Pharmaceutical packaging challenges - an overview

Designing pharamaceutical packaging is more complex and challenging since it requires high attention due to critical nature of the molecules and products to protect throughout the shelf life. It has become all the more complex due to increased requirements from regulatory authorities. Packaging materials and the design can also be influenced by markets due to ever increasing Government regulations, customer expectations, and price competition

Packaging challenges can be broadly classified into

• Molecule/ formulation challenges
• Regulatory requirements
• Process challenges for implementation
• Intellectual property protection
• Threat from counterfeits
• Safety requirements
• Price competition with global players and price control measures from government bodies.

Packaging has a significant role in understanding and overcoming the above through systematic and innovative approach.

In this article focus is given to solid dosage forms for oral administration. There are many packaging challenges in other dosage forms such as liquids, parenterals, inhalation products etc.

• Pack presentations which are widely available are
• Blister packs ( for unit dose)
• Strip pack ( for unit dose)
• Container pack (for multidose)
• Sachet pack for granules/ pellets/powder for unit dose
• Pouch pack for semifinished bulk ( ready to compress granules)
• Pouch pack for bulk transfer pack for repacking

Molecule / formulation challenges
Of late the molecules which generic industry is focusing are complex in nature and highly sensitive to moisture , oxygen or both which impacts physical and chemical stability. Each molecule has two or more polymorphs and it is essential to control the change of one polymorph to other to ensure stability and compliance. Change of polymorph will impact dissolution and bio equivalency and also impurity levels . The change may occur not only during storage but during usage also . Hence packaging has a big challenge to control the same.

In addition molecule sensitivity to moisture, oxygen, light and heat also poses problem in stabilizing the formulation and control of in impurity levels within the regulatory limits. Hence selection of right primary packaging material with desired barrier properties is crucial for providing stability throughout the shelf life. Some times the increase in impurities may not surface during accelerated stability studies hence worst case studies shall be planned depending on probable degradation products such as hydrolytic impurities or N-oxide impurities.

Selection of desiccants such as silicagel, molecular sieves, their quality and quantity also plays important role in stabilizing the API/formulation . Some times excessive dessication also poses problem of over drying and brittleness especially for formulations in hard gelatin capsules.

Regulatory challenges
Requirements from regulatory agencies are increasing in the interest of patient safety both in developed and emerging markets. Elaborate data regarding selection of packaging materials, MSDS, identification tests, pack development report, stability compatibility studies , DMF /EDMF access letters , food grade certificate, heavy metals content etc. needs to be submitted along with the dossier. For alternate vendor development, equivalency report with stability data back up needs to be submitted.

Also data on extractables and leachables , migration of ingredients of inks and adhesives to be submitted. It is also observed migration of UV curing agents such as Benzophenone and 4- Methyl Benzophenone from the printing inks on a label into the formulation through the container closure system. Hence it is necessary to ensure inks free from above ingredients and carryout worst case studies at high temperature for short time.

Apart from these they are specific labelling requirements for each country which need to be complied .

Patent challenges
There are many patent challenges in packaging covering container closure system , barrier properties , Child resistant packaging solutions and type of folding of a pack outsert etc.

Process related challenges
In spite of selecting the best Primary packaging, process/ operational issues such as leak test failure, ink lifting, delamination ,pinhole formation, improper nitrogen flushing and control etc. can degrade the quality and impact stability of the product . This will increase quality checks, pack stock failure, wastage of packaging material and low yield which will increase operational cost. Hence proper machine trials and packaging validation are advised to overcome the above issues. Also we need to exercise controls in usage of oxygen absorbents to avoid unnecessary exposure to environment .

Customer convenience and safety
In the regulated markets especially US there is a requirement for child resistant packs both for unit dose and multi-dose packs. This requirement is for unit of use packs ( packs reaching the customer directly). The container-closure

System shall be child resistant at the same time senior friendly. While selecting container closure system this requirement also to be considered and the pack needs to be evaluated by authorized testing agency for compliance. Subsequent variation if any in the container closure system or the design of opening mechanism needs to be evaluated before introducing into market. Designing of blister pack and the forming and sealing materials shall be decided based on Toxicity value( ‘F’ value) of the molecule. Every manufacturer needs to generate’ General certificate of conformance’ stating the CR testing details for each batch of the product to be marketed in the US.

Counterfeits
Most of the pharmaceutical companies all over the world are facing threat from counterfeits which impacts both top line and bottom line of the company. Counterfeits also spoil the brand image and corporate image .

Counterfeitors copy the packaging to make it identical to the original product . Hence packaging technologists have a major challenge to make the packaging complex and difficult to copy through design and printing and also build overt features( which can be identified by customer without any special gadget) and covert features ( authentification features which need special gadgets for identifying the same such a UV torch or polarised screen etc). It is advisable to have a combination of overt and covert features on the pack.

Many countries are adopting serialization /track and trace to ensure supply chain integrity and authentification of product by customer. This requires complete upgradation of packaging line to build parent-child relation among the primary, secondary and tertiary packs and re-designing of packs .

Cost
While complying to all the regulatory and statutory requirements one needs to be competitive in the market. There are multiple players in the generic segment hence stiff  competition in the global markets. Some times it is observed packaging cost will be more than the API /excipients especially for older molecules. Also there are markets governed by tenders where in it is necessary to be price competitive. Change in government policies also impact pricing and margins. Hence it is important to control the packaging cost by avoiding over- packaging, increasing automation and with continuous improvement .

Packaging technologists shall pay proper attention to all these challenges during selection of primary/ secondary packaging and design necessary controls and validation studies to overcome the same . This will avoid any surprises in meeting the launch schedules , meeting customer expectations most importantly regulatory compliance .