Microbiological quality of pharmaceutical products is essential for patient safety and product stability. As we know, the sterile products are manufactured in a sterile environment, but non-sterile products like tablets, capsules and liquid pharmaceutical products are manufactured in non-sterile manufacturing area.
It is essential to control the manufacturing environment to reduce the microbial count in the products. Consumption of contaminated products can cause problems to patients and the company may face product recalls and regulatory actions. The company must have microbiological control on the manufacturing process to produce safe and effective products.
In this post we will understand strategies, practices and quality systems to enhance microbial control in manufacturing of non-sterile pharmaceutical products.
1. Pathogenic organisms: Pathogens like E. coli, Salmonella, S. aureus, P. aeruginosa can cause diseases when found in pharmaceutical products.
2. Spoilage organisms: These organisms are not harmful but can affect product stability, order, color or viscosity.
3. Other Contamination: Contamination from equipment, water system, personnel handling the material or from the environment.
To eliminate these risks manufacturers must have an effective microbiological control program integrated with quality management system (QMS).
All pharmacopoeias and regulatory agencies have clear guidelines on microbial contamination of non-sterile products
Corrective actions are revision of cleaning procedures and validation of the clean-in-place process, reformulated product with a broad-spectrum preservative and staff retraining for aseptic sampling techniques. These changes result in a 90% drop in microbial failures within 6 months and regulatory inspection passed without any observation.
By implementing strong microbiological control strategies, pharmaceutical companies can reduce their recalls and enhance products shelf life. If you have any issues in your manufacturing facility, you can contact us to get a suitable contamination control strategy.
It is essential to control the manufacturing environment to reduce the microbial count in the products. Consumption of contaminated products can cause problems to patients and the company may face product recalls and regulatory actions. The company must have microbiological control on the manufacturing process to produce safe and effective products.
In this post we will understand strategies, practices and quality systems to enhance microbial control in manufacturing of non-sterile pharmaceutical products.
Understanding the Risks: Why Control Is Necessary
Non-sterile pharmaceutical products like tablets, capsules, syrups, ointments, creams etc are not sterilized during manufacturing. Due to this they can have growth of bacteria, yeast or molds during their production or shelf life. Following are some key microbial risks involved with nonsterile pharmaceutical products.1. Pathogenic organisms: Pathogens like E. coli, Salmonella, S. aureus, P. aeruginosa can cause diseases when found in pharmaceutical products.
2. Spoilage organisms: These organisms are not harmful but can affect product stability, order, color or viscosity.
3. Other Contamination: Contamination from equipment, water system, personnel handling the material or from the environment.
To eliminate these risks manufacturers must have an effective microbiological control program integrated with quality management system (QMS).
Regulatory Expectations
All pharmacopoeias and regulatory agencies have clear guidelines on microbial contamination of non-sterile products - USP Chapter 1111: Microbiological Examination of Non-Sterile Products
- USP Chapter 61 and 62: Microbial Enumeration and Tests for Specified Microorganisms
- ICH Q9: Quality Risk Management
- WHO GMP Guidelines
- PIC/S Guidelines
- FDA 21 CFR Part 211: Good Manufacturing Practices for Finished Pharmaceuticals
Key Strategies to Improve Microbiological Control
Let us understand different strategies to have microbial control on manufacturing process of non-sterile products.1. Risk-Based Product Development
Microbiological control begins with product development stage. Choose an effective and appropriate preservative to control wide range of microbes found in the environment. Formulation parameters like pH, water activity and solubility must be adjusted to minimize microbial growth. Preservative efficacy test must be performed according to pharmacopeial requirements during the product development.2. Supplier Qualification and Raw Material Control
Raw materials are the most common source of contamination in pharmaceutical products. Vendors must be audited and qualified for their microbial control. Strict microbial testing must be implemented for all raw materials and materials with high bioburden must be avoided.3. Control of Water Systems
Purified water used in non-sterile product manufacturing must be monitored closely. The water system must be designed with loop circulation and should have minimal dead legs. Water samples must be monitored for microbial count on a regular basis. A trend analysis must be conducted to detect any system failures.4. Environmental Monitoring (EM) and Facility Design
Environmental conditions in non-sterile pharmaceutical manufacturing are less stringent than sterile areas, but controlled environments are necessary to control contamination. It is necessary to have controlled temperature and humidity levels. An environmental monitoring program must be implemented for all non-sterile production areas, including air and surface sampling. Here, a cleaned surface, HEPA filters and unidirectional workflow always improve contamination control.5. Equipment Cleaning and Sanitization
Poor cleaning of equipment and area can result in microbial contamination and carryovers from previous batches. Cleaning procedures must be validated using swabs and rinse samples. Disinfectants must be rotated to prevent microbial resistance and ensure their efficiency against microorganisms. Establish a system that includes visual inspection and maintains equipment cleaning logs. Clean-in-place and steam-in-place cleaning systems should be used as required.6. Personnel Hygiene and Gowning
Handling of material and product is a major source of contamination in non-sterile product manufacturing. Implement good personal hygiene practices including hand washing and trimmed nails. Use appropriate gowning for various production areas. Conduct regular training and requalification of personnel on hygiene and contamination awareness. Hand and garment swabs for monitoring personal hygiene can improve microbiological control in the production area.7. Robust Sampling and Testing Procedures
Always use pharmaceutical methods like USP chapters 61 and 62 for microbial count and pathogen testing. Test raw materials, in-process materials and finished products for microbial count and pathogens. Sample storage, preparation and handling should not compromise simple integrity.8. Microbiological Trending and Data Review
Trending plays an important role in microbial analysis. Make trends for product testing, water analysis, environmental monitoring, equipment swabs and raw materials. Use charts and statistical tools to detect any microbiological risk in the early stage. Investigate promptly and perform effective root cause analysis and preventive actions.9. CAPA and Continuous Improvement
Out of specification results must be handled properly by thorough investigations, corrective and preventive actions and process revalidation. Continuous learning from failures strengthens the microbial control over time.10. Documentation and Data Integrity
Good documentation practices are an essential part of microbiological control in pharmaceutical industry. Record data in real-time without any manipulation. Maintain traceability of sample analysis and record analyst signature and test conditions. Ensure all the records meet data integrity standards and ALCOA+ principles.Case Study: Improving Microbial Control in a Syrup Production Line
An oral syrup manufacturing company noticed frequent microbial contamination in their products. A complete review of their manufacturing process revealed inadequate cleaning of holding tanks, ineffective preservatives and poor sampling techniques.Corrective actions are revision of cleaning procedures and validation of the clean-in-place process, reformulated product with a broad-spectrum preservative and staff retraining for aseptic sampling techniques. These changes result in a 90% drop in microbial failures within 6 months and regulatory inspection passed without any observation.
By implementing strong microbiological control strategies, pharmaceutical companies can reduce their recalls and enhance products shelf life. If you have any issues in your manufacturing facility, you can contact us to get a suitable contamination control strategy.
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