The revised EU GMP Annex 1 guideline places contamination prevention within a coordinated, risk-based strategy. It identifies containers, closures, supplier approval, and outsourced activities as elements to include in a Contamination Control Strategy (CCS). For drug manufacturers, the practical task is to link component specifications and supplier controls to their own processes, with evidence that the controls work together.

This comprehensive strategy requires looking closely at specific sources of risk, as primary packaging components such as a stopper or plunger can introduce contamination before a drug reaches the filling line. Their formulation, manufacturing environment and handling all influence the risks that pharmaceutical manufacturers must assess. Developing a contamination control strategy (CCS) ready for EU good manufacturing practice (GMP) Annex 1 therefore involves understanding how primary packaging components are manufactured and prepared for use.

According to Alison Phillips, PhD., Technical and Scientific Expert at Datwyler: “Instead of just telling you what to do, [the revised Annex 1] demands you understand why you’re doing it through science and data.”

Preventing contamination during component manufacture

When manufacturing primary packaging components, particulate control starts well before final washing. Raw materials, equipment, utilities, and personnel can all introduce contamination, so the design of the manufacturing environment is an important factor when evaluating a packaging component supplier.

Datwyler is a leading supplier of stoppers, plungers, and aluminium seals for pharmaceutical packaging. The company’s FirstLine® manufacturing approach progressively tightens environmental controls as components move towards completion. Separate visitor and operator corridors, together with distinct product and waste flows, help limit opportunities for contamination. Datwyler also has paper-free manufacturing areas at its Middletown facility in Delaware, where barcodes and scanners replace paper records, removing a potential source of cellulose particles.

Automation can reduce operator handling during processes such as moulding, spray coating and washer loading. Camera inspection provides further control by removing components with detectable defects before they reach the customer. These measures support prevention and detection at multiple stages, rather than leaving the pharmaceutical manufacturer to address the entire contamination burden during filling.

Purchasers should also determine which processing steps are included in their chosen supply format. Bulk components leave washing and sterilisation to the customer. Ready-to-sterilise components arrive washed but still need sterilisation, while ready-to-use components arrive washed and sterilised. Datwyler reports that its ready-to-sterilise and ready-to-use FirstLine® products undergo a validated wash programme that reduces contaminants by at least 99.9%.

Supplier processing can reduce the customer’s equipment and validation workload. However, the pharmaceutical manufacturer must still assess how incoming components, handling and transfer align with its CCS.

Selecting materials for the full process

Component selection also influences contamination risk during a drug’s use phase. Friction between components can generate particles, and some silicone emulsions can add to the particulate load. Coatings should therefore be chosen with both functional performance and cleanliness in mind.

Datwyler’s OmniFlex® stopper and NeoFlex® plunger coatings use fluoropolymer spray technology to reduce friction and create a protective barrier between the drug and rubber. Phillips explains that the coatings are paired with the company’s FM457 bromobutyl formulation to support drug compatibility and minimise extractables and leachables. Supplier data should inform assessments of the intended drug, packaging configuration, and processing conditions.

Sterilisation compatibility belongs in that early assessment. Where a sterilised component subsequently undergoes terminal sterilisation within the filled container, manufacturers need to evaluate the combined exposure. A material suitable for one sterilisation method may not be suitable for every sequence or combination.

“The pharma customer will need to understand their end-to-end sterilisation strategy before starting development,” says Phillips.

Packaging and transfer require the same attention. Annex 1 calls for qualified packaging compatible with the selected sterilisation method and validated sealing processes. It also requires consideration of sterile barrier integrity and assigned shelf life. Ported bags can support transfer into controlled environments, but the receiving facility must demonstrate their suitability within its process.

Turning supplier controls into audit evidence

Audit readiness depends on documenting how these decisions address identified risks. Quality teams should request evidence of washing and sterilisation validation, cleanroom qualification, environmental monitoring, inspection processes, and applicable component specifications.

Phillips says Datwyler has a general CCS, along with site-specific strategies, which it shares with customers during audits. The company also includes sterilisation parameters in certificates of analysis, helping customers link supplied components to their processing history.

That evidence should guide supplier qualification, including the assessment of backup sources. Comparable specifications should be supported by an understanding of the manufacturing and contamination controls behind them.

An effective component strategy integrates material selection, processing, protective packaging, and supplier documentation to the pharmaceutical manufacturer’s operations. Establishing these connections early gives quality teams a stronger basis for defending decisions and maintaining contamination control throughout the product lifecycle.

To find out more about how Datwyler can support your contamination control strategy and Annex 1 readiness, download the whitepaper below.