of bacteria, yeast and mould. Media used for surface
sampling shall be supplemented with additives
to neutralise the effects of disinfecting agents
(for example, TSA with lecithin and polysorbate
80) that may persist on surfaces. The media is
subject to growth promotion testing using the
recommendations found in USP <61> Microbiological
Examination of Non-Sterile Products: Microbial
Enumeration Tests. The plates used in environmental
monitoring are incubated between 20 and 35°C for
5–7 days. A commonly used incubation schema in
the pharmaceutical industry is 20–25°C for 2–3 days
followed by 3–5 days at 30–35°C to promote fungal
growth.
Monitoring methods
Acceptable methods for monitoring the
microbiological quality of the environment include
surface monitoring product contact on surfaces,
floors, walls, and equipment with swabs and
contact plates, active air monitoring with impact or
centrifugal air samplers and passive air monitoring
with settling plates.
Contact plates
are used to detect
and enumerate
microorganisms on flat,
non-porous surfaces
such as the stainless
steel working surface in
a laminar flow hood or
biological safety cabinet.
They may be used for
personnel monitoring
of cleanroom gowns,
sleeves, and gloves. Disposable plastic plates, with
a 55-mm diameter, are filled with TSA with the
convex meniscus of the agar above the rim of
the plate to make contact with the surface being
sampled. Alternatively, regular-sized plates may
be used for full palm imprints. When the surfaces
The NECC outbreak in 2012 resulted
in 753 fungal meningitis infections
in at least 20 states and 64 deaths
due to Exserohilum rostratum from
contaminated preservative-free MPA
steroid injections
samples have been disinfected, neutralising agents
are incorporated in the medium. Tween 80 (0.5%
polysorbate) is used to neutralise residual phenolic
disinfectants and 0.07% lecithin is used to neutralise
quaternary ammonium compounds. The sampling
is achieved by touching the entire meniscus on the
surface and using a rolling uniform pressure on the
back of the plate to effect contact. After incubation,
the number of CFUs are counted and the results
expressed as CFU per plate or per square centimetre.
For active or passive air monitoring 90-mm
diameter TSA plates are exposed during sample
collection. High-efficient air samplers are available
from multiple vendors that may sample a cubic
metre of air (1000 litres) in the order of 10 minutes.
After incubation, the number of CFUs are counted
and the results expressed as CFU per cubic metre
of air (active air sampling) or after a four-hour
exposure (settle plate or passive exposure).
Media fills
USP <797> requires that after successfully
completing hand hygiene and gowning qualification
that all compounding personnel have their sterile
technique evaluated using a media-fill test using the
worst-case compounding procedure and processing
conditions they encounter during a work shift by
replacing the CSP with soybean–casein digest broth.
Personnel are re-qualified at least annually.
requirements of the US federal good manufacturing
practices regulations found in 21 CFR Part 211
that require facilities to establish and follow
appropriate written procedures that are designed
to prevent microbiological contamination of drug
products purporting to be sterile, and that include
validation of all aseptic and sterilisation processes
(21 CFR 211.113(b)) and establish an adequate
system for monitoring environmental conditions in
aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
Recommendations on how facilities can comply with
these GMP requirements are found in the 2004 FDA
Guidance for Industry Sterile Drug Products Produced by
Aseptic Processing – Current Good Manufacturing Practice.
The industry practice in ISO 5 (Grade A) areas is to
conduct air, surface, and personnel monitoring each
shift, and in ISO 7 (Grade B) areas it is daily. Other
surrounding support areas would be monitored
weekly.
Environmental monitoring excursions
When environmental monitoring results exceed
the action levels (see
Table 1) or the trending
rules and alert levels
established in your
facility, the excursion
should be investigated
to determine if there is
a loss of environmental
control within the
facility, a disinfection
failure or poor aseptic
practices. Once the
probable root cause
of the excursion is found, corrective and
preventative actions should be taken in the areas
of environmental control and aseptic practices.
UK situation
What is the situation in the UK? In 2003, the
British Government modernised the hospital
pharmacy manufacturing unit (PMU) network.
The network was rationalised from small hospitalbased
operations into a network of 13 large lead
units and support units.
These units have a diverse range of activities
including:
• Sterile manufacturing of terminally sterilised
products
• Aseptic manufacturing of pre-filled syringes,
eye-drops and other items
• Non-sterile manufacturing
• Aseptic compounding, that is, total parenteral
nutrition, chemotherapy, centralised intravenous
admixture services and diagnostic radiopharmaceuticals
• Extemporaneous dispensing services.
In addition to the PMU network, there are about
120 aseptic compounding units in British hospitals.
Section 10 of the UK Medicines Act enables
a pharmacist to supervise preparation of products
against a prescription without needing a specials
license from the Medicines and Healthcare Products
Regulatory Agency (MHRA). The MHRA is currently
reviewing the regulation of unlicensed medicines.
There will undoubtedly be greater control over
what may be manufactured, testing requirements,
enhanced requirements for stability information,
and pharmacovigilance.
Outsourcing sterile compounding facilities
In the US, so-called Section 503B outsourcing sterile
compounding facilities must comply with the
Sterility testing of sterile compounded
preparations
US sterile compounding pharmacies that comply
hospitalpharmacyeurope.com | 2019 | Issue 91 | 37