MNI1412 Compounding and Personnel - Microbiology …microbiologynetwork.com/content/file/Webinar_PDF/MNI1412...and Personnel Control Scott Sutton, Ph.D. [email protected]

Compounding Pharmacies and Personnel 10/2/14

© 2014 Microbiology Network, Inc. 1

Compounding Pharmacies and Personnel Control

Scott Sutton, Ph.D.

[email protected]

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Disclaimer

• I am making this presentation as an independent agent

• I am not making this presentation as a representative of USP, PDA, PMF, SCA, PSSNY or any other organization with which I am currently associated.

• The views expressed in this presentation are offered as mine alone.

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© 2014 Microbiology Network, Inc.



Overview of Webinar• <797> Introduction

• <797> Responsibility of Compounding Personnel

• <797> Training of Compounding Personnel

• <797> Personnel Training and Competency Evaluation of Garbing, Aseptic Work Practices, and Cleaning/Disinfection Procedures

• Expectations of <1163> “Quality Assurance in Pharmaceutical Compounding”

• Expectations of FDA under cGMP

• Summary

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Personnel - <797>

“It is generally acknowledged that direct or physical contact of critical sites of CSPs with contaminants, especially microbial sources, poses the greatest probability of risk to patients. Therefore, compounding personnel must be meticulously conscientious in precluding contact contamination of CSPs both within and outside ISO Class 5 (see Table 1) areas.”

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Personnel - <797>

“Some differences between standards for sterile compounding in this chapter and those for nonsterile compounding in Pharmaceutical Compounding - Nonsterile Preparations <795> include, but are not limited to, ISO-classified air environments (see Table 1); personnel garbing and gloving; personnel training and testing in principles and practices of aseptic manipulations and Sterilization; environmental quality specifications and monitoring; and disinfection of gloves and surfaces of ISO Class 5 (see Table 1) sources.”

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• Summary

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<797> - Responsibility of Compounding Personnel

“Compounding personnel are responsible for ensuring that CSPs are accurately identified, measured, diluted, and mixed and are correctly purified, sterilized, packaged, sealed, labeled, stored, dispensed, and distributed. These performance responsibilities include maintaining appropriate cleanliness conditions…”

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<797> - Responsibility of Compounding Personnel SUPERVISORS SHALL ENSURE

1. Compounding personnel are adequately skilled, educated, instructed, and trained to correctly perform and document the following activities in their sterile compounding duties:

a. perform antiseptic hand cleansing and disinfection of nonsterilecompounding surfaces;

b. select and appropriately don protective garb;

c. maintain or achieve sterility of CSPs in ISO Class 5 (see Table 1) PEC devices and protect personnel and compounding environments from contamination by radioactive, cytotoxic, and chemotoxic drugs (see Hazardous Drugs as CSPs and Radiopharmaceuticals as CSPs);

d. identify, weigh, and measure ingredients; and

e. manipulate sterile products aseptically, sterilize high-risk level CSPs, and label and quality inspect CSPs.

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2. “Ingredients have their correct identity, quality, and purity.

3. Opened or partially used packages of ingredients for subsequent use in CSPs are properly stored under restricted access conditions in the compounding facility. Such packages cannot be used when visual inspection detects unauthorized breaks in the container, closure, and seal; when the contents do not possess the expected appearance, aroma, and texture; when the contents do not pass identification tests specified by the compounding facility; and when either the BUD or expiration date has been exceeded.”

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4. Water-containing CSPs that are nonsterile during any phase of the compounding procedure are sterilized within 6 hours after completing the preparation in order to minimize the generation of bacterial endotoxins.

5. Sterilization methods achieve sterility of CSPs while maintaining the labeled strength of active ingredients and the physical integrity of packaging.

6. Measuring, mixing, sterilizing, and purifying devices are clean, appropriately accurate, and effective for their intended use. when either the BUD or expiration date has been exceeded.”

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Eight more expectations for CSP quality and labeling expectations are listed in this section.

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Personal Hygiene/Gowning

• Avoid contact with all unnecessary surfaces.

• Consciously avoid nervous mannerisms such as scratching or touching other body parts.

• Reduce excessive and unnecessary movement in order to minimize particulate contributions.

• Minimize working or moving gloved hands below the first primary work surface.

• Keep gloved hands above waist level.

