Control Strategies for Managing Medical Device Combination Products

What is Control Strategy?

A control strategy is comprehended as a planned set of controls derived from the understanding of process and product while assuring the product’s performance, process, and quality. The control strategy begins with understanding the product and process. In general, a control strategy comprises the following components:
• Composition materials
• Components
• Constituent parts
• The final drug-device combination product
• Critical process parameters

The product control strategy is heavily associated with risk management. This risk management is the process of identifying hazards, evaluating, mitigating, and controlling any associated risks, and monitoring the effects of the controls in place. In general, the control strategies for combination products must focus on the safe and effective use of the device, the combination product, and the drug. In this regard, the components of the device can be divided into two categories:
• Essential functions and components: These components and functions can potentially harm the patient while affecting the combination product’s mechanics and clinical performance.
• Non-essential functions and components: These are the remainder of the functions and components that are not considered essential enough.
Manufacturers can only devise an effective control strategy if they take a holistic approach to evaluating the normal controls. Also, if their control strategy is effective, they must focus on essential controls and components contributing to the device’s performance.

Medical devices and combination products

The Role of ICH Q12 and EPRs in Building the Control Strategy

ICH Q12 and the Control Strategy

The ICH Q12 (Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management) presents several essential concepts related to the established conditions. These established conditions are necessary elements of a control strategy that assure a product’s quality. If there is a post-approval change in the established conditions, an update of regulatory submission will be required. Although the use of ICH Q12 is supported by regulatory agencies, such as the US FDA, many local agencies have reservations since this guidance is particularly new.

EPRs and the Control Strategy

The EPRs or Essential Performance Requirements are a subset of design controls assuring that the device’s clinical performance is enough to comply with the performance of the combination product during dosing.

How is a Control Strategy Built?

The most important consideration while building a control strategy is a risk-based consideration f routine controls emphasizing the following.
• The essential functions of the combination product, and
• The aspects of the components contributing to those essential functions
Aside from the combination products, a process map is necessary to build the control strategy. This process map should be developed and documented to help people understand the factors influencing the combination product’s CAQs (Critical Quality Attributes). This process map also helps establish control points based on the impact on these CAQs.

The Main Focal Points of Building a Control Strategy

In any control strategy, the focal points must be regarding the safe and effective use of
• The drug product
• The device
• The combination product
Moreover, the processing must also consider how much each perspective, i.e., the materials perspective, the components perspective, and the total systems perspective, is influenced by the processing.

Risk Considerations for the Drug being Used

The following important components regarding drugs must be kept in mind:
• The formulation of the drug
• Any change in intended use that might affect its safety and efficacy
• Any physical discomfort associated with its use, such as the increased injection force, longer time duration for administering the drug, etc.
• Dosage inaccuracies, i.e., under-dosing, overdosing, or adverse drug reactions related to dose

Risk Considerations for the Device Being Used

The important risk considerations concerning the device being used are:
• Its product differentiation
• Its technological characteristics
• Its intended use of administering route, i.e., any needled extension required to protrude the subcutaneous and intramuscular space
• Clarity regarding measurement units
• Clarity regarding dose completion
• Activation of drug delivery, e.g., any required spring compression force, injection time, or impacting injection force
• Assembly lines for scaling up the production
Aside from drug and device, risk considerations regarding the environment in which the users are using the device must also be kept in mind while devising the control strategy. Examples of patient-related risk considerations include:
• Storage of the device and drug, e.g., refrigeration, shelf-life, keeping it away from children, etc.
• The user of the drug and device, i.e., senior population, pediatric population, caregiver, medical personnel
• Required training adequacy (if any)
• Environmental complexities, such as distractions, high user stress levels
• Clear labeling and Instructions for Use (IFU)
• Any potential consequences that might be faced due to user errors
• Any cognitive requirements
• Any physical and sensory requirements
• User habits related to the combination product, i.e., if they can easily adhere to the dosage regimen, etc.

Which Controls are Necessary to be Considered Throughout the Building Process?

The necessary controls and their components for the building process are:
External manufacturing controls: External manufacturer controls, in-process controls, and release testing
Incoming controls: Procedures for incoming inspection and release, incoming specifications, deviation disposition, and statistical justification(s)
Packaging and labeling controls: Controlling packaging and labeling of materials throughout components and suppliers
Purchasing/supplier controls: Material and supplier specs., supplier quality agreements, component manufacturer controls, in-process controls, and release testing
Manufacturing control plans: Incoming inspection and release procedures, incoming specifications, deviation disposition, and statistical justifications
Final testing and release: Incoming inspection and release procedures, incoming specifications, deviation disposition, and statistical justifications

Building Control Strategies for Combination Products in Your Company

Every organization manufacturing these combination products should take a holistic approach and keep the overall product quality and performance in mind. It can achieve this by maximizing advantages related to connectivity, digitization, monitoring control, and data-driven decisions taken in real time.
Compared to the traditional approach where products were only tested just before their batch was released, companies and manufacturers should check each and every aspect of the product along the different key points and production stages. But opting for this strategy requires the manufacturers and companies to understand these key points thoroughly and their impact on the final combination product. If you want any help in this regard you can contact our experts.

About the Author

Waqas Imam

S. M. Waqas Imam is associated with TS Quality as a Regional Partner. He is also an ambassador of Medical Device Community. He is an Industrial Engineer by qualification and served the manufacturing industry since 2011. He is also IRCA CQI Lead Auditor of ISO 9001 and other management system standards. He had served as Quality Assurance and Regulatory Affairs Manager in QSA Surgical Pvt. Ltd. and Ultimate Medical Products. He managed requirements of ISO 13485:2003, EU directives, CE marking and FDA. He also served as Expert Blog Writer for 13485Academy and wrote expert articles on various topics of ISO 13485:2016.