SMW

If there were 2 populations of cells, and if the fetal cells were ABO incompatible with the maternal sample however D positive, the fetal cells could have been hemolyzed in vitro by the time the sample was retested 10 hours later.  Since the fetal cells were no longer intact, the repeat testing would have been on exclusively maternal cells and tested as D-negative. 
 
I realize your initial forward type did not detect/report the presence of mixed field agglutination.  With monoclonal ABO antibodies and using tube testing, it is often very difficult to detect mixed field reactions with small populations of other cells.  It seems the monoclonal ABO antibodies are so avid, the agglutinates seem to "trap" the other population of cells in the agglutinate rather than remaining free to be resuspended. This was demonstrated years ago when the AABB offered "damp" workshops where samples were provided for testing, registrants reported their results and results were tallied and presented to attendees.  During the time when the older polyclonal ABO reagents were still in use and the monoclonal reagents were just being introduced, the results indicated a significant difference in the detection of mixed field agglutination in the forward ABO testing between the groups using polyclonal reagents (MF detected) vs. monoclonal reagents (MF not detected).

I'm curious which standard was referenced in your non-conformance and did your response/corrective actions address that specific standard or just the examples listed as objective evidence supporting the non-conformance?
Just taking a guess here but for example, if the non-conformance cited was to 1.3 Policies, Processes, and Procedures--"Quality and operational policies, processes, and procedures shall be developed and implemented to ensure that the requirements of these BB/TS Standards are satisfied. All such policies, processes....." and the objective evidence included some examples of procedures/policies/processes that did not meet standards, simply modifying the specific procedures listed as examples supporting the non-conformance would not address the non-conformance of having a process to meet the Standards in the first place. If 1.3 was the non-conformance, it's highly unlikely you would have been able to effectively identify the root cause during the course of the assessment, let alone develop a corrective action plan.
As for suggestions to identify the root cause in the above example, perhaps you could start by using the 5 Whys......(the responses may obviously be different and would take you down a different path of follow-up questions so are just examples, but)
Why was standard A not included in procedure X and standard B not addressed in procedure Y?

Because the author/reviewer did not know the Standards had changed.
Why did the author/reviewer not know the Standards had changed?

Because the Medical Director received the new Standards but the individual(s) writing/reviewing the procedure did not receive a copy.
Why do the individuals writing/reviewing procedures not have access to the Standards?

etc., etc.
Once you run out of "whys" you've likely identified the root cause(s) and can start with the corrective actions to "fix" those causes.

Physician signature is required by FDA so that would trump any local or state laws or rules for other providers to sign. 
See 21CFR 606.160((3)(v): Emergency release of blood, including signature of requesting physician obtained before or after release. 
 
Note that the signature is required for the emergent release of the blood and not necessarily the transfusion.  Also note that the requesting physician may not necessarily be the transfusing physician.
 

I'm curious which standard was referenced in your non-conformance and did your response/corrective actions address that specific standard or just the examples listed as objective evidence supporting the non-conformance?
Just taking a guess here but for example, if the non-conformance cited was to 1.3 Policies, Processes, and Procedures--"Quality and operational policies, processes, and procedures shall be developed and implemented to ensure that the requirements of these BB/TS Standards are satisfied. All such policies, processes....." and the objective evidence included some examples of procedures/policies/processes that did not meet standards, simply modifying the specific procedures listed as examples supporting the non-conformance would not address the non-conformance of having a process to meet the Standards in the first place. If 1.3 was the non-conformance, it's highly unlikely you would have been able to effectively identify the root cause during the course of the assessment, let alone develop a corrective action plan.
As for suggestions to identify the root cause in the above example, perhaps you could start by using the 5 Whys......(the responses may obviously be different and would take you down a different path of follow-up questions so are just examples, but)
Why was standard A not included in procedure X and standard B not addressed in procedure Y?

Because the author/reviewer did not know the Standards had changed.
Why did the author/reviewer not know the Standards had changed?

