We all know that medicinal products require protection from environmental variables that accelerate degradation – namely, moisture, light and oxygen. And though the common stability guidelines established by the International Council for Harmonization (ICH) cover the basic requirements for stability studies, I find them rather general in nature and not always well-matched to real-world market circumstances. Often, the guidelines lead to after-the-fact stability studies of packaged products performed to validate – rather than shape – the primary packaging process. Today, many packaging solutions are able to prevent or retard efficacy loss, and advanced computer simulation and study tools can subject products to rigorous evaluation. By considering a product’s moisture, light and gas barrier requirements (along with its physical dimensions), it is possible to design packaging that passes stability testing – and to do so cost effectively.
Despite the availability of solutions, why are packaging optimization tools not in widespread use? A number of obstacles exist. Understandably, pharma companies tend to pay more attention to drug development than drug stabilization. Following years of expensive research, development and clinical studies, companies are always eager to get their product to market. To that end, the stabilization documentation required by regulatory bodies is often handled via the path of least resistance. And that means that most drugs are actually over-packaged. Although erring on the side of caution may seem like a good idea, it’s a waste in terms of cost. On the other hand, failing to fully understand your product’s packaging needs can also lead to problems in more challenging environments, such as very hot and humid climates. Regulatory guidelines are purposefully broad; it is simply impossible to list and address each and every potential scenario. Recognizing this, regulatory bodies are now advising pharma manufacturers to do their homework in terms of understanding the specific stability challenges of their products in real-life market challenges. The FDA has issued a guideline that encourages quality, safety and efficacy controls to be incorporated into the production process that adhere to Quality by Design principles (1). Though this is a step in the right direction, I believe that greater regulatory oversight could – and should – be put into place, particularly as so many technologies to aid packaging optimization are so readily available. One reason for the delay in rolling out such technologies is that medicines – particularly tablets and capsules – are often packaged differently depending on the country they will be sold in. In many parts of the world, solid dose medicines are packaged directly in unit dose format in approved manufacturing sites under clean and controlled environments. They then travel through the supply chain in their original packaging until the last pill is consumed by the patient, all of which helps ensure product stability. However, in the USA, the initial validation process is essentially eradicated all too often. Products typically go through multiple re-packs to suit bulk packaging supplies of pharmaceutical producers. Consumers often receive their 30- or 90-day pill prescription in vials – and it’s amazing how often these are stored in bathrooms or kitchens, which offer far-from ideal conditions for storage in terms of temperature and humidity! Such vials are opened and exposed to environmental conditions daily, which can potentially limit product potency. Medicines are not usually tested against this level of exposure.
It’s not easy to change supply chain infrastructure or end-consumer practices, but some companies are waking up to the problem and I am seeing a movement towards more protective unit dose packaging in the US, such as blister packing with barrier protection. Although ICH stability studies do not adequately address real-life environmental supply chain challenges faced by pharmaceutical products, they remain the basis for FDA product market approval. It is time for that to change. Pharmaceutical scientists, packaging experts and regulatory authorities must come together to formalize a better drug stabilization approach that will benefit the entire pharmaceutical community – including patients.
Newsletters
Receive the latest analytical science news, personalities, education, and career development – weekly to your inbox.
References
- FDA, “Quality by Design for ANDAs: An Example for immediate-Release Dosage Forms”, (2012). Available at: http://bit.ly/2j5GX8M. Accessed January 11, 2017.
