NovaPure®: The Quality by Design Portfolio to Meet Your Drug Primary Packaging Needs for EU GMP Annex 1

Since 25 August 2023, the revised European Union guidelines for Good Manufacturing Practice (EU GMP) Annex 1 has imposed requirements to implement a Contamination Control Strategy (CCS) across the facilities of finished drug product manufacturers, to ensure higher quality and sterility of medicinal products for human and veterinary use.

With Section 2.5 (Part vi) of the EU GMP Annex 1 listing Product Containers and Closures as an element to be considered within a CCS, new challenges are likely encountered in finding the ideal elastomeric closure that can meet the more stringent needs of a high value drug, now that primary packaging components are added into the scope of this globally endorsed document.

Furthermore, with Section 8.2 stating "Primary packaging containers and components should be cleaned using validated processes to ensure that particulate, pyrogen and bioburden contamination is appropriately controlled” and Section 8.36 emphasizing "All sterilization processes should be validated", the revised Annex 1 will require finished drug product manufacturers to have more knowledge of the container closure system used.

While finished drug product manufacturers will have to bear the final responsibility for ensuring compliance with the EU GMP Annex 1, NovaPure® elastomeric components are a premium portfolio by West that can be part of the solution to ensure the CCS objectives are met.

All NovaPure® elastomeric components are laminated with FluroTec™ film, treated with B2 coating, go through validated wash process and further sterilization (for Ready-to-Use products) and finally 100% Envision™ automated vision inspection.

Firstly, FluroTec™ barrier film is a proprietary poly(ethylene tetrafluoroethylene) barrier film that reduces risk of chemical or drug interactions with the elastomer when molded onto the plug side, which will be critical for maintaining drug purity and potency. With nearly three decades' history, FluroTec™ film-laminated components have a demonstrated track record of supporting a broad range of molecules for drug product approvals across the global regulatory agencies.

B2 coating is a technology licensed from Daikyo Seiko, Ltd which involves spraying of cross-linkable poly(dimethylsiloxane) to the surface of elastomeric closures, followed by an additional step of cross-linking by UV light. Compared to the conventional siliconization process where loose silicone oil is applied, B2 coating reduces the amount of potentially-extracted silicone oil, particularly at higher pH levels, and is demonstrated to have lower levels of particles. . Collectively, FluroTec™ film and B2 coating mitigate significant risks related to E&L, drug potency, and at the same time improve machinability by providing lubricity. Most importantly, particulates, which is a primary concern in CCS, are greatly reduced.

Secondly, the pharmaceutical wash process by West for all NovaPure® components is validated on an annual basis according to cGMP requirements to demonstrate an endotoxin content reduction by at least 99.9% (3.0 log₁₀). The particulate, bioburden and endotoxin levels are reported in the quality certificate that is provided with every wash load, which is one of the many critical documents that a primary packaging component supplier like West can provide to prove compliance to Section 8.2 of Annex 1.

For Ready-To-Use grade, NovaPure® elastomeric components further undergo the steam sterilization process to assure a minimum sterility assurance level of 10⁻⁶ that is based on ISO 17665-1 and 17665-2. Biological indicators are used to demonstrate appropriate kill as part of the validation approach, which is also compliant with the cGMP requirements in Section 8.36 of Annex 1.

Lastly, prior to the bagging process, the NovaPure® elastomeric components undergo Envision inspection, which is an automated high-resolution vision inspection process that takes place in an ISO 5 (Grade A-equivalent per EU GMP Annex 1 classification) environment. This validated process consisting of multiple camera arrangements is configured according to the individual component design and formulation and provides consistent control of >99% critical visual defects. With a feedback loop principle, the information on the defects collected is provided back to the manufacturing stage (from compounding to trimming) for continuous improvement. By detecting defects and gross particulates (detection limit of >0.05mm²) at an early stage after the pharmaceutical wash process, Envision process reduces instances of end-of-line rejects at the filling process and could help to cut down on the loss of high-value drug products.

NovaPure® Vial Stoppers

With vial containment being the conventional solution for many sensitive, high-value biologics and small molecule drugs, the configurations available in the NovaPure® portfolio are 13mm and 20mm for both serum and lyophilization stoppers. The stoppers are available in two halobutyl formulations (bromobutyl and chlorobutyl) to cater to the myriad of drugs with varying properties.

Notably, NovaPure® stoppers are also part of the West ReadyPack™ offering, a vial containment solution in which the sterile and ready-to-use components comprising vials, stoppers and seals have been designed to be used and dimensionally fit together by testing for Container Closure Integrity. ReadyPack™ is suited for multiple development and commercial purposes and offers a smooth transition from early-stage pilot manufacture.

NovaPure® Pre-filled Syringe & Glass Cartridge Components

In a survey of health care providers (HCPs) and patients conducted by APCP Insight, there is significant interest in self-administered injectables and on-body delivery systems (OBDS). 90% of patients and 93% of HCPs say administering prescription injectable medicines at home helps patients be more involved in their health.¹ As evident, the global prefilled syringes market and global pharmaceutical cartridges market were estimated to be worth USD 7.27 billion² and USD 1.41 billion³ respectively in 2023.

In view of this market trend, the NovaPure® components portfolio includes the 1ml long & 1-3ml plungers for pre-filled syringes used in auto-injectors, as well as 3ml cartridge plungers and 8mm lined seals for use in 3ml glass cartridges, which are the typical primary containers for wearable injectors and auto-injectors. These NovaPure® components are steam-sterilized and come in the bromobutyl formulation, which promises the tightest particulate specifications within West.

Designed without need for added silicone oil to optimize break loose and glide force performance and released to a Process Capability Index (CpK) of ≥ 1.33 for Critical Dimensions, NovaPure® plungers have consistent dimensions with low variability, leading to reliable functional performance and consistent injection rates, which are critical for auto-injector drug applications.

In addition, the NovaPure® 8mm lined seal, which is for single-puncture use, has a stopper-like elastomer liner instead of the conventional disc-shaped one. It has been specially designed for sensitive biologics and complex drug products, which warrants an improvement in the performance compared to the traditional cartridge components.

Flexible Secondary Packaging Options for NovaPure® products

To address the wide-ranging needs within the medicinal product industry, NovaPure® components are available in Ready-to-Sterilize grade (for stoppers only) or Ready-to-Use grade (for stoppers and plungers), allowing flexibility in the drug development and manufacturing process. Not to mention, the components are packaged in both small quantities for trial testing needs as well as large quantities in STERILizableBAG™ or ported bags for use with Restricted Access Barrier Systems (RABS) and isolator filling lines. RABS and isolators are the two barrier technologies strongly recommended in the CCS as mentioned in Section 4.3 of the Annex 1, whereby "any alternative approaches to the use of RABS or isolators should be justified."

In summary, NovaPure® elastomeric components is a line of products developed with in-depth product and process knowledge based on Quality by Design (QbD) principles that are driven by Voice of the Customer (VoC) and offers the best-in-class levels of quality, performance, and risk mitigation. With the QbD approach, there is commitment to continuous improvement in offering the tightest particulate specifications through a systematic and science-based approach in the manufacturing process.

To find out more about how cGMP-compliant NovaPure products and the services offered by West can help with your CCS strategy while keeping patient safety as a top priority, contact us here.