Gap Analysis of ISO 11737-1: 2018 & ISO 11737-1: 2006

2018 2006
Clause Clause
No Clause Gap/Description No Clause Gap/Description
1 Scope 1 Scope
Normative Normative
2 References 2 References
Terms &
3 Definitions 3 Terms & Definitions
3.1 Batch
3.2 Bioburden 3.1 Bioburden
3.3 Bioburden correction factor 3.3 Correction factor

Bioburden estimate- numerical value

established by applying a bioburden correction
3.4 factor in a bioburden count

Bioburden method suitability- Assessment of

latest method to demonstrate its ability to allow
3.5 microbial growth

Bioburden spike- individual bioburden value that

is significantly greater than other bioburden
3.6 values
3.7 Correction 3.2 Correction
3.8 Corrective action 3.4 Corrective action
3.9 Culture Condition 3.5 Culture Condition
3.10 Establish 3.6 Establish

Facultative microorganism- microoranism

capable of both aerobic & anaerobic
3.11 metabolism
3.12 Health care product 3.7 Medical Device
3.13 Microbial characterisation 3.8 Microbial characterisation

Obligate anaerobe- organism that lives and

3.14 grows in the absence of molecular oxygen
3.15 preventive action 3.9 preventive action
3.16 product 3.10 product
3.11 Recognised Culture collection
3.17 recovery efficiency 3.12 recovery efficiency
3.18 requalification
sample item portion (SIP)- Defined part of health sample item portion (SIP)- Defined part of
3.19 care product that is tested 3.13 health care product that is tested
3.20 Specify 3.14 Specify
3.21 Sterile
3.22 Sterile barrier system
3.23 validation 3.15 validation
 General
4 Requiements 4 General Requiements
4.1 Documentation 4.1 Documentation
Procedure for determination of bioburden shall Procedure for determination of bioburden shall
4.1.1 be specified 4.1.1 be specified

Documents & records required shall be Documents & records required shall be
approved by designated personnel and shall be approved by designated personnel and shall be
4.1.2 controlled 4.1.2 controlled

Records retained shall include all original Records retained shall include all original
observations, calculations, derived data and final observations, calculations, derived data and
reports. The records shall include the identity of final reports. The records shall include the
all the personnel involved in sampling, identity of all the personnel involved in
4.1.3 preparation and testing 4.1.3 sampling, preparation and testing
Calculations & data transfers shall be subject to Calculations & data transfers shall be subject to
4.1.4 appropriate checks 4.1.4 appropriate checks
Managements Managements
4.2 Responsibility 4.2 Responsibility

The responsibility & authority for implementing The responsibility & authority for implementing
and performing the procedure shall be specified and performing the procedure shall be specified
and reponsibility shallbe assigned to competent and reponsibility shallbe assigned to competent
4.2.1 personnal 4.2.1 personnal

if requirements of this document are if requirements of this document are

undertaken by organisation with separate QMS, undertaken by organisation with separate QMS,
the responsibilities & authorities of each party the responsibilities & authorities of each party
4.2.2 shall be specified 4.2.2 shall be specified

All items of equipment required for the correct All items of equipment required for the correct
perormance of the specified tests & perormance of the specified tests &
4.2.3 measurements shall be available 4.2.3 measurements shall be available
Product
4.3 Realisation 4.3 Product Realisation

Procedures for purchasing shall be specified. Procedures for purchasing shall be specified.
These procedures shall conform with 13485, These procedures shall conform with 13485,
4.3.1 15189 or 17025 4.3.1 15189 or 17025

A documented system conforming with 13485, A documented system conforming with 13485,
15189, 17025 or ISO 10012 shall be specified for 15189, 17025 or ISO 10012 shall be specified
4.3.2 caliberation of all equipment 4.3.2 for caliberation of all equipment

Methods shall be specified for the preparation Methods shall be specified for the preparation
and sterilisation of materials used in and sterilisation of materials used in
determination of bioburden, including determination of bioburden, including
4.3.3 appropriate quality tests 4.3.3 appropriate quality tests
 Measuremetn,
Analysis &
4.4 improvement

