Environmental Monitoring using Laminar Air Flows (LAF) in Pharmaceutical Sterile Compounding Sites.

Pharmaceutical compounding sites are facilities where pharmacists or specially trained personnel prepare customized medications based on the individual needs of patients. These types of companies are subject to strict regulatory requirements to ensure patient safety and quality control since the medications prepared in these facilities are customized for individual patients. This means that they cannot be subject to the same level of regulatory oversight as commercially available medications.

Therefore, the responsibility for ensuring the safety and efficacy of these medications falls squarely on the shoulders of the compounding facility. This implies:

Patient safety: Patients who require customized medications are often those with complex medical conditions and compromised immune systems. Any contamination or error in compounding can have severe consequences for them.
Efficacy of the medication: Compounding is a delicate process that requires careful measurement and mixing of ingredients. If the facility’s equipment or processes are not properly maintained, the efficacy of the medication may be compromised, and the patient may not receive the intended benefit.
Compliance with regulations: Sterile compounding facilities must comply with strict regulations, such as USP General Chapter <797>, the European Pharmacopeia General Chapter 5.17, and other governing bodies to ensure that medications are prepared safely and accurately. Failure to comply with these regulations can result in penalties, fines, or even closure of the facility.

A Laminar Air Flow (LAF) system is an essential component of a pharmaceutical compounding site. Its role is to provide a clean, disinfected, low-particulate environment for the preparation of sterile medications. The LAF system works by filtering air through high-efficiency particulate air (HEPA) filters, which remove airborne contaminants.

The sterile compounding area, also known as the direct compounding area (DCA), is located within the LAF, and personnel working within this area must wear appropriate garb and follow strict procedures to prevent microbiological and particle contamination that could compromise the quality of the medication.

**Figure 1: Example of sterile compounding inside a LAF**

Working in a pharmaceutical compounding site requires personnel to meet specific quality requirements to ensure that medications are prepared safely and accurately. Here are some of the requirements for personnel working in a compounding facility:

Education and training: Personnel should have the necessary education and training to understand the compounding process, including aseptic techniques, medication calculations, and quality control measures.
Good Manufacturing Practices (GMP): Personnel should be familiar with GMPs and should follow them strictly to ensure that medications are prepared in a sterile, controlled environment.
Personal protective equipment (PPE): Personnel should be trained to wear the appropriate PPE, such as sterile gowns, gloves, and masks, to prevent contamination of medications during the compounding process.
Standard operating procedures (SOPs): Personnel should be trained to follow SOPs, which outline the steps to be taken during the compounding process, including documentation, labeling, and quality control checks.
Ongoing training and tracking: Personnel should receive ongoing training and personnel results should be tracked for competency to ensure that they remain up to date with best practices and regulations.

The USP General Chapter <797> has undergone a significant revision and will become official in November 2023 There are several changes and updates introduced to improve patient safety and quality of compounding practices. Here are some of the main novelties of the new chapter:

Compounding Categories: The new version of USP <797> now identifies three compounding Categories for compounded sterile preparations (CSPs): Category 1, Category 2, and Category 3. This risk-based approach, which considers the location in which the CSP was prepared, allows for more targeted and appropriate quality control measures based on the level of risk associated with the CSP.
Environmental monitoring: More frequent environmental monitoring of the ISO classified spaces is now required. This ensures the sterile compounding facility meets the required air quality standards. Monitoring includes regular air sampling, surface sampling, and personnel monitoring to detect any potential sources of contamination.
Cleaning and disinfection: The revised version of USP <797> introduces more stringent requirements for cleaning and disinfection of compounding facilities and equipment, with specific guidance on the use of sporicidal agents and other disinfectants.
Quality control measures: The chapter now includes more detailed guidance on quality control measures, including documentation, labeling, and testing of CSPs to ensure that they meet the required standards.
Personnel qualifications and training: The revised version of USP <797> introduces more specific requirements for personnel qualifications and training, including ongoing competency assessments, and documentation of training and qualifications.
Sterility testing: More detailed guidance on sterility testing, including the use of rapid microbiological methods is also included in the revisions.