Because the Medical Director received the new Standards but the individual(s) writing/reviewing the procedure did not receive a copy.
Why do the individuals writing/reviewing procedures not have access to the Standards?

etc., etc.
Once you run out of "whys" you've likely identified the root cause(s) and can start with the corrective actions to "fix" those causes.

I'm curious which standard was referenced in your non-conformance and did your response/corrective actions address that specific standard or just the examples listed as objective evidence supporting the non-conformance?
Just taking a guess here but for example, if the non-conformance cited was to 1.3 Policies, Processes, and Procedures--"Quality and operational policies, processes, and procedures shall be developed and implemented to ensure that the requirements of these BB/TS Standards are satisfied. All such policies, processes....." and the objective evidence included some examples of procedures/policies/processes that did not meet standards, simply modifying the specific procedures listed as examples supporting the non-conformance would not address the non-conformance of having a process to meet the Standards in the first place. If 1.3 was the non-conformance, it's highly unlikely you would have been able to effectively identify the root cause during the course of the assessment, let alone develop a corrective action plan.
As for suggestions to identify the root cause in the above example, perhaps you could start by using the 5 Whys......(the responses may obviously be different and would take you down a different path of follow-up questions so are just examples, but)
Why was standard A not included in procedure X and standard B not addressed in procedure Y?

Because the author/reviewer did not know the Standards had changed.
Why did the author/reviewer not know the Standards had changed?

Because the Medical Director received the new Standards but the individual(s) writing/reviewing the procedure did not receive a copy.
Why do the individuals writing/reviewing procedures not have access to the Standards?

etc., etc.
Once you run out of "whys" you've likely identified the root cause(s) and can start with the corrective actions to "fix" those causes.

I'm curious which standard was referenced in your non-conformance and did your response/corrective actions address that specific standard or just the examples listed as objective evidence supporting the non-conformance?
Just taking a guess here but for example, if the non-conformance cited was to 1.3 Policies, Processes, and Procedures--"Quality and operational policies, processes, and procedures shall be developed and implemented to ensure that the requirements of these BB/TS Standards are satisfied. All such policies, processes....." and the objective evidence included some examples of procedures/policies/processes that did not meet standards, simply modifying the specific procedures listed as examples supporting the non-conformance would not address the non-conformance of having a process to meet the Standards in the first place. If 1.3 was the non-conformance, it's highly unlikely you would have been able to effectively identify the root cause during the course of the assessment, let alone develop a corrective action plan.
As for suggestions to identify the root cause in the above example, perhaps you could start by using the 5 Whys......(the responses may obviously be different and would take you down a different path of follow-up questions so are just examples, but)
Why was standard A not included in procedure X and standard B not addressed in procedure Y?

Because the author/reviewer did not know the Standards had changed.
Why did the author/reviewer not know the Standards had changed?

Because the Medical Director received the new Standards but the individual(s) writing/reviewing the procedure did not receive a copy.
Why do the individuals writing/reviewing procedures not have access to the Standards?

etc., etc.
Once you run out of "whys" you've likely identified the root cause(s) and can start with the corrective actions to "fix" those causes.

I'm curious which standard was referenced in your non-conformance and did your response/corrective actions address that specific standard or just the examples listed as objective evidence supporting the non-conformance?
Just taking a guess here but for example, if the non-conformance cited was to 1.3 Policies, Processes, and Procedures--"Quality and operational policies, processes, and procedures shall be developed and implemented to ensure that the requirements of these BB/TS Standards are satisfied. All such policies, processes....." and the objective evidence included some examples of procedures/policies/processes that did not meet standards, simply modifying the specific procedures listed as examples supporting the non-conformance would not address the non-conformance of having a process to meet the Standards in the first place. If 1.3 was the non-conformance, it's highly unlikely you would have been able to effectively identify the root cause during the course of the assessment, let alone develop a corrective action plan.
As for suggestions to identify the root cause in the above example, perhaps you could start by using the 5 Whys......(the responses may obviously be different and would take you down a different path of follow-up questions so are just examples, but)
Why was standard A not included in procedure X and standard B not addressed in procedure Y?

Because the author/reviewer did not know the Standards had changed.
Why did the author/reviewer not know the Standards had changed?

