Control requirements - help needed

[galvania]

Dear all

Please can someone tell me exactly what the latest official FDA or AABB requirement is for the frequency of running reagent controls? Is it every day, every time you open a new lot, every shift, every week.................

Thanks

Anna:thanks:

[Lcsmrz]

Each reagent may have a different requirement -- check the product insert -- but generally, it's a minimum of a positive and negative control on each day of use. ABO reagent QC is optional, since the forward and reverse correlation act as their own QC. We check diluents and potentiators with a negative control as part of our Daily QC.

We define "day of use" as a calander day, from 0001 - 2400.

[galvania]

I think I should further clarify my question. It is specifically for anti-A, anti-B, and anti-D reagents used for routine typing, as well as the use of a reagent control (ie. like the ctl well in the gel cards). I'm after a specific FDA or AABB requirement. A direct quote would be nice

[pdavenport]

The FDA requirement is found in CFR 606.65. But what that boils down to when FDA comes to call, are you following the manufacurer's product insert?

[galvania]

thank you pdavenport. Unfortunately I don't have access to CFR 606.65. Also I have never seen a manufacturer's box insert that states the frequency at which reagents should be controlled; not all of them even state that controls should be put up!

[bbbirder]

Anna,

Try this link to search the FDA's 21CFR, where most BB regulations are found.

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm

(Hopefully this will work!).

Linda F

[rcurrie]

There is a nice little AABB book that has all of the FDA regulations in it. It is a nice reference, although it would be even better if it had an index (it is just a compilation). It costs around $100 and is a good investment.

BC

[galvania]

Thank you. To Linda - I will try the link as soon as I'm back in the office. (I'm in Kuwait for a few days). To R. Currie - can you give me the book's title or ISBN number

thanks

Anna

[rcurrie]

Anna, I can't, but maybe someone else on this site can. I retired from the laboratory medicine business and went back to work for the railroad.

BC

[Karen Olsen]

Anna,

I looked it up in the 2008 Publications from aabb. The $100 (member price) CFR Mini-handbook which contains the most important portions of the Code of Federal Regulations was in it. ISBN #978-1-56395-258-6. It is a soft cover 512 page book from Sept. 2007.

Hope this helps!

[TStec]

CAP Sept 2007 Checklist:

**REVISED** 10/31/2006

TRM.31400 Phase II N/A YES NO

Do records document acceptable reactivity and specificity of typing sera and reagent cells on each day of use, including a check against known positive and negative cells or antisera, or are manufacturer’s directions for daily quality control followed?

NOTE: Unless manufacturer instructions state otherwise, the following apply:

· Each cell used for antibody detection must be checked each day of use for reactivity of at least one antigen using antisera of 1+ or greater avidity.

· Typing reagents such as anti-D, anti-K, anti-Fy(a), etc., must be checked each day of use.

· Anti-IgG reactivity of antiglobulin reagents may be checked during antibody screening and crossmatching.

· Typing sera and reagent cells must be checked for reactivity and specificity on each day of use, including a check against known positive and negative cells or antisera.

This checklist requirement can be satisfied by testing one vial of each reagent lot each day of testing.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7171 [42CFR493.1217].

AABB Stds BBTS 5.1.3 & 5.1.4 which references FDA 21 CFR 660.20 to 660.28 and FDA Memorandum, March 1992, "Recommended Methods for Blood Grouping Reagents Evaluation" (draft) [Docket No.84S-0181].

Joint Commission CLIA waived testing is covered under PC.16.50.

As previously stated, follow manufacturer's insert. Aceptance criteria for reagents should include review of package insert for revision of standard operating procedures.

We started to use reagent QC as competency assessment tool for all techs on every shift to document for CAP;

TRM.40120 Phase II N/A YES NO

Are control specimens tested in the same manner and by the same personnel as patient samples?

NOTE: It is implicit in quality control (QC) that control specimens are tested in the same manner as patient/client specimens. Moreover, QC specimens must be analyzed by personnel who routinely perform patient/client testing. This does not imply that each operator must perform QC daily, so long as each instrument and/or test system has QC performed at required frequencies, and all analysts participate in QC on a regular basis. To the extent possible, all steps of the testing process must be controlled, recognizing that pre‑analytic and post‑analytic variables may differ from those encountered with patient/clients.

COMMENTARY:

N/A

REFERENCE: Department of Health and Human Services, Centers for Medicare and Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register. 2003(Jan 24):7166 [42CFR493.1256(e)(1)].

