Risk-based Environmental Monitoring Program · 2020. 9. 24. · Poor Aseptic Behavior 0ur investigator observed multiple poor aseptic practices during the set-up and filling of (b)(4)

Risk-based Environmental Monitoring Program

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Presented by

Ziva Abraham

President

Microrite, Inc.

5019 New Trier Avenue

San Jose, CA 95136

Phone: 408-445-0507 Fax: 408-445-1236

Email: [email protected] www.microrite.com

mailto:[email protected]

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Ziva Abraham is the President and Founder of Microrite, Inc., a California based consulting firm providing consulting and training services to pharmaceuticals, biotechnology, medical devices and in vitro diagnostics in the areas of quality assurance, quality control, microbiology, and validation.Ziva has over 35 years of academic, research, clinical and industrial experience in microbiology, and quality assurance. Ziva has received her Master’s Degree in microbiology with a focus on Mycology and has conducted research on developing microbial Insecticides using entomogenous bacteria and fungi for her Ph.D. degree. Her career also includes founding and managing clinical laboratories for Maccabi Medical in Israel. She has trained personnel from various industries in microbiology techniques and methods. She uses her extensive experience to teach why assessing risk of microbial contamination should be in the forefront of any company that has products for human/veterinary use. Her experience in clinical laboratories has provided her with the framework to understand the effects of microbial contamination in products from a patient safety perspective.

About the Presenter

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Environmental Monitoring is not an isolated activity; to develop a risk based environmental monitoring program, risk across the lifecycle of the facility, process, personnel and operations must be assessed utilizing pertinent knowledge! Quality Risk Management (QRM): concept:• Risk Management is NOT an Exercise!!!• Real-world risk must be considered and addressed• Risk Management should be:o Pragmatico Scientifically Sound o Utilize Current Technology and Current Best Practices

Learn from experience and from the mistakes of others!No single SME can be an expert in all aspects of Risk Assessment!

Main Message

5Current Regulatory Expectations

FDAFDA: Guidance for Industry Sterile Drug Products

Produced by Aseptic Processing -Current Good

Manufacturing Practice:2004

GMP Annex 1 Manufacture of

Sterile Medicinal Products:

2008, Drafts 2017 and 2020

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These risk assessments should be re-evaluated at defined intervals in order to confirm the effectiveness of the site’s environmental monitoring program, and they should be considered in the overall context of the trend analysis and the contamination control strategy for the site.

• Facilities age

• Barrier and cleanroom design and integration may not be optimal

• Leaks in the room occur

• Membranes tear

• Filters get loaded

• Gowns wear

• Personnel leave

Why a Risk Based Environmental Monitoring Program?

7Risk Assessment??

8FDA 483 Observation

Poor Aseptic Behavior

0ur investigator observed multiple poor aseptic practices during the set-up and filling of (b)(4) batch (b)(4).

For example, during the aseptic filling of vials, an operator used restricted access barrier system (RABS) (b)(4) to remove a jammed stopper by reaching over exposed sterile stoppers in the stopper bowl.

The RABS (b)(4) disrupted the unidirectional airflow over the stopper bowl, creating a risk for microbial contamination. After the operator removed the jammed stopper, the filling line was restarted, but the affected stoppers were not cleared.

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Our inspection also revealed poor aseptic processing operation behaviors. In response to this letter, provide:

Your plan to assure appropriate aseptic practices and cleanroom behavior during production. Include specific steps to ensure routine supervisory oversight for all production batches. Also describe the frequency of quality assurance oversight during aseptic processing and other operations.

Comprehensive identification of all contamination hazards with respect to your aseptic processes, equipment, and facilities.

Provide a risk assessment that covers all human interactions with the ISO 5 area, equipment placement and ergonomics, air quality in the ISO 5 area and surrounding room, facility layout, personnel flow, and material flow.

Also include a detailed CAPA plan, with timelines, to address the findings of the contamination hazards risk assessment.

FDA 483 Observation

10Understanding Contamination Sources and Risk

• Using rating scales that are neither specific nor appropriate to a given situation

• Perceived risk instead of understanding real-world risk

• Not acknowledging uncertainty or missing important information

• Neglecting to keep risk assessments current (reflecting current regulatory

expectations)

• Performing paper-based risk assessments without understanding systems,

workflows and all possible sources of contamination

• More about the presentation rather than the risk

• One person performs the entire risk assessment?