Because the Medical Director received the new Standards but the individual(s) writing/reviewing the procedure did not receive a copy.
Why do the individuals writing/reviewing procedures not have access to the Standards?

etc., etc.
Once you run out of "whys" you've likely identified the root cause(s) and can start with the corrective actions to "fix" those causes.

You will have to check with your local/state regs. to deteremine what licensure is required. Whatever you decide, be sure to involve legal counsel and make sure all the responsibilities of each party are clearly specified in the service agreement.
Also, be careful to review the reimbursement guidelines. If the clinic you're currently providing is legally part of the hospital, those patients may be considered "hospital out-patients" and therefore subject to APC reimbursement guidelines. But physician offices, nursing homes, etc. are not considered "hospital out-patients" so the Medicare reimbursement guidelines do not apply to these settings. If you decide to provide compatibility testing and products to these types of facilities you should consider billing the facility and not the patient. If the location does not qualify as a "hospital out-patient" there is basically very little to no reimbursement for these activities. If the facilities are charged, the clinic facility will quickly realize they are losing tons of money and determine they no longer want to offer this service (unless it's a boutique service and their patients can afford to pay out-of-pocket accordingly). If your facility is directly billing the patients, your facility will be likely be losing money for each transfusion provided. Dialysis centers have their own unique Medicare reimbursement rules

You will have to check with your local/state regs. to deteremine what licensure is required. Whatever you decide, be sure to involve legal counsel and make sure all the responsibilities of each party are clearly specified in the service agreement.
Also, be careful to review the reimbursement guidelines. If the clinic you're currently providing is legally part of the hospital, those patients may be considered "hospital out-patients" and therefore subject to APC reimbursement guidelines. But physician offices, nursing homes, etc. are not considered "hospital out-patients" so the Medicare reimbursement guidelines do not apply to these settings. If you decide to provide compatibility testing and products to these types of facilities you should consider billing the facility and not the patient. If the location does not qualify as a "hospital out-patient" there is basically very little to no reimbursement for these activities. If the facilities are charged, the clinic facility will quickly realize they are losing tons of money and determine they no longer want to offer this service (unless it's a boutique service and their patients can afford to pay out-of-pocket accordingly). If your facility is directly billing the patients, your facility will be likely be losing money for each transfusion provided. Dialysis centers have their own unique Medicare reimbursement rules

Earlier this week at the 2015 AABB Annual Meeting "Ask the Standards" session, the AABB confirmed testing performed by the donor center as specified in this standard, DOES meet the intent since the Standard does not specify WHO does the testing, only that it be performed before transfusion. 

Most anti-E and anti-c reagents are not intended to be tested at the antiglobulin phase.  If the control in use as perscribed by the package insert (which is generally not at the antiglobulin phase) was negative, the test results are valid.

If there were 2 populations of cells, and if the fetal cells were ABO incompatible with the maternal sample however D positive, the fetal cells could have been hemolyzed in vitro by the time the sample was retested 10 hours later.  Since the fetal cells were no longer intact, the repeat testing would have been on exclusively maternal cells and tested as D-negative. 
 
I realize your initial forward type did not detect/report the presence of mixed field agglutination.  With monoclonal ABO antibodies and using tube testing, it is often very difficult to detect mixed field reactions with small populations of other cells.  It seems the monoclonal ABO antibodies are so avid, the agglutinates seem to "trap" the other population of cells in the agglutinate rather than remaining free to be resuspended. This was demonstrated years ago when the AABB offered "damp" workshops where samples were provided for testing, registrants reported their results and results were tallied and presented to attendees.  During the time when the older polyclonal ABO reagents were still in use and the monoclonal reagents were just being introduced, the results indicated a significant difference in the detection of mixed field agglutination in the forward ABO testing between the groups using polyclonal reagents (MF detected) vs. monoclonal reagents (MF not detected).

If there were 2 populations of cells, and if the fetal cells were ABO incompatible with the maternal sample however D positive, the fetal cells could have been hemolyzed in vitro by the time the sample was retested 10 hours later.  Since the fetal cells were no longer intact, the repeat testing would have been on exclusively maternal cells and tested as D-negative. 
 
