By Michael Heald
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02 Dec, 2019
When devices are being developed for the delivery of pharmaceutical drug, two worlds collide. Pharmaceutical regulation meets medical device regulation, and what is at ground zero? The primary pack*. The bit of the device that holds and protects the drug substance. Often the device itself is referred to as secondary packaging, which hardly does justice to the amazing engineering that can go into it. Then there are more ordinal layers of packaging with trays, cartons, sleeves, wraps, multipack boxes etc. Beyond Primary Pack there seem to be no hard and fast rules for packaging nomenclature, so it is a good idea for everyone to agree on packaging terminology early in a project. But I digress. Going back to the Primary Pack, I should point out that containers designed to do no more than hold and protect a drug substance are not regulated as devices, and therefore are not subject to medical device regulation. As soon as a container plays a part in controlling the delivery of a drug, it is moving into medical device territory, and the medical device regulations are invoked. There are, of course, grey areas. Eye dropper bottle design seems to be one. From a regulatory point of view, and the Americans are particularly clear on this, you need to run both drug and device quality systems for drug delivery devices. There are drug constituent parts, and there are device constituent parts. And then there is the Primary Pack, which is both. It is the common interface between device and drug. For the pharma development team, the Primary Pack has to hold the right amount of drug, and it needs to prevent deterioration or undesirable exchange between the drug, primary pack and environment, all for the entirety of its shelf life. The contents may also need to be kept sterile. For the device development team, the Primary Pack has to allow accurate, often metered, delivery of the drug. To do this the Primary Pack becomes an integral part of a precision mechanism, which necessitates tight control over dimensional tolerances and operating forces. There are also shared interests, such as drug visibility, labelling, filling requirements and container closure integrity. Shared interests further extend to compatibility with certain manufacturing processes, so someone from Manufacturing needs to get involved too. Put simply; the pharma development team and the device development team need to collaborate closely on the design of the Primary Pack from the start. It is surprising, especially in parenterals, how often project risk is unwittingly invited by one-sided Primary Pack decision making. So which team should have custody of the Primary Pack specification? I think that the right answer to this question is that it doesn’t matter. As long as the controlling team and the governing processes ensure that collaboration is effective, and that both drug and device regulations are met, then ownership is irrelevant. Traditionally the pharma guys have it. One particularly tricky aspect of developing devices for sterile injection is container closure integrity testing (CCIT). Not very long ago CCIT was subject to a pharmacopeia re-boot with USP <1207> and the industry is upping its game by abandoning old probabilistic methods and moving to deterministic ones. This field of testing is evolving quickly, which is why went along to the Container Closure Integrity Testing workshop run by PDA Europe in March. If you have read this far, maybe you would like to take a look at the CCIT blog that resulted. * Apart from the Primary Pack, other parts of the drug delivery device can demand a similar mode of co-operation. Typically, these are other components that are in direct drug contact, though usually contact duration is transient instead of being measured in months or years.