Without knowing the risk, risk cannot be monitored!


Aseptic garments worn in the filling area were also non-integral.“We observed 7 of (b)(4) sterile gowns with tears or holes; 8 of (b)(4) had loose threads. We observed 2 of (b)(4) sterile hoods with tears or holes; 12 of (b)(4) had loose threads. We observed 8 of (b)(4) sterile booties with tears or holes; 11 of (b)(4) had loose threads.”

Procedure "Handling of Aseptic Area Garments" required production personnel to examine the garments for tears, holes, and loose threads, but our investigator found that these checks were not being performed.

https://www.microrite.com/wp-content/uploads/2020/01/MICROBIOLOGICAL-FAILURES-DUE-TO-HUMAN-

BORNE-CONTAMINATION-CLEANROOM-GARMENT-AND-MANAGEMENT-GAPS-2020v1.pdf

https://www.microrite.com/wp-content/uploads/2020/01/MICROBIOLOGICAL-FAILURES-DUE-TO-HUMAN-BORNE-CONTAMINATION-CLEANROOM-GARMENT-AND-MANAGEMENT-GAPS-2020v1.pdf

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4.7 There should be systems in place for disqualification of personnel from entry into cleanrooms based on aspects including ongoing assessment and/or identification of an adverse trend from the personnel monitoring program and/or after participation in a failed APS. Once disqualified, retraining and requalification should be completed before permitting the operator to have any further involvement in aseptic practices. 4:15 Clean area clothing should be cleaned in a dedicated laundry facility using a qualified process ensuring that the clothing is not damaged and/or contaminated by fibres and particles during the laundry process. Inappropriate handling and use of clothing will damage fibres and may increase the risk of shedding of particles. After washing and before packing, garments should be visually inspected for damage. The garment management processes should be evaluated and determined as part of the garment qualification program.Operators performing aseptic operations should adhere to aseptic technique at all times to prevent changes in air currents that introduce air of lower quality into the critical zone. Movement adjacent to the critical zone should be restricted and the obstruction of the path of the unidirectional (first air) airflow should be avoided. Airflow visualisation studies should be considered as part of the operator’s training programme.

Personnel

GMP/EU Annex 1-2020 Draft

13How gowns affect EM results

• Gowns not correctly sized

• Compromised gowns, such as fraying cuffs, open seams, etc.

• No control on quality

• No control over the number of laundries including detergents

• Inappropriate storage of gowns

• Inadequate gowning procedures

14Premises


5.1 The manufacture of sterile products should be carried out in appropriate cleanrooms, entry to which should be through changing rooms that act as airlocks for personnel and airlocks for equipment and materials. Cleanrooms should be maintained to an appropriate cleanliness standard and supplied with air which has passed through filters of an appropriate efficiency.

Controls and monitoring should be scientifically justified and capable of evaluating the state of environmental conditions for cleanrooms, airlocks and pass-throughsused for material and equipment transfer.

15Premises


5.12 Airflow patterns within cleanrooms and zones should be visualised to demonstrate that there is no ingress from lower grade to higher grade areas and that air does not travel from less clean areas (such as the floor) or over operators or equipment that may transfer contaminant to the higher-grade areas. Where air movement is shown to be a risk to the clean area or critical zone, corrective actions, such as design improvement, should be implemented.

Airflow pattern studies should be performed both at rest and in operation (e.g. simulating operator interventions). Video recordings of the airflow patterns should be retained. The outcome of the air visualisation studies should be considered when establishing the facility's environmental monitoring program.

16Premises


5.4 Grade B area: For aseptic preparation and filling, this is the background cleanroom for the Grade A zone (where it is not an isolator). When transfer holes are used to transfer filled, closed products to an adjacent cleanrooms of a lower grade, airflow visualization studies should demonstrate that air does not ingress from the lower grade cleanrooms to the Grade B.

Pressure differentials should be continuously monitored. Cleanrooms of lower grade than Grade B can be considered where isolator technology is used.

17Poor RABS Design

Aseptic Filling Operation:“Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance. (21 CFR 211.63)

The sterile filling line for injectable products lacks unidirectional airflow in the ISO 5 aseptic filling zone. The RABS airflow in the filling zone is not sufficiently robust to protect the sterile injectable product during interventions involving operator entry into the aseptic filling line.