I realize your initial forward type did not detect/report the presence of mixed field agglutination.  With monoclonal ABO antibodies and using tube testing, it is often very difficult to detect mixed field reactions with small populations of other cells.  It seems the monoclonal ABO antibodies are so avid, the agglutinates seem to "trap" the other population of cells in the agglutinate rather than remaining free to be resuspended. This was demonstrated years ago when the AABB offered "damp" workshops where samples were provided for testing, registrants reported their results and results were tallied and presented to attendees.  During the time when the older polyclonal ABO reagents were still in use and the monoclonal reagents were just being introduced, the results indicated a significant difference in the detection of mixed field agglutination in the forward ABO testing between the groups using polyclonal reagents (MF detected) vs. monoclonal reagents (MF not detected).

If you are simply making aliquots, e.g., just providing a smaller sample of the same product, FDA registration is not required.  If you're making a new product or doing other manipulations, such as adding Plasma to Red Blood Cells to create a Reconstituted Whole Blood unit or washing the RBCs, then FDA registration is required.
 
 

If there were 2 populations of cells, and if the fetal cells were ABO incompatible with the maternal sample however D positive, the fetal cells could have been hemolyzed in vitro by the time the sample was retested 10 hours later.  Since the fetal cells were no longer intact, the repeat testing would have been on exclusively maternal cells and tested as D-negative. 
 
I realize your initial forward type did not detect/report the presence of mixed field agglutination.  With monoclonal ABO antibodies and using tube testing, it is often very difficult to detect mixed field reactions with small populations of other cells.  It seems the monoclonal ABO antibodies are so avid, the agglutinates seem to "trap" the other population of cells in the agglutinate rather than remaining free to be resuspended. This was demonstrated years ago when the AABB offered "damp" workshops where samples were provided for testing, registrants reported their results and results were tallied and presented to attendees.  During the time when the older polyclonal ABO reagents were still in use and the monoclonal reagents were just being introduced, the results indicated a significant difference in the detection of mixed field agglutination in the forward ABO testing between the groups using polyclonal reagents (MF detected) vs. monoclonal reagents (MF not detected).

If there were 2 populations of cells, and if the fetal cells were ABO incompatible with the maternal sample however D positive, the fetal cells could have been hemolyzed in vitro by the time the sample was retested 10 hours later.  Since the fetal cells were no longer intact, the repeat testing would have been on exclusively maternal cells and tested as D-negative. 
 
I realize your initial forward type did not detect/report the presence of mixed field agglutination.  With monoclonal ABO antibodies and using tube testing, it is often very difficult to detect mixed field reactions with small populations of other cells.  It seems the monoclonal ABO antibodies are so avid, the agglutinates seem to "trap" the other population of cells in the agglutinate rather than remaining free to be resuspended. This was demonstrated years ago when the AABB offered "damp" workshops where samples were provided for testing, registrants reported their results and results were tallied and presented to attendees.  During the time when the older polyclonal ABO reagents were still in use and the monoclonal reagents were just being introduced, the results indicated a significant difference in the detection of mixed field agglutination in the forward ABO testing between the groups using polyclonal reagents (MF detected) vs. monoclonal reagents (MF not detected).

Earlier this week at the 2015 AABB Annual Meeting "Ask the Standards" session, the AABB confirmed testing performed by the donor center as specified in this standard, DOES meet the intent since the Standard does not specify WHO does the testing, only that it be performed before transfusion. 

I believe you have this backwards.  The patient cells, which are more likely to contain reticulocytes, will be lighter and at the top, with the older donor cells towards the bottom. That's providing the patient is not aplastic and is actually producing RBCs. This is the premise behind the reticulocyte separation method which has been used as a method to attempt to phenotype a patient that has been transfused.

Also did not use cord blood results for transfusion purposes.  You can never be sure what is labeled as cord blood is actually cord blood and not maternal sample.  Blood type differences may help but still better to have a standard practice. On the other hand, if you're transfusing only group O RBCs and AB plasma probably not as significant until sometime after 4 months when the patient is typed again and a different result is obtained. 
 
