Cag-009-00 Eff. Jan. 31, 2012 Cnbt Study Guide

Front 1

Differentiation of the facility risk level with the risk assessment.

2 Statements

Back 1

1. The facility risk level is described as high, medium and low. This is determined by pharmacy personnel and is based upon compounding practices and materials used during compounding.

2. A risk assessment is completed while developing the sample plan and determining viable sample site locations. CAG refers to the FDA Aseptic Guidelines, "Therefor the number of sample locations is increased in areas where there is a greater potential for contamination to product."

Front 2

Activity Level

3 Statements

Back 2

All viable sampling is conducted while cleanroom is in an active or dynamic state.

Do not confuse activity level with "passive" air sampling (use of settling plates) or "active" air sampling (volumetric sampling).

If concern for product contamination, sampling can be conducted during media fills or while producing product that will go unused.

Front 3

For information regarding the appropriateness of an active air sampler refer to ???

Back 3

ISO 14698-1:2003(E) Annex B Guidance on Validating Air Samplers.

Request a copy of the ISO compliance validation document from the manufacturer.

Front 4

MPN is ??

Back 4

A statistical correction that must be applied to air sample data if the manufacturer has indicated one. Make sure the lab applies it for you.

Front 5

When using duplicative plate methods, what should you discuss with lab?

Back 5

Bacterial colonies may be recovered on mold plates, mold on bacterial plates. This may go unreported and may be considered a failure. Discuss how to handle before submitting samples.

Front 6

What are the two types of gloved fingertip sampling requirements of USP <797> Pharmaceutical Compounding- Sterile Preparations?

Back 6

1. Gowning Evaluation

2. Gloved fingertip sampling (described as completed at end of a media fill preparation). Study Guide Author suggests sampling can occur at the end of a preparation also.

Acceptance criterion for the Gloved fingertip sampling is not more than 3 CFU/glove.

Front 7

Definition: Backwash Area

Back 7

Areas in a cleanroom that introduce particles and/or interfere with the intended patterns of airflow due to equipment placement, personnel flow, personnel operations and/or cleanroom design.

Front 8

Definition: Contact Plates

Back 8

A convex sampling device containing a growth media supplemented with neutralizers used to sample surfaces for viable organisms.

Front 9

Definition: Swab

Back 9

used to sample uneven surfaces for viable organisms. Assure it contains an appropriate neutralizer.

Front 10

Definition: Viable

Back 10

Capable of living, developing, or germinating under favorable conditions.

Front 11

Viable air sampler is needed equipment.

4 Statements.

Back 11

1. Impaction is preferred method of volumetric air sampling.

2. Calibrated and disinfected- capable of collecting up to 1000L or more of air with sufficient rate that will not dry media.

3. Sampler must not interfere with air flow patterns of PEC which could introduce contamination.

4. Procure media filled strips or plates appropriate for the sampler.

Front 12

Media

What is important about neutralizers?

Back 12

Document all cleaners used in that cleanroom and compare to neutralizer used in your media to determine if capable of neutralizing those chemicals.

Front 13

Media

4 general items.

Back 13

1. Should be a known manufacturer.

2. Accompanied by c of a w/ documented results of QA testing.

3. Double or triple bagged and irradiated.

4. If not terminally sterilized, then each plate must be pre-incubated (might dry out media!)

Front 14

Media

How to deem acceptable?

Best Practice?

Back 14

1. Section 15.0 QC Testing of Media

2. perform sterility and growth support testing.

3. One positive, one negative control.

4. Per media, per lot and per shipment.

1. Include two pieces unopened media.

Front 15

Facility Risk Level

3 items.

Back 15

1. Determined by facility

2. Outlined by USP <797>

3. If more than 1 risk level, test to the highest risk level

Front 16

Sampling Plan

5 items.

Back 16

1. Meet with facility to perform risk assessment and develop a ROBUST plan.

2. Must include all areas and ancillary areas where compounding occurs (e.g. nursing, OR, etc)

3. Areas that pose the greatest risk of contamination to product must be included.

4. Samples in all PECs as well as areas of close proximity.

5. Most air samples at working height (some samples different, e.g. sampling a backwash area).

Front 17

Areas posing greatest risk:

Back 17

PEC, buffer, ante, pass thorough, etc.

Consider backwash areas and CSP pathways.

Identify backwash areas with smoke studies.

Front 18

Frequency

10 items!