Smoke studies demonstrated that the filling line design permits turbulence above and below open vials. Opening the enclosure significantly disrupts airflow. This turbulent air in the aseptic filling zone poses a significant contamination hazard.

18Uncleanable Surfaces

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“It is useful to assume that the operator is always contaminated while operating in the aseptic area.

If the procedures are viewed from this perspective, those practices which are exposing the product to contamination are more easily identified.”

Hank Avallone – 1989

“a gowned operator may release as many as 10,000 CFU/hour or more…

(Reinmuller and Ljungqvist).

Common Unrecognized Issues

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Smoke Studies are often approached as a “Rubber Stamp Test”, often conducted under the assumption that they will pass because other cleanroom tests have passed.

• Air Volume and Air Velocity

• Particle Count

• Differential Pressure

• Filter Integrity

This Approach coupled with other factors contribute to Smoke/AFV Study Errors that lead to:

• Contamination of Sterile Products

• Inspectors Comments

• Warning Letters

AFV/Smoke Studies is the MOST Misunderstood CR Test!

21Frequent Inspector’s Comments on Smoke Studies

• Smoke Studies not conducted during dynamic conditions simulating operations with equipment

running, filling and stoppering

• Only Grade A areas and not support Grade B areas tested

• Only one angle recorded during dynamic smoke studies

• Smoke Study Video not available for inspectors

• Dynamic Smoke Study Video does not reflect actual operations as indicated in Media Fill

• Dynamic Smoke Study does not simulate all interventions

• Smoke Generator does not generate adequate smoke to evaluate the aseptic process

• Smoke Manifold is not over the Operators during the intervention

• Smoke Studies do not fully demonstrate air flow movement away from work surfaces during

interventions

• Turbulence observed with no corrective action identified


FDA 483 Observation: “Equipment for adequate control over air pressure is not provided

when appropriate for the manufacture, processing, packing or holding of a drug product.”

• Specifically your firm lacks a system of continuous monitoring of differential pressure limits

during aseptic processing of drugs intended to be sterile.

• Your current practice is to log the differential pressure readings from your positive pressure

differential pressure gauges, representing the differential pressure across your clean room

and adjacent gowning room.

• Because these gauges are located outside of the clean room itself, if a loss of positive

pressure in the clean room occurred during aseptic processing, you may not notice until the

clean room differential pressure gauges are read again.

• Your current clean room differential pressure system has no audible alarm; thus, transient

excursions of ~pressure would not be observed or recorded.

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Grade AAir Inlet to

LAF

Grade BAir Supply

Poor Cleanroom/Barrier Integration Limits the HEPA

Filtered Air Delivered into the Grade B Support Area

Air Return

UDAF

Air Return

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Door Closed Condition

RABS Air Inlet

First Air is Flowing Over Product Contact Surfaces When the RABS Door is Closed

Grade B HEPA Supply Air


KEY:First Air

Non-FirstAir Inside RABS

Air That Should be Considered Contaminated

Open Active RABSSmoke Manifold

Position for documenting “FIRST AIR”

Air Return

UDAF

Air Return

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Smoke Manifold

Position for Inside RABS

Air That Should Be Considered Contaminated is Flowing from the floor and across the Operator.

The Inlet of the RABS is stronger than the HVAC Air Return. Creating an upwards air flow pattern that is DETRIMENTAL to contamination control

KEY:First Air

Non-FirstAir Inside RABS

Air That Should be Considered Contaminated

”SHORT CIRCUIT’HEPA Filtered Air intended for keeping Grade B area clean is re-directed to the RABS inlet. Reducing the contamination control for the Grade B Zone.

Poor Cleanroom/Barrier System Integration

Open Active RABSRABS Air Inlet

26Biological Safety Cabinet

27Case Study: Poorly Designed Sterile Filling Line

Cleanroom was Qualified including Air Flow

Visualization Studies.

• EM Data from Media Fills (Settle Plates)

were registering CFUs.

• The sample locations were suspect;

however the picture tells us everything.

• NO separative airflow between the RABS

and the operating personnel.

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Low Wall Returns

Passive RABS recycles air from the surrounding environment.

