current activities and enhancements performed by microbiology · current activities performed by...
TRANSCRIPT
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Current activities and enhancements
performed by Microbiology
2020 PDA Asia Pacific Pharmaceutical
Manufacturing & Quality
September 22 – 24, 2020
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Current activities and enhancement performed by Microbiology
▪ I will focus on the activities that Microbiologist’s are engaged in and how
their engagement has a positive impact, with a comparison of trends
▪ I am not going to present or talk about microbiological analyses per se
▪ But first, as a point of reference, some of you folks may have heard me
say, (for years) “we need to get the microbiologist out of the laboratory”
NOTE: (this is not to say they will not be in the laboratory)
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We (FDA) at times say…
▪ that we can teach a Microbiologist to be an Investigator but we can’t teach
an Investigator to be a Microbiologist
What does this mean?
▪ As an example,
✓ Engineers understand from an engineering perspective e.g., manufacturing
utilities function and how they support manufacturing operations
✓ Maintenance understand, repair and/or replace many things that need to be
fixed and their repairs have a direct impact upon manufacturing operations
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Question
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▪ What happens if, or what are the possibilities, for example, when
you have a Microbiologist (who is not working in the QC laboratory)
perhaps working in the Quality Assurance Department or for that
matter in the Production Department?
✓ You folks know better than I
✓ I am just an observer for a short period of time during any
inspection
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Consider - all the good folks that observe, for example
▪ initial personnel entry into the manufacturing facility;
▪ personnel and material flow within your manufacturing operations;
▪personnel gowning practices and entry into the Controlled &
Classified manufacturing areas;
▪Airflow visualization program (aka smoke studies);
▪ the aseptic filling operations, filling equipment set-up, personnel
activities and movements within the ISO-5 & ISO-7 areas;
▪Environmental Monitoring (EM) of production & personnel; and,
▪Cleaning & Sanitization regimePDA Singapore 22-24/09/20
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Consider - the preceding bulleted items in a cascading sequence of activities
I am now observing more Microbiologists, for example -
▪ either working within the QA and/or in the Production Department;
▪with respect to microbial contamination they are part of the discussions &
deliberations with the QA and/or the Production Departments;
▪ they are part of the EM Program evaluation process, which affords an
enhanced appreciation of possible microbial contamination locations
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Consider - the microbial contamination / excursions that occur in a facility
The Microbiologist working within the QA and/or in the Production Department
has an intimate knowledge and understanding of the examples provided in
Slide #5 bulleted items and briefly summarized below;
▪ initial personnel entry into the manufacturing facility;
▪personnel and material flow within your manufacturing operations;
▪personnel gowning practices and entry into the Controlled & Classified
manufacturing areas;
▪ the aseptic filling operations, filling equipment set-up, personnel
activities and movements within the ISO-5 & ISO-7 areas
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Consider - the microbial contamination / excursions that occur in a facility
Regarding the Microbiologist working within the QA and/or in the
Production Department that has the intimate knowledge,
understanding and enhanced appreciation, for example, of the
personnel and material flow, aseptic filling processing operations,
etc.
Question - of what value does this provide?
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Perhaps…
1. a reduction of microbial contamination / excursions that occur during aseptic
filling activities and/or negative impact the finished drug products;
2. identifying the root cause(s) of the microbial excursions e.g., personnel
activities and/or source(s) of the microbial contaminants;
3. assist with implementing the corrective measure(s) to prevent recurrence of
the microbial contamination / excursions;
More importantly, what do you folks think?
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I applaud the organizations
▪ that have implemented programs that include having a
Microbiologist being part of and engaged at the discussion table
regarding microbiology related deviations / excursions;
▪Anecdotally speaking, I am always mindful if companies have the
right people with the needed expertise at the deliberations /
discussions, which ultimately assist to address, establish and
implement the necessary corrective measures.
