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Administrator
Posts: 578
Registered: ‎02-22-2010

Re: Sterility Tests and BUD Webinar

More from our live presentation:

 

Q: The Gri-fill system 3.0 automated compounding device has been used to extend dating from single dose vials of chemotherapy. Is it possible to do this manually using a 0.22 micron filter? The article was from Pharmacy Practice News Vo 37,#6, June 2010.

 

Q: If you are using automation (RIVA) can one use PST to extend BUD, does this move into manufacturing?

 

Q: How much better is a barrier isolator than an open hood?

 

Q: If you just draw up 1ml of furosemide for a dose in a syringe. Is this considered compounding or are there other rules?

 

Q: Are multi-dose vials of vaccines an exception to the 28-day expiration rule?

 

Q: If a product passes sterility testing compliant with USP 71, how is BUD then extended?

Expert
Posts: 1,174
Registered: ‎02-23-2010

Re: Sterility Tests and BUD Webinar

Q: The Gri-fill system 3.0 automated compounding device has been used to extend dating from single dose vials of chemotherapy. Is it possible to do this manually using a 0.22 micron filter? The article was from Pharmacy Practice News Vo 37,#6, June 2010.

A:I have not read the article so I cannot give you an informed opinion but knowing something about the Grif-fill device and doing it manually, I would say it is not possible to it manually since there is an aseptic manipulation distal to the filter. 

 

Q: If you are using automation (RIVA) can one use PST to extend BUD, does this move into manufacturing?

A: The key in using automated compounding systems is the minimization or elimination of the human interaction/intervention.  Any technology should be media qualified to demonstrate aseptic processing ability.  Has the manufacturer's of RIVA provide any data about the aseptic ability of their device?   Using a robot does not move you into manufacturing.  Depending on your state pharmacy laws, you may be able to prepare non-patient specific CSPs to other pharmacies. 

 

Q: How much better is a barrier isolator than an open hood?

A: Your question is rather broad.  Relative to what? Aseptically, I believe that isolators give people a false sense of security.  Anything your gloved hands touch in an isolator can be transferred to CSPs. The key in using an isolator is to routine check the integrity of the isolator gautlet sleeves and know that sterile gloves need to be worn on the inner most glove when compounding CSPs. 

 

Q: If you just draw up 1ml of furosemide for a dose in a syringe. Is this considered compounding or are there other rules?

A:  Yes, I answered this question earlier.  Please read the introduction to USP 797.

 

Q: Are multi-dose vials of vaccines an exception to the 28-day expiration rule?

A: According to the CDC, yes.  Please refer to the APIC article I attached in an earlier post.

 

 

Eric S. Kastango, MBA, RPh, FASHP

It's all about the patient.
Administrator
Posts: 578
Registered: ‎02-22-2010

Re: Sterility Tests and BUD Webinar

And more questions from our live presentation with Eric:

 

Q: Did you say that batches of 25 or less items do not need to be tested when dealing with BUD?

 

Q: Do manufacturers follow these guidelines that are on the BUD table?

 

Q: WIth the current shortages (such as D50), does transferring D50 from a larger bag to empty sterile vials considered compounding?

 

Q: Does RDIS have a demonstrated equivalence to USP 71? 

 

Q: Regarding the 14-day incubation period for sterility testing, do we dispense the drug with the hope that nothing grows, then retrieve the drug if something does grow?

 

Q: When compounding batched products, when am I required to track lot numbers?

Expert
Posts: 1,174
Registered: ‎02-23-2010

Re: Sterility Tests and BUD Webinar

Q: Did you say that batches of 25 or less items do not need to be tested when dealing with BUD?

A: Yes, with a caveat.  The actual chapter language is as follows:

All high-risk level CSPs that are prepared in groups of more than 25 identical individual single-dose packages (e.g., ampuls, bags, syringes, vials) or in multiple-dose vials (MDVs) for administration to patients or that are exposed longer than 12 hours at 2 to 8 and longer than 6 hours at warmer than 8 before they are sterilized shall meet the sterility test (see Sterility Tests 71 ) before they are dispensed or administered.

 

Q: Do manufacturers follow these guidelines that are on the BUD table?

A: The pharmaceutical companies have to prove chemical stability and microbiological sterility when manufacturing drugs. Outsource provides need to comply with applicable laws based on their licensure. If they are a pharmacy, they need to comply with USP 797. If they are also registered with the FDA, the requirements are not as clear since these operations do not neatly fit into the FDA regulations for human drugs 21 CFR 210 and 21 CFR 211 (current Good Manufacturing Practices)

 

Q: WIth the current shortages (such as D50), does transferring D50 from a larger bag to empty sterile vials considered compounding?

A: Yes, this activity would be considered compounding.

 

Q: Does RDIS have a demonstrated equivalence to USP 71? 

A: Based on the research that I have done, it can demonstrate equivalency to USP 71.  It would be important to demonstrate that you have proof of the equivalency. This is done by performing sterility testing using membrane filtration and media along with RDIS.  If you can show equivalency for three tests, then you have the evidence to support your decision. 

 

Q: Regarding the 14-day incubation period for sterility testing, do we dispense the drug with the hope that nothing grows, then retrieve the drug if something does grow?

A: Sterility depends on many factors and if you have confidence in your compliance with the chapter and the behavior of your compounding personnel and have a history of negative sterility tests, you could decide to dispense prior to test results.  The chapter says:  When high-risk level CSPs are dispensed before receiving the results of their sterility tests, there shall be a written procedure requiring daily observation of the incubating test specimens and immediate recall of the dispensed CSPs when there is any evidence of microbial growth in the test specimens. In addition, the patient and the physician of the patient to whom a potentially contaminated CSP was administered are notified of the potential risk. Positive sterility test results should prompt a rapid and systematic investigation of aseptic technique, environmental control, and other sterility assurance controls to identify sources of contamination and correct problems in the methods or processes.

