Safeguarding medicines

In a tropical country like India, drugs are particularly sensitive to the adverse effects of climatic variations and environment conditions. Usha Sharma analyses

"Once the medicine is packed in proper temperature and RH conditions, it becomes suitable to be stored at various climate conditions. However, during storage, precautions have to be taken to avoid exposure to light, moisture and temperature adversely affecting the medicine packed" - Dinesh Gupta President Bry-Air Asia and Bry -Air equipment

The criticality of product packaging cannot be understated; more so in the pharmaceutical industry where the products could make the difference between life and death. As an industry, the packaging segment in India is estimated to account for a turnover of Rs 15,000 crore by the end of the current fiscal.

Product packaging works at two basic levels: aesthetic and utilitarian. At the first level, external designing and minute design details become the 'identity' consumers look out for and associate with a particular brand. Hence packaging is increasingly becoming an influential factor in the purchase decision cycle. Currently, manufacturers are striving to innovate and improve all attributes and features of a product package, starting from the packaging material being used to its creative designing.

At the second level, product packaging has to also protect. Various inventive methods are being employed to enhance the longevity of a pack, making it user friendly and cost effective. This level is critical in the pharma industry as this industry faces a big threat from moisture and humidity, which shortens shelf life and compromises quality of the packed medicines.

The effect of humidity on drugs depends on climatic parameters like temperature, humidity, light and gases, which would affect the longevity of the drug. The role of primary packaging is to protect the product against these parameters. In the pharma segment, different products have distinct sensitivity and hence it requires different types of packaging materials to protect the product against specific degrading environmental parameters. Hence the selection of the packaging mode and material is very critical.

Currently, the most common types of pharma packaging are blister packaging, bottle packaging, strip packaging, pouches and vials. Of these, the most vulnerable packaging mode, both from end consumer and industry point of view, is strip packaging as the metal/chemicals of the strip may adversely affect the medicine over a period of time.

In search of the perfect packaging

Most medicines are in a powder state and since most powders are hygroscopic, there will be a tendency to absorb moisture. Therefore solid dosage forms will have different moisture contents at different levels of relative humidity (RH). During the storage and packaging process, conditions need to be maintained to ensure that the claimed shelf life and desired effect of given level of dosage is maintained.

Quality of the product is also determined by the quality of water added to the product during the production process and the environmental (air quality) where the product is packed. Undesired environmental conditions will lead to contamination, increased moisture content, mottling etc. These small slip ups during the production process are most often ignored by pharma companies until it is too late to undo the damage, resulting in huge setbacks in the markets.

Most packaging materials do not provide comprehensive protection against all environmental parameters. In fact, no standard packaging provides protection against temperature or time. Similarly, many packaging materials which are good moisture barriers will not be good gas barriers. For instance, a significantly costly and very high moisture barrier packaging material like Aclar (which is used by most innovator companies) does not prevent product degradation due to temperature, light or even gases. Therefore many theoretically good packaging materials may not be practical, both from the cost as well as protection angles.

Regulatory benchmarks

"Cost issue activity will not affect the pharma industry in a major way, as the products of better quality will have more market. In a competitive market, people substituting low cost for quality will automatically get thrown out" - Ravindra Wagh, General Manager, Formulations, Intas Biopharmaceuticals

Other than temperature, humidity or moisture is the main reason for drug degradation as many products are moisture sensitive. These products when exposed to higher humidity or higher moisture content degrade faster. Hence, it is very important that the product be protected against moisture by providing high moisture barrier primary packaging. Actual humidity conditions in many parts of the country are significantly higher than the humidity conditions under which stability tests have been conducted and submitted for getting product approval. Thus passing stability studies under standard stability study conditions does not guarantee that the product will be stable in the actual conditions prevailing in most parts of the country.

To compete with these issues on a worldwide basis, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has already designed standard stability conditions for packaging different products, which were originally designed for the US, Europe, Japan markets. As per ICH guidelines, product stability is to be checked and confirmed before the product is introduced in the market. Today, the same conditions are more or less followed all over the world including India, though clearly these conditions are not sufficient for countries with tropical climatic conditions. To a certain extent, there are certain extra conditions specified by World Health Organisation (WHO) to take care of this problem, but clearly these are not enough. However, the standard practice is to follow the ICH guideline as it is accepted by developed countries.

In general, pharma companies work as per US Food And Drug Administration (FDA) regulatory requirements rather than actual requirements. However, companies doing research in drug discovery and formulation undertake certain forced degradation studies to understand effects of various climatic conditions on products and take necessary precautions. Quality conscience manufacturers would rather 'over pack' the product or follow the innovator's example to reduce the risk.