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A brief note on the EM program
▪My complements on the EM trending and evaluating that is
performed to determine the presence and absence of microbes in
the manufacturing environment and with the personnel monitoring
considerations
▪As you know there are so many folks and departments actively
engaged in assessing the manufacturing areas e.g., Engineering,
Production, QA and the department responsible for the Cleaning
and Sanitation of the areas, to name a fewPDA Singapore 22-24/09/20
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Related to EM - I ask the folks that perform the airflow visualization studies
If they evaluated the airflow patterns and unidirectional flow of air, the
departments submit, as an example
1. Engineering responds that the HVAC unit provides the requisite air, air exchange
rate and air pressures are established and maintained per procedure;
2. Validation submits that the HEPA filters are integrity tested and provide the
requisite quality of air;
3. Production accepts the HEPA filtered air is unidirectional; and,
4. QA agrees that the unidirectional airflow is acceptable
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I pose the same question of the Microbiology Department…
If the airflow patterns have air turbulence / air eddies and could they present
conditions that foster the possibility of microbial cross contamination; I
normally don’t get a response right away…hmmm…
For the Microbiology Departments that do perform an evaluate for the air
turbulences / air eddies, when I ask to read their evaluation report to better
appreciate the well thought out considerations and the impact of the air
turbulence / air eddies, the response –
here’s the rub “there is no written evaluation”
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Current activities and enhancement performed by Microbiology
▪ Briefly on Microbiological rapid test automated equipment and computer
based systems –
✓ there a number of automated microbiological characterization and
identification systems e.g., Vitek, ScanRDI, MicroSEQ ID, Biolog, etc.
▪ We have all experienced the realities related to authenticating (aka data
integrity) the analytical data that is used in support of finished drug product
and APIs;
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Current activities and enhancement performed by Microbiology
▪ Notwithstanding the I.T. Department’s practices and procedures, the
Microbiology department is maintaining the electronic data and mindful of
the ALCOA principles;
1. Attributable ALCOA +
2. Legible 1. Complete
3. Contemporaneous 2. Consistent
4. Original 3. Enduring
5. Accurate 4. Available
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Current activities and enhancement performed by Microbiology
Microbiologist are appropriately trained with the operation of the automated
equipment and navigation within the computer system software/platform
▪ though, I don’t know if the Microbiology department performs the actual
equipment qualification and/or the process validation
▪ perhaps the above is perform by the validation department, which may
or may not include the I.T. Department
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Current activities and enhancement performed by Microbiology
We do know computer based system capture alarmed events / errors
that occur during routine operations
Questions –
1. Who evaluates the alarmed events/errors; and,
2. Do the alarmed events/errors impact upon the microbial
identifications?
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Current activities and enhancement performed by Microbiology
Let’s agree that an individual alarmed event and/or error is evaluated and it
does not negatively impact upon the equipment qualification and/or process
validation…
Questions -
1. Over a period of time, collectively, do the alarmed events / errors
present less than optimal operating conditions?
2. And, if so….did/how does impact the microbial identification,
equipment qualification and/or process validation?
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Current activities and enhancement performed by Microbiology
▪ So then, if the Microbiology department did not perform the actual
equipment qualification and/or the process validation,
Questions -
1. Who then would evaluate ?
2. Would it include the Validation Department and/or I.T. Department ?
3. And, to address the concern, what is the communication mechanism
between the Microbiology, Validation and/or I.T. Departments ?
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Current activities performed by Microbiology
Folks, can we agree that there has been an abundance of positive activities,
engagement and oversight performed by many departments to include the
Microbiology laboratory e.g.,
1. the implementation of state of the art microbial identification and
characterization computer based automated equipment
2. engagement and implementation of ALCOA principles
3. I genuinely offer my complements to the many organizations and
dedicated staff for the hard work that has been accomplished
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A current activity performed by Microbiology
Before I conclude the presentation, I do have a kind request to ask of you and
I need help so that I can better appreciate the following activity; this has to do
with some basic fundamental microbiology i.e.,
1. a color photograph is taken of microbial contamination that’s on an agar
plate; that’s ok, it’s not an issue;
2. colony morphology of the microbes on the agar plate are observed and the
morphological characteristics are documented; that’s great; and,
3. perhaps at one time or other the microbial contamination may have been
subject to characterization / identification to a genus & species;
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A current activity performed by Microbiology
Now then, henceforth if there are any microbial contaminates e.g.,
water samples, EM samples from aseptic filling operations and/or from
personnel monitoring etc., observed on subsequent agar plates, the
genus & species are verified by referring to the color photograph, no
additional microbiological analysis is performed.
Question –
What do you folks think?
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A summary of events – with respect to Microbiology
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Acknowledgement & many thanks
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Simone E. Pitts - National Expert, Pharmaceutical
Office of Regulatory Affairs
Office of Pharmaceutical Quality Operations
email – [email protected]
tele - 203-579-5822 x103
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Thank you!
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Thomas J. Arista - National Expert, Pharmaceutical
Office of Regulatory Affairs
Office of Pharmaceutical Quality Operations
email – [email protected]
tele – 214.253.4920