reconstituted whole blood for exchange transfusion

[monroe]

Does anyone out there prepare reconstituted whole blood for exchange transfusion? our facility is not FDA registered and we are looking for an alternative to this product. we tried just issuing the red cell unit and a FFP unit as individual components that could be combined at bedside by physician, but physician did not like this solution. Any other suggestions, besides, getting FDA registered?

[John C. Staley]

Please remind me why you need to be FDA registered to prepare this product for exchange transfusion within your own facility. We did this in my previous life and were not registered. We did have an over zealous Transfusion Service QA department and they would never have let us get away with it if they thought of an instant that it violated any FDA regulaitons.

You don't want a physician/nurse doing it at the bedside. They have no way of making the calculations to get the Hct correct or to determine if they did get it close.

:eyepoppin

[monroe]

it is required by FDA that if you mix 2 different components to make a third component, a facility must be FDA registered. exchange transfusion is specifically stated and that was FDA's answer to me. That is why I am trying to find out what other facilities do if they are not registered. Also we would make the calculations for the physician and nursing staff so that the 2 products combined would meet the intended hematocrit.

[John C. Staley]

I wonder when that changed or maybe we were in violation through ignorance. Thanks for the up date, one more reason to be glad I'm out of the business.

[Brenda K Hutson]

An exchange transfusion unit is not considered creating a "new product." A Transfusion Service would need to register with the FDA only if they: leukoreduced blood, irradiated blood, and/or washed blood. An exchange transfusion does not change the inherent properties; it is just "combining" 2 types of products (just as pooling Platelets or Cryo is not creating a new product; it is just combining products). So, bad news; you cannot use the FDA to get out of doing Exchange Transfusions (ha ha).

I am not surprised that the MD would not accept the products separately in that they are trying to create the optimal product to replace the baby's normal blood; one with a specific Hematocrit. There are formulas you can use to determine how much FFP to add to a given RBC; based on the volume and pre-hematocrit of the RBCs. It is tedious; but do-able (is that word?).

Brenda Hutson, CLS(ASCP)SBB

Does anyone out there prepare reconstituted whole blood for exchange transfusion? our facility is not FDA registered and we are looking for an alternative to this product. we tried just issuing the red cell unit and a FFP unit as individual components that could be combined at bedside by physician, but physician did not like this solution. Any other suggestions, besides, getting FDA registered?

[rravkin@aol.com]

Brenda,

Just one question; the pooling of like products (Platelets an Cryo) would not alter too much, but here they are speaking of combining unlike products, and for the most part, from too different donors. Is your informative post a case of comparing apples to oranges? Could there not conceivably be some extent or level of alteration to a final whole blood product comprised of packed rbc's from one donor and plasma from a different donor? My biggest concern would be lysing or crenation of red cells.

[snilon]

We have been going round and round about this at my facility! We have an email into the FDA waiting for response. It was our understanding that if you are making a new product-reconstituted RBC-that you would need to relabel the product portion, therefore would need to be registered by the FDA. I will let everyone know when we hear something.

[Malcolm Needs ☆]

You certainly would in the UK; but then, if you so much as breathe on a bag of blood here, the MHRA consider you a Blood Establishment.

[monroe]

I have spoken to FDA and the FDA inspector said that a facility must be registered if the facility prepares "reconstituted whole blood". this process calls for the combining of 2 very different products to create a third different product. I also was able to find this info at the FDA web site in one of their "Ask the FDA" sessions. We are not trying to get out of supplying a product. We just want to do it within regulatory requirements.

[MAGNUM]

For the recipe see the AABB Technical Manual ninth edition pages 315 and 316.

[SMW]

An exchange transfusion unit is not considered creating a "new product." A Transfusion Service would need to register with the FDA only if they: leukoreduced blood, irradiated blood, and/or washed blood. An exchange transfusion does not change the inherent properties; it is just "combining" 2 types of products (just as pooling Platelets or Cryo is not creating a new product; it is just combining products). So, bad news; you cannot use the FDA to get out of doing Exchange Transfusions (ha ha).

Brenda Hutson, CLS(ASCP)SBB

It appears the FDA has a different position.........