In the current scenario, pharma companies have started outsourcing packaging development studies to specialised companies like Bilcare Research, who undertake research on the drug stabilisation process. Bilcare has developed scientific and proven methods to perform product sensitivity profiling as well as develop optimum packaging based on product requirements. Other mandates are to protect products from diverse environmental conditions, confirm stability and efficacy during the expiry period or extend expiry period.

Ajith Sashidharan, Vice President, Global Research Services and Quality Assurance, Bilcare Research, says, "Pharma packaging should depend upon environment to ensure product stability and efficacy and safety of the consumer. However, today (packaging in the) pharma industry is more of a regulatory exercise than a scientific exploration. Over packing is the only way to ensure protection as there is no scientific method followed to identify optimum requirement. Hence the statement of better protection, higher packaging cost could be true. On the other hand, costly packaging cannot ensure protection."

However, in many cases, innovators opt for high barrier packaging as they can afford the cost of the packaging and want to avoid any failure in stability studies which would delay introduction of the product. Many generic suppliers have a tendency to follow the innovators' packaging system, though it is not affordable for them because it is proven and do not want to take any chance. Still the fact is that it might be proven only in US or Europe markets, where climatic conditions are drug friendly and the product does have a long shelf life. Also, product stability depends on the formulation process, not only the Active Pharmaceutical Ingredient (API) and therefore if the formulation changes from the innovator's, the packaging requirement also changes.

Beating the heat

Drug products requiring special temperature conditions need to be always transferred through validated cool chain packing. Hence vaccines and other products are only sold packed in thermos flasks or through cold chain.

To ensure that the cold chain is maintained, the Maharashtra FDA confirms that these conditions are met before issuing any license for storage facilities at the manufacturing centre and at depots where such products are stored. Likewise, licenses for chemists are granted subject to availability of refrigerators and air conditioners. All such precautions confirm that the product's potency is maintained throughout its shelf life.

The APIs may lose potency thereby losing set quality parameters. Therefore reputed pharma companies add overages of the API in formulations to further ensure proper potency throughout the specified shelf life. Improper humidity conditions during filling of powder injections, tablets and capsules also leads to sub-standard quality of the finished product. Powder injections tend to become crystalline and change colour. Tablets become loose and disintegrate into powder, while capsules become soft and become difficult to swallow.

As pharma packaging is a very critical operation and the products while packing are exposed to external atmosphere, control of the environment to ensure non-contamination is necessary. This cost gets absorbed very easily if the product is a high value or high volume product. "This activity will not affect the pharma industry in a major way, as products of better quality will have more market. In a competitive market, companies substituting low cost for quality will automatically get thrown out. For such quality products, marketing should focus more on non-regulatory markets, from where companies will fetch more revenues. Companies which do follow environmental norms during packaging will have less chance to enter international markets," comments Ravindra Wagh, General Manager, Formulations, Intas Biopharmaceuticals.

Some solutions

Today, consumer and industry awareness is high and therefore we observe that life savings drugs are labelled and stored at proper temperature conditions at various chemist shops and even at big malls. Pharma companies conduct training programmes at all Clearing and Forwarding Agents (C&FAs) on cool chain management, proper environmental condition maintenance etc. These companies keep withdrawing samples from various depots and keep records of the potency of drugs stored at various places, thereby proving the SISPQ (Safety, Identity, Strength, Purity and Quality or efficacy) of a product.

The advent of desiccant based dehumidifiers about fifty years ago has eased the woes of the industry on the humidity count. In India, Bry Air has been serving the industry for more than 30 years to maintain desired conditions irrespective of outside humidity conditions. "Once the medicine is packed in proper temperature and RH conditions, it becomes suitable to be stored at various climate conditions. However, during storage, precautions have to be taken to avoid exposure to light, moisture and temperature adversely affecting the medicine packed," says Dinesh Gupta, President, Bry-Air Asia and Bry -Air equipments.

Scientifically developed and designed optimum packaging can balance protection with cost by selecting the packaging material having the exact barrier requirement that prevents product degradation and optimum weight. This exercise also ensures higher yield (material consumption per unit packing) and also design which reduces material consumptions per unit packing. "The scientific development of packaging by understanding the actual product requirement rather than selecting the packaging material as per regulatory requirement is the only way to compete with this problem," sums up Sashidharan.

usha.sharma@expressindia.com