Back 18

1. Semi-annual

2. Recommended after initial certification procedures BUT prior to recertification to provide "as found"

3. after any situation impacting operation of CR or PEC

4. after moving equipment

5. after servicing

6. after patient incident where CSP suspected

7. After changes to process affecting CR

8. After observation of incorrect work practices

9. After identified problems with end product

10. Significant changes to work flow or new procedures/equipment.

Front 19

Air Volume

Back 19

1000L min ISO 5

400L min 7-8

Not acceptable to do 500L TSA and 500L SDA for for ISO 5.

Front 20

Activity Level

3 items

Back 20

Must be dynamic (operational or competency testing)

Surface sample AFTER compounding/competency testing

Static sampling may be performed for information.

Front 21

Documentation of Sampling Protocol

12 items

Back 21

1. Procedure

2. volume

3. ISO classes

4. method of collection

5. frequency

6. activity level

7. action levels

8. response to exceeded levels

9. media type(s)

10. risk level

11. lab analysis

12. incubation time/temperatures

Front 22

Sampling Plan/ Map

3 items.

Back 22

notes locations

types of samples

Must be taken in same areas each time for trending to be meaningful.

Front 23

Chain of Custody: Generally included info:

11 items

Back 23

Activity

Volumes

facility name/code

tech name/initials

date/time of sampling

media types, lot, exp

alert/action levels

ISO Classification

requested microbial testing

name of your company!

contact info

Front 24

Chain of Custody: Best Practice

5 items

Back 24

1. # of people present in area

2. equip SN, cal date

3. ISO class

4. Time

5. Any deviations from normal procedures that may impact results

Front 25

Sample Plate Labeling:

6 "should" items

Back 25

1. date and location or code

2. facility name or code

3. media type

4. sample type (air vs surface)

5. volume if appropriate

6. labeled on bottom, NOT the lid

Front 26

Report

10 items

best practices= 4 items

Back 26

1. microbial count

2. results indicating any presence of objectionable organisms

3. ID to at least genus level

4. growth promotion/sterility test results

5. media lot/exp

6. alert/action levels

7. date/time of sampling

8. activity level

9. pass/fail status

10. signature of lab analyst AND reviewer

Additional info best practice:

equipID, calibration, ISO class, incubation time/temp

Front 27

Sampling Procedures: General Items

10 items.

Back 27

1. Gown according to facility protocol and/or 797

2. Disinfect all instruments, cart, materials when transferring into cleanroom.

3. Disinfect staging area.

4. Examine media for growth and integrity.

5. Sample clean to least clean.

6. Label plate

7. Disinfect gloves before/after each sample

8. Disinfect sampler head periodically and when possibly compromised

9. Aseptically handle- when in doubt throw it out (but not in controlled environment)

10. Controls travel with samples, and are not opened.

Front 28

Sampling Procedures Best Practice

Back 28

Viable should occur prior to other testing criteria.

Front 29

Examining Media:

5 items.

Back 29

1. for cracks

2. missing sections

3. dryness (pull away from edge)

4. excess moisture

5. verify convex surface

I'd also add type/expiration

Front 30

Viable Air Sampling

6 items

Back 30

1. Autoclave or disinfect air sampler head and sampler.

2. Select volume

3. Aseptically load.

4. Move to location.

5. Operate (according to manual)

6. Remove, replace and secure lid.

Front 31

Surface Sampling

3 items

Back 31

1. Carefully remove lid.

2. Roll convex agar surface:

in one direction

across surface of site

immediately replace lid

3. Apply brief spray 70% IPA and wipe or use pre-saturated wipe.

Front 32

Surface sampling with Swabs

4 items

Back 32

1. Remove swab, allow excess media to drain before removing completely.

2. Scrub using a twisting motion.

3. Entire area (up to 2" x 2"). Document size of sample area.

4. Apply brief spray IPA, wipe.

Front 33

Isolator Specifics

Back 33

1. Move equipment in and out of isolator transfer/main chambers according to manufacturers instructions.

2. DO NOT sample surface of pass through or main chamber where equipment has been placed.

3. Compounding personnel simulate compounding while air sampler is running.

4. When simulation/competency is complete, personnel perform gloved fingertip sampling on both hands. DO NOT disinfect gloves prior.

5. All gloves present must be tested (i.e. for 3 glove CAIs)

6. Don't remove air sampler until simulation/competency is complete.

7. After compounder removes arms, then perform surface sampling.

8. Work from main chamber to transfer.

9. Load/unload in main chamber.

Front 34

Isolator Classification of pass throughs

5 items

Back 34

1. Differences of opinion.

2. NOT unreasonable to expect ISO 5 is operating correctly and sampled correctly.

3. If not met, can trend.

4. If isolator in uncontrolled space, PT cannot exceed ISO 8

5. If isolator in ISO 8 space, PT cannot exceed ISO 7.

Front 35

Transporting Samples

9 items.