Low Wall Returns

Open Passive RABS via LAF:

7.6 -15 cm gap between HEPA Filter and top of RABS

No Pressure Differential Between RABS and Where Operators are Working

Membrane diffuser

GAP Between Filters Causes Turbulance

Only the LAF for the Filling Machine Nothing for the Room

HEPA HEPA

RABS Air Inlet Creates Upwards Air Flow

LAF Unit

Barrier System Flaw: Poor Cleanroom / Open Passive RABS Integration

29ISO Doctrine of Contamination Control

ISO 14644-4Cleanroom

Design, Construction

& Startup

ISO 14644-2Monitoring &

Periodic Testing

ISO 14644-5CleanroomOperations

MonitoringRisks

ISO 14644-3Test Methods:(Particle, TempRH, Δ Pressure)

...

ISO 14644-1Classification of Air Cleanliness

byParticle

Concentration

Specifications for Cleanroom Class

Specification for Additional Tests

Cleanroom Qualification Testing

Monitoring Additional Cleanroom Parameters& Qualification

Requalification(Periodic Testing or After Corrective Actions)

Specification for Monitoring & Periodic Testing

Pre Tests

Continuous Operation IF Routine or Continuous

Monitoring Data is within Specification

ISO 14644-7 Seperative devices, (clean air hoods, gloveboxes isolators and mini-environments)

30Particle Monitoring

Environmental Monitoring as Addressed in Draft Annex 16.9 Particle counters should be qualified (including sampling tubing). Portable particle counters with a short length of sample tubing should be used for qualification purposes.

Study performed for evaluation resulted in:• Company was using 3

types of particle monitoring devices

• 50% discrepancy in particle transport efficiencies

• Discrepancy in reading from system to system

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Regulatory Thinking on Particle Sample Tubing:

GMP Annex 1: Clause 11

Cleanroom and clean air device monitoring

• “The system selected must be appropriate for the particle size considered.

• Where remote sampling systems are used, the length of tubing and the radii of any bends in the

tubing must be considered in the context of particle losses in the tubing.“

PIC/S Recommendation: “GMP Annex 1 Revision 2008, Interpretation of Most Important Changes for

the Manufacture of Sterile Medicinal Products” January 2010

• “Recommendation: This section addresses concerns especially for the sedimentation of 5 µm particles

in remote systems (as a rough example, s-shaped bent tubing of 1.5 m length can already absorb

about 30% of the 5 µm particles.)”

• “The company must qualify their particle sampler and sampling system for both particle sizes, 0.5 µm

and 5 µm.”

Particle Monitoring

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Sample Tubing for NV Particle Counting:

ISO 14644-1:2015 for Particles >5 micron, no greater than 1 meter

1 Bend Radius (>15cm)

1 ASTM F50-12:2015 Standard Practice for Continuous Sizing and Counting of

Airborne Particles in Dust-Controlled Areas and Clean Rooms Using

Instruments Capable of Detecting Single Sub-Micrometer and Larger Particles

Particle Monitoring

33483 regarding non-viable monitoring

“No representative non-viable particle (NVP) monitoring data supports your current ISO-

5 classification for the product path from the (b)(4) to the (b)(4), which transfers product

to the (b)(4) during aseptic processing of finished drug products.

During our inspection, we documented that your NVP probes are placed (b)(4) surface

instead of near the working area. Placing the probe (b)(4) instead of near the working

area means you are unable to detect NVPs where sterile drugs are exposed during

aseptic processing.

Additionally, transferring (b)(4) vials from the filling suite to the (b)(4) can take up to

(b)(4). This extended exposure time may increase contamination hazards. However, your

firm lacks adequate environmental monitoring of this part of the operation. It is essential

that your sampling plan include areas where (b)(4) and product are exposed to the

environment, and at greater risk of contamination.”

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• Function of the nozzle size and air flow through the impactor, as this determines

velocity through a given nozzle (Slit or Hole).

• Distance between nozzle exit and collection surface.

• Smaller Holes and Higher Flow Rates Collect Smaller Particles.

Particle Size Capture

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9.4 Risk assessments should be performed in order to establish a comprehensive environmental monitoring program, i.e. sampling locations, frequency of monitoring, monitoring method used and incubation conditions (e.g. time, temperature(s), aerobic and/or anaerobic conditions). These risk assessments should be conducted based on detailed knowledge of; the process inputs and final product, the facility, equipment, specific processes, the operations involved, historical monitoring data, monitoring data obtained during qualification and knowledge of typical microbial flora isolated from the environment. Consideration of other information such as air visualization studies should also be included. These risk assessments should be reviewed regularly in order to confirm the effectiveness of the site’s environmental monitoring program. The monitoring program should be considered in the overall context of the trend analysis and the CCS for the site.

