Working in the pharmaceutical industry, ‘recall’ might be one of the words nobody wants to hear. It could indicate a series of consequences, from critical ones of harming patient safety to major ones of tarnishing a company’s reputation. Unfortunately, despite the regulators’ and industry’s best efforts, pharmaceutical packaging remains one of the principal reasons for recalls, globally. The robustness of the packaging and distribution process, hence, plays a critical role in ensuring patient safety.
This article series will address the principle and measures applied to patient safety assurance, with a focus on pharmaceutical packaging and distribution.
The series will come in 2 parts:
- Part 1: Quality by design
- Part 2: Operations and distribution
Quality by design
Quality should not be assured by testing, but be built into the design – to begin with the end in mind.
1. Package Design
The pharmaceutical package design intends to address why we need to pack medicinal products – to name a few critical aspects:
a) To protect medicinal products from the external environment, hence, to assure its safety and efficacy
The external environment brings in numerous types of contamination from which the medicinal products need to be protected. This will require the appropriate format, material and integrity of the primary packaging.
A very common packaging format for injectables is a glass vial with a rubber stopper which is a fantastic sealing material attributed to its elasticity – so it keeps the container closure intact even going through a lyophilisation process. Also, the rubber stopper makes it possible to insert an injection needle into the vial and draw the product without opening the stopper, which reduces the contact of the medicine with the environment.
But meanwhile, the primary packaging itself could potentially contaminate the product. Hence any interaction between the packaging material and product, any leachable and extractable from the material, must be controlled to an acceptable level.
The packaging material quality shall be strictly controlled through systems and procedures including Supplier Assurance, Sampling and Testing, and Storage and Handling, as part of PQS.
b) To provide sufficient identification and traceability of the medicinal product
Globally, increasing efforts have been spent on fighting counterfeit medicines. Safety features, including unique identifiers, are required under the EU Commission Delegated Regulation 2016/161. An organisation supplying the global market should establish its global/group procedures (e.g. Labeling & Artwork, Serialisation and Product Tracking procedure) considering prevalent regulations including EU Directive 2011/62/EU, US Drug Supply Chain Security Act (DSCSA), China Electronic Drug Supervision Regulation, etc.
Once the unique identifier is generated by the pharmaceutical manufacturer, this record is required to be maintained by the manufacturer for a defined duration. It is also required to be uploaded to the national repository system, as well as the EU repository system (wherever applicable) until decommissioned. In this manner, the authentic medicinal products are registered in the database, and hence the counterfeit ones are easily identified.
c) To provide necessary instructions to users (patient or healthcare professionals)
Having empathy for the end-user is crucial for the pharmaceutical industry. The information presented by the packaging and labelling might be the most direct communication or education we could achieve with our end-users. Beyond the regulatory requirement on packaging and labelling, the assurance shall be obtained that the information provided to a patient or healthcare professional is sufficient, accurate and comprehensive to ensure the correct application, handling and storage of the medicinal product.
Certainly, there is more to consider when it comes to packaging and labelling design, e.g. protecting the person handling the (toxic) product, and easing the transportation process.
2. Equipment Design
The Product Requirement (packaging design) determines the Process Requirement (e.g. vial filling, blister packing, serial number printing etc.) which will further translate into requirements on the equipment design.
Quality, built into Equipment Design, is achieved by understanding and focusing on the Critical Design Elements (CDEs) which are derived from Critical Process Parameters (CPPs) whose variability have an impact on Critical Quality Attributes (CQAs) and therefore should be monitored or controlled to ensure the process produces the desired quality.
The equipment suppliers should be treated as an ‘extension of the manufacturing shop floor’. Their knowledge of the equipment and innovation should be leveraged into the process and facility design. Involving the equipment suppliers in the early design stage will help answer the process need with more innovative and integrated solutions. While pharma companies are specialised and focused on drug discovery and manufacturing, it’s best to leave the innovation and fabrication of equipment to the supplier.
Certainly, we will need to gain confidence for the leveraging approach by establishing a solid quality system to assure suppliers’ competency and ensure the supplier has a proper quality system. It’s also important to understand that equipment suppliers only supply and assure the initial quality and functionality of the equipment. Once it is accepted and qualified on-site, the care and custody are transferred to the site. Maintaining the equipment’s qualified status and its performance is highly dependent on site procedure(s), i.e. Asset Management, Access Control, Maintenance and Calibration.
3. Facility Design
Both, the pharmaceutical dosage form and packaging equipment impact the facility design. For instance, filling a parenteral drug in an Isolator will most likely require a Class C cleanroom environment, while filling the same parenteral drug in a RABS will require a Class B cleanroom environment. Also, even with the same functionalities, filling lines or isolators from different manufacturers might come in various arrangements and dimensions. Hence the ideal situation would be feeding the equipment dimension and arrangement information into the equipment layout design.
Cleanroom protects the product and process from environmental contamination. Meanwhile, cross-contamination from other products or from other process steps shall be prevented as well, through sufficient segregation and properly designed material flow and personnel flow. Physical segregation is always the preferred and most secured method. Whenever physical segregation is not achievable, Temporal Segregation might take place – by carefully sequencing the activities in a way that operations with potential contamination would not happen in the same space at the same time. Temporal Segregation is achieved through procedure control, which is the last level of defence to risks – after risk elimination and engineering control (physical segregation).
Please access the second part of this series on pharmaceutical packaging, which talks about operations and distribution as a critical aspect to ensure patient safety.
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With 15 years of experience in the global pharmaceutical industry, predominantly in Process, CQV, Process Automation and Project Management, Shanshan has held both Consultant and End User roles. With increasing involvement in the GMP remediation and GMP audit projects, she has been building in-depth compliance knowledge as well as interaction with authorities globally.