2007 AABB “Ask the FDA”

MODERATOR: Question 13: Under what circumstances are establishments that perform compatibility testing only, required to register with the FDA? If they are not, could you please provide examples of what activity would result in a requirement to be registered with the FDA? For example, would mixing red cells and FFP for an exchange transfusion or performing electronic crossmatches, require than an establishment be registered?

MS. CALLAGHAN: We will take this in several parts. Under what circumstances would an establishment have to register? If all you are performing is compatibility testing, including electronic crossmatch, you do not have to register. If you are performing any other processes listed in the exemptions under 607.65, such as pooling platelets or packing red cells you do not have to register. However, if you are irradiating or washing red cells or you are mixing red cells and FFP for exchange transfusions, you do have to register with the FDA.

2008 AABB “Ask the FDA”

Question 37: I have a question regarding exchange transfusion. Can we issue AB plasma & RBCs in two separate bags that have been sterile docked together, but separated by use of a clamp so that the RNs can open the clamp and transfuse the product? Do we need FDA registration to do this?

Response:

If you sterile-dock plasma and RBC units together and issue it as a final product, you are performing a manufacturing step that is not covered by the exemption from registration in 21 CFR 607.65(f). You must register as a hospital blood bank.

If you combine all or part of a red cell unit and a plasma unit and issue it as a final product, this is also manufacturing not covered by the exemption from registration, so you must register as a hospital blood bank. If you issue separate red cell and plasma units, the administration of these products is a practice of medicine for which we would not require registration.

We encourage you to take a quality approach. Decide what process will minimize the risk and maximize the benefit to your patients, then determine the requirement for you to register with FDA.

2009 AABB “Ask the FDA”

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(? 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.

[lwalton]

We are also struggling with this issue. We have prepared a reconstituted product 2 or 3 times in the last 14 years since I've been at this facility, and at least one of those was not transfused. We struggle with the concept of maintaining staff competency for a procedure that is done so infrequently, however the director of our NICU does not want us to remove the policy/procedure, "just in case". At this time, we have a policy/procedure in our manual but we are not FDA registered as we don't perform any other procedures which would require registration. I guess we're living dangerously. One of our sister hospitals was told by their FDA field agent that since they also did it so infrequently, registration was not necessary.

[Brenda K Hutson]

You know what, I stand "humbly" corrected on this! I do see the logic of differentiating "pooled" products from exchanges; just did not recall seeing this in the "list" of functions requiring FDA registration. Some days the S in SBB in ones certifications can stand for something other than Specialist; I think this is one of those days! Ha Ha

Brenda Hutson, CLS(ASCP)"S" BB

[Brenda K Hutson]

You know, I kept thinking about this last night so I looked again in the Technical Manual this morning. I do see the reference above where Ms. Callaghan from the FDA (who I have spoken to many times in the past; called for clarification on issues) lists Exchange Transfusions as a process requiring FDA Registration. But looking back at the Technical Manual and the list of procedures that fall under this category, it used the term rejuvenation (which is not the same as Exchange Transfusion). Specifically, it lists the procedures requiring registration as: Irradiation, Washing, Lab Leukocyte Reduction (vs filter at the bedside), freezing, deglycerolization, and rejuvenation.

I have to believe the statements above are correct if she stated that; but I am going to call her for my own clarification now because I have to say, that has never been my understanding (which certainly does not mean it is not true).

Stay tuned....

Brenda Hutson

[cthherbal]

Brenda: Were you able to find an answer from the FDA? We are struggling with revising this procedure at my facility. We are not FDA registered and have probably done 2 WB exchange transfusions in 15 years. I would like to validate a procedure where the neonatologist can use separate products (charter med makes a 2 or 3 syringe/filter set) that would run into one line. As long as the calculated volume was correct (we give entire bag of RBC and FFP), and neonatologist determines how much of each to run, product goes through a blood warmer and an infusion pump, into one infusion line into baby. In theory it sounds like it would work, but I'm not sure if its breaking rules with the FDA to do this. Of course we would fully develop the procedure in conjunction with the neonatologist who would actually be performing the transfusion.

[Brenda K Hutson]

Sorry, we are still trying to clarify something with them. In the FDA Registration Form under Item 11, PRODUCTS: Exclude products prepared under emergency conditions. They define an emergency as a situation that demands immediate action that has been suitably documented in writing by a responsible person. Do not list products that are pooled or divided into pediatric aliquots.

