The Critical Role of Primary Packaging

Material properties, the need for a cost/benefit approach to material selection and manufacturing, and best approaches in process validation, were highlighted in a session on “Critical Selection of Primary Packaging” at Interphex.
 
“The importance of packaging is underestimated. That is one reason we are seeing a lot of issues being raised with recalls,” said presenter Shams Haque Rustom, senior director, product development and manufacturing, Labopharm (www.labopharm.com).
 
As packaging that immediately envelopes the product, primary packaging “provides most of the strength and barrier needed to safeguard the product’s purity, potency, and integrity from the time it leaves the assembly line until it is used by the consumer,” Rustom said.
 
Rustom described four criteria that influence package selection.
 
● A company’s national or global strategy and goals that accounts for local regulations and sku popularity in different countries.
 
● Assuring product stability against different climate zones.
 
● Requirements for compliance features such as senior-friendly and child-resistant.
 
● Also, material cost and benefits. “I call this ‘profitable manufacturing practice.’ In a very competitive global market place, we need to put continuous effort in cost reduction. Cost effective packaging material needs to be selected at an early stage of the package development process,” Rustom said.
 
Blister film and film structures feature moisture vapor transition rates (MVTR) ranging from the near-perfect barrier of cold form foil to a low-barrier 25µ PVC monofilm.
“Blister films are complicated and difficult to choose. The blister film industry is rapidly growing and evolving with new innovations appearing every year,” said Rustom.
 
In barrier blister films, triplex structures have offered manufacturing advantages.
Triplex PVdC-coated PVC films feature less shrinking in thermoforming, as these films provide medium barrier against moisture and oxygen. Triplex PCTFE laminations also “are more forgiving in thermoforming and are historically the material of choice (versus PCTFE duplex structures).
“But the duplex PCTFE structure is gaining greater acceptance as a structure with better clarity, higher yield, and lower cost,” Rustom said, noting the PCTFE duplex films are widely used outside of North America.
 
PCTFE copolymers have 95% PCTFE content, and 40% to 50% less barrier than PCTFE homopolymers. “The PCTFE homopolymer is a more recent introduction and is more cost effective,” Rustom said.
In comparing PCTFE with PVdC, Rustom noted that PCTFE provides a longer shelf life without yellowing. PVdC offers oxygen barrier properties.
 
Suppliers offer support and different kinds of tools for evaluating blister film performance before and after forming. Some suppliers also offer quick service to evaluate the optimum barrier required for a specific drug product using their own software tools.
This can provide a great deal of time and cost savings for the client, Rustom said.
“The MVTR in a PVdC-coated PVC film increases post-forming as thinning reduces the barrier. PCTFE also has post-forming degradation but not to the same degree. By optimizing your process you can control the thickness of the product. And PCTFE will be better for forming angular cavities. PCTFE can be cost effective versus PVdC, but it depends on the barrier you need,” Rustom said.
 
Rustom said that manufacturers should take care to specify the winding of the PCTFE or PVdC side out or in for the slitting roll depending on the machine configuration.
“This is a simple issue, but it can go wrong. You need to verify and check the incoming material as to whether the PVC is wound in our out. The alu lidding always seals to the PVC side,” Rustom said.
 
Manufactured in a cost effective co-extrusion process, COC’s barrier depends on its thickness. The polymer’s advantages include that it is halogen, chlorine, and PVC-free and features excellent clarity and thermoformability.
COC films are a viable alternative to PVdC 90 gram weight and up, and PCTFE high moisture barrier films of 0.35 to 0.23 g/m2/day at 38C/ 90 RH.
“COC is the highest moisture barrier polyolefine, though it doesn’t have the best oxygen barrier,” he said.
In bottle packaging, glass provides perfect barrier and inertness, but is fragile and heavy weight.
 
Among polymer bottles, PET and HDPE offer the advantages of light weight and excellent impact resistance, but may have component migration that affects product stability. Widely used in pharma for its stiffness, toughness, strength, and high moisture resistance, HDPE is however more permeable to oxygen than PET-G and O-PET. “An HDPE bottle can be the best and cheapest choice, if the target market allows it,” he says.
 
A packaging trial strategy should precede packaging process validation. Speed and temperatures parameters are established for critical SKUs in the trial.
In the validation process, a cost effective matrix approach can be used for multiple SKUs, if the appropriate design space is established during the packaging trial. A number of batches are selected to run for each sku and the range of each critical process parameters is validated during the run.
 
In packaging material changes, changes are classified with CDER as minor changes if a CDER-approved material provides the same or better properties and the product contact layer remains the same. Packagers must document with CDER that “any new primary packaging component materials have been used in and been in contact with CDER approved products of the same type. Document the changes in the next annual report to FDA for each drug product.”
 
“In the next five to ten years, we will continue to see changes in materials. Packaging accounts today for up to 50% of the cost of goods” and price increases in certain materials have added to packaging costs.
“Suppliers need to provide value added service and share information, as manufacturers and suppliers work together to decide on needs and processes,” Rustom said.
 
 
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