GB 18280.2-2015Sterilization of health care products—Radiation—Part 2: Establishing the sterilization dose (English PDF)

3.1 Acronyms

3.1.1

Adjustment value ffp down to FFP dose.

3.1.2

CD *

In the process of verification dose experiment 2, the number of positive tests obtained from 100 sterile product unit.

3.1.3

d *

Extracted from a given batch of products production unit, so the incremental dose experiment, obtained from the test dose.

3.1.4

D *

To test products meet the initial estimate of the dose 10-2SAL.

NOTE. This value is generally the value of a given product 3d * values.

3.1.5

D **

Test test product is estimated to reach 10-2SAL final dose, the dose used to calculate the sterilization dose.

3.1.6

DD *

The method of verification dose experiment 2 the dose.

3.1.7

DS

DD * After radiation, the estimated value of D10 microorganisms present in the product.

3.1.8

D value Dvalue

D10 value D10value

Under specified conditions, killing 90% of the dose or amount of time required for the microorganism.

[ISO /T S11139.2006]

Note. In this section, D10 value is only used dose, not for time.

3.1.9

The first positive fraction dose firstfractionpositivedose

ffp

Series of incremental doses of radiation extracted from a given product batch production units, after 20 radiation has at least one unit of product

Sterility test negative for the lowest dose.

3.1.10

The first positive fraction dose FirstFractionPositivedose

FFP

So 20 sterility testing positive for 19 doses calculated by subtracting from the value of A 3ffp obtained.

3.1.11

No positive first dose FirstNoPositivedose

FNP

Estimated dose 10-2SAL used to compute DS.

3.1.12

VDmax15

Verify that the maximum dose given bioburden, can be achieved using 15kGy 10-6SAL.

3.1.13

VDmax25

For a given maximum dose verification bioburden, can be achieved using 25kGy 10-6SAL.

3.2 Terms and Definitions

3.2.1

Batch batch

We expect consistent in character and quality, and produced in a defined manufacturing cycle a predetermined amount of product.

[ISO /T S11139.2006]

3.2.2

Bioburden bioburden

A product/or and/or wherein the total number of viable microorganisms and sterile barrier system.

[ISO /T S11139.2006]

3.2.3

False positive falsepositive

Turbidity test results are interpreted as a product or share microbial growth, and microbial growth is due to microbial contamination of alien

Or cloudiness is caused due to the result of the product or share test medium and influence each other.

3.2.4

Positive fraction fractionpositive

In the number of positive tests for sterility molecules to the test as the denominator of the quotient.

3.2.5

Incremental doses incrementaldose

A series of products for a number of radiation dose or a share in the dose setting methods for obtaining or confirm the sterilization dose.

3.2.6

Sterile negative test negativetestofsterility

In sterility testing, product or share the product after the culture can not check the growth of microorganisms.

3.2.7

Packaging systems packagingsystem

Sterile barrier system and protective packaging combination.

[ISO /T S11139.2006]

3.2.8

Sterile positive test positivetestofsterility

In sterility testing, product or share after training to check the growth of microorganisms.

3.2.9

Sample share sampleitemportion; SIP

Of the share covered by the detection unit of health care products.

3.2.10

Sterile barrier systems sterilebarriersystem

Prevent microbial products into the smallest package for the product when used in a sterile condition and use.

3.2.11

Sterility assurance level sterilityassurancelevel; SAL

The probability of a viable microorganism present on product after sterilization unit.

NOTE. SAL represents a value, generally 10-6 or 10-3, 10-6 compared with 10-3 although small, but larger than the guarantee provided by 10-3.

3.2.12

Sterilization dose audit sterilizationdoseaudit

It confirmed the suitability of the established activities sterilization dose.

3.2.13

Verify dose verificationdose

The establishment of the sterilization dose, sterilization dose to achieve the predetermined SAL>=10-2.

4 dose setting, confirm and define the dose sterilization dose audit product family and holding

4.1 General

Establish the sterilization dose and the sterilization dose audit is the process of implementation of the definition (see Chapter 8 GB 18280.1-2015) and maintaining the validity of the process

Part of the activities (see GB 18280.1-2015 Chapter 12). For these activities, the products into product family, product family is divided main root

According to the product or product in the memory of the number and types of microorganisms (bioburden). Microbiological reflects its resistance to radiation. Production division

Does not consider the product density and product packaging systems in loading mode product family, because these factors do not affect the biological load.

Use product family in establishing the sterilization dose and the sterilization dose audit, in the production process, unexpected changes in the radiation found to affect the validity of

The ability to reduce the risk is very important. Moreover, the use of a single product represents the product family may not find the other members of the product family changes occur.

Should assess the risk of changes in other product family members found reduced capacity, and before the beginning of the sterilization process should be developed and implemented to maintain production

Product family plan.

