File Name: manufacture of sterile and non sterile products .zip
- Regulatory Update: How FDA Assesses Microorganisms in Drug Products
- Sterile vs Non-Sterile Compounding Pharmacies
- Aseptic Manufacturing and Sterile Fill-Finish for Complex Drug Products
Regulatory Update: How FDA Assesses Microorganisms in Drug Products
The presence of microorganisms in sterile drug products is of paramount concern to patient safety. However, it may be less obvious why concern for the presence of microorganisms in non-sterile drug products NSDPs exists. The routes of administration for NSDPs typically have less access to areas of the body, which could result in extreme immune system responses or patient fatality.
The presence of microorganisms in NSDP is obviously considered lower risk when compared to sterile drug products.
However, the presence of microorganisms in NSDPs still poses a risk to pharmaceutical manufacturing and patient safety and, therefore, must be controlled. Recent NSDP incidents with contaminants, such as Burkholderia cepacia complex in non-sterile aqueous products, resulting in serious product adverse events, deaths, and recalls have highlighted FDA focus on the microbial quality of NSDPs.
FDA requires data to support the control of microorganisms during the manufacturing of drug products as well as in the finished dosage form. The amount and type of data required to support a drug product application differs depending upon the risk to the patient. Thus, microbial contamination associated with the manufacturing process as well as the finished dosage form must be controlled. It is recommended that NSDP manufacturers perform a risk-based impact assessment that considers the product specific characteristics e.
Many compendial excipients have microbial limits. This focuses on limiting the total levels of the microorganisms, including bacteria, yeast and mold, and the absence of potentially pathogenic bacteria e. Control of microorganisms in the manufacturing environment should also be demonstrated. Facilities should also be compliant with all current good manufacturing practices and this compliance will typically be scrutinized during facility inspection.
Developers should also scrutinize the ability for microorganisms to proliferate during the manufacturing process. For microorganisms to grow and proliferate, they need nutrients which may be present in the product formulation , water which some product manufacturing processes require , and time since their growth is logarithmic.
Other factors affecting microbial growth are the temperature and pH during the different phases of manufacture. Some of these variables can be controlled and should be, while others may not i. It is important to control those variables which can be and be aware of those that cannot be controlled. Typically, the time, especially any holding periods during the manufacturing process, is best to be controlled and kept minimal, when possible.
It is also possible to include antimicrobial manufacturing steps, such as high heat or pressure, to minimize microbial contamination. Some products must also be antimicrobial. Testing for BCC was developed due to numerous adverse events reported, especially in aqueous product where BCC may be associated with manufacturing water systems.
FDA has a risk-based assessment of non-sterile drug products, which includes that all NSDPs must have a microbial control strategy. The release and stability testing requirements are scaled to patient risk and control of upstream manufacturing. Reduced testing may be applicable to products based on their characteristics and manufacturing process.
Solid oral dosage forms may be good candidates for reduced testing. As mentioned above, it is possible to demonstrate the microbiological aspects of a NSDP by end-product testing. However, inherent flaws in testing methods may exist when dealing with living microorganisms which may be present at low levels or undetectable levels depending upon test sampling size and techniques.
This control is vital to manufacturing safe and quality NSDPs. Contact Us. Previous Next Post. Learn More. Read Article. We are always available for a conversation. First Name. Last Name. Email Address. Helena St. Communication Preference Yes, I would like to receive marketing communications including industry insights and trends from Parexel International.
Sterile vs Non-Sterile Compounding Pharmacies
The presence of microorganisms in sterile drug products is of paramount concern to patient safety. However, it may be less obvious why concern for the presence of microorganisms in non-sterile drug products NSDPs exists. The routes of administration for NSDPs typically have less access to areas of the body, which could result in extreme immune system responses or patient fatality. The presence of microorganisms in NSDP is obviously considered lower risk when compared to sterile drug products. However, the presence of microorganisms in NSDPs still poses a risk to pharmaceutical manufacturing and patient safety and, therefore, must be controlled.
P harmaceutical products are classified into two groups according to the microbiological point of view: 1 sterile products and 2 non-sterile products. The sterilized term refers to the products that are free of any microorganisms, their production were done under aseptic conditions, but the production of non-sterile products were not under aseptic conditions 1 ; they are not free from microorganisms; for this type of products legal authorities defined microbial limit ranges. The requirements for non-sterile products acceptance depending on the legal authorities of different countries or even different pharmaceutical companies may vary slightly. These microorganisms can grow under certain temperature and nutritional conditions and could affect the quality and safety of the product. Contamination at any stage of the process can represent a serious risk to the final product and must be controlled so to maintain the quality and safety of the product 3.
Aseptic Manufacturing and Sterile Fill-Finish for Complex Drug Products
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The amount of environmental control, environmental monitoring, and finished product testing necessary to ensure medicinal product microbiological safety and product quality depends on factors such as the product dosage form, route of administration and, if applicable, the method of product sterilization. For instance, non-sterile products for oral administration possessing little or no water activity may require minimal environmental monitoring to ensure finished product microbiological quality. Likewise, sterile medical devices e. For these types of products, the level of environmental control depends on the nature of the product, pre-sterilization bioburden requirements, and the method of product sterilization. Like sterile drug or biological products, sterile implantable devices must provide a sterility assurance level SAL of at least 10
What FDA Considers When Assessing Microorganisms in Non-Sterile Drug Products
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