The frequency of Aseptic Performance Simulation (APS) testing in a Laminar Air Flow (LAF) system in a pharmaceutical compounding site depends on several factors, including the category of the compounded sterile preparations (CSPs), the complexity of the compounding process, and regulatory requirements.

How to assure quality on Compounding Facilities?

USP <797> requires that the aseptic manipulation competency be performed at a minimum of every six months for Category 1 and 2 CSPs and every three months for Category 3 CSPs. However, this is considered a minimum requirement, and some facilities may choose to perform competency testing more frequently based on their internal policies and risk assessment.

It is also important to note that competency testing should be performed in accordance with established procedures and documented appropriately. Any deviations or failures must be thoroughly investigated, and corrective actions taken promptly to ensure the continued safety and quality of the CSPs.

For those reasons, at SherpaPharma we have developed two new functionalities that will help the tracking and documenting steps for environmental control during aseptic activities using LAF in Pharmaceutical Compounding companies.

1.- New sampling point type: LAF Control

To increase the quality control of the environment, apart from air and surface control, Aseptic Process Simulations / Aseptic Manipulation Competences are performed using different methods and frequencies according to its internal procedures and local regulations:

A.- Daily control with a vial media broth open inside the LAF that is opened at the beginning of the activity and closed at the end of the manufacturing process. This vial can collect any microbiological contaminant that can be present in the air.

B.- More complete control can be performed by passing media broth through all the installation.

In both cases, the media is incubated for a specific period and temperatures. Several readings of the transparency of the vial will be done to detect any turbidity that indicates microbiological contamination. This type of sample can be included in the Sampling Session and several readings can be performed and registered to document the different days of sample control.

**Figure 2: Example of vial with media for LAF Control**

*Figure 3: Mixed Sampling Session in the Handheld device*

*Figure 4: Mixed Sampling Session in the Software application*

2.- Mixed Sampling Session: Environmental and Personal samples together

In addition, the traceability of all technicians who have performed any operation during the activity inside the LAF must be ensured.

To do this, a mixed sampling plan has been developed. The type of sampling plan allows combining environmental sampling with personnel sampling. All the personnel (as many as needed) that participate in the process at different stages can be tracked together with the samples they are taking.

This enables having all the samples in the same sampling session, favoring their subsequent review and approval, increasing control, and ensuring product quality and patient safety.

***Figure 5: Mixed Sampling Session in the Software application. Environmental, LAF Control and Personnel samples grouped.***

Santi Tintoré

General Manager at Tiselab | + posts

Santi studied telecommunications engineering and an MBA. Since 2005 he works at Tiselab, where he has helped to consolidate the current team, achieving sustained growth, and diversifying the company into various divisions. In 2016, he started the SherpaPharma project after realizing that pharmaceutical companies had an opportunity for significant improvement in Environmental Monitoring.

Santi estudió ingeniería de telecomunicaciones y un MBA. Desde 2005 trabaja en Tiselab, donde ha ayudado a consolidar el equipo actual, consiguiendo un crecimiento sostenido y diversificando la compañía en varias divisiones. En 2016 inició el proyecto SherpaPharma al ver que en las compañías farmacéuticas había una oportunidad de mejora importante en la Monitorización Ambiental.

Enric Adsera

Project Manager at Tiselab | + posts

Enric Adserà has a degree in Chemistry, Chemical Engineering and MBA from ESADE. Since 2018 he works in Tiselab as Project Manager of SherpaPharma providing his experience and knowledge in the application of Environmental Monitoring solutions in the pharmaceutical industry.

Enric Adserà es Licenciado en Químicas, Ingeniería Química y MBA por ESADE. Desde 2018 trabaja en Tiselab como Project Manager de SherpaPharma aportando su experiencia y conocimientos en la aplicación de soluciones de Monitorización Ambiental en el sector farmacéutico.

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