When the packaging becomes the burning question

Cleanroom-compatible plastic packaging ensures the quality and hygiene of pharmaceutical products. (Image: Strubl)

The EU Regulation PPWR introduces new requirements for packaging materials – also in the sensitive field of medical technology. (Image: Strubl)

Cleanroom packaging made of plastics ensures the quality of pharmaceutical products – but is under pressure due to new EU regulations balancing patient safety and sustainability. This article shows how PPWR and GMP requirements can be harmonized.

In the production of pharmaceutical or medical device products, high standards for product quality, cleanliness, and hygiene must be met. The avoidance of particulate, chemical, and microbiological contamination is possible when primary packaging materials are produced in a qualified cleanroom environment. However, plastic packaging has come under scrutiny in recent years as a critical element in environmental and sustainability discussions. The European Union has responded with the recently adopted Packaging & Packaging Waste Regulation (PPWR). For cleanroom plastic packaging, these changed framework conditions must be analyzed and assessed based on risk.

Risk-based consideration of cleanroom plastic packaging

The importance of primary packaging materials, especially for pharmaceutical products, is beyond question and is clearly articulated in the GMP guideline in Chapter 5.45: “The selection, qualification, approval, and ongoing monitoring of suppliers of primary and printed packaging materials should receive as much attention as that given to raw material suppliers.” Packaging is therefore classified at the same qualitative level as pharmaceutical raw materials. This applies to the entire process chain for manufacturing pharmaceutical products.

And a risk-based assessment of the primary packaging materials made of plastics is unavoidable. Essentially, four groups of underlying contamination sources can be identified:

• Raw material risks: Here, the focus is on the interaction between packaging and product and the resulting risks to product quality. This should be analyzed in advance through migration studies or extractables/leachables studies and avoided through specifications for compliant raw materials. These risks are also addressed in VDI 2083, Sheet 9.2, Section 16.2 "Packaging Materials": “Contamination of the product through migration... must be excluded.”
• Process risks: It is essential to ensure that contamination of the cleanroom or GMP environment by inadequately qualified packaging is avoided.
• Logistics risks: It must be clarified how the ingress and egress of products and consumables/usage materials are to be managed.
• Product risks: Here, the focus is on product-technical criteria of the packaging, such as tightness, strength, sealability, and sterilization barrier properties.

GMP-compliant cleanroom production creates quality

The goal is to prevent contamination of sensitive products. Microbiological and particulate contamination must be avoided to ensure product protection and patient safety. The motto “Create quality, not test it” means producing the plastics used in a cleanroom environment and GMP-compliant. This is understandable when considering the chemical processes involved in product-contacting packaging. The function of migration analyses for food packaging under the EU Regulation 10/2011 on plastics materials and articles, as well as extractables & leachables studies in pharmaceuticals—such as those described in FDA, EMA, USP, EP guidelines—is precisely to identify, qualify, and assess the critical effects of packaging materials on the product ex ante, based on risk. This ensures consumer—and patient—protection.

Primary packaging in EU Regulation 2025/40 (PPWR)

Packaging has become a topic of societal debate for various reasons. On one hand, it is important to reduce packaging waste and reintroduce it into the circular economy to improve sustainability and environmental standards. On the other hand, packaging plays a significant role in product and patient safety. The sustainability discussion is centered around keywords such as recyclability, material reduction, mono- versus multi-materials, labeling requirements, chemical recycling, bio-based plastics, or biodegradable plastics. The EU has established binding requirements with Regulation 2025/40 (PPWR - Packaging & Packaging Waste Regulation). From the perspective of pharmaceutical and medical device primary packaging, Articles 6 (Recyclable packaging) and 7 (Minimum recycled content in plastics) are particularly relevant, as there are important exceptions to consider. Articles 6, Section 11, and Articles 7, Sections 4 and 5, regulate exceptions, including for primary packaging, contact-sensitive packaging of medical devices and in-vitro diagnostics, and packaging necessary to meet specific requirements for maintaining product quality.

The pharmaceutical process chain must clarify:

• Which provisions of PPWR apply to the specific packaging system?
• Which exceptions are applicable, and if not, what does the use of recycling quotas mean for approvals and specifications?
• Independently, it makes sense from an environmental and sustainability perspective to scrutinize the used packaging and, as far as possible and sensible, apply principles of ecodesign as proposed by the “Round Table” initiative. It’s about “Design for Recycling.”

From the perspective of GMP or cleanroom packaging, the requirement for mandatory recycled content quotas presents a particular challenge. It concerns questions of approval, material purity, and formulation consistency. For example, how does the use of post-consumer recycled material (PCR) affect extractables & leachables studies as a prerequisite for approval? What consequences are expected regarding process purity in the cleanroom? It would be disastrous if the safe, clean, and efficient plastics used as primary packaging materials—proven to serve the purpose of protecting the product—become a contamination risk due to PPWR regulations, thereby potentially endangering product and patient safety.