Page 256 - Assurance of Sterility for Sensitive Combination Products and Materials

Regulatory pathway for labeling combination products as sterile 233

EN 556-1 has a single requirement, that for a terminally sterilized med-
ical device to be designated “STERILE”, the probability of there being
a viable microorganism present on/in the device is equal to or less than
−6
1 × 10 . Compliance with this requirement is the demonstrated provision
of documentation and records which demonstrate that the devices have
been subjected to a validated sterilization process fulfilling this requirement.
While complying with a harmonized standard such as EN 556-1 pro-
vides a presumption of conformity with applicable regulatory requirements,
following a harmonized standard is not mandatory. A note in EN 556-1
indicates that permission for acceptance of a probability greater than that
specified can be sought through the appropriate regulatory bodies. The note
continues by indicating that such permission depends on the individual
situation, including consideration of the risk management activities un-
dertaken by the manufacturer of the medical device. The corrigendum to
the standard that was issued in 2006 was to update the cross reference in
the note to EN ISO 14971, the standard for risk management for medical
devices. EN 556-1 does not provide any additional guidance on situations
where a greater sterility assurance level might be accepted or the detailed
considerations that would need to be addressed in such circumstances. ISO
TS 19930 was prepared with the intention of providing such guidance and
experts from several European countries participated in its preparation.
In contrast to AAMI ST 67, EN 556-1 does not indicate that there is
−3
acceptance of application of a maximal sterility assurance level of 10 for
certain devices based on their intended use not coming into contact with
breached skin or compromised tissue.

9.5.3 New guidance from ISO

The most recent guidance concerning assurance of sterility and SAL is ISO
TS 19930: 2017, Guidance on aspects of a risk-based approach to assuring sterility of
terminally sterilized, single-use health-care product including that unable to withstand
−6
processing to achieve maximally a sterility assurance level of 10 . This guidance
was developed to provide information that could be used to meet the Note
in 4.1 of EN 556-1: 2001, which specifies that permission for acceptance
−5
−6
of a sterility assurance level of greater than 10 (e.g., 10 ) may be sought
through appropriate regulatory bodies, with risk management by the man-
ufacturer being required. ISO TS 19930 also provides information in this
regard to meet the requirements in “clauses” 4.2.4 of AAMI ST67: 2019.
The scope of ISO TS 19930 is clear in that it does not specify an SAL to
−6
be used in circumstances where a product cannot be sterilized to a 10 SAL.