We would probably only perform an Exchange Transfusion once every 6 years or so! Babies born with problems at that level are usually transferred to our local Children's Hospital. And if it was known ahead of time (mom with positive antibody screen; antibodies identified; baby being monitored and perhaps even needing intrauterine transfusions), the pregnant woman would certainly have been referred to this local Hospital (which is connected to a large Medical Center where I used to work) for High Risk pregnancies.

We are going to see if performing something that infrequently qualifies under this rule. If not, we will meet with NICU and discuss either giving them the 2 products separately (RBCs and FFP), or, letting them know they would have to transfer the baby to the Children's Hospital if they needed an Exchange Transfusion.

Our QA Coordinator is trying to reach the FDA for this clarification and I will get back to all of you just as soon as he knows something.

Brenda Hutson

Brenda: Were you able to find an answer from the FDA? We are struggling with revising this procedure at my facility. We are not FDA registered and have probably done 2 WB exchange transfusions in 15 years. I would like to validate a procedure where the neonatologist can use separate products (charter med makes a 2 or 3 syringe/filter set) that would run into one line. As long as the calculated volume was correct (we give entire bag of RBC and FFP), and neonatologist determines how much of each to run, product goes through a blood warmer and an infusion pump, into one infusion line into baby. In theory it sounds like it would work, but I'm not sure if its breaking rules with the FDA to do this. Of course we would fully develop the procedure in conjunction with the neonatologist who would actually be performing the transfusion.

[Brenda K Hutson]

I have heard of other places doing it as you described (and as I mentioned, may be what we change to); that is to give them the Red Cells and FFP separately. Not ideal but it is hardly worth becoming FDA Registered just to perform 1 exchange transfusion every 50 years (so to speak).

Brenda

Brenda: Were you able to find an answer from the FDA? We are struggling with revising this procedure at my facility. We are not FDA registered and have probably done 2 WB exchange transfusions in 15 years. I would like to validate a procedure where the neonatologist can use separate products (charter med makes a 2 or 3 syringe/filter set) that would run into one line. As long as the calculated volume was correct (we give entire bag of RBC and FFP), and neonatologist determines how much of each to run, product goes through a blood warmer and an infusion pump, into one infusion line into baby. In theory it sounds like it would work, but I'm not sure if its breaking rules with the FDA to do this. Of course we would fully develop the procedure in conjunction with the neonatologist who would actually be performing the transfusion.

[Brenda K Hutson]

Ok, so here is the "scoop" from a conversation our QA Coordinator had with the FDA today. We were trying to clarify one of the points listed on the INSTRUCTIONS FOR COMPLETING BLOOD REGISTRATION FORM 2830. Specifically, it has a list of tasks that require one to be registered with the FDA. "Item 11; paragraph 2 (in part).PRODUCTS: Similarly, exclude products prepared under emergency conditions. We define an emergency as a situation that demands immediate action that has been suitably documented in writing by a responsible person."

So, in my 4+ years at my current Institution, we have had only 1 Exchange Transfusion. According to this FDA Inspector, that would fall into the category of something performed under emergency conditions (keeping in mind not only that we are performing it extremely infrequently, but also that those procedures are almost always ordered as STATS). She said the only thing then we would need to add to our protocol would be to require the Physician to sign an Emergency Release Form.

So some of you are probably asking; how infrequently (or vice versa, frequently) does one have to perform something for it to be considered "infrequent" and "emergent?" This FDA Inspector said to the QA Coordinator; "now if you find down the road that the frequency changes and you are performing them maybe every 6 months or once a year, she would recommend becoming registered with the FDA."

So, there is some clarity on the subject; but at the same time, it is somewhat vague depending on frequently your Institution performs this task.

This is the 6th Hospital of my career. All of the other Institutions where I worked were AABB accredited and FDA Registered. However, I was at one other Institution about the same size as my current one (about 400 beds). We also performed infrequent Exchange Transfusions. We were FDA Registered because we occassionally washed blood. But we did that so infrequently (maybe once a year) that I discontinued that process and we obtained them from our Donor Facility. Even though we still performed the infrequent Exchange Transfusion, we dropped our registration with the FDA w/o issue.