For the purpose of bioburden test methods and

results, measirement uncertainity, precision and
bia typically do not apply and therefore this
type of data analysis may not be necessary,
except in evaluating overall competency of the
4.4.1 laboratory
Measuremetn,
For control of nonconforming products, Analysis & For control of nonconforming products,
procedures for investigation of out of improvement- procedures for investigation of out of
specfication results and for correction, Control of specfication results and for correction,
corrective action and preventive action shall be nonconforming corrective action and preventive action shall be
4.4.2 specified 4.4 product specified
Selection of
5 products 5 Selection of products
General
5.1 Requiements 5.1 General Requiements

procedures for selection & handling of products procedures for selection & handling of products
for determination of bioburden shall ensure that for determination of bioburden shall ensure
the selected product is representative of routine that the selected product is representative of
production, including packaging materials & routine production, including packaging
5.1.1 processes 5.1.1 materials & processes

If product(s) are grouped in a product family for If product(s) are grouped in a product family for
the purpose of determination of bioburden, the the purpose of determination of bioburden, the
rationale for inclusion of a product within a rationale for inclusion of a product within a
product family shall be racorded. The rationale product family shall be racorded. The rationale
shall ensure that bioburden determined for a shall ensure that bioburden determined for a
product selected from the product family is product selected from the product family is
5.1.2 representative for the whole product family 5.1.2 representative for the whole product family

Consideration shall be given to the timing of Consideration shall be given to the timing of
determination of bioburden relative to determination of bioburden relative to
manufacturing because bioiburden can change manufacturing because bioiburden can change
5.1.3 with the passage of time. 5.1.3 with the passage of time.
Sample item
5.2 portion (SIP)

Either the entire product(SIP = 1) or a portion of

product (SIP<1) may be used for determination
5.2.1 of bioburden
 If an SIP<1 is used, The SIP shall be of sufficient
size to adequately represent the bioburde of the
entire product. Determination of selected
portion shall be based on whether bioburden is
5.2.2 evenly distributed or not

When the bioburden distribution is known, When the bioburden distribution is known,
following applies- following applies-
- if bioburden is evenly distributed, the SIP may - if bioburden is evenly distributed, the SIP may
be slected from any portion of item be slected from any portion of item
- if bioburden is not evenly distributed, the SIP - if bioburden is not evenly distributed, the SIP
shall include either portions of the product shall include either portions of the product
selected that proportionately represent each of Sample item portion selected that proportionately represent each of
5.2
material from which product is made or the (SIP) material from which product is made or the
portion having most severe microbial challenge portion having most severe microbial challenge
5.2.3 to the sterilisation process to the sterilisation process

If the bioburden distribution is not known, The If the bioburden distribution is not known, The
sIP shall consist of portions of the product sIP shall consist of portions of the product
slected that proportionally represent each of the slected that proportionally represent each of
5.2.4 materials from which the product is made the materials from which the product is made
SIP can be calculated on the basis of SIP can be calculated on the basis of
5.2.5 dimensional characteristics dimensional characteristics

Methods of Methods of
determination determination and
and microbial microbial
characterisation characterisation of
6 of bioburden 6 bioburden
Determination of Determination of
6.1 bioburden 6.1 bioburden

The method shall be appropriate to the

The method shall be appropriate to the purpose purpose for which the data are to be used. The
for which the data are to be used. The method method shall comprise techniques for the
shall comprise techniques for the following- following-
neutralisation of inhibitory substances, if neeed neutralisation of inhibitory substances, if neeed
Selection of an - removal of microorganism, if appropriate - removal of microorganism, if appropriate
appropriate - culturing of microorganisms Selection of an - culturing of microorganisms
6.1.1 method - enumeration of microorganisms 6.1.1 appropriate method - enumeration of microorganisms
 If the physical or chemical nature of product is If the physical or chemical nature of product is
such that substances can be released that such that substances can be released that
adversely affect the detection of product adversely affect the detection of product
bioburden, then a system shall be used to bioburden, then a system shall be used to
Neutralisation of neutralise, remove or minimize effect of any neutralise, remove or minimize effect of any
inhibitory such released substance. effectiveness of such such released substance. effectiveness of such
6.1.2 substances system shall be demonstrated 6.1.2.3 system shall be demonstrated
Removal of Removal of
6.1.3 microorganisms 6.1.2 microorganisms

