the consequences of treating PAIs as checklist exercises rather than opportunities for quality system maturation. The facility’s progression from 483 observations to OAI status and finally warning letter underscores three critical lessons:
Proactive Data Governance: Holitisic data overnance and data integrity, including audit trail reviews that encompass all GxP systems – legacy or modern.
Cultural Transformation: Quality metrics must drive executive incentives to prevent recurrent failures.
Manufacturers must adopt holistic systems integrating advanced analytics, robust knowledge management, and cultural accountability to avoid a costly regulatory debacle.
PAI Readiness Best Practices
Pre-Inspection Preparation
Gap Analysis Against CPGM 7346.832 Facilities should conduct mock inspections evaluating:
Conformance between batch records and application data
Completeness of method validation protocols
Environmental monitoring trend reports
Data Integrity Audits Forensic reviews of electronic records (e.g., HPLC chromatograms, equipment logs) using FDA’s “ALCOA+” criteria—ensuring data is Attributable, Legible, Contemporaneous, Original, and Accurate.
Facility Hardening Preventive maintenance programs for critical utilities:
Steam-in-place systems
HVAC airflow balances
Water for injection loops
Post-Approval Vigilance
The Sanofi case underscores the need for ongoing compliance monitoring post-PAI:
Quality Metrics Tracking: FDA-required metrics like lot rejection rates and CAPA effectiveness
Regulatory Intelligence: Monitoring emerging focus areas through FDA warning letters and guidance updates
Process Robustness Studies: Continued process verification per 21 CFR 211.110(a)
Add me to the list of people who are disheartened y the silence of the Pharmaceutical Research and Manufacturers of America and the Biotechnology Innovation Organization to the cuts at the FDA. In an interest to write something that should be coming loud and clear from our industry groups, I give you…
The Impact of Recent FDA Layoffs on Agency Capacity and Public Health
The recent wave of layoffs at the U.S. Food and Drug Administration (FDA), enacted as part of broader illegal federal workforce reductions under the Trump administration, has exacerbated long-standing staffing challenges at the agency. By targeting probationary employees—recent hires and those promoted within the past two years—the cuts have disproportionately affected early-career professionals with cutting-edge technical expertise, disrupted workforce development pipelines, and weakened oversight in critical areas such as medical device regulation, food safety, veterinary medicine, and emerging technologies. These reductions come at a time when the FDA is already grappling with recruitment challenges, inspection backlogs, and increasing demands for regulatory innovation.
Scope and Targets of the Layoffs
The Department of Health and Human Services (HHS), under Secretary Robert F. Kennedy Jr., terminated approximately 5,200 probationary employees across its agencies in mid-February 2025, including hundreds at the FDA. While the agency’s drug review divisions were largely spared, layoffs hit staff in the Center for Devices and Radiological Health (CDRH), the Center for Food Safety and Applied Nutrition (CFSAN), the Center for Veterinary Medicine (CVM), and the Center for Tobacco Products (CTP).
Medical Devices and Digital Health
In CDRH, at least 230 employees were dismissed, including specialists in artificial intelligence (AI) and digital health—fields undergoing rapid technological advancement. These roles are critical for evaluating AI-driven diagnostic tools, wearable devices, and software-as-a-medical-device (SaMD) products. The loss of early-career researchers and engineers threatens the FDA’s ability to keep pace with industry innovation, potentially delaying approvals for technologies like neural interfaces and AI-powered imaging systems.
Food Safety and Additives
CFSAN lost staff responsible for reviewing new food additives, colorings, and ingredients—a priority area for Kennedy, who has advocated for stricter chemical regulations. With approximately 2,000 uninspected food and drug facilities globally, the FDA’s inspection backlog is now likely to grow further, raising risks of contamination incidents similar to recent outbreaks linked to infant formula and baby food.
