AGON’s Post

💡 Understanding and Addressing Contamination in Sterile Products Manufacturing: A Key Focus of EU GMP Annex 1 2022 💡 📖 Definition of Contamination; #Contamination refers to the undesired introduction of impurities such as chemical, physical, or microbiological elements into a substance or environment, resulting in the spoilage or degradation of the substance or environment. ⏩ Environmental contamination refers to the undesired introduction of impurities such as non-viable particles, #viable particles (#bacteria and #fungi), chemicals, or other substances into a manufacturing environment. These contaminants can originate from various sources, including: 1.    Non-viable particles: Non-viable particles comprise a diverse array of inanimate particles, such as dust, fibers, and other debris that can compromise product quality or interfere with manufacturing processes. 2.    Viable particles (bacteria and fungi): Viable particles encompass microorganisms that can cause spoilage, product degradation, or pose a risk to patient safety by adding #Endotoxin into the products. ⏩ Cross-contamination; #Cross-contamination involves the transfer of impurities between different products, equipment, or environments. This can occur through direct contact, airborne transmission, or intermediary materials. In a manufacturing facility, shared equipment, inadequate cleaning procedures, or ineffective segregation can result in cross-contamination, which may lead to serious consequences. 📖 Contamination Control Strategy; A contamination #control #strategy is a comprehensive, #risk-based approach that aims to prevent, detect, and correct potential contamination events during the manufacturing process. This includes assessing and mitigating risks related to the facility, equipment, materials, personnel, and procedures.  🔑Key components of a contamination control strategy include: Proper #facility design and maintenance Robust environmental monitoring programs Personnel #training and #gowning protocols Proper #Equipment design Effective cleaning and disinfection procedures Validated sterilization processes 👉A robust contamination control strategy is critical to ensuring product quality and patient safety in sterile product manufacturing.  📖 The recent revision of the European Union Good Manufacturing Practice (#GMP) Annex 1, released in 2022, places a heightened focus on contamination control. It provides detailed guidance on various aspects of contamination control, including facility design, environmental monitoring, and personnel and material management. Additionally, it emphasizes the importance of employing a comprehensive, risk-based approach to identify and mitigate potential contamination sources. By adhering to the latest regulatory guidelines, manufacturers can strengthen their contamination control strategies and ensure the highest levels of product quality and patient safety. 👍 Like, comment, share 📲 and re-post 🔄 if you found this to be useful

Your Contamination Control Strategy (CCS) is not meeting its objective. If your products need to comply with EU GMP Annex 1 (Sterility Manufacturing), you must have a CCS. Your CCS might be perfect, but I have seen a common issue in some companies. CCS is NOT just a REFERENCE DOCUMENT. If your CCS only references other documents without explaining your contamination control strategy, you are missing the "Strategy" in CCS. You do not need to rewrite everything in the CCS or make it a 200-page document. If so, consider renaming it to CCB for "Bible". 😂 Your CCS should include at minimum: ➡ Overview of the manufacturing plant design, including layouts and premises ➡ Personnel: Gowning, training, cleanroom clothing, gowning requirements, monitoring ➡ Utilities ➡ Raw material/vendor control ➡ In-process controls ➡ Product containers and closures ➡ Qualification and release of materials ➡ Validation of sterilized processes ➡ Process risk assessment ➡ Preventative maintenance: ensuring no additional risk of contamination ➡ Microbiological monitoring of the environment: air monitoring, surfaces, etc. At GMP Bridge, we have reviewed, drafted, and audited many CCS documents. The most important aspect is not the content itself but how the document is constructed. It should guide you through a COHESIVE STRATEGY to control contamination: how you PREVENT, DETECT, and MINIMIZE contamination at your manufacturing site.

✨Strategies to reduce risk with Contamination Control Strategies in the Pharmaceutical and Biotech industry✨ Why are they crucial? Let's dive into the essential reasons and discover the remarkable benefits that come with their implementation. Rigorous Cleanliness Protocols: Instituting meticulous cleanliness protocols and procedures across all facility zones—be it manufacturing, laboratories, or storage—ensures an environment of pristine purity. This encompasses regular cleansing schedules, validation of cleaning processes, and deployment of potent disinfectants effective against a broad spectrum of microorganisms. Aseptic Mastery: Crafting and sustaining a sterile milieu during manufacturing operations via aseptic techniques stands as paramount. This entails utilizing sterile apparatus and containers, donning sanitized attire, and executing procedures within controlled cleanroom surroundings. Embracing Disposable Apparatus and Materials: Embracing single-use equipment and supplies obviates the need for elaborate cleansing and sterilization, significantly curtailing the jeopardy of contamination and inter-batch cross-contamination. Empowering the Workforce: Furnishing comprehensive training on contamination control and aseptic practices ensures employees comprehend and diligently adhere to designated protocols. Encompassed within this is instruction on proficient employment of personal protective gear, adept use of sterile methodologies, and precision in cleansing procedures. Consistent Environmental Vigilance: Conducting regular environmental monitoring throughout the premises—comprising air and surface sampling—facilitates the early spotting of prospective contamination sources. Deft oversight of water systems also holds crucial import. Robust Quality Surveillance: Enforcing stringent quality control measures assures alignment with stipulated product quality benchmarks. This spans tests targeting microbial taint, potency, purity, and stability. Nurturing a Culture of Cleanliness: Fostering sterling personal hygiene practices, galvanizing employees to promptly report potential contamination origins, and inculcating a profound sense of custodianship for sustaining an immaculate and sterile milieu coalesce to fashion a pervasive culture of cleanliness permeating the entire organization. #ContaminationControl #Pharma #Biotech #Biopharmaceuticals #PatientSafety #BioCleaningConsulting Check this out for more blogs: https://lnkd.in/gFHGCHWz