Back 35

1. Stack together. Lids can't come off.

2. Keep cool, but not frozen

3. NO DRY ICE

4. Samples can't touch ice pack

5. Can be repackaged in bag given by supplier

6. should be transported/stored inverted to minimize condensation

7. Must ship overnight

8. Samples should ship overnight, but not longer than 4 days and must be refrigerated prior to shipping

9. Package to prevent contamination

Front 36

Growth Promotion: Bacterial Media

3 items

Back 36

1. Innoculate < 100 CFU bacillus subtilis, Psedu aerugiinosa and staph auerus in individual prtions.

2. Incuate not more than 3 days at 30-35C.

3. OK if clearly visible typical growth for each organism within allotted time.

Front 37

Growth Promotion: Fungal Media

3 items

Back 37

1. Innoculate < 100 cfu Aspergillus brasiliesis and candida albicans in individual portions.

2. Incubate no more than 5 days at 20-25C

3. Clearly visible growth within allotted time for each organism

Front 38

Media Sterility Testing

Back 38

Incubate control with samples.

OK if no growth.

Front 39

Sample Incubation: Single Plate

Back 39

1. Invert at 30-35C for 48-72 hours then 26-30C for 5-7 days.

Front 40

Duplicate Plate Method:

Back 40

General micrbiological media

Incubate 30-35C for 48-72 hours inverted

Mycological media or other media capable of supporting fungi:

26-30C for 5 -7 days inverted

Front 41

Analysis of Samples: Single Plate Method

Back 41

1. After initial incubation, record total number of colonies

2. After second incubation, removed and count ALL recovered colonies

Front 42

Analysis of Samples: Duplicate Plate Method

Back 42

Count recovered BACTERIAL colonies on plates incubated at 30-35C.

Count recoved mold/yeast on plates uncubated at 26-30.

Add bacterial/fungal plate CFUs for each location.

Front 43

Analysis of IDs:

Back 43

1. at least to genus level.

2. Determine if any coag positive staph.

3. Determine if any mold, yeast, gram negative rods, coag positive staph.

Front 44

Swab total microbial count

Back 44

Add bacterial/mold yeast counts and multiply by the dilution factor

Front 45

Data Expression

Back 45

1. Viable air= CFU per cubic meter

2. Contact=CFU per plate

3. Swabs= CFU/swab or /area sampled

4. Zero CFU= "<1 cfu/plate"

Front 46

Pass/Fail

Back 46

Fingertip Post Fill= >3

Gowning/Gloving >0

ISO 5 Air >1

ISO 5 surface >3

7 air >10

7 ss >5

8 air >100

8 ss >100

Front 47

Pass/Fail on ID

Back 47

Recovery of mold, yeast, coag + staph, or gram - rods considered not to be in compliance with USP <797> and requires immediate remediation and investigation into cause.

Front 48

If report exceeds action levels:

Back 48

1. Report to personnel responsible at site

2. Personnel responsible for:

cleaning

resample

Front 49

Review

Back 49

Facility personnel responsible for review and analysis for trends.

Analyze periodically (usually yearly) and set appropriate alert/action levels.

Front 50

Gowning Evalation: Frequency

Back 50

All risk levels: Initially before compounding, must pass 3.

Low and medium: Annually thereafter (and only one trial)

High risk: SEMI annually thereafter, one trial.

Front 51

Gowning Evaluation: Isolator specifics

Back 51

1. Garb same method as normal compounding.

2. If replace gloves prior to compounding, do that prior to sampling.

3. If donning sterile gloves inside isolator prior to compounding, do that.

Front 52

Gowning Evaluation:

6 items

Back 52

1. Must be trained with audio/visual and/or professional resources in gowning

2. Complete a written test

3. Must be observed gowning

4. Touch all four fingers and thumb on surface of plate. Enough for light impression without cracking/breaking media. Repeat with other hand (different plate)

5. Degown.

6. Repeat 3 times initially.

Front 53

Gowning Evaluation: Incubation

2 items!

Back 53

1. 30-35 for 48-72 hours.

2. Best practice: Also incubate 20-25C x 5-7 days more for mold.

Front 54

Gowning Evaluation Pass/Fail

Back 54

Zero CFU and passing written test.

Front 55

THE END