global perspectives in cleaning validation

8/11/2019 Global Perspectives in Cleaning Validation

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Global Perspectives InCleaning Validation

Presented by

Bill Hall


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Why are global GMPs so significant?

Everyone on the same page

Minimize culture effects

e.g. single signatures of critical steps in Europeand double signatures of critical steps in US


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Speaking of Global, as inCompetition

China is expected to become the fifth largestpharmaceutical market in the world, doubling itspresent $12 billion in sales by the end of the

decade.


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Until recently, Chinas pharmaceutical industryhas largely focused on generic manufacturingand counterfeiting of brand name drugs.

But now the Chinese pharmaceutical industry isshifting from imitation to innovation, with morethan 5000 research and development

institutions including 500 to 1000 biotechcompanies. More than 20 biotech parks can befound throughout the country


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And finally, regarding China

More than 3700 manufacturers are certifiedin Chinese Good Manufacturing Practices(GMP) standards


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Technology is changing

More technical tools are available Near IR for sampling/ID

Airport scanning devices have been considered

for cleaning validation (advantage is speed ofdetermining whether surfaces are truly clean)but have not worked out in actual practice inpharmaceutical applications so far

Total Organic Carbon-is being used widely forwater analysis and cleaning validation studiesespecially for cleaning agents


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Speed of Analysis

Time is money

Time is also delaying justice North Carolina currently has such a large

backlog of samples in the labs of the StateBureau of Investigation (SBI) that habitualfelons are having to be released and then arebeing rearrested multiple times for committing

additional felonies while awaiting trial. (Trialcannot proceed until all evidence, including labanalysis, is available)


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Excerpt from Drug Discovery &Development (February 2006)

Title of Article = Crafting Smaller andFaster Technologies

The high-throughput mass spectrometry(HTMS) system allowed them to cut samplepreparation time from 30 seconds to 3seconds.

Everything boils down to speed


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Additional quotes from same article

The Ultra Performance LC was designed fromthe ground up to reduce run times by up to10 times using low-dispersion, high speed

detectors and 1.7 m small particlechemistries for columns


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and

The chemists come up and say they now trythings that theyve never tried before orhardly ever tried before because of time

constraints and because of the cost of thecompound to run a reaction on a certainscale and have it fail.


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In my opinion

It is time to steal technology from otherindustries just as we took dust collectors(Torits) from the lumber industry and

clean-in-place (CIP) technology from thedairy industry

Specifically, Im speaking of applyingbioluminescence (ATP ADP + light)from the food industry and apply it topharmaceutical surfaces


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Microbial Analysis

Has always been slow (by the time we getthe results of our water testing it is too lateto do anything about it)

We need to borrow the new bioluminescenttechnology being used by the food industryto evaluate cleaned surfaces in restaurants

and food preparation areas for microbiallevels


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APIs, Contaminants, Counterfeiting, andBioterrorism Issues

Cleaning or contamination issues arepotentially very great in our raw materials. Why can they make the APIs so cheaply in

other countries? (This is an era where we canbuy mfging equipment on e-bay)

How good are we at detecting contaminants inour raw materials, particularly bioactive or

highly toxic impurities? Are our assays (whichare based mainly on assay of knownconstituents) good enough in all cases?


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Some Myths in Cleaning Validation(Reference: Destin LeBlanc, PharmTech Europe, Dec 2005

and Feb 2006

1. Regulatory authorities do not like rinsesampling

2. You must correlate rinse sampling results

with swab sampling results3. You cannot use nonspecific analytical

methods

4. If you use total organic carbon (TOC) youmust correlate it with a specific methodsuch as HPLC (continued on next slide)


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Some Myths in Cleaning Validation(continued from previous slide)

5. Any measured residue is unacceptable

6. Dose-based calculations are unacceptable

7. Recovery percentages of different spikedlevels should be linear

8. You cannot validate manual cleaning


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Thanks very much !

Questions?

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