Veterinary Medicine
The Center for Veterinary Medicine (CVM) saw cuts to reviewers assessing the safety of pharmaceuticals for pets and livestock. These roles ensure that medications for animals are effective and that residues in products like milk and eggs remain safe for human consumption. Reductions here could delay approvals for veterinary drugs and weaken monitoring of antimicrobial resistance.
Exacerbating Existing Staffing Challenges
The FDA has historically struggled to recruit and retain specialized staff due to competition from higher-paying private-sector roles. The layoffs worsen these issues by destabilizing workforce development and eroding institutional knowledge.
Loss of Early-Career Talent
Probationary employees—often younger professionals with advanced degrees in fields like data science, bioengineering, and toxicology—represent the FDA’s pipeline for replacing retiring staff. By targeting this group, the cuts disrupt the “learning chain” essential for maintaining expertise. As Kenneth Kaitin, a Tufts University professor, noted: “You’re eliminating the learning chain of people who come into the agency. There’s a long learning curve, and you’re eliminating people at the early stage” (https://www.biopharmadive.com/news/fda-layoffs-trump-doge-hhs-cuts-impact/740499/).
Increased Workloads and Burnout
Remaining staff now face expanded responsibilities. For example, CDRH’s device reviewers, already managing a surge in AI and digital health submissions, must absorb the work of dismissed colleagues without additional support. Similarly, food safety inspectors—many of whom were hired post-pandemic to address backlogs—are now stretched thinner, increasing the likelihood of oversights.
Recruitment and Morale
The layoffs have demoralized the workforce and damaged the FDA’s reputation as a stable employer. As Mitch Zeller, former FDA tobacco director, stated: “The combined effect of what they’re trying to do is going to destroy the ability to recruit and retain talent” (https://www.startribune.com/trump-administration-cuts-reach-fda-employees-in-food-safety-medical-devices-and-tobacco-products/601223844). With hiring frozen under an executive order requiring agencies to replace only one employee for every four departures, the FDA cannot easily rebuild capacity.
The Training Bottleneck
The probationary period at the FDA (1–2 years for new hires) is designed to provide hands-on training in complex regulatory science. Dismissing employees during this phase wastes significant investments in onboarding and delays the development of proficiency.
Specialized Skill Development
Reviewers in areas like AI-driven medical devices or gene therapies require months of training to evaluate technical dossiers, assess clinical data, and understand regulatory precedents. Losing these employees resets progress, forcing the FDA to restart the training process once hiring resumes.
Cross-Departmental Collaboration
New hires often rotate through multiple divisions to build interdisciplinary expertise. For instance, a food additive reviewer might collaborate with toxicologists and epidemiologists to assess long-term health risks. Disrupting these rotations limits opportunities for knowledge-sharing, weakening the agency’s ability to address novel public health challenges.
Long-Term Consequences for Public Health
Slower Product Reviews
User fee-funded positions—which account for nearly half of the FDA’s $6.9 billion budget—were not spared from cuts. Since these roles are financed by industry to expedite reviews, their elimination could delay approvals for new drugs, devices, and food ingredients without reducing federal spending.
Weakened Outbreak Response
The FDA collaborates with the CDC to trace contamination sources during foodborne illness outbreaks. With fewer inspectors and scientists, the agency’s capacity to identify pathogens like Salmonella or Listeria will diminish, prolonging outbreaks and increasing hospitalization risks.
Erosion of Global Leadership
The FDA’s regulatory standards influence global markets. Slower reviews and outdated technical capacity could push companies to seek approvals in regions with more predictable oversight, such as the EU or Singapore, undermining U.S. competitiveness.
Conclusion
The FDA layoffs represent a shortsighted approach to government efficiency that prioritizes short-term spending cuts over long-term public health. By targeting probationary employees, the administration has exacerbated recruitment challenges, disrupted workforce development, and weakened oversight in critical areas. Rebuilding the FDA’s capacity will require reversing hiring freezes, increasing salaries to compete with the private sector, and safeguarding user fee funds from political interference. Without these steps, the agency’s ability to ensure food safety, evaluate emerging technologies, and respond to health crises will continue to erode—with dire consequences for consumers, industry, and global health security.