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Important Consideration

First Air

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Gowning/Hygiene

• Goal is to contain the main source of contamination in the cleanroom

• Minimize challenge to gown by minimizing bacterial shedding potential

• Make sure that gown is complete

• Endure that procedure to gown is designed to encourage aseptic exterior of gown

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Methods of Spread

• Dispersion• Generate particulate matter

• Viable microorganisms attached to particles (dead skin, hair, fibers)

• Touch Contamination

• Aerosols

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Personnel Shedding – Particles per Minute by Activity

10,0001,000,000

5,000,000

10,000,000

0

2,000,000

4,000,000

6,000,000

8,000,000

10,000,000

Motionless Head andArms

WalkingSlowly

BriskActivity

Reinmuller, B and B Ljungqvist. 2000. Evaluation of Cleanroom Garments In a Dispersal Chamber - Some Observations. Euro J Parenteral Soc 5(3):55-58

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Ljungqvist, B and B Reinmüller. 2005. Aseptic Production, Gowning Systems, and Airborne Contaminants. Pharm Technol May, 2005


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Ljungqvist, B and B Reinmüller. 2005. Aseptic Production, Gowning Systems, and Airborne Contaminants. Pharm Technol. May, 2005










• Summary

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Training of Personnel

“Personnel who prepare CSPs shall be trained conscientiously and skillfully by expert personnel and through audio-video instructional sources and professional publications in the theoretical principles and practical skills of aseptic manipulations and in achieving and maintaining ISO Class 5 (see Table 1) environmental conditions before they begin to prepare CSPs.”

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Competency“Compounding personnel shall perform didactic review and pass written and media-fill testing of aseptic manipulative skills initially, at least annually thereafter for low- and medium-risk level compounding, and semiannually for high-risk level compounding. Compounding personnel who fail written tests or whose media-fill test vials result in gross microbial colonization shall be immediately re-instructed and re-evaluated by expert compounding personnel to ensure correction of all aseptic practice deficiencies.”

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Media-Fill Challenge Testing

• “The skill of personnel to aseptically prepare CSPs may be evaluated using sterile fluid bacterial culture media-fill verification…”

• “Media-fill testing is used to assess the quality of the aseptic skill of compounding personnel”

• “Media-fill challenge tests that simulate high-risk level compounding are also used to verify the capability of the compounding environment and process to produce a sterile preparation.”

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• Summary

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<797> Personnel Training and Competency Evaluation of Garbing, Aseptic Work Practices, and Cleaning/Disinfection Procedures

• Introduction

• Competency Evaluation of Garbing and Aseptic Work Practice

• Surface Cleaning and Disinfection Sampling and Assessment

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• Introduction is a review of previous training session, with less emphasis on media-fills

• Describes using contractors for cleaning/disinfection. These need training (and demonstrate competence) in:

o Proper hand hygiene

o Garbing

o Cleaning and disinfection procedures

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Competency Evaluation of Garbing and Aseptic Work Practice

Competency check shall be done initially and at every media-fill using form similar to “Sample Form for Assessing Hand Hygiene and Garbing Related Practices of Compounding Personnel (see Appendix III)” and fingertip sampling.

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Garbing And Gloving Competency Evaluation

• Visual observation

• Document results

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Gloved Fingertip Sampling

• “All compounding personnel shall successfully complete an initial competency evaluation and gloved fingertip/thumb sampling procedure (zero cfu) no less than three times before initially being allowed to compound CSPs for human use.”

• Procedure provided:

• TSA w/lecithin + polysorbate

• Incubate 30o-35o for 48-72 hours

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Aseptic Manipulation Competency Evaluation

• This section is about how the media-fill is an evaluation of the skill of personnel to aseptically prepare CSP.

• This is an error – the media fill should be used to document the capability of the facility, equipment, process and personnel to aseptically formulate. It should be performed on all compound process “families” at a minimum.

• Incubate media-fill vials for 14 days.

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Aseptic Work Practice Assessment and Evaluation via Personnel Glove Fingertip Sampling

Use contact plates – recommended levels:

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• Introduction

• Competency Evaluation of Garbing and Aseptic Work Practice

• Surface Cleaning and Disinfection Sampling and Assessment

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Surface Cleaning and Disinfection Sampling And Assessment

• Introduction

• Cleaning and Disinfecting Competency Evaluation

• Surface Collection Methods

• Action Levels, Documentation, and Data Evaluation

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Competency Evaluation of Garbing and Aseptic Work Practice

• Surface sampling is useful for evaluating facility and work surface cleaning and disinfecting procedures and employee competency in disinfection

• Surface sampling shall be performed in all ISO classified areas on a periodic basis.