Viable and non-viable environmental monitoring

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9.7 The monitoring of Grade A zones should demonstrate the maintenance of aseptic processing conditions during critical operations. Monitoring should be performed at locations posing the highest risk of contamination to the sterile equipment surfaces, container, closures and product.

The selection of monitoring locations and the orientation and positioning ofsampling devices should be justified and appropriate to obtain reliable data from the critical zones.


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Note 1: The particulate limits given in the table for the “at rest” state should be achieved after a short “clean up” period (defined during qualification with a guidance value of 15 to 20 minutes) in an unmanned state, after the completion of operations (refer to paragraph 4.30 and 4.31).

Note 2: With regards to the monitoring of airborne particulates ≥5 μm particulate concentration, the limit of 29 (Grade A) is selected due to the limitations of monitoring equipment. Alert levels should be set based on historical data, such that frequent sustained counts below the action limit which may be indicative of system contamination or deterioration should trigger an investigation. For the Grade A zone and Grade B area the importance of monitoring the ≥5 μmparticulates is to identify negative trends as defined in the manufacturer's CCS.


38Premises: Cleanroom & Clean air device Qualification

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5.25 For cleanroom classification, the airborne particulates equal to or greater than 0.5 and 5 µ m should be measured. For Grade A zone and Grade B at rest, classification should include measurement of particles equal to or greater than 0.5 µ m; however, measurement using a second, larger particle size, e.g. 1 µ m in accordance with ISO 14644 may be considered. This measurement should be performed both at rest and in operation. The maximum permitted airborne particulate concentration for each grade is given in Table 1.How can you monitor what you haven’t qualified?

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9.15 The Grade A zone should be monitored continuously (for particulates ≥0.5 and ≥5 µ m) and with a suitable sample flow rate (at least 28 litres (1ft3) per minute) so that all interventions, transient events and any system deterioration is captured. The system should frequently correlate each individual sample result with the limits in Table 6 at such a frequency that any potential excursion can be identified and responded to in a timely manner. Alarms should be triggered if alert levels are exceeded. Procedures should define the actions to be taken in response to alarms including the consideration of additional microbial monitoring.

9.16 It is recommended that a similar system be used for Grade B area although the sample frequency may be decreased. The Grade B zone should be monitored at such a frequency and with suitablesample size that the programme captures any increase in levels of contamination and system deterioration. If alert or action levels are exceeded, alarms should be triggered.


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9.18 The selection of the monitoring system should take into account any risk presented by the materials used in the manufacturing operation (for example, those involving live organisms, powdery products or radiopharmaceuticals) that may give rise to biological or chemical hazards.9.21 The size of monitoring samples taken using automated systems will usually be a function of the sampling rate of the system used. It is not necessary for the sample volume to be the same as that used for formal classification of cleanrooms and clean air equipment. Monitoring sample volumes should be justified.9.24 Monitoring conditions such as frequency, sampling volume or duration, alert levels andaction limits and corrective actions (including an investigation) should be established in each manufacturing area based on data generated during the initial qualification process, ongoing routine monitoring and periodic review of data.


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9.25 Where aseptic operations are performed, microbial monitoring should be frequent using a combination of methods such as settle plates, volumetric air sampling, glove, gown and surface sampling (e.g. swabs and contact plates). The method of sampling used should be justified within the CCS and should be demonstrated not to have a detrimental impact on Grade A and B airflow patterns.9.27 Continuous viable air monitoring in the Grade A zone (e.g. air sampling or settle plates) should be undertaken for the full duration of critical processing, including equipment (aseptic set-up) assembly and filling operations. A similar approach should be considered for Grade B cleanrooms based on the risk of impact on the aseptic processing. The monitoring should be performed in such a way that all interventions, transient events and any system deterioration would be captured and any risk caused by interventions of the monitoring operations is avoided.9.29 Sampling methods and equipment used should be fully understood and procedures should be in place for the correct operation and interpretation of results obtained. The recoveryefficiency of the sampling methods chosen should be qualified.


