KSR: As a supplier to the pharmaceutical industry, how are you overcoming the challenges associated with aseptic processing?
ES: Safety and protection have been key DuPont values, for both internal and external processes, since the early days of the company in 1802. This heritage was converted into a variety of businesses that addressed the protection needs of people, products and processes in a number of industries.
With regard to the pharma/healthcare sector, DuPont’s Tyvek material is largely specified and proven to work in personal protective equipment and for protective packaging. Medical-grade Tyvek, mostly used for primary medical device packaging, is designed to comply with EN ISO 11607-1 — as noted in the EU Medical Device Directive (MDD) — and its future successor, the EU Medical Device Regulation (MDR).
The strong, ongoing market demand for this decades-old product line has prompted us to invest in a new production facility in Luxembourg, which is currently under construction. Such capacity expansion reflects our long-term commitment to supply the market with quality product. Many of our end user customers may remember the testing and data generation efforts we made to mitigate change management work at end-user level.
This so-called Tyvek Medical Packaging Transition, completed in 2015, meant we could successfully interact with many value-chain players and end-users in both the medical device and the pharmaceutical industry to address their questions at this time.
KSR: What are the biggest issues to address when it comes to product protection in pharmaceutical manufacturing?
ES: It’s not news, but microbiological and particulate contamination risks are the biggest challenges in aseptic processing. Yet, the rapid rise of biologics has triggered a more intense focus on contamination control. The review drafts of EU GMP Annex 1 emphasise the use of a more holistic approach when designing a contamination control strategy.
Manufacturers need to validate the packaging process and apply quick response manufacturing (QRM). As there is more automated processing nowadays, packaging configurations need to allow for easy and safe processing (dimensionally stable with low variability).
Any manual intervention owing to packaging failure may involve high costs and contamination risks, not to mention downtime mitigation and reduced line speed. In automated processes, the performant and reliable protective packaging of ready-to-use primary packaging containers, for example, can make a difference.
KSR: What contribution can a material supplier, given the multiple intermediates, bring to the pharmaceutical value chain?
ES: Indeed, direct interaction between a material supplier and a CDMO or primary manufacturer can be a challenge when there is no direct contact between the material and the pharmaceutical product. Yet, the industry increasingly calls for completely integrated solutions, material safety and trusted suppliers. So, there are certain things a material supplier such as DuPont can do:
- provide a complete product data set
- collaborate with value chain partners to support product quality (made with a specified material)
- ensure product education at all levels of the supply chain.
This requires adequate capabilities and resources — people — who are connected to the market. It’s important to note that DuPont Tyvek material is not used for the primary packaging of pharmaceuticals … but to manage cross-contamination risks and protect the primary packaging until the point of filling. However, looking at the suppliers of glass or polymers for primary packaging, I’m confident that the same or even more stringent criteria apply.
KSR: What’s your take on the cost containment versus higher quality debate?
ES: In this very globalised industry, everyone wants worldwide presence and reach. Global access enables both local-for-local production and the ability to export from lower-cost countries.
From a product perspective, we believe that a material that enables fast sterilisation cycles — as a result of high porosity while maintaining a very efficient microbial barrier even under the rigours of global transport — contributes a lot to managing total manufacturing and quality costs.
That same material must not release particulate contaminants to the packaged goods or the cleanroom environment. This is something we try to focus our education on, especially with new users who may regard the material cost as a sole barrier to entry.
KSR: Are there any new product offerings in the pipeline that offer material innovations for pharma product protection?
ES: At the moment, the industry is not desperately seeking innovation in the secondary packaging materials area. Packaging material changes generally result in major validation work. There’s a stronger focus on using capacities more intelligently. This may include different packaging designs … but only to an extent that allows for a level of standardisation and automation; for example, we see increased interest in RtU packaging for nested vials.
However, we are looking at potential innovations in sterilisation that may determine the use of certain material substrates. Shorter-term, we see more interest in protection solutions (such as covers) for equipment and larger machine parts that require autoclave sterilisation but don’t need sterile barrier system packaging.
Depending on the specific requirements, there’s room to upgrade our offering and, of course, we’ll continue to examine ecofriendly solutions while collaborating with our global customers.
KSR: What are the required performance criteria, test methods and procedures for a cleanroom garment system?
Humans are the biggest source of contamination in cleanrooms and controlled environments.
JFT: The quality of the garment used in EU-GMP grade A/B areas is critical to minimise the risk of contaminating the manufacturing environment and products.
When workers are exposed to hazardous substances, the garment system is the only barrier against biological and chemical contamination. The garment and/or the packaging itself may be or become a source or cause of contamination. It’s therefore vital to define a clear user requirement specification (USR) for a cleanroom garment system.
To make an appropriate choice, QRM principles and quality by design (QbD) concepts should be applied to validate the garment system during its entire lifecycle. It’s important to focus on validating both the clothing itself and the associated processes, such as (repeated) laundering, (repeated) sterilisation and repair. Also, the influence of time, transport and storage conditions on the quality of the cleanroom garment system must be covered by validation.
KSR: What risks are operators working in a pharmaceutical cleanroom exposed to and when is a PPE solution required?
JFT: The new Personal Protection Equipment (PPE) Regulation will manifestly affect the cleanroom industry. Aiming to ensure common PPE standards in terms of protecting the health and safety of users, PPE Directive 89/686/EEC has now been replaced by PPE Regulation (EU) 2016/425.
The key role of PPE clothing in the pharmaceutical industry is to protect personnel from hazardous chemicals and biological substances such as infective agents, cytostatics and other harmful substances, such as highly potent active ingredients, antibiotics or potentially addictive painkillers.
It is important to guarantee the health and safety of pharmaceutical staff by wearing an appropriate protective garment (PPE); however, it is also important to protect sensitive pharmaceutical products and processes from particles and micro-organisms that may adversely affect their quality.
KSR: How can DuPont Personal Protection overcome the new cleanroom challenges?
JFT: Cleanroom garment systems play a crucial role in reducing the risk of contamination; therefore, it’s of the utmost importance to evaluate the benefits and to understand the limitations of the different systems available on the market to specify the right solution for the different types of cleanroom applications (non-hazardous versus hazardous).
It is equally important to understand, assess, validate and audit the entire value chain of the garments, from fabric production and garment conversion to packaging, sterilisation and, if applicable, to the laundry process as well. Companies, such as DuPont can provide the tools and the help you need for these types of risk assessments.
This article appeared in the May issue of Manufacturing Chemist. Read more here.