For an identified product where the removal of For an identified product where the removal of
viable microorganisms is part of the method, the viable microorganisms is part of the method,
efficiency of removal shall be considered and the efficiency of removal shall be considered
outcomes of this consideration recorded. and outcomes of this consideration recorded.
Consideration shall, at least, be given to Consideration shall, at least, be given to
following- following-
- ability of technique to remove microorganism - ability of technique to remove microorganism
- possible type of microorganism and their - possible type of microorganism and their
location on product location on product
-effects of removal technique on the viability of -effects of removal technique on the viability of
microorganisms microorganisms
- the physical or chemical nature of the product - the physical or chemical nature of the product
6.1.3.1 under test 6.1.2.1 under test

For an identified product where removal of

viable microorganism is not part of the method,
For an identified product where removal of the efficiency of the enumeration of
viable microorganism is not part of the method, microorganisms shall be considered and the
the efficiency of the enumeration of outcomes of this consideration recorded.
microorganisms shall be considered and the Consideration shall , at least, be given to
outcomes of this consideration recorded. following-
Consideration shall , at least, be given to - possible type of microorganism & their
following- location on product
- possible type of microorganism & their location - physical or chemical nature of product under
on product test
- physical or chemical nature of product under - aggregates of cells forming single colonies due
6.1.3.2 test 6.1.2.2 to in-situ culturing

Culture conditions shall be selected after

consideration of the type of microorganusms
likely to be present and physical or chemical Culture conditions shall be selected after
nature of product to be tested. Results of consideration of the type of microorganusms
Culturing of consideration and rationale for decisions shall Culturing of likely to be present. Results of consideration
6.1.4 microorganisms be recorded 6.1.3 microorganisms and rationale for decisions shall be recorded
 The technique for enumeration shall be selected The technique for enumeration shall be
after consideration of the types of selected after consideration of the types of
microorganism likely to be present. The result of microorganism likely to be present. The result
Enumeration of this consideration and rationale for the decision Enumeration of of this consideration and rationale for the
6.1.5 microorganisms reached shall be recorded 6.1.4 microorganisms decision reached shall be recorded

Microbial Microbial
characterisation characterisation of
6.2 of bioburden 6.2 bioburden

Appropriate techniques for microbial Appropriate techniques for microbial

6.2.1 characterisation of bioburden shall be selected 6.2.1 characterisation of bioburden shall be selected

Microbial Characterisation shall be

Bioburden shall be characterised using one or characterised using one or more of following
more of following techniques- techniques-
- colony morphology - colony morphology
-cell morphology -cell morphology
- differential straining - straining properties
- culture using selective and/or differential - culture using selective and/or differential
conditions conditions
- biochemical properties - biochemical properties
- genotype analysis - genetic sequence data for which there is an
6.2.2 - proteomic methods 6.2.2 adequate database

Validation of the Validation of the

methods for methods for
determining determining
7 bioburden 7 bioburden
The methods for determining bioburden shall be The methods for determining bioburden shall
7.1 General validated and documented 7.1 be validated and documented
 validation shall consist of the following-
-assessment of test method suitability to
validation shall consist of the following- demonstrate lavk if inhibition of growth in the
-assessment of test method suitability to test
demonstrate lavk if inhibition of growth in the - assessment of adequacy of technique for
test removal of microorganisms from a product
- assessment of adequacy of technique for - Determination of recovery efficiency in order
removal of microorganisms from a product that a correction factor be derived
- assessmewnt of adequacy of the technique for - assessmewnt of adequacy of the technique for
enumeration of microorganisms, including enumeration of microorganisms, including
culture conditions and microbiological counting culture conditions and microbiological counting
techniques techniques
- assessment of suitability of technique of - assessment of suitability of technique of
7.2 Validation microbial characterisation 7.2 microbial characterisation