Note. See YY/T 0316 and risk management guidelines.

4.2 product family is divided

4.2.1 division of product family standards should be documented. According to these standards and to consider similar review the product of potential product family members.

Should take into account changes in the product could affect the bioburden, including but not limited to the following factors.

Nature and source of a) raw materials, sources of raw materials if more than one place, but also its impact;

b) constitute a product;

c) product design and size;

d) the production process;

e) production equipment;

f) the production environment;

g) Production address.

Results record review and consideration (see GB 18280.1-2015 in 4.1.2).

4.2.2 only have to prove that products related changes (see 4.2.1) and similar controlled, this product can be attributed to a product family.

4.2.3 only when the volume and variety of product bioburden similar to attributed to a product family.

4.2.4 product family is included in more than one place of production and should prove that this classification is justified and recorded (see

GB 18280.1-2015 in 4.1.2), it should consider its role in biological load.

a) Geographic and (or) climatic differences between different locations;

b) any differences in the production process or environmental control;

c) sources of raw materials and auxiliary materials (for example. water).

4.3 verification dose experiments and sterilization dose audits for product family represent the product design

4.3.1 product family representative products

4.3.1.1 on product volume and type of microbial bioburden is to select the product family represents the product basis.

4.3.1.2 product family may be composed of representatives of the following products.

a) the main product (see 4.3.2); or

b) equivalent product (see 4.3.3); or

c) simulation products (see 4.3.4).

4.3.1.3 4.3.1.2 determined in accordance with three possible products on behalf of any one as a representative product review should be formal, documented

of. In the review, should consider the following questions.

a) the number of bioburden microorganisms;

b) the presence of microorganisms environment;

c) size of the product;

The number of components d) products;

Complexity e) of product;

f) the degree of automation in the production process;

g) production environment.

4.3.2 Main Products

If the assessment indicates that a biological challenge for product family product family is greater than the other products, this product can be identified based production

Goods. In some cases, there are several products that can be identified based products, in this case, according to 4.3.3, any of these products are a

It can be set as the main product, representing the product family.

4.3.3 Equivalent products

If the assessment (see 4.3.1.3) indicate a product family of products require the same sterilization dose, the product family of products can be considered, etc.

The same product. Chosen to represent the equivalent product family that is representative of the product may be. a) random; it can be b) according to a schedule Select a product family

Different products. Select equivalent product should be considered representative of the product family and product production feasibility.

4.3.4 Analog Products

In the sterilization process, when the analog products than the product or family of products are equivalent to a larger biological challenges, this product can be used as the analog

Representative product family. Packing and packaging materials used for analog products should be the same as the actual product.

Note. The analog products are not used clinically only for establishing and maintaining the sterilization dose.

Analog products can be.

a) the actual product of similar materials and dimensions, through a similar process, for example. after the complete production process of an implant

Materials; or

b) product family combination product components, in use, is not a typical example. containing a complex filter, clip, set of soft piston

Tube, these components of the product family in other products, too.

4.4 product family holding

4.4.1 Periodic review

This review shall be carried out within a predetermined frequency to determine the product family and represents the product family of products remain in force. Review the product and/or process

May affect product family of products, the assessment should be assigned the responsibility to capable people. Such a review at least once a year. Review of Results

Fruit should be recorded in accordance with GB 18280.1-2015 4.1.2.

4.4.2 modify products and/or production process

Modifications to the product, such as. raw materials (nature and sources), product design or components (including size) and/or modification of the production process (for example.

Equipment, the environment and workplace) should be formal, documented change control system review. Such modifications may change according to the product family divided

According to representatives of the ethnic products or select a product basis. Major changes require redrawing new product family and provide for different representative products.

4.4.3 Records

Shall keep a record of product family (see GB 18280.1-2015 in 4.1.2).

4.5 Effect of the establishment of the sterilization dose and the sterilization dose audit failures of the product family

A product family in the establishment of the sterilization dose or sterilization dose audit failures, should consider all of the product family of products affected, the follow-up measures

Product family should be applied for all product implementation.

5.1 Nature of the product

5.1.1 Products shall be used for sterilization of the following composition.

a) in their packaging system, an independent health care products;

b) a packaging system components, installed by the composition of health care products, but need to be used in conjunction with the necessary accessories;

c) In a packaging system the same number of pieces of health care products;

d) a device package contains a variety of associated health care products.

Complete dose setting and confirm the desired product extraction unit according to Table 1.

