Designing Packaging Systems for Regulatory Compliance and Quality

Manish Jain is the Founder & Managing Director of Cilicant, a global leader in active pharmaceutical and food packaging solutions. With over 30 years of expertise in active packaging chemistry, he has pioneered regulatory-compliant, shelf-life-extending, and sustainable desiccant technologies that safeguard product efficacy across pharmaceuticals, nutraceuticals, medical devices, and FMCG.

A few months ago, I came across the story of an Indian pharmaceutical exporter whose shipment to the US market was rejected at the port. This rejection had nothing to do with product formulation or its manufacturing and safety process.

But they found later that improper moisture protection had compromised the product’s stability during transit. The result of this was a heavy financial loss – in millions. The hidden impact was even greater - months of regulatory remediation and the slow work of regaining the trust of the US FDA.

And this is not a one-off case. In 2023, 14 percent of FDA import refusals for pharmaceuticals cited packaging or labelling-related challenges. At Cilicant, we manufacture desiccants and oxygen absorbers for pharmaceutical applications, and from our years of experience, we know how one misstep in packaging can set off a chain of compliance related challenges across geographies. The math is simple. Proactive packaging design costs thousands, reactive corrections cost millions. Yet active packaging continues to be an afterthought in too many organisations.

For India’s pharmaceutical sector, which exports to over 150 countries and contributes around 50 billion dollars annually to the economy, packaging compliance has moved beyond a technical concern. It is now central to business continuity, profitability, and global reputation.

Also Read: Balancing Innovation and Affordability in Medical Solutions for India

The multi-market challenge

For Indian manufacturers, Schedule M lays the foundation for packaging compliance. But for pharmaceutical manufacturers who export, this is just the starting point.

Our manufacturing facility routinely manages specifications that must satisfy India’s CDSCO guidelines, the US FDA’s 21 CFR requirements, and the European Medicines Agency’s stringent standards simultaneously. The real difficulty arises in material specifications. Schedule M prescribes GMP processes, but it does not define the detailed performance metrics that regulators abroad demand.

Take container closure integrity, for example. The FDA requires precise validation of MVTR and OTR limits. European regulators add their own emphasis on extractables and leachables, expecting pharmaceutical-grade materials backed by extensive toxicological assessments; thus requiring a manufacturer to make a strategic choice. They can either develop multiple packaging variants for different markets or invest in materials that meet the highest global standards. While the second choice requires a higher upfront cost, it enables smoother entry across multiple geographies and eliminates reformulation or revalidation delays.

Performance parameters that shape compliance

One of the most common oversights we see involves understanding the right moisture protection for a formulation. Products headed to tropical climates need desiccants that maintain relative humidity below 40 percent throughout its journey from manufacturing, to shipping, storage, and distribution.

These calculations are complex. A 100-tablet bottle may demand very different desiccant capacities depending on how hygroscopic the drug is, the container’s moisture barrier, and the intended shelf life. Many specifications that pass six-month stability studies end up failing under 24-month real-time conditions because cumulative moisture ingress was underestimated.

Oxygen-sensitive formulations bring their own challenges. Products such as biologics and vitamins can lose potency if oxygen levels cross even 2 percent in the headspace. Standard calculations often ignore two critical realities — oxygen transmission through closures and oxygen released by excipients during storage. If this is not accounted for, degradation may only be discovered during stability testing, when it is too late to adjust.

What actually causes failures

In many cases, failures happen because real-world conditions are very different from laboratory assumptions. Consider a batch of tablets manufactured with 3 percent moisture content, packaged with a desiccant designed for temperate climates. If this shipment spends weeks in a shipping container at 40°C and 90 percent humidity, the original calculations no longer hold.

We once worked with a generic manufacturer preparing for a US launch whose oxygen ingress tests exceeded targets. By switching to a higher-capacity oxygen absorber and validating it for 24 months, they secured FDA approval six weeks ahead of schedule, avoiding an estimated Rs 9 crore in market delays.

The value of certified manufacturing

ISO 15378 is the benchmark for pharmaceutical primary packaging material manufacturing. It integrates GMP principles into the quality management system for materials in direct contact with medicines.

In our own cGMP-compliant facility, every batch undergoes stringent quality control. Raw materials are qualified, environments are monitored, in-process tests are documented, and final products are released under strict protocols.

This alignment matters during audits because regulators do not just audit the pharma manufacturers but also scrutinise their suppliers. ISO 15378 certification attests that packaging suppliers follow the same discipline as the pharmaceutical companies they serve. It protects regulatory standing by transferring compliance responsibility to qualified vendors. Certifications, supported by Drug Master Files, strengthen a manufacturer’s ability to demonstrate diligence when failures are investigated.

Also Read: How PLI Scheme is Reshaping India's Drug Production Future

Looking ahead: Sustainability and Smart systems

The future brings new pressures. Sustainability is all that the packaging community is talking about. Regulators and consumers are both calling for greener packaging. But the current biodegradable or recyclable packaging options do not offer the same protection against moisture and oxygen as the traditional packaging materials do. The trade-off requires a balance between environmental goals, product stability, and patient safety.

Serialization and track-and-trace systems are another force reshaping packaging. Electronic components embedded for tracking can create microclimates inside packages. Temperature shifts from these components can accelerate moisture migration or change absorption dynamics. This requires recalibrating desiccant and oxygen absorber performance from the start.

At the same time, testing protocols are evolving. The shift towards real-time monitoring of package headspace conditions may soon replace traditional end-point stability checks. This will pave the way for smart packaging with continuous feedback, but also demand higher sophistication in material specifications and supplier validation.

Practical considerations for manufacturers

For any company evaluating packaging material suppliers, three questions are fundamental.

1. Do they provide relevant certifications for pharmaceutical packaging?

2. Do they maintain relevant Drug Master Files?

3. Can they demonstrate batch-to-batch consistency with validated data?

It is equally important to ask for performance data that reflects actual shipping and storage conditions. Generic test results rarely capture the real journey from the manufacturing line to the consumer. This is where accelerated aging studies become critical, helping predict stability across the product’s intended shelf life. This data not only supports regulatory submissions but also provides confidence in label claims and market commitments.

The way ahead

Packaging materials are often seen as cost centers. In reality, they are as vital to product quality as the formulation itself. Compliance is not just about passing inspections, but it is also about maintaining patient safety, protecting brand reputation, and ensuring consistent market access.

From where I stand, the question is no longer whether pharmaceutical manufacturers can afford to invest in high-quality packaging materials. The real question is whether they can afford the risks of not using them.