Along the same lines, we also required a neonatal/heelstick sample in cases where the mother was Rh-neg and the cord blood sample tested the same ABO/Rh as mother as confirmation that RhIgG was not required.  Did not see discrepancies that often however they did occur and one missed RhIgG prophylaxis resulting in immunization is enough to justify practice. 

Also did not use cord blood results for transfusion purposes.  You can never be sure what is labeled as cord blood is actually cord blood and not maternal sample.  Blood type differences may help but still better to have a standard practice. On the other hand, if you're transfusing only group O RBCs and AB plasma probably not as significant until sometime after 4 months when the patient is typed again and a different result is obtained. 
 
Along the same lines, we also required a neonatal/heelstick sample in cases where the mother was Rh-neg and the cord blood sample tested the same ABO/Rh as mother as confirmation that RhIgG was not required.  Did not see discrepancies that often however they did occur and one missed RhIgG prophylaxis resulting in immunization is enough to justify practice. 

Also did not use cord blood results for transfusion purposes.  You can never be sure what is labeled as cord blood is actually cord blood and not maternal sample.  Blood type differences may help but still better to have a standard practice. On the other hand, if you're transfusing only group O RBCs and AB plasma probably not as significant until sometime after 4 months when the patient is typed again and a different result is obtained. 
 
Along the same lines, we also required a neonatal/heelstick sample in cases where the mother was Rh-neg and the cord blood sample tested the same ABO/Rh as mother as confirmation that RhIgG was not required.  Did not see discrepancies that often however they did occur and one missed RhIgG prophylaxis resulting in immunization is enough to justify practice. 

This phenomenon has also been reported with infectious disease testing instruments, e.g. Hamilton automated pipetor.  In those cases it is also associated with a high titer/load of the previous sample, e.g., Hepatitis B carrier, and the pipetting device is “inoculating” the next sample with Hep B surface antigen.  It may also depend on how many “inoculations” the second sample receives and the order of sampling before testing positive.  As for the first 4-5 years, it may just be the right (or wrong!) sampling order and strength of the antibody, e.g. if weaker antibody in first sample you may just see nebulous reactions in the second sample rather than an identified antibody and not identified or recognized it as a potential carry-over issue. 

No.   

,
aafrn is correct.  In the US, the product label can state "Fresh Frozen Plasma" for 24 hours after thawing.  After 24 hours (at least in the US), the product label must be changed to Plasma if the dating is extended to 5 days after thawing and not make a claim as "Fresh Frozen Plasma.".  See Circular of Information, these 2 producs are different animals.

You may find the following FDA response of interest:
 
2009 AABB Ask the FDA Transcript
 
"Question 14:  At previous Ask the FDA sessions, the FDA has explained that combining Plasma and Red Blood Cells to create a "reconstituted" Whole Blood for neonatal exchange transfusion is considered manufacturing and requires FDA registration. Is there a threshhold frequency before registration is required (for this or other infrequent occurrences), e.g., if a procedure is only performed 1-4 times per year, is the facility required to register with the FDA for these infrequent activities?
               
MS. CIARALDI:   FDA does require registration for this procedure because the reconstitution of red cells and plasma to make a third product, the Whole Blood, meets the general definition of manufacture in 21 CFR 607.3(d). There is no threshold frequency that is described in any of our guidance documents or regulations, but we feel, if you have established procedures for performing this process, you must register regardless of the frequency. 
                I would like to add a comment on top of that because it just came in right before I came to the meeting and it came in from a field investigator.  There was a concern expressed and I do want to share that with you.  If you are having staff members perform a procedure as infrequently as described in the example on the slide, how will you ensure their competency, consistent with our requirements in 21 CFR 606.20 (b ?  For procedures performed infrequently, there may be a GMP issue with making sure that staff are competent and experienced and knowledgeable about doing these procedures.  It is just something to think about."
 
As a separate consideration, how would you feel having staff (at the bedside as well as in the Blood Bank) performing a procedure on your newborn that they had never or only performed once 10 years ago?  Might vs.should performed are very different!