Corporate Partner Spotlight: EMD Millipore Corporation
Author: Karen Chronholm
Director Regional Marketing
EMD Millipore Corporation
290 Concord Road
Billerica, MA 01821 USA
Phone: +1 978-715-1748
Increasing Control in the Product Manufacturing Process with QC Microbiology Programs
While microbiological testing programs are an essential part of any compounding pharmacy’s operation, it can be challenging for an organization to define the optimal approach to testing. The United States Pharmacopeial Convention’s USP <797> Compounding-Sterile Preparations addresses testing and microbiological quality measures for sterile, compounded drugs conducted by US and Canadian facilities and provides guidelines for areas in which compounded sterile preparations are prepared, stored and dispensed. However, several US states do not have laws providing guidance for sterile compounding, and USP <797> guidelines were written to allow for flexibility, which can make it difficult when companies are trying to implement or maintain a microbiological testing and sampling program. Adding to the challenge is that regulations are likely to evolve in coming months and years in response to recent, well-publicized contamination events.
Microbiological testing and sampling programs are used to monitor and identify microbial contamination in raw and in-process materials, as well as non-sterile finished products. Independent of regulations, robust microbiological testing is crucial to preventing contamination and ensuring patient safety. In a stringent and evolving regulatory environment, a number of factors should be considered when establishing or updating existing QC microbiology programs.
Compounding pharmacies should perform a formal assessment to identify where risk is present in the manufacturing process. To conduct a thorough evaluation, it is important to know every detail about the product and process, as well as where possible exposure to contamination might exist. A proper risk evaluation includes knowledge of the facility, utilities, raw materials and how training is executed and documented. It is important for laboratory personnel to have a complete understanding of the product and processes with which they are working, either from microbiological experience or an effective operator training program.
Once an assessment is complete, companies can mitigate exposure to risk through implementation of appropriate environmental monitoring technologies, which are used to determine the microbial and particulate content of cleanroom air and surfaces. Data collected from environmental monitoring are a vital component of a compounding pharmacy’s microbiological testing program. Results are used for quality assurance, identifying conditions contributing to excessive microbial and particulate levels, as well as to alert personnel to conditions exceeding classification.
Proactive environmental monitoring not only helps to avoid risks, but also prevents the release of potentially contaminated products into the market, which can lead to product recall and compromise consumer safety. Thus, timely and regular testing is a critical success factor for a robust microbiological testing and sampling program.
In our experience, most compounding pharmacies conduct environmental monitoring assessments on a six-month interval during which an outside company comes in and “certifies” the lab. The certification serves a valuable function as it verifies the cleanrooms and HEPA filters are working properly at the time of inspection.
While the certification process is conducted every six months, it does not verify that a cleanroom has been in compliance for the previous six months. Thus, routine environmental monitoring should be conducted on each operator, each shift and each product batch. Doing so will reduce risk and adhere to the certification, especially in an environment where aseptic operations are being carried out every day, with multiple products, time points and personnel.
To further ensure high quality products that are manufactured to the tightest specifications, vendors that provide technologies and supplies to the compounding pharmacy should be carefully scrutinized. Vendors themselves must also have a robust QC system to ensure that the final product being released is not contaminated.
For added control in the product manufacturing process, standard operating procedures, Corrective Actions/Preventative Actions (CAPA), and validation protocols need to be in place and communicated to all personnel working with compounding product.
Standard Operating Procedures
Standard operating procedures for compounding sterile products need to be documented and available to all personnel involved in production. Documents should be updated as policies and procedures change to reflect current standards of quality and any changes must be properly communicated to all personnel. Policies and procedures should include training requirements, product acquisition, storage and handling of products and supplies, storage and delivery of final products, use and maintenance of facilities and equipment, appropriate personnel uniform, process validation, preparation technique, labeling, documentation and quality control.
CAPA and Validation Protocols
and investigation protocols are part of the FDA’s good manufacturing practices (GMP) and are undertaken to collect and analyze information about product and quality problems. The system is used to effectively correct and prevent recurrence through communicating corrective actions to responsible people, providing any relevant information and effectively dealing with product or device failures.
Validation protocols should be put into place regarding all processes involved in product production, including procedures, equipment, techniques and criteria for acceptance. Process validation allows determination of whether a process will consistently produce the intended results when performed by qualified personnel.
Another component of a successful microbiological testing program is the incorporation of the latest environmental monitoring technologies, which will be described in part three of this series. New technologies for air and surface monitoring enable companies to identify contamination sooner and help release products to market faster. Highlighted technologies include active and passive air samplers, particle counters, and contact plates and swabs. Benefits of new technologies for environmental monitoring versus traditional methods will be discussed.
An effective microbiological testing and sampling program is critical to maintain the highest level of product quality and patient safety. As such, it should encompass the requirements outlined in this article to ensure products are manufactured to the highest quality. While USP chapters are the subject of various interpretations and can be relied on as guidance for decision making and validation of a process, it is ultimately up to the company producing the final product to be responsible for determining that its process and product are in a state of control.