Reading Strukmyer LLC’s recent FDA Warning Letter, and reflecting back to last year’s Colgate-Palmolive/Tom’s of Maine, Inc. Warning Letter, has me thinking of common language In both warning letters where the FDA asks for “A comprehensive, independent assessment of the design and control of your firm’s manufacturing operations, with a detailed and thorough review of all microbiological hazards.”
It is hard to read that as anything else than a clarion call to use a HACCP.
If that isn’t a HACCP, I don’t know what is. Given the FDA’s rich history and connection to the tool, it is difficult to imagine them thinking of any other tool. Sure, I can invent about 7 other ways to do that, but why bother when there is a great tool, full of powerful uses, waiting to be used that the regulators pretty much have in their DNA.
The Evolution of HACCP in FDA Regulation: A Journey to Enhanced Food Safety
The Hazard Analysis and Critical Control Points (HACCP) system has a fascinating history that is deeply intertwined with FDA regulations. Initially developed in the 1960s by NASA, the Pillsbury Company, and the U.S. Army, HACCP was designed to ensure safe food for space missions. This pioneering collaboration aimed to prevent food safety issues by identifying and controlling critical points in food processing. The success of HACCP in space missions soon led to its application in commercial food production.
In the 1970s, Pillsbury applied HACCP to its commercial operations, driven by incidents such as the contamination of farina with glass. This prompted Pillsbury to adopt HACCP more widely across its production lines. A significant event in 1971 was a panel discussion at the National Conference on Food Protection, which led to the FDA’s involvement in promoting HACCP for food safety inspections. The FDA recognized the potential of HACCP to enhance food safety standards and began to integrate it into its regulatory framework.
As HACCP gained prominence as a food safety standard in the 1980s and 1990s, the National Advisory Committee on Microbiological Criteria for Foods (NACMCF) refined its principles. The committee added preliminary steps and solidified the seven core principles of HACCP, which include hazard analysis, critical control points identification, establishing critical limits, monitoring procedures, corrective actions, verification procedures, and record-keeping. This structured approach helped standardize HACCP implementation across different sectors of the food industry.
A major milestone in the history of HACCP was the implementation of the Pathogen Reduction/HACCP Systems rule by the USDA’s Food Safety and Inspection Service (FSIS) in 1996. This rule mandated HACCP in meat and poultry processing facilities, marking a significant shift towards preventive food safety measures. By the late 1990s, HACCP became a requirement for all food businesses, with some exceptions for smaller operations. This widespread adoption underscored the importance of proactive food safety management.
The Food Safety Modernization Act (FSMA) of 2011 further emphasized preventive controls, including HACCP, to enhance food safety across the industry. FSMA shifted the focus from responding to food safety issues to preventing them, aligning with the core principles of HACCP. Today, HACCP remains a cornerstone of food safety management globally, with ongoing training and certification programs available to ensure compliance with evolving regulations. The FDA continues to support HACCP as part of its broader efforts to protect public health through safe food production and processing practices. As the food industry continues to evolve, the principles of HACCP remain essential for maintaining high standards of food safety and quality.
Why is a HACCP Useful in Biotech Manufacturing
The HACCP seeks to map a process – the manufacturing process, one cleanroom, a series of interlinked cleanrooms, or the water system – and identifies hazards (a point of contamination) by understanding the personnel, material, waste, and other parts of the operational flow. These hazards are assessed at each step in the process for their likelihood and severity. Mitigations are taken to reduce the risk the hazard presents (“a contamination control point”). Where a risk cannot be adequately minimized (either in terms of its likelihood of occurrence, the severity of its nature, or both), this “contamination control point” should be subject to a form of detection so that the facility has an understanding of whether the microbial hazard was potentially present at a given time, for a given operation. In other words, the “critical control point” provides a reasoned area for selecting a monitoring location. For aseptic processing, for example, the target is elimination, even if this cannot be absolutely demonstrated.