 

Q: When compounding batched products, when am I required to track lot numbers?

A: You should track all lot numbers all the time.  It is a good compounding practice.  Currently, there is a recall of eggs, how do you know if the eggs you have at home are at risk?   There is a lot number of the carton so you can determine if you are at risk. Could you do the same for the patients receiving your CSPs?

Eric S. Kastango, MBA, RPh, FASHP

It's all about the patient.
Highlighted
Administrator
Posts: 578
Registered: ‎02-22-2010

Re: Sterility Tests and BUD Webinar

[ Edited ]

Here are questions from our live webinar:

 

Q: If we employ an outside company to do sterility testing, how often are they required to do it?

 

Q: Single-use items like premixed bags that are used to draw up multiple syringes of the solution require what BUD? Do they require sterility testing?


Q: Can you comment on the stability of heparin in sodium chloride in syringes?


Q: Can growth promotion be done in-house? Or will it represent a risk for the environment?

Q: I am trying to find stability of Heparin in sodium chloride with a final concentration of 2 units/ml drawn into syringes. One study shows that heparin at 500 units/ml can be stored up to 3 weeks without refrigeration in polypropylene syringes (Am J Hosp Pharm. 1981 Jul;38(7):1001-4. ) Can we use the same stability for heparin at 2 units/ml.?

Expert
Posts: 1,174
Registered: ‎02-23-2010

Re: Sterility Tests and BUD Webinar

Q: If we employ an outside company to do sterility testing, how often are they required to do it?

A: Sterility testing is required for each and every batch that exceeds the BUD in USP 797.

 

Q: Single-use items like premixed bags that are used to draw up multiple syringes of the solution require what BUD? Do they require sterility testing?

A: I would consider them medium-risk level CSPs if you drawing multiple doses from a single bag.  If you exceed the BUD of USP 797, then sterility testing is required.


Q: Can you comment on the stability of heparin in sodium chloride in syringes?

A: Not sure what you are looking for me to address by your question.  Is heparin stable in sodium chloride?  It is yes and Trissel's Handbook of Injectable would be the first resource I would consult.


Q: Can growth promotion be done in-house? Or will it represent a risk for the environment?

A: I believe that if you get the microorganisms stipulated in USP 71 (which is near impossible due to security reasons), it would pose a threat to the integrity of the pharmacy environment.  You don't want live microorganisms in your pharmacy that are actively growing.


Q: I am trying to find stability of Heparin in sodium chloride with a final concentration of 2 units/ml drawn into syringes. One study shows that heparin at 500 units/ml can be stored up to 3 weeks without refrigeration in polypropylene syringes (Am J Hosp Pharm. 1981 Jul;38(7):1001-4. ) Can we use the same stability for heparin at 2 units/ml.?

A: I spoke with Larry Trissel about your question and heparin stability depends on the solution it is in and storage conditions. No studies have been done at 2 units/mL at all. No studies done for 30 to 45 days in the literature. I don't believe you can use that data to extrapolate the stability of 2 unit/mL.

Eric S. Kastango, MBA, RPh, FASHP

It's all about the patient.
Regular Visitor
Posts: 2
Registered: ‎12-12-2011

Re: Sterility Tests and BUD Webinar


EricKastango wrote:

Q: Did you say that batches of 25 or less items do not need to be tested when dealing with BUD?

A: Yes, with a caveat.  The actual chapter language is as follows:

All high-risk level CSPs that are prepared in groups of more than 25 identical individual single-dose packages (e.g., ampuls, bags, syringes, vials) or in multiple-dose vials (MDVs) for administration to patients or that are exposed longer than 12 hours at 2 to 8 and longer than 6 hours at warmer than 8 before they are sterilized shall meet the sterility test (see Sterility Tests 71 ) before they are dispensed or administered.

 

 

We are a compounding pharmacy which predominately makes high risk CSPs.  We are having a debate about the interpretation of sterility & endotoxin testing of these products.  My interpretation is that we need to test batches of 25 or more single dose units and all MDV batches (regardless of the size of the batch).   Others read it as needing to test 25 units or larger of single dose units and batches of 25 or larger of multi-dose vials or units .  Can you give any insight?

Expert
Posts: 1,174
Registered: ‎02-23-2010

Re: Sterility Tests and BUD Webinar

Kjersten,

 

I believe that we are splitting hairs with your question.  I agree with your interpretation but the language is not clear and something that the USP committee is working on cleaning up.  It should read any MDVs.  The concern is mass casaulties when you are preparing large amounts of high-risk level CSPs or MDVs (think about the Alabama PN contamination).  Can you demonstrate that your processes, regardless of the employees working them, can provide CSPs that are sterilty and pyrogen free and do you have evidence to demonstrate that state of control?  That is key to keeping the patient safe.  Thanks.

Eric S. Kastango, MBA, RPh, FASHP

It's all about the patient.
Regular Visitor
Posts: 2
Registered: ‎12-12-2011

Re: Sterility Tests and BUD Webinar

Thank you for your reply.  This will be helpful in going forward and getting all on the same page.

 

Kjersten

Senior Member
Posts: 3
Registered: ‎07-28-2011

Re: Sterility Tests and BUD Webinar

Can you clarify two things:

1. If all CSP's are given the appropriate B.U.D. as per 797 and this date is never  exceeded, is any sterility or potency testing required?

2. Can you comment on JACOH's requirement that STABILITY data used can only come from the manufacturer of the product and not published studies, and other stability references? (I heard this on a WEBINAR presented by a JACOH representative)

Pablo Montelongo Pharm.D., BCNSP