From the cleanroom for the cleanroom

Fig. 1: Typical use of foil bags in a cleanroom production at Röchling-HPT.

Example: Cleanroom bag for primary packaging

Example: Cleanroom bag for pharmaceutical products / API

Preventing contamination is one of the main concerns of risk analyses related to the cleanroom environment. All factors must be examined for their respective contamination risks. Packaging plays a special role here because it serves as a primary packaging that directly contacts the product, and handling of the packaging is relevant to cleanroom processes. STRUBL Kunststoffverpackungen has developed special cleanroom packaging for this highly sensitive application, which can be used in cleanroom- and GMP-compliant environments and helps avoid contamination risks to the product and in the process.

The classic packaging functions can be described based on the characteristics of protection function (contamination, counterfeiting), logistics function (transport, distribution, storage, handling), and information function (identification, instructions for use, advertising). However, for the fields of medical technology and pharmaceuticals, these functions must be expanded to include additional industry-specific factors, as these industries produce under controlled conditions. These requirements are described in numerous standards and guidelines. The focus is on GMPs, cleanroom, and medical device requirements. Cleanroom production is found both in the life sciences sector – i.e., pharmaceuticals, medical technology (see Figure 1), food – but also in technical industries such as chip manufacturing, (micro)electronics, optics, photovoltaics, or automotive. The product spectrum manufactured in cleanrooms is enormous and includes, for example, active pharmaceutical ingredients, implants, medical components, parts, and assemblies. As a result, cleanroom consumables in general and packaging materials in particular pose special contamination risks for the pure product and the pure production environment.

With the publication of VDI Guideline 2083 Sheet 9.2 titled "Cleanroom Technology – Consumables in the Cleanroom" in January 2017, a practical guide for assessing consumables and packaging materials is also available. Packaging materials, including plastic packaging such as tubing, bags, sacks, pouches, and heat-sealable bags, must not impair or contaminate the cleanroom environment due to their high quality standards in an ISO 14644 cleanroom.

The GMP guideline binding for pharmaceuticals emphasizes the importance of packaging by requiring that packaging materials be subject to the same quality standards as raw materials and other starting materials: "The selection, qualification, approval, and maintenance of suppliers of primary and printed packaging materials should receive as much attention as that given to suppliers of starting materials." (see GMP Chapter 5.45).

Plastic packaging – including bags, sacks, gusseted bags, cuttings, films, and tubing made of plastic – is the widely used packaging medium in GMP and cleanroom production at all levels of the value chain. Raw materials and starting materials are packaged in plastic packaging just as intermediate products, assemblies, individual parts, and of course the final product. From the perspective of each product, film packaging is also classified as a "primary packaging material" at every stage of the value chain. Accordingly, the requirements for producers of these primary packaging materials are very high, as it concerns risk, safety, and the avoidance of contamination risks:

• Product safety in terms of consumer protection: protecting the product from contamination by the packaging
• Process safety in terms of GMP and cleanroom suitability: protecting the process environment at the user of the packaging materials

In summary: Packaging used in GMP/cleanroom environments must meet the same quality requirements as the product manufactured in GMP/cleanroom conditions. A detailed packaging specification must serve as the basis. The GMP guideline defines the following requirements in Section 4.11: "Specifications for starting materials and packaging materials: The specifications for starting materials and primary or printed packaging materials should (where applicable) include: a) a description of the materials with the designated name and internal reference code; if available, reference to a pharmacopoeia monograph; indication of approved suppliers and, if possible, the original manufacturer of the products; a sample of the printed packaging material; b) provisions for sampling and testing or reference to relevant procedures; c) qualitative and quantitative requirements with permissible limits; d) storage conditions and any precautions; e) the maximum storage duration until re-evaluation."

STRUBL Kunststoffverpackungen has met these demanding requirements by developing a production system for manufacturing GMP- and cleanroom-compliant plastic packaging. The system considers the recommendations of various relevant standards, which can be used for process or product design, such as:

• EC Guidelines on Good Manufacturing Practice
• DIN 15378, DIN 15593, DIN 11607, DIN 11137, DIN 11737
• Cleanroom technology: DIN 14644, DIN 14698, VDI 2083
• Food packaging, IFS / BRC, EU 10/2011
• EU Pharmacopoeia / USP / FDA 21 CFR

An important factor in the development and selection of plastic packaging in pharmaceuticals and medical technology is the assessment of the raw materials used. The new VDI guideline 2017 "Medical-grade Plastics" provides an important framework here. It also emphasizes the critical collaboration within the supply chain, from raw material manufacturer through plastic processor or packaging manufacturer to the end user of the plastic products and packaging materials, to ensure high reliability and transparency.

STRUBL develops and produces customized cleanroom packaging for individual customer specifications: in addition to flat and (semi-)tubular films, mainly bags and sacks, gusseted bags, block-bottom bags, multi-chamber, double bags, and sterilization bags. A particularly interesting solution for loading and unloading in multi-stage cleanroom zone concepts is the use of so-called sack systems. STRUBL supplies these as interlocked sack systems. At the customer site, they are opened, and the inner bag is filled with products. Then, the individual bags are sealed separately and can later be removed sequentially in the cleanroom process, similar to a "onion skin" model. This eliminates the complicated handling during filling in the cleanroom. The products are manufactured in a GMP-compliant cleanroom using state-of-the-art technology. Based on an ISO 9001 quality management system, a professional GMP system has been implemented. This includes specifications, monitoring, hygiene management, cleaning concepts, risk analysis, traceability, validation, and more. With over 70 years of experience, the medium-sized family business supplies renowned manufacturers in the pharmaceutical and medical technology industries, as well as companies in chemistry, automotive, food, and microelectronics, with these cleanroom packaging solutions.