The HACCP approach can easily be applied to pharmaceutical manufacturing where it proves very useful for microbial control. Although alternative risk tools exist, such as Failure Modes and Effects Analysis, the HACCP approach is better for microbial control.
HACCP provides a systematic approach to identifying and controlling potential hazards throughout the production process.
Step 1: Conduct a Hazard Analysis
List All Process Steps: Begin by detailing every step involved in your biotech manufacturing process, from raw material sourcing to final product packaging. Make sure to walk down the process thoroughly.
Identify Potential Hazards: At each step, identify potential biological, chemical, and physical hazards. Biological hazards might include microbial contamination, while chemical hazards could involve chemical impurities or inappropriate reagents. Physical hazards might include particulates or inappropriate packaging materials.
Evaluate Severity and Likelihood: Assess the severity and likelihood of each identified hazard. This evaluation helps prioritize which hazards require immediate attention.
Determine Preventive Measures: Develop strategies to control significant hazards. This might involve adjusting process conditions, improving cleaning protocols, or enhancing monitoring systems.
Document Justifications: Record the rationale behind including or excluding hazards from your analysis. This documentation is essential for transparency and regulatory compliance.
Step 2: Determine Critical Control Points (CCPs)
Identify Control Points: Any step where biological, chemical, or physical factors can be controlled is considered a control point.
Determine CCPs: Use a decision tree to identify which control points are critical. A CCP is a step at which control can be applied and is essential to prevent or eliminate a hazard or reduce it to an acceptable level.
Establish Critical Limits: For each CCP, define the maximum or minimum values to which parameters must be controlled. These limits ensure that hazards are effectively managed.
Control Points
Critical Control Points
Process steps where a control measure (mitigation activity) is necessary to prevent the hazard from occurring
Process steps where both control and monitoring are necessary to assure product quality and patient safety
Are not necessarily critical control points (CCPs)
Are also control points
Determined from the risk associated with the hazard
Determined through a decision tree
Step 3: Establish Monitoring Procedures
Develop Monitoring Plans: Create detailed plans for monitoring each CCP. This includes specifying what to monitor, how often, and who is responsible.
Implement Monitoring Tools: Use appropriate tools and equipment to monitor CCPs effectively. This might include temperature sensors, microbial testing kits, or chemical analyzers.
Record Monitoring Data: Ensure that all monitoring data is accurately recorded and stored for future reference.
Step 4: Establish Corrective Actions
Define Corrective Actions: Develop procedures for when monitoring indicates that a CCP is not within its critical limits. These actions should restore control and prevent hazards.
Proceduralize: You are establishing alternative control strategies here so make sure they are appropriately verified and controlled by process/procedure in the quality system.
Train Staff: Ensure that all personnel understand and can implement corrective actions promptly.
Step 5: Establish Verification Procedures
Regular Audits: Conduct regular audits to verify that the HACCP system is functioning correctly. This includes reviewing monitoring data and observing process operations.
Validation Studies: Perform validation studies to confirm that CCPs are effective in controlling hazards.
Continuous Improvement: Use audit findings to improve the HACCP system over time.
Step 6: Establish Documentation and Record-Keeping
Maintain Detailed Records: Keep comprehensive records of all aspects of the HACCP system, including hazard analyses, CCPs, monitoring data, corrective actions, and verification activities.
Ensure Traceability: Use documentation to ensure traceability throughout the production process, facilitating quick responses to any safety issues.
Step 7: Implement and Review the HACCP Plan
Implement the Plan: Ensure that all personnel involved in biotech manufacturing understand and follow the HACCP plan.
Regular Review: Regularly review and update the HACCP plan to reflect changes in processes, new hazards, or lessons learned from audits and incidents.
Investigations of a Dog 