Routine
determination of Routine
bioburden & determination of
interpretation of bioburden &
8 data 8 interpretation of data

Routine determination of bioburden shall be Routine determination of bioburden shall be

performed by employing documented sampling performed by employing documented sampling
8.1 General plan that specify size and sampling frequency 8.1 plan that specify size and sampling frequency

the determination of bioburden shall be

performed using method specified for a product
Limits of or a product family. Method shall take into the determination of bioburden shall be
detection and account factors that will affect results, such as performed using method specified for a
8.2 plate counting limits of detection and plate counting 8.2 product or a product family.

Microbial characterisation of bioburden shal be Microbial characterisation of bioburden shal be

performed to a degree dependent on purpose performed to a degree dependent on purpose
Microbial for which data derived from determination of for which data derived from determination of
8.3 characterisation bioburden are to be used 8.3 bioburden are to be used

If bioburden are to be used to establish the

If bioburden are to be used to establish the extent of treatment of a sterilisation process,
extent of treatment of a sterilisation process, any requirements applicable to use of
any requirements applicable to use of bioburden bioburden data specified in the appropriate
Bioburden data data specified in the appropriate standard for standard for development, validation and
for extent of development, validation and routine control of routine control of sterilisation process, shall be
8.4 treatment sterilisation process, shall be met 8.4 met
 If bioburden data demonstrate a test result that
is significantly greater than other values, these
data shall be evaluated for impact as
appropriate depending on the purpose for the
8.5 Bioburden spikes data

Acceptable levels for bioburden shall be Acceptable levels for bioburden shall be
specified. If these levels are exceeded, action specified. If these levels are exceeded, action
shall be taken. Acceptable levels shall be shall be taken. Acceptable levels shall be
8.6 Bioburden levels reviewed and revised as necessary 8.5 reviewed and revised as necessary

Data derived from determination of bioburden Data derived from determination of bioburden
8.7 Data Analysis obtained shall be used to identify trends 8.6 obtained shall be used to identify trends

if used, the application of stastical methods to if used, the application of stastical methods to
Statistical define sample size, sampling frequency and/or define sample size, sampling frequency and/or
8.8 Methods acceptable levels shall conform with iso 13485 8.7 acceptable levels shall conform with iso 13485

Maintenance of Maintenance of the

the method for method for
determining determining
9 bioburden 9 bioburden

Change to the product and/or manufacturing

process shall be reviewed to determine whether
they are likely to alter bioburden with
consideration to the purpose for which Change to the product and/or manufacturing
bioburden data are to be used. The results of process shall be reviewed to determine
review shall be recorded. If there is a potential whether they are likely to alter bioburden. The
Changes to the for alteration of bioburden, specific Changes to the results of review shall be recorded. If there is a
product and/0r detemination of bioburden shall be performed product and/0r potential for alteration of bioburden, specific
manufacturing to evaluate extent & nature of any effect of the manufacturing detemination of bioburden shall be performed
9.1 process change 9.1 process to evaluate extent & nature of any change

Any change to the bioburden determination

shall be assessed. This shall include-
Changes to the Any change to the bioburden determination Changes to the - evaluation of the effect of change on outcome
method for shall be assessed. This shall include evaluation method for of determination
determining of effect of change on outcome of determining - establishment of recovery efficiency of the
9.2 bioburden determination. The results shall be recorded 9.2 bioburden method following the change
 The original validation data and any subsequent The original validation data and any subsequent
requalification data shall be reviewed at requalification data shall be reviewed at
Requalification of specified intervals in accordance with a Requalification of the specified intervals in accordance with a
the method for documented procedure. The outcome of the method for documented procedure. The outcome of the
determining review and any requalification undertaken shall determining review and any requalification undertaken shall
9.3 bioburden be recorded 9.3 bioburden be recorded