• Done at end of compounding

• Sample sites are constant, and defined

• Use solid agar or swabs for sampling

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Surface Cleaning and Disinfection Sampling And Assessment

• Introduction

• Cleaning and Disinfecting Competency Evaluation

• Visual observation – document results

• Surface Collection Methods

• Brief instruction on sampling methodology

• Action Levels, Documentation, and Data Evaluation

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Action Levels, Documentation, and Data Evaluation

• Excursions should be investigated

• Areas to investigate:

• HVAC systems

• Damaged HEPA filters

• Changes in personnel garbing or working practices.

• The source of the problem eliminated

• The affected area cleaned

• Resampling performed

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Analysis of Microorganisms Recovered

• CFU are an approximate measure of environmental microbial bioburden

• “Action levels are determined on the basis of cfudata gathered at each sampling location and trended over time.”

• All active air sampling recovery to be identified.

• “Highly pathogenic microorganisms”• Gram-negative Rods

• Coagulase positive Staphylococcus aureus

• Molds and Yeasts

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• Expectations of <1163> Quality Assurance in Pharmaceutical Compounding


• Summary

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Quality Assurance“The responsibility and authority for a quality assurance program should be clearly defined and implemented. Personnel responsible for the quality assurance program should have the education, training, and experience necessary to perform the assigned functions. Quality assurance personnel should assure that documentation, verification, and testing are performed in accordance with written policies and procedures. If deviations from approved policies and procedures occur, it is the responsibility of the quality assurance personnel to investigate and to implement appropriate corrective action. Documentation of any investigations and corrective actions is the responsibility of the quality assurance personnel. Responsible personnel in the quality assurance program are essential in assuring the safety, identity, strength, quality, and purity of compounded drug preparations.”

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• Expectations of <1163> Quality Assurance in Pharmaceutical Compounding


• Summary

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Frequent 483 Citations - Current

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81.90%78.70% 76.60% 76.60% 74.50%

68.10%61.70% 60.60% 60.60% 58.50%

51.10% 51.50%

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

90.00%84 Reports

9/25/14




Frequency of Issue Cited

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Issue Frequency

Inadequate/ImproperEM 81.90%

ValidationofSterilization:MediaFills 78.70%

LabProcedures:Testing 76.60%

InadequateGowning 76.60%

SOPstoPreventMicrobialContamin 74.50%

StabilityProgram 68.10%

BatchRelease 61.70%

ControlofEquipment 60.60%

InadequateFacility/SmokeStudies 60.60%

InadequateCleaning/Disinfection 58.50%

ControlofPyrogenicContamination51.50%

Investigations 51.10%


Frequency of Issue Cited

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Issue Frequency

QAU/ProductionSOPsNotfollowed/effective 36.20%

SeparationofClean&DirtyOps/StorageofMaterials 29.80%

InadequateRawMaterialControl 24.50%

ContainerPreparation 22.30%

SOP/ControlofProduction 16.00%

SafeguardAgainstPenicillin/CephalosporinCrossContamination 12.80%

LabelingIssues 12.80%

RecordsNotAvailable 12.80%

PersonnelNotTrained/InadequatelyTrained 11.70%

ObviousProductContamination(Micro/Particulate) 3.20%

ChangeControl 3.20%




483 of 3/8/13

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483 Issued 3/6/14

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483 Issued 2/4/14

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Review of Webinar• <797> Introduction






• Summary

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QUESTIONS?

Scott Sutton, Ph.D.

[email protected]

+1 585-298-0767 (cell)

http://www.Rx-GCP.com

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Microbiology Network, IncConsulting

• Contamination Control/Sterility Assurance• Quality Assurance• Quality Control

• Microbiology Lab Operations/Design/Audits• Microbiology Process/Procedure

• Product Development

Turn-key ProjectsWe will supply national expert supervision and/or bench-level assistance for short term or long-term needs (facility qualification, laboratory creation/expansion)

Training• In-house Training• Distance (web-based) training

• Next Compounding Webinar –Oct 16 - Compounding Pharmacies and Investigations

• Custom webinar training

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Thank you for your attentionScott Sutton, Ph.D.

[email protected]

+1 585-298-0767

http://www.linkedin.com/in/scottvwsutton

Twitter - @microbiologynet

Documents

MNI1412 Compounding and Personnel - Microbiology …microbiologynetwork.com/content/file/Webinar_PDF/MNI1412...and Personnel Control Scott Sutton, Ph.D. [email protected]