Meeting and exceeding strict regulations for parenteral packaging

Datwyler Healthcare's Tabassam Sharif, regulatory affairs manager, and Eugene Polini, technical key account manager, explain how parenteral packaging suppliers are optimising their technologies and processes to meet regulatory requirements.

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Key highlights:

• Regulatory professional are the pharma industry's eyes and ears - foreseeing what could go wrong and implementing rules to ensure requisite standards are met.
• Pharma companies are increasingly engaging with packaging suppliers in the early stages of drug development. They study the impact of packaging materials on a specific formulation to avoid surprises at later stages.
• Primary packaging must act as a frontline defence to ensure drug products are kept free of contamination, and easy to dispense, even after prolonged storage.

Meeting increasingly strict regulations for parenteral packaging is certainly a challenge. Nevertheless, regulations serve as a guide for pharmaceutical companies and help to ensure that the products brought to the public are safe. After all, it all revolves around patient safety. Regulations help standardise and supervise healthcare. They ensure the safety, effectiveness, and overall quality of drugs.

Navigating the regulatory maze

An increasingly complex web of international regulations can create hurdles for international drug producers—especially as they face delays and shortages in today’s marketplace. That is especially true when the regulations themselves are long and complicated. For example, the European Medical Device Regulation published by the European Commission on 25 May 2017 with three-years transition period to the industry for compliance, was 175 pages long, 10 chapters, 123 articles and 17 annexes.

Generally, said regulation is applicable on medical devices but according to Article 117, device parts of combination products (both integral and non-integral) like prefilled syringe, pen-injectors, and co-packaged drugs, also come under the ambit of this regulation. For compliance of device parts as per General Safety and Performance requirements (GSPR) given in Annex-1 of the EU MDR, a notified body opinion is required.

In China, pharmaceutical companies are still adjusting to matters concerning the Bundling Review system implemented in 2016 by the China Food and Drug Administration (CFDA), now named as National Medical Products Administration (NMPA). The bundling review system of China reviews the packaging component’s Drug Master File (as well as API and excipient DMFs), at the same time as it reviews the new drug product application. This system is comparable with the drug product application review system of FDA, United States, however requirements for DMFs in China are more extensive than for the US. Prior to this, there was a license system for packaging materials in China, which was far less strict than what it is today.

The Bundling Review system of China as well as the EU-MDR, however, fosters more opportunities for pharmaceutical and packaging companies to work together. They understand, it takes a village to drive excellence in the industry. Pharmaceutical companies understand that it takes investing in research and development, hiring packaging experts and equipping their team with the proper resources to help raise the bar.

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The industry’s eyes and ears

It is important for the industry to acknowledge the predictive ability of regulatory professionals. In a sense, they are the pharmaceutical industry’s eyes and ears. They foresee what could possibly go wrong and implement rules to ensure that pharmaceutical companies manufacture quality drugs meeting requisite standards. Without these regulatory bodies/professionals, the industry may progress but without having a clear sense of direction.

The main goal is to safely deliver a drug product to the patient as intended. Within the context of patient safety, it is important to consider the administration of it in its entirety. What is being administered? Where is it being administered? How is it being administered and who is administering it? Moreover, how will it be transported from point A to point B? Asking these questions help pharmaceutical companies comply with safety regulations and ensure an environment that does not jeopardise safety and quality of the drug product.

With so many steps in the drug delivery process, there are multiple points of concern, not just during processing and packaging, but also throughout transportation and distribution. For instance, during air shipment of a liquid vaccine, air pressure fluctuates This might trigger movement of rubber stopper/plunger within the syringe and may impact sterility of the product. Secondly, if a drug product needs to be stored at -80 °C, this might lead the rubber to reach its glass transition temperature which could essentially impact its ability to seal, and thereby, may affect the drug quality and safety.

The drug products must be pure, effective, free of contamination, and easy to dispense, even after prolonged storage. For the said objective, primary packaging materials have a key role because they act as a frontline defense and protect drugs from all physical, chemical and microbial damages. Therefore, the primary packaging materials should meet the highest quality standards to keep the drug product safe and effective. Foreign particles from processes, and undesirable and potentially harmful extractables and leachables from the packaging could also react with the drug product.

Pharmaceutical companies want to partner with suppliers that offer an extensive product portfolio with advanced coating technology that provides barrier properties to control leachables into the drug products. Container closure integrity (CCI) throughout the shelf life of the drug product is the overriding priority. An effective container closure system also extends the shelf life of a drug, as a seamless CCI will prevent exposure to the surrounding environment, which could cause hydrolysis or oxidation. Primary packaging, therefore, is largely responsible for keeping a drug safe and viable for an extended period of time, which has major implications for both patient safety and cost. Additionally, in some cases packaging plays an additional role when it takes part in system performance. For example, plunger movement in a syringe or autoinjector or pen-injector. To ensure suitability and proper functioning of packaging material and to avoid any risk of under or overdose, strict regulations are promulgated by the authorities.

Mitigating risks to benefit patients

So how are pharmaceutical companies finding their way through the maze of increasingly strict regulations around parenteral packaging lately? It is critical for the pharmaceutical companies to be proactive about challenges that may impact patients’ lives for better or worse. Continuously, one must work to maximise the value of drug products to customers – from the discovery and development stage all the way to FDA post-market drug safety monitoring. This includes new indications, improved formulations, new delivery systems and packaging as well as device connectivity solutions that help expand the utility and improve upon efficacy, safety, and patient experience.

Increasingly, pharmaceutical companies are engaging with packaging suppliers at the early stages of drug development. They study the impact of packaging materials on a specific formulation so that they don’t have any surprises at a later stage. Companies are also conducting frequent audits and cultivating closer relationships with packaging suppliers to fortify their supply chain. It’s the prevention of errors and adverse events to patients associated within healthcare.

Given the intricacies, pharmaceutical companies also benefit from the expertise of a packaging supplier who has a thorough understanding of the industry’s regulations, the material science of packaging components, and the impact of different packaging materials on specific drug formulations. Expert consultation is key to help determine the best plan of action.