Laboratories Adaptation to HPAPI handling

Yossi Shapira, Teva Pharmaceuticals Ltd., Israel (yossi.shapira@teva.co.il )

IS- 1530 –Standard for laboratories (quotation):
Laboratory is a site in which samples are taken, tests are performed, analysis, synthesis, experiments, R&D, training, studying and teaching while handling dangerous elements. In this list similar sites in educational institutes (schools) as it Is defined in1949 educational duty law, in other governmental and religious governmental schoo;ls as defined in religious governmental law of schools from the year of 1953……..etc.

Even the IS regulation is using the phrase "while handling dangerous elements".

What are these dangerous elements? Flammables, explosives, biologicals, toxics and HPAPI.

Since I mostly experiencing the pharmaceutical laboratories engineering, a well known fact should be pointed out: the handled chemicals in the laboratory are becoming more potent: exposure to smaller quantities creates non controlled, non-desired, non-selected, pharmacological reactions within the no properly protected chemist's body. Chemists might find themselves endangered.
In the past in regular medical daily dosage forms, API quantity reached 500-1000mg. Today, due to new drugs discovery, inventing new targeted drugs, hormones, vitamins dosage forms, discovering new milling and micronizing technologies, smaller potent drugs quantities are found in the daily dosage form. From few miligrams to 0.2.(200 nanograms)per unit. Laboratory needs to handle these quantities while developing or while testing.

10 micrograms of this active drugs located in a small vial can hardly be detected by the bare eye. But below 5-7 micrograms level, pharmaceutical ingredients, dyes powder pesticides aerosols might not be detected while still creating pharmaceutical activity if penetrating the non-protected chemist/operator natural barrier.

Hydrophilic chemicals are dissolved while penetrating through mucutic tissues to human body blood stream. Hydrophobic powders and solutions can penetrate even through our skin arriving also to the blood stream.

Laboratory environment and its exposure to potent drugs is monitored while using units of micrograms contaminant/m3 of inhaled air. You cannot expect to visually detect it. Contaminant particles are in the size is of bacteria!. It is flying in the ambient air flawless, attracted to horizontal and vertical surfaces where it accumulates, it can fall on our benches, floors laboratory equipment and instruments and clothes. It is attracted to surfaces mainly by electrostatic power. You cannot wipe it, the laboratory is not a friendly environment to clean and to decontaminate.

We are, the laboratory personnel are the most common contaminant spreading by creating air turbulence and in relation to the accumulated amount of contaminant.

What should be done?
We must trap the contaminant as close as possible to point of generation. Following the amount of contaminated air treatment is minimized.

According to international companies toxicity/potency regulatory strategy, laboratory/site handled chemicals are divided into 5-6 groups. While the 1st group is the innocent compounds (allowed few thousands microgram of powder in 1 m3 of inhaled air, and the 6th group is of the most potent – less than 1 μgr/m3 inhaled air. Yet we tend to forget to measure surfaces contamination.
To achieve non contaminated environment physical segregation is recommended between operator, environment and potent drug. In other words: isolation, containment.
It is accepted strategy to isolate materials handling belonging to band 4 and above.
The proper isolator will be designed to supply the optimal conditions to handle potent materials in safe and hygienic high protection level while wearing civil clothes with no additional protecting devices.
Internally it will allow potent drug processing,
preventing cross contamination between previously handled materials
Proper containment will be designed to allow safe
Proper containment will be designed to technically fit and contain the process instrumentation and equipment while maintaining safe and clean and cleanable atmosphere within the isolator.
Isolators manufacturers, or plants engineers are experts in metal and plastic and machinery processing/handling. They do not recognize your process. They need detailed customer's requirement.
What are the requirements? Whose function is to define it? How shall we know that nothing is forgotten?
URS, MOCKUP TEST, SAT, FAT .