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9.31 Action limits for viable particle contamination

(a) Settle plates should be exposed for the duration of operations and changed as required after 4 hours (exposure time should be based on validation including recovery studies and it should not have any negative effect on the suitability of the media used). Individual settle plates may be exposed for less than 4 hours.

(b) It should be noted that for Grade A, any growth should result in an investigation.


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9.33 Microorganisms detected in Grade A zone and Grade B area should be identified to species level and the potential impact of such microorganisms on product quality (for each batch implicated) and overall state of control should be evaluated.

Consideration should also be given to the identification of microorganisms detected in Grade C and D areas (for example where action limits or alert levels are exceeded or where atypical or potentially objectionable microorganisms are recovered). The approach to organism identification and investigation should be documented.


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10.9 Media used for environmental monitoring and APS should be tested for its growth promotion capability, in accordance with a formal written program

10.10 Environmental monitoring data and trend data generated for classified areas should be reviewed as part of product batch certification. A written plan should be available that describes the actions to be taken when data from environmental monitoring are found out of trend or exceeding the established limits. For products with short shelf life, the environmental data for the time of manufacture may not be available; in these cases, the certification should include a review of the most recent available data.

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Quality Control

45Quality Control of Media

Accuracy of viable monitoring results depend upon media quality and incubation. Common causes for erroneous results :• Discoloration or hemolysis• Storage location• Integrity of packaging• Broken or cracked petri dishes• Quality and accuracy of labeling• Condensation in petri dishes• Retracted medium• Dried and cracked media• Sloped or uneven filling of petri dishes• Contamination• Gel strength• Pitted surface or large bubbles• Presence of leakage….

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Data should be reviewed continually, not only during batch release. The purpose of EM is to ensure controls are working and there is no contamination risk to product.

Microbial identification should be considered as a critical component of a risk-based monitoring program.

Though each colony from plates may not be identified; only unique colonies may be identified, however the counts of each unique type of colony should be recorded. This should be considered during trending to understand contamination sources and remedial actions necessary.

Trends; beyond the data for each room, should depict excursions, investigations, remedial actions, etc.

Predominance of microorganisms in each room should be assessed to evaluate risk to product and patient.

This information should be used to improve cleaning procedures, evaluate facility or operational flaws.

Compromised agar media should not be used for monitoring; this requires a comprehensive quality control program for incoming media.

Risk Based EM Program

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Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)For example, during inspection of the QC microbiology testing laboratory, our investigators observed:

A. No growth on the positive control plate for media used to test microbiological (b)(4) samples. When a positive control fails to yield growth, test results cannot be considered valid due to the potential for false negatives.

FDA 483 Observation

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B. Desiccation of a contact media plate used during environmental monitoring of the sterility testing area. Desiccated, cracked, or otherwise damaged (b)(4) compromises microbial growth promotion and accurate enumeration, and can lead to artificially low microbiological counts and false negatives. Using deficient media compromises the validity of your microbiological test results.

Also, you did not appear to routinely identify (i.e., to species level) bacterial and fungal isolates recovered during environmental monitoring of your aseptic processing room.

C. Air bubbles between filtration (b)(4) and (b)(4) plates in 13 out of (b)(4) microbiological (b)(4) system sampling plates. Inadequate contact between the filter (b)(4) and the (b)(4) plate may compromise recovery.

FDA 483 Observation

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Fungal ID System and Methodology

ID

System

Library/

Database

Presence or absence

• Capable of identifying maximum organisms

Reliability

• Can identify consistently

Diversity

• How was the library created

Polyphasic Approach Images

Keeping up with

Taxonomic

ChangesTaxonomy is importantIf you don’t have consistent names, trending or investigations have no value!!

Multiple ID systems is not the solution-final product and EM IDs should be correctly and consistently identified!!

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• Evaluate Environmental Controls

• Evaluate Facility Condition

• Evaluate Personnel Behavior

• Evaluate Gowning Procedures

• Evaluate Aseptic Techniques

• Evaluate Risk to Product

• Patient Safety

Reasons for Environmental Monitoring

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Questions??

Risk-based Environmental Monitoring Program · 2020. 9. 24. · Poor Aseptic Behavior 0ur investigator observed multiple poor aseptic practices during the set-up and filling of (b)(4)

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