Current activities and enhancements performed by Microbiology · Current activities performed by...

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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)

PDA Singapore 22-24/09/20

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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


▪ 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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▪ 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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▪ 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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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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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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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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▪ 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


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!


Thomas J. Arista - National Expert, Pharmaceutical

Office of Regulatory Affairs

Office of Pharmaceutical Quality Operations

email – [email protected]

tele – 214.253.4920

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