How to Provide Evidence of Product Conformity during Manufacture?

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chum84

The business I'm doing a project for currently reconstitutes drugs and sells them off. This reconstitution essentially creates a drug of a specific concentration and a specific volume using a more concentrated form of the drug (powerdered or aqueous) and a base solution (saline or glucose). Essentially its making a more diluted form of a drug from its concentrated form. The dosage is based on measurements gathered from a patient.
The actual reconstitution process occurs within a CDSC Laminar Flow cabinet - that is, a sterile cabinet. Testing of the product will be destructive.

Im thinking of excluding Part of Section 7.6: Control of Monitoring and Measuring Devices. I'm also unsure how to provide evidence/records of that the realisation process is meeting customer requirements. Heres my thinking/reasoning


EXCLUSION FROM 7.6
All work done is by employees manually. The process consists of drawing liquid using a syringe (concentrate) and then drawing another liquid to dilute it to its specific concentration (base solution). It is absolutely ridiculous to measure each sample of liquid taken out each time - taking it out of a sterile cabinet is not possible for electronic measuring and its absolutely inappropriate to use an electronic syringe/measuring and drawing device (if there is one) because you cannot assure its sterility (try autoclaving an electronic device haha!). The syringes are pre-calibrated to 1ml increments and come sterile. Having said that 1ml increments are quite large but it is totally acceptable to guesstimate inbetween measurements - its widely accepted by all doctors, organisations etc..., and doesnt have much bearing on a patient that you gave them 10.4 mls instead of 10.5 or 10.6. The valildation that the amount drawn up is done by the employee visually. Validation that the employee is competant to do this process is assessed every year by an accredited organisation.

Having said all that , i have no idea how to provide evidence that the product realisation process is conforming to customer requirements - even if i did make a check list of every step of the process, you couldnt take that checklist inside the cabinet (unsterile) and its just plain stupid to stop what you are doing after drawing say 5.5ml, then taking your hands outside the cabinet to write down you drew 5.5ml and ticking and signing it. Also unfeasable to get an assistant to look over your shoulder and verify what you are doing. I dont think i can provide evidence of conformity during manufacture - conformity in this case means following a manufacturing sheet that has been checked by an employee and verified and signed by a registered pharmacist. Evidence of conformity will be shown through any cases of people getting sick after administration of the drug, but that hasnt happened and wont.

I've got a series of checks and processes to fulfill the requirement for 7.5.2: Validation of processes for production and service provision.

Do you think i can exclude myself from PART of 7.6 Calibration of Measuring and Monitoring Devices clauses a-e, but not the other paragraphs?. How do i go about providing evidence of conformity during manufacture?
 
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Gert Sorensen

I'm thinking in the lines of either weighing the finished product or using optical sensors to assure that there is the correct amount in the containers + a good documentation of the training of the operators.

But, why don't you make larger batches and dispense them instead of mixing very small amounts one at a time??
 
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chum84

Coury Ferguson said:
Is this not the same post?

http://elsmar.com/Forums/showpost.php?p=160027&postcount=1

Is there some reason that you have posted the question twice?


sorry my bad, i got an error when i first posted it so i decided to try to post it again.

Gert: - the drugs are created for cancer patients. Its specific to each patient and also is made in accordance to their schedule of drugs for the week. These drugs also have a specific expiry date, sometimes even 24h, so its not feasible to make a massive batch. We have good documentation too. As for weighing, you'd have to figure out the density of each liquid used, the weight of the container for the liquids and have a very sensitive scale. It costs shi*tloads for a sensitive scale, the manufacturer would have to give us its density measurement and its too time consuming to do that as well. As for optical sensors.... seems far too expensive and impractical for a company that has 5 people. Considering it doesnt have to be perfect when measuring i dont see the need.
 

Coury Ferguson

Moderator here to help
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chum84 said:
sorry my bad, i got an error when i first posted it so i decided to try to post it again.

Not a problem. Most of us have made that error before.
 
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ddunn

I understand your problems. My wife worked in a pharmacy where custom meds mixes were made for cancer patients. Since the realisation process is done by the employee visually can you set up a camera and record the process each time. This would provide evidence/records of that the realisation process is meeting customer requirements.

Just a thought.
 
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chum84

a good idea but i think impractical and rather expensive. I would have to set up two cameras inside a clean room, which is unacceptable, and the other inside a laminar flow cabinet, which is also unacceptable. The amount of money to set up a system like that would be phenominal.
 
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Greg B

You said you use a checklist...This is your evidence of conformity (for the process). As long as the employee has been trained in the correct methodolgy, keeps accurate records (post process because of the cabinet restrictions) and regular audits are conducted then I do not see a problem. With the 9K2K standard you don't have to have everything documented to the n'th degree like in the old standard.

The clause in question is more about how you monitor and calibrate your test equipment. Do you keep accurate records? Do you do prestart calibrations against test measurements or weights , are machines zeroed before use? etc
 
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chum84

Ill have to talk to my boss to see what he thinks about it. As far as checklists go, we dont use it. Isn't it pointless filling out a check list after manufacture - if someone has to mix 15 drugs, filling out a checklist after they have done it will be confusing and i'm sure their memory isnt good enough either.

We can prove adequate training, good SOPs, and evidence from audits but as far as providing post-manufacturing records, im up the creek.
 
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Greg B

The checklist does not have to be something that maps his/her every move. I can be a simple sheet that identifies specifications, requirements, pre start checks etc and after 'the process' has been completed, it can include such things as work order numbers, signature to say the work was carried out IAW instructions etc. There needs to be some responsibility by the operator showing they have complied with their instructions, the medicines are correct, batches match patients (whatever). Just do a basic flow chart of the requirements and see what should be checked off, for example:

1: Pre start check, cleanliness, inspection
2: Calibration
3: Correct meds/chemicals/drugs
4: Correct Order or Patient match up/details etc
5: Operator signature and date

Is there mandatory Department of Health/TGA checks etc that must be carried out?

Just keep it simple
 
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