All of the above are reasons that for me, I was shocked to hear that performing Exchange Transfusions required FDA Registration (because it was never an issue where I worked).

Hope that helps...

Brenda Hutson, CLS(ASCP)SBB

[Mabel Adams]

Does anyone confirm the ABO of the AB FFP used to reconstitute the unit? Our procedure has said to do that and I understand why, but I think it might be overkill given the extremely low rate of mislabeled units.

[Malcolm Needs ☆]

Does anyone confirm the ABO of the AB FFP used to reconstitute the unit? Our procedure has said to do that and I understand why, but I think it might be overkill given the extremely low rate of mislabeled units.

How do they do that anyway Mabel? I've seen plenty of adult samples from A, B and O individuals that have no discernable anti-B, anti-A or anti-A,B.

[Mabel Adams]

Well, I guess if it had no antibody reactivity in the plasma in a segment we took off we would be ok calling it an AB and filling the baby up with it (even if the donor's RBCs weren't AB). I'm sure the root of it was the idea of giving a baby an entire plasma volume that might be incompatible with its RBCs (or at least any of them that remained or were produced soon after the exchange transfusion with O RBCs). Like I said, I am pretty sure this is unnecessary but wanted to make sure no one else was doing it.

[Liz0316]

yes, I do have a procedure that may work for you; based on the premise that an adsol unit is approximately 50 - 55% HCT. I had to come up with a procedure that generalist could do on the night shift. Normally a unit for exchange trx in a neonate is requested at 50% Hct. So we spin the unit down (hard spin) and remove the plasma, measuring how many mls we are removing (by extracting with a 60 cc syringe), then replace the plasma with AB thawed FFP (the same amount we removed). Considering you will never remove all the original plasma, the final product comes out to be approx 50%. We label the product with additional information regarding the unit # and blood type & volume of the "overlay" of FFP. Our original RBC must be an adsol unit, O neg, CMV neg, irrad, and Hgb S neg. If you don't have a refrigerated centrifuge, I think keeping the intended RBC inverted will work as well. When we get our neonate units in from our supplier we store them upside down. When we started this procedure we tested the units Hct and each time the Hct was approx 50%. I believe, as long as the FDA reg # from the supplier is obscured, or replaced with your own # you should be ok. We release the unit as a full unit, allowing NICU to transfuse as they wish, but we will not aliquot into syringes for them. We issue both products in LIS with a comment regarding the overlay with unit # ........

Liz

[marvy1]

User dmpollock had a different answer to this question in 2009:

Hopefully most transfusion services are aware that they have to register with FDA, and thus will be inspected by FDA if they "manufacture" products. "Manufacturing" includes drawing donors and making components (other than splitting components). Even if the facility does not draw donors, but they leukoreduce products in the lab, or irradiate, they must be registered.

I recently found that they require registration for preparing reconstituted whole blood. I am curious what people think of this and how they are handling it.

From this page:

http://www.aabb.org/Content/Programs...cripts2008.htm

Question 37: I have a question regarding exchange transfusion. Can we issue AB plasma & RBCs in two separate bags that have been sterile docked together, but separated by use of a clamp so that the RNs can open the clamp and transfuse the product? Do we need FDA registration to do this?

Response:

If you sterile-dock plasma and RBC units together and issue it as a final product, you are performing a manufacturing step that is not covered by the exemption from registration in 21 CFR 607.65(f). You must register as a hospital blood bank.

If you combine all or part of a red cell unit and a plasma unit and issue it as a final product, this is also manufacturing not covered by the exemption from registration, so you must register as a hospital blood bank. If you issue separate red cell and plasma units, the administration of these products is a practice of medicine for which we would not require registration.

We encourage you to take a quality approach. Decide what process will minimize the risk and maximize the benefit to your patients, then determine the requirement for you to register with FDA.

[Kathy]

I do not have the 9th edition of the Technical Manual, but I do have a formula from another institution that I worked at. Is the following correct? : Hematocrit of unit x volume of rbc unit / desired hematocrit = total volume of reconstituted unit. Subtract the volume of the rbc unit from the total volume of the reconstituted unit to give you the volume of FFP to add to the red cells. I did this on a few units of washed cells (HCT 70%) and it worked well.