Hygiene Monitoring in Pharmacies and Pharmaceutical Settings

Patient safety is the highest priority. Therefore, pharmaceutical products are manufactured under strict controls. Microbial monitoring plays a crucial role in ensuring compliance with GMP regulations and demonstrates that manufacturing processes—particularly in aseptic production—are well controlled.

Hygiene monitoring in pharmacies, for example during the production of sterile medicinal products or in compounding, is legally regulated and must be carried out systematically to document compliance with hygiene standards. It is primarily based on the German Pharmacy Operating Regulations (§ 35 ApBetrO) and the EU GMP Guidelines (Annex 1 – for sterile medicinal products).

The hygiene monitoring workflow always includes the following steps:

• Create a sampling plan based on a risk analysis
• Prepare sampling materials and transfer them to the cleanroom or compounding area
• Perform sampling and document the samples
• Incubate the samples
• Evaluate and document the results

1. Types of Hygiene Monitoring

A. Air Monitoring (Airborne Microbial Sampling)

• Goal: Control of microbial load in cleanroom air
• Method: Active air sampling using an air sampler, or passive air sampling via sedimentation (sedimentation plate placed on the workbench)
• Materials:
• Air sampler MAS-100 VF, from Merck, suitable for use in controlled environments such as cleanrooms per ISO 14698
• 90 mm CASO agar plates (Casein-soybean peptone; English: TSA = Tryptic Soy Agar): See appropriate agar selection table below (depending on cleanroom class/isolator and used disinfectants)
• Incubator: For incubating the agar plates at 30–35 °C for bacteria. Example  Memmert Incubator IN30, natural convection, Single-Display

B. Surface Monitoring

• Goal: Checking work surfaces, walls, and equipment for microbial contamination
• Method: Sampling with contact plates, known as RODAC plates (Replicate Organisms Detecting And Counting), or swab tests
• Materials:
• 55 mm CASO agar contact plates (see selection table below)
• ICR swab kit for hard-to-reach surfaces in Class A cleanrooms and isolators
• Surface markers (for standardization)
• Disinfectant for post-sampling treatmen

C. Personnel Hygiene

• Goal: Monitoring contamination caused by personnel (especially gloves and sleeves)
• Method: Contact plate tests on gloves and clothing after work
• Materials:
• 55 mm CASO agar contact plates (see selection table below)

D. Particle Monitoring (Non-Microbial)

• Goal: Monitoring air cleanliness based on particle count
• Method: Particle counter (e.g., for cleanroom classification qualification)
• Materials:
• Laser particle counter (calibrated)

2. Additional Required Materials and Conditions

• Disinfectants (effective against bacteria, fungi, and viruses – e.g., alcohol-based)
• Sterile protective clothing: disposable gowns, caps, sterile gloves)
• Validated cleaning and disinfection procedures
• Documentation & Standard Operating Procedures (SOPs) and protocol forms

3. Frequency of Monitoring

The frequency of hygiene monitoring depends, among other things, on the cleanroom classification (see below) and whether sterile medicinal products are being produced. This must be assessed individually and defined for each pharmacy. Here's an example:

Cleanroom Classes in German Pharmacies

In German pharmacies—especially in compounding or manufacturing pharmacies—specific classifications for cleanrooms apply, based on the EU-GMP Guidelines (Good Manufacturing Practice) and the German Pharmacy Operating Regulations (ApBetrO).

Cleanroom classes A to D are typically used in German pharmacies. Class A is mandatory for sterile production steps, while the surrounding environment (Class B or C) is selected based on a risk assessment.

Pharmacies operating under Cleanroom Class A often use isolators. An isolator in a pharmacy is a closed system that creates a controlled and sterile environment for the manufacturing and handling of medicinal products. Its purpose is to separate the operator, the product, and the environment from each other in order to prevent contamination or cross-contamination.

Selection of Agar Plates for Hygiene Monitoring

When selecting agar plates for hygiene monitoring, you can refer to the table below (not included in your message). The following aspects should be considered:

• Plate type: 90 mm diameter for sedimentation plates used in air sampling, 55 mm diameter for surface sampling (e.g., lab coats, fingers, work surfaces))
• Microbial analysis: CASO agar for total microbial count, Sabouraud agar for yeasts and molds
• Packaging: Triple-wrapped and gamma-irradiated for cleanroom classes A, B, and isolators to minimize contamination risk, Single-wrapped for non-critical applications
• Neutralizers against disinfectants: Since pharmacy and cleanroom areas are disinfected, agar plates must contain neutralizing agents, common neutralizers include: LTHTh = Lecithin, Tween 80, Histidine, Thiosulfate
• Volume/fill weight: An increased fill volume/weight of 25 or 30 ml (or grams) is required if plates are left out for more than 3 days, to prevent drying out