CLEAN AREA SEPARATION: 1. An essential part of contamination prevention is the adequate separation of areas of operation. 2. To maintain air quality, it is important to achieve a proper airflow from areas of higher cleanliness to adjacent less clean areas. 3. It is vital for rooms of higher air cleanliness to have a substantial positive pressure differential relative to adjacent rooms of lower air cleanliness. 4. For example, a positive pressure differential of at least 10-15 Pascals (Pa) should be maintained between adjacent rooms of differing classification (with doors closed). 5. When doors are open, outward airflow should be sufficient to minimize ingress of contamination, and it is critical that the time a door can remain ajar be strictly controlled. 6. In some cases, the aseptic processing room and adjacent cleanrooms have the same classification. 7. Maintaining a pressure differential (with doors closed) between the aseptic processing room and these adjacent rooms can provide beneficial separation. 8. In any facility designed with an unclassified room adjacent to the aseptic processing room, a substantial overpressure (e.g., at least 12.5 Pa) from the aseptic processing room should be maintained at all times to prevent contamination. 9. If this pressure differential drops below the minimum limit, it is important that the environmental quality of the aseptic processing room be restored and confirmed. 10. The Agency recommends that pressure differentials between cleanrooms be monitored continuously throughout each shift and frequently recorded. 11. All alarms should be documented and deviations from established limits should be investigated. 12. Air change rate is another important cleanroom design parameter. 13. For Class 100,000 (ISO 8) supporting rooms, airflow sufficient to achieve at least 20 air changes per hour is typically acceptable. 14. Significantly higher air change rates are normally needed for Class 10,000 and Class 100 areas. 15. A suitable facility monitoring system will rapidly detect atypical changes that can compromise the facility’s environment. 16. An effective system facilitates restoration of operating conditions to established, qualified levels before reaching action levels. 17. For example, pressure differential specifications should enable prompt detection (i.e., alarms) of an emerging low pressure problem to preclude ingress of unclassified air into a classified room. REFERENCE: GUIDANCE FOR INDUSTRY - STERILE DRUG PRODUCTS PRODUCED BY ASEPTIC PROCESSING — CURRENT GOOD MANUFACTURING PRACTICE - SEPTEMBER - 2004.

Aseptic Processing demands expertise and experience to prevent microbiological contamination. Understanding “why” we do behind “what” we do is crucial, and the fundamentals of aseptic processing are not difficult to grasp. From the warning letter (Ref: https://lnkd.in/guj2VR_J) issued on August 29th, there are several important lessons: 1. The smoke study was not simulated under actual dynamic condition, thus it’s use is questionable at best. 2. Since it is questionable all product manufactured are in the scope of the investigation. 3. Media fill failure was not investigated properly and invalidated - invalidation is inappropriate. In one case media fill investigation has not been completed for 2 years - thus the question - is the investigation system appropriate? 4. Continuous Building Monitoring System (BMS) must be present and monitored for differential pressure. All deviations from established limits should be appropriately investigated to rapidly detect atypical changes that can compromise the facility’s environment. Prompt detection of an emerging problem is essential to preventing contamination of your aseptic production operations. - cross contamination is possible and this suggests lack of effective contamination control strategy. 5. Cleaning validation study lacked recovery and limit of detection study - thus method is inadequate at best. Without proper cleaning, cross contamination is a possibility 6. Quality unit is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities - FDA is holding higher management accountable for quality concerns. In summary, key takeaways include the need for dynamic condition simulations for smoke studies, meticulous attention to media fill and related investigations, proper validation of cleaning methods, and effective oversight of differential pressure monitoring is required to ensure proper aseptic processing. #qualityassurance #biopharmaquality #asepticprocessing #contaminationcontrol

