-May of 2001 in California

- 38 patients afffected: 3 deaths

- Root Cause #1: Improper facilities (carpet in cleanroom, plant on top of hood, fish tank in cleanroom)

-Root Cause #2: Improper employee training/education

-Root Cause #3: Improper use of equipment: Autoclave was never actually turned on--> nothing ever truly sterilized.

-Result: Pharmacist committed suicide, license revoked

- One patient died, 4 others suffered effects of fungal meningitis

- Cases occurred up to 152 days AFTER injection (due to fungus being slow-growing)

- Fungus is native to SC; personnel propped open door of clean room with a fan to cool down, which in turn exposed the products to the fungus

-Root Cause #1: Untrained personnel

-Root Cause #2: Failure to achieve sterility

Results: FDA Class 1 recall, pharmacy license revoked, owner filed bankruptcy

1) Requires maintaining sterility when using stuff that is already sterile

2) Requires the achievement of sterility when using stuff that is not already sterile

3) ISO classified air environments

4) Personnel garbing and gloving

5) Personnel training and testing in aseptic technique

6) Environmental quality specs & monitoring

7) Disinfection of gloves & surfaces of ISO Class 5 source

Arrange these in order from least to most sterile:

Buffer Area, DCA, ISO Class 7/8, ISO Class 5, Ante Room

Primary: Where you're actually preparing the sterile product (the hood)

Secondary: Facility Design (ante/buffer area)

Choose between horizontal flow, vertical flow, or both.

1)Laminar Air Flow Workbench: ______________

2)Biological Safety Cabinet: _________________

3)Compounding Aseptic Isolator: _____________

1) Both: primarily horizontal but can be vertical

2) Vertical

3) Vertical

Fill in the Blank:

________ toward compliance, "following the rules," and being vigilant will ultimately determine the success or failure of any program, especially aseptic compounding.

Attitude.

Holy crap, this is absolutely ridiculous. Let's all hold hands & sing Kum bah yah.

Give the term for the definition:

When parenteral dosage forms are combined for administration as a single entity

True or False:

An antearea is maintained under negative pressure in comparison to the rest of the pharmacy, but positive to the buffer area. The antearea does not have to be supplied with HEPA filtered air.

FALSE!

An antearea is maintained under positive pressure in comparison to the rest of the pharmacy, but negative to the buffer area. The antearea does have to be supplied with HEPA filtered air.

Give the term for the definition:

Usually an ISO Class 7 area where the laminar flow hood is located. It has positive pressure to the rest of the pharmacy and is supplied with HEPA filtered air.

Give the term for the definition:

Areas where sterilized product or container/closure is exposed to the environment. An ISO Class 5 area.

Critical Areas

(this is inside the hood)

Give the term for the definition:

Surfaces which come in contact with sterilized product or container/closure.

Critical Surfaces

(this is like the vial itself)

Give the term for the definition:

Any opening or surface which can provide a pathway between the sterile product and the environment. 

Give examples of this.

Critical Site

Examples include:

the hub of the needle, the ribs of the plunger on a syringe, the tip of the syringe, the open neck of the ampule, and the top of the vial closure

Give the term for the definition:

A critical area within the ISO Class 5 Primary Engineering Control (PEC) where critical sites are exposed to unidirectional HEPA filtered air known as "first air"

Fill in the Blank:

ISO Standards are based around the counts of particles __________ and larger per _________ of air.

Give the particle count and the old FDA name for:

ISO Class 5

ISO Class 7

ISO Class 8

ISO Class 5: 3,520/m³ ; Class 100

ISO Class 7: 352,000/m³ ; Class 10,000

ISO Class 8: 3,520,000/m³ ; Class 100,000

Give the term for the definition:

Free of all living microorganisms.

Nope!

Sterility is an absolute, either you are or you aren't.

Give the term for the definition:

A filter which, when challenged with the micro-organism B. Diminuta, at a minimum concentration of 10⁷ organisms per cm² of filter surface, will produce a sterile effluent.

Give the size of this filter.

Sterilizing filter

0.22 micron

Give the term for the definition:

A device such as a laminar airflow workbench, biological safety cabinet, or compounding aseptic isolator, which provides an ISO Class 5 environment for the exposure of critical sites when compounding sterile preparations.

Primary Engineering Control

Remember:  ISO Class 5!!

Give the term for the definition:

Airflow moving in a single direction, in a robust and uniform manner, and at a sufficient speed to reproducibly sweep particles away from the critical processing area.

Give the term for the definition:

Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications ad quality attributes.

1) Air is drawn in through the pre-filter

2) The pre-filtered air is pressurized in the plenum

3) The air is blown through the HEPA filter across the work surface toward the operator

Fill in the Blank:

The HEPA filter is _______% efficient at removing particles ________ and larger.

99.97%

0.3 microns

The Buffer Area needs to be ISO Class ....?

With (positive/negative) pressure between this area and the antearea?

ISO Class 7

positive

How many air changes per hour must an ISO Class 7 area achieve?

How many of those changes can come from a PEC?

30

15

1) Shoe Covers

2) Hair Covers (Beard covers if necessary)

3) Face Mask

4) Wash hands/forearms for at least 30 seconds (after scrubbing under nails)

5) Completely dry hands

6) Non-shedding gown that fits tightly at wrists & closes at neck

7) Alcohol hands

8) Gloves

9) Alcohol gloved hands again