Table 1 required to establish and validate the sterilization dose unit of a product characteristics

product type

Bioburden evaluation, verification and/or

Incremental doses required for a product Test

principle

An independent health in their packaging system

Spa care products

Single independent health care products used in clinical practice of every health care products

A packaging system in a health care

Product Components

All components together all the components of the product as a product used in clinical practice

In its packaging systems in several health care

product

Packaging single system of health care products

Every health care products are used in clinical practice independently in their

Packaging Systems SAL single health care products are met

Selected SAL, plus packaging system, SAL may be higher

It includes a variety of associated health care products

An equipment package a

One type of equipment package consisting of medical insurance

Health Products

An independent health care products used in clinical practice

Note 1.5.1.1b) of the product features see 5.2 SIP usage guidelines.

Note 2.5.1.1d) of the product features, see Chapter 4 product family usage guidelines.

a sterilization dose setting, select the highest sterilization dose of health care products for the sterilization dose.

5.1.2 If the product requires partial sterilization, sterilization dose established only in accordance with this section.

Example. If the product has a label declaration only sterile fluid passage, only the sterilization dose is determined according to the fluid passage bioburden testing and sterility test results.

5.2 Sample share (SIP)

5.2.1 For the average bioburden greater than or equal to 1.0 of the product, when feasible, according to Table 1, the need to detect a complete product (SIP equal

1.0), if the complete product is not feasible, some of the products can be used as an alternative, the selected ratio as large as possible, in order to conduct experiments

Operating room, the size of the range you want in the lab can handle.

5.2.2 For the average bioburden is equal to or less than 0.9 products, a complete according to Table 1, the product should be detected (SIP equal to 1.0).

5.2.3 If the biological load is evenly distributed over the product and/or wherein, SIP can be selected from any part of the product. If the bioburden

Unevenly distributed randomly selected part of the SIP, this divided proportionally represent each material products. If the bioburden

Distribution is known, SIP can choose sterilization process bioburden challenge the most demanding part.

SIP can be calculated (see Table 2 in the example) depending on the length, mass, volume and surface area.

The examples in Table 2 SIP calculated

Products SIP based computing

The tube length (diameter consistent)

powder

Overalls

The implant (resorbable)

Volume of the fluid

Surface area

Implants (non-absorbable)

Tube (diameter inconsistent)

5.2.4 SIP preparation and packaging should implement environmental controls under biological minimum load change conditions, whenever possible, should be equivalent to most packaging materials

The final product.

5.2.5 choose SIP adequacy should be demonstrated. SIP bioburden apply the following test to prove. to 20 non-irradiated sample SIP

Do sterility test results should be at least 17 positive (eg. 85% positive). If you reach this standard shall be expanded in order to meet this standard SIP

quasi. If the sample selection of a complete product (SIP equal to 1.0), need not comply with sterility testing 20 samples must have 17 male

Of standards.

5.3 Sampling method

5.3.1 for establishing and auditing the sterilization dose product shall represent conventional processes and conditions. Usually used to determine the bioburden or sterility

Test every product should have a separate packaging system.

5.3.2 Sample selection and bioburden should reflect the time it takes from the time of the last step of the production interval between sterilization products.

Samples can be taken from the production process out of the product, and these products are qualified products has undergone the same process and conditions.

5.4 Microbiology

5.4.1 bioburden determination and sterility testing were in accordance with ISO 11737-1 and ISO 11737-2.

When a single media do sterility testing, we recommend the following conditions. tryptic soy broth culture temperature (30 ± 2) ° C, culture

Period of 14 days. When reason to suspect that this medium and temperature and can not support the existing growth of microorganisms, can use other suitable training

Support groups and culture conditions. See Herringetal, 1974 [12]; Favero, 1971 [10]; NHB5340.1A, 1968 [7] and the like.

Wherever practicable, the product should be available in its original form and packaging systems to accept irradiation. However, in order to reduce the false positive sterility test, the sample

Product before irradiation can be split and re-packaging. Any loaded with biological effects of radiation treatment or significant changes are not acceptable (for example,

Such as. the presence of microorganisms changes in the chemical environment, typically. partial pressure of oxygen). Repackaging of the sample material to be able to withstand radiation dose and after

Continued treatment in order to reduce possible contamination.

5.4.2 is used to determine the bioburden sample to go through the packaging process.

Note. In general, in the bioburden is determined from the product after the packaging system of the embodiment, therefore, it ignores the contamination from the packaging system.

5.5 Irradiation

5.5.1 irradiated samples for establishing and auditing the sterilization dose to one GB 18280.1-2015 after installation qualification, operational qualification according to

And the irradiation means properties were identified. For verification dose or incremental dose experiment, make proper dose distribution to determine the products eligible

Maximum dose and minimum dose obtained.

5.5.2 dosimetry and radiation sources used should meet the requirements of GB 18280.1-2015.

Note. See GB/T 18280.3 aspects of radiation sterilization dose guidelines.

The method established dose

6.1 If, according to GB 18280.1-2015 in 8.2.2a) to establish the sterilization dose (product-specific ster...

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