CLEAN AREA SEPARATION: 1. An essential part of contamination prevention is the adequate separation of areas of operation. 2. To maintain air quality, it is important to achieve a proper airflow from areas of higher cleanliness to adjacent less clean areas. 3. It is vital for rooms of higher air cleanliness to have a substantial positive pressure differential relative to adjacent rooms of lower air cleanliness. 4. For example, a positive pressure differential of at least 10-15 Pascals (Pa) should be maintained between adjacent rooms of differing classification (with doors closed). 5. When doors are open, outward airflow should be sufficient to minimize ingress of contamination, and it is critical that the time a door can remain ajar be strictly controlled. 6. In some cases, the aseptic processing room and adjacent cleanrooms have the same classification. 7. Maintaining a pressure differential (with doors closed) between the aseptic processing room and these adjacent rooms can provide beneficial separation. 8. In any facility designed with an unclassified room adjacent to the aseptic processing room, a substantial overpressure (e.g., at least 12.5 Pa) from the aseptic processing room should be maintained at all times to prevent contamination. 9. If this pressure differential drops below the minimum limit, it is important that the environmental quality of the aseptic processing room be restored and confirmed. 10. The Agency recommends that pressure differentials between cleanrooms be monitored continuously throughout each shift and frequently recorded. 11. All alarms should be documented and deviations from established limits should be investigated. 12. Air change rate is another important cleanroom design parameter. 13. For Class 100,000 (ISO 8) supporting rooms, airflow sufficient to achieve at least 20 air changes per hour is typically acceptable. 14. Significantly higher air change rates are normally needed for Class 10,000 and Class 100 areas. 15. A suitable facility monitoring system will rapidly detect atypical changes that can compromise the facility’s environment. 16. An effective system facilitates restoration of operating conditions to established, qualified levels before reaching action levels. 17. For example, pressure differential specifications should enable prompt detection (i.e., alarms) of an emerging low pressure problem to preclude ingress of unclassified air into a classified room. REFERENCE: GUIDANCE FOR INDUSTRY - STERILE DRUG PRODUCTS PRODUCED BY ASEPTIC PROCESSING — CURRENT GOOD MANUFACTURING PRACTICE - SEPTEMBER - 2004.

🚨 FDA 483s on EM, Aseptic Processing & Contamination Here are some reasons that are described in many FDA observations: 🧼No Established Cleaning Procedures for Equipment and Utensils : Proper cleaning protocols are essential to prevent cross-contamination and ensure product integrity. It's imperative to develop and document comprehensive cleaning procedures for all equipment including utensils used in production. 🧪Inadequate Sampling and Testing of Environment and Personnel : Regular sampling of both the environment and personnel is crucial for detecting potential contaminants. It is imperative to test in the key, critical points of your contacts and to not just sample to sample. 🏭Poor Design of Equipment and Facilities : The design of our equipment and facilities should facilitate minimize contamination risks. Reviewing and improving facility design can significantly enhance overall aseptic processing conditions. Action Steps: 🔬 Establish Robust Cleaning Protocols: Develop detailed cleaning procedures and ensure all staff are trained to follow them rigorously. 🔬 Enhance Sampling & Testing: Implement more frequent and thorough environmental and personnel monitoring to promptly identify and address any issues. 🔬 Optimize Equipment & Facility Design: Evaluate and upgrade equipment and facility designs to support better hygiene and contamination control. By addressing these observations, we can reinforce our commitment to quality and safety, ensuring that we meet and exceed FDA standards. #qualitysystems #pharma #environmentalmonitoring #contamination

🚨 FDA 483s on EM, Aseptic Processing & Contamination Here are some reasons that are described in many FDA observations: 🧼No Established Cleaning Procedures for Equipment and Utensils : Proper cleaning protocols are essential to prevent cross-contamination and ensure product integrity. It's imperative to develop and document comprehensive cleaning procedures for all equipment including utensils used in production. 🧪Inadequate Sampling and Testing of Environment and Personnel : Regular sampling of both the environment and personnel is crucial for detecting potential contaminants. It is imperative to test in the key, critical points of your contacts and to not just sample to sample. 🏭Poor Design of Equipment and Facilities : The design of our equipment and facilities should facilitate minimize contamination risks. Reviewing and improving facility design can significantly enhance overall aseptic processing conditions. Action Steps: 🔬 Establish Robust Cleaning Protocols: Develop detailed cleaning procedures and ensure all staff are trained to follow them rigorously. 🔬 Enhance Sampling & Testing: Implement more frequent and thorough environmental and personnel monitoring to promptly identify and address any issues. 🔬 Optimize Equipment & Facility Design: Evaluate and upgrade equipment and facility designs to support better hygiene and contamination control. By addressing these observations, we can reinforce our commitment to quality and safety, ensuring that we meet and exceed FDA standards. #qualitysystems #pharma #environmentalmonitoring #contamination

*** Annex 1 (APS) - Sterility Assurance *** After not being in the space for a bit of time I'm getting back to grips with what is causing work for contractors. I've heard that Annex 1 is causing issues for companies and the need for Sterility experts is high across Europe. I know that a big revision is around the Aseptic process "Media Fill" and greater care is placed not only on filtered liquids but also on non-filterable formulations, sterile powders (including sterile APIs), lyophilized products and production campaigns. Two main challenges I have heard from speaking to Consultants are: 1) Contamination Control Strategy 2) Quality Risk Management I'd love to hear people's thoughts on APS and other challenges they have seen? #Sterile #Aseptic #Manufacturing #Annex1