Quality

Sterility Testing For Medical Devices

- Dr. Nishodh Saxena, Scientist, B.V. Patel Pharamceutical Education Research Centre (PERD), Ahmedabad, Gujarat, India.

6.  Antibiotic soild: 

Constitute the test articles and filter through the membrane. Give sufficient washing with rinsing fluid to wash the residual antimicrobial substance on the membrane.

7.   Devices with pathways labeled sterile:  

Aseptically pass not less than 10 pathway volumes of fluid D through each device tested. Collect the fluids in an appropriate sterile vessel. Aseptically transfer the total collected volume into one or more separate membrane filter units . Immediately pass through the filter with the aid of vacuum or pressure. Aseptically remove the membrane from the holder, cut the membrane in half, and immerse half of the membrane in each of the specified medium.

In the case of sterile , empty syringes, draw sterile diluent into the barrel through the sterile needle, if attached, or through a sterile needle attached for the purpose of the test, and express the contents into a sterile pooling vessel. Proceed as directed above.

2.  Direct transfer method:

Draw suitable quantity of the substances and transfer aseptically to sufficient quantity of culture medium directly. This method is applicable to the following  substance

1. Non filterable liquids:

2. Ointments, Oils and Nonfilterable liquids insoluble in Isopropyl Myristate:

3. Solids

4. Purified cotton, Gauze, Surgical dressings, Sutures and Related articles:

5. Sterile devices:

Articles can be immersed intact or disassembled. To ensure that device pathway are also in contact with the media, immerse the appropriate number of unit per medium in a volume of medium sufficient to immerse the device completely.

For catheters where the inside lumen and outside are required to be sterile, either cut them into pieces such that the medium is in contact with the entire lumen or fill the lumen with medium, and then immerse the intact unit.

Procedure:

Incubate the test mixture under the specified condition. Examine the media visually for growth.

Where the material being tested renders the medium turbidity, so that the presence or absence of microbial growth cannot be determined by visual examination, transfer suitable portions of the medium to fresh containers of the same medium at least once during the period from the third to the seventh day after the test is started. Continue incubation of the original and of the transfer containers for a total of not less than 14 days from the original inoculation.

Interpretation of test result:

The article meets the requirements of the test for sterility when no microbial growth is observed.

When microbial growth is observed and confirmed microscopically, the article does not meet the requirements of the test for sterility.

However if the microbial growth can be without a doubt ascribed to faulty aseptic techniques or materials used in conducting the sterility testing procedure, the test is invalid and must be repeated.

 Comparison  of  open funnel and  closed  system  sterility  testing  

Pharmacopoeial Guidelines on Sterility Testing:

1.     USP 24  (71) - Sterility tests  

A suitable filter unit of an assembly that facilitates aseptic handling of the test and allows the processed membranes to be removed aseptically for the transfer to a media or an assembly where sterile media can be added to the sealed filter unit and the membrane incubated in situ.

(A clear recognition of the closed system are the only sealed units for sterility testing)

2.     USP 24 (71) -. USP 24 (71)  

If using a sealed filter unit, use the one that is designed to preclude product residues at the filter- unit interface.

(A closed canister is designed specifically for antibiotic testing wherein product residues normally found in the conventional MF technique are clearly avoided). This is possible because of the enhanced drain design which ensures rinsing is perfect and no antimicrobial activity is ever present.

3.     USP 24(71)  

The filter unit and the membrane must be sterilized and stored in the manner that maintains the performance characteristics of the membranes and ensures that the filter and the assembly remains sterile.

(The closed canisters are sterilized using ETO whose effectiveness has been proved by introduction of biological indicators prior to sterilization and later on incubated in media). The ETO sterilization method ensures that the performance characteristics of the filter remain unchanged unlike other methods used for sterilization. To support the claim of the performance characteristic manufacturers provides certificate documenting the pore size of the membrane, flow rate, retention, recovery, endotoxin level, toxicity levels etc.

4.     USP24(71)  

Because sterility testing is an exacting process, where asepsis of the procedure must be ensured for correct interpretation of the results, it is important that the personnel be properly trained and qualified.

(The closed system because of its futuristic design ensures closed sterility testing minimizing the number of manipulations and protection from the external environment). This ensures reduction in false positives, repeatability and reproducibility of the test results and tracibility of  the entire test documentation, which is gone into manufacturing the sterility testing equipment).

EP1997 - Validation for Bacteriostasis and Fungistasis.

For antibiotics use strains of microorganisms sensitive to the antibiotic.

If the cultures containing the product to be examined shows weaker growth, delayed growth or no growth of microorganism when compared to the cultures not containing the product, the latter has antimicrobial property which must be eliminated by filtration, dilution or neutralization before or during the test for sterility.

(Using closed unit for antibiotics ensures that the traces of antimicrobial agents can be completely eliminated because of the special drain system. This particular aspects ensures elimination of worst to worst case of false negatives).

EP supplement 1998 2.6.1  

Test for sterility of the product to be examined :

1. Membrane filtration - Use membrane filters having a norminal pore size of not greater than 0.45mm whose effectiveness to retain microorganisms has been established----------------------------- specially adapted filters may be needed for certain products for eg. antibiotics (the closed device incorporates membranes whose pore size of 0.45mm has been tested and certified on a 100% basis. The closed canisters incorporate membranes whose efficiency to  retain Pharmacopoeial organisms has been well documented and are accompanied by a test certificate).

2. The apparatus is so designed that the solution to be examined can be introduced and filtered under aseptic conditions-------------------------------------or it is suitable for carrying out the incubation to the apparatus itself.

(Using a closed system ensures minimizing your botheration on account of the false negatives which is as a result of deviation from the strict aseptic procedures).

The above points mentioned are only a guideline for stating the relevance of the closed system to the various Pharmacopoeias.

The key features of the closed system is mentioned below:

1. Traceability

2. Dependability

3. Reproducibility

4. Reducing false positive and avoiding false negatives. 

QUALITY TESTING OF MEDICAL DISPOSABLES

NISHODH SAXENA

RESEARCH SCIENTIST

DEPARTMENT OF MICROBIOLOGY

B. V. PATEL PERD CENTRE

THALTEJ,

AHMEDABAD

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