[David Saikin]

Theoretically, anti-A,-B,-D have to be checked each day of use. Tha anti-A and anti-B only need to be qc'd with a + cell. The anti-D must be checked with a + and neg cell. Also, if your lab does sufficient numbers of ABOs, the front and back types may be used to verify quality performance on that day (you don't have to perform actual QC). You determine what is "sufficient". I have a problem with QC of one bottle of a lot/day. If you are a large BB, you may have multiple racks in use. I believe that each rack should be quality assured, not just the lots. (personal bias).

[jwikoff]

How about panel cells? The package insert states that reactivity MAY be checked by testing antigens likely to deteriorate such as Lea along with doing a visual inspection.

Thanks!

[Cliff]

This checklist requirement can be satisfied by testing one vial of each reagent lot each day of testing.

For those accredited by the Joint Commission unfortunately this is not true. It is each open vial each day of use.

Standard QC.5.220

The laboratory tests for reactivity the potency and reliability of reagents used for ABO grouping, Rh typing, antibody detection, and compatibility determinations.

Elements of Performance for QC.5.220

1. The laboratory defines its procedures for reactivity testing in writing.

2. Each opened vial of antisera, reactive cells, and reagents is tested for reactivity on each day of use and when a new lot of reagents is first used.

3. The laboratory confirms that each reagent reacts as expected.

4. Results are documented.

[jwikoff]

Would choosing one antigen typing sera and testing all 12 cells each day of use be acceptable then?

Thanks Cliff!

[Cliff]

Would choosing one antigen typing sera and testing all 12 cells each day of use be acceptable then?

Thanks Cliff!

My opinion, yes. Otherwise you'd be performing a validation of the panel itself. We use a positive and negative control with each panel we run.

[Lcsmrz]

I vaguely remember -- Man, I'm getting old! -- that my panel's product insert stated that routine QC is not required. It would be difficult to justify, other than merely "to be doing something" to show an inspector, and is horrendiously expensive. Like Daily Reagent QC, it doesn't seem to have much value in determining the quality of reagents.

In addition to a visual inspection, I use the correlation between screen cells and panel as my "panel QC". I expect to see equiavlent reactivity from homozygous and heterozygous cells (Sorry, Dr Judd).

Using expired panel cells in decision-making is a whole different topic ...

[David]

Are I understanding your JCAHO interpertation right, that I need to test each panel cell (all 10 or 12 or 16 or 20 vials) with some antisera (anti-Fya for example) every day I use that panel? What if I pull 3 more selected cells from a 2nd panel. They also need to be tested with the antiserum?

[BSIPHERD]

Each cell used for antibody detection must be checked each day of use for reactivity of at least one antigen using antisera of 1+ or greater avidity.

I believe this is talking about the cells used for antibody screening (antibody detection) as opposed to those used for Antibody Identification.

On CAP surveys, Antibody Detection and Antibody Identification are different things. So I don't believe this address panel cells, only screening cells.

[jwikoff]

thanks bsipherd. can you tell me how you qc your panel cells?

[David Saikin]

I qc my panels upon receipt. 0.8% cells are checked with a 1:10 dilution and 3% cell are checked with a 1:4 dilution (I use anti-c). Cells are visually examined each day-of-use.

[bbbirder]

Here is some of what CLIA says about QC for panels:

§493.1271 Standard: Immunohematology.

(a) Patient testing.

(a)(1) The laboratory must perform ABO grouping, D(Rho) typing, unexpected antibody detection, antibody identification, and compatibility testing by following the manufacturer’s instructions, if provided, and as applicable, 21 CFR 606.151(a) through (e).

Interpretive Guidelines §493.1271(a)(1)

When condition level deficiencies in Immunohematology are in any or all phases of testing, use D5026.

There are no daily quality control requirements for reagent red cell panels used in antibody identification. Panel quality control is a combination of serological test results, such as: strength of reactions and patient phenotype; statistical probability, patient’s medical history; and laboratory standard of practice (i.e., how the laboratory handles compatibility testing for patients with unexpected antibodies). However, the QC requirements pertaining to new batch, lot, shipment of identification systems at §493.1256(e)(1) must be met.

[galvania]

Thank you everyone for your help. Sorry it's taken me so long to get back to everyone - I've been away and I've only just had a chance to get back to this site.

And (a bit late) Happy New Year to everyone