Hello everyone,
I work in Regulatory since a couple of years ago, but in my background I've been also internal QMS auditor for about 18 years now.
This portion of the post send by Annonimous makes me think about production controls as well:
Cleaning procedures
· Interviewed employee explained to investigator that some but not all components required cleaning and that the cleaning step was not included in the work instructions.
Here some potential questions that you could add into your investigation (maybe starting wth Fishbone, 5Whys, Sequence of Events, or any other available):
Is the cleaning process a validated step?
Are the cleaned components included on the finished device, which was also tested and later failed?
Is there any documented way to know if the "cleaning" process was even executed on such failed lot? (I doubt it, as this is not required per procedure). [I've seen some cases where a validaded process is not even included on the procedures, but actually people is trained during the vaidation stage, so it remains as tribal knowledge within operators].
Which is the criteria used as decision making to clean or not clean the items.
Also consider including some investigation related to production environment controls (how the are is cleaned, frequency, records, trainig records of the operators responsible to clean), air quality/monitoring/records related to it.
Any excursion during such manufacturing dates?
Existing controls focused to prevent sick people to be in contact with production lines.
These are some ideas I would be interested to look at.
And, also, include an interdisciplinary team when performing such investigation.
Wish you the best,
Celia.
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Celia Encinas
Regulatory Affairs Specialist
Medtronic Mexico
Tijuana, B.C.
Mexico
celia.encinas@medtronic.com------------------------------
Original Message:
Sent: 14-Mar-2017 07:55
From: Michael Hellerstein
Subject: Bioburden limits
It's important to be very careful about this. It's common for companies to get into trouble for "testing into compliance." Don't initiate any retesting until you're sure that it's justified by your investigation, authorized as per your SOPs, and in full compliance with the regs.
The previous responses all have good suggestions on how to conduct the investigation. From what I see in your initial post, it appears that the main problems are likely to be in the production process and not in QC micro.
ASQ has resources (books, articles, white papers, etc.) to help you with investigations and root cause analysis.
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Michael Hellerstein
GeoVax, Inc.
Smyrna GA
United States
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Original Message:
Sent: 13-Mar-2017 17:42
From: Jennifer Travis
Subject: Bioburden limits
I see... so you need to get all of the results from the testing lab, including materials trace/QC.
Some clarification...
1. My question about which investigation process the lab follows was directed at your testing lab.
a. If they did an investigation, get a copy
2. For your production room and staff:
a. Do you have environmental monitoring controls? Plates, viable air, swabs, etc.
b. Do you have personnel monitoring controls? Plates, swabs, etc.
c. Are gowning proficiencies current?
d. Is your PQ current in the room, have you had any service or work done on the room/hoods?
e. Trending
3. Have you reviewed all of your batch records for any excursions?
4. For the document, if this is the cited deficiency (root cause), how long has the document been effective? If it has been in place for sometime, why is this the first time that staff has brought attention to the cleaning step missing?
- for a proper investigation, you'll need to evaluate all batches/builds in the past.
- blaming documents and training brings up lots of rabbit holes to address.
Good luck!
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Jennifer Travis
Front Range Labs
Loveland CO
United States
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Original Message:
Sent: 13-Mar-2017 14:52
From: Anonymous Member
Subject: Bioburden limits
This message was posted by a user wishing to remain anonymous
Jennifer thank you so much for answering my question.
I don't have that book.
Do you know what method your first lab used? They used Tryptic Soy Agar, Sabouraud Dextrose Agar and Phosphate Buffered Saline.
What is your predetermined restesting procedure? Does it include sending it to an alternate lab? You likely CANNOT throw out the original results unless there was a lab error that invalidates the test.
What OOS or NCR process does your lab follow? You need to understand their investigation as well. Is not a lab is a controlled environment room
Do you use a fishbone or other mechanism for investigations? this is the first time that occurs, I usually used the 5 why's
Were you able to identify the organisms? NO.
Do you have any results from your environment/personnel that would align with the time frame of the build? was only 3 person in the room at that time and none of them where sick.
Original Message:
Sent: 13-Mar-2017 13:31
From: Jennifer Travis
Subject: Bioburden limits
Good morning! Not a fun way to start the week for certain.
Do you have access to this book: Microbial Limit and Bioburden Tests by Lucia Clontz? If not, add it to your list of books to buy immediately.
Do you know what method your first lab used?
What is your predetermined restesting procedure? Does it include sending it to an alternate lab? You likely CANNOT throw out the original results unless there was a lab error that invalidates the test.
What OOS or NCR process does your lab follow? You need to understand their investigation as well.
Do you use a fishbone or other mechanism for investigations?
Were you able to identify the organisms? This will be an important step to allow you to investigate your environment and personnel. Do you have any results from your environment/personnel that would align with the time frame of the build?
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Jennifer Travis
Front Range Labs
Loveland CO
United States
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Original Message:
Sent: 13-Mar-2017 10:14
From: Anonymous Member
Subject: Bioburden limits
This message was posted by a user wishing to remain anonymous
Good Morning to everyone
The following issue is driving me crazy. Quality levels (bioburden results) on a Class II product exceeded the action limit of 100 CFU, with a test result of 152 CFU prior of sterilization. How I can investigate this issue. I am new in Regulatory and I don't know where to start. Any advise or example on how I can solve this issue.
My immediate action was to send another batch to the lab to compare the results, the amount of personal didn't change so I don't know how to get the real root cause of the problem.
Any advise? See below for example.
Thanks.
Problem Description (state below – attach additional page(s) as needed) |
Quality levels (bioburden results) on Control Cric product exceeded the action limit of 100 CFU, with a test result of 152 CFU. This result initiated an internal investigation / review of our Control Cric Component cleaning process. |
Investigation and Root Cause (state below – attach additional page(s) as needed) |
Personnel · Interviewed team member who participated in the build. Cleaning procedures · Interviewed employee explained to investigator that some but not all components required cleaning and that the cleaning step was not included in the work instructions. ROOT CAUSE Inadequate training and training material (work instructions). |