Op Ex & Lean Six Sigma

6 Tips for Mitigating Manufacturing Risk

Medical device manufacturers partner with contract manufacturers to identify potential risks and help produce safe, reliable, high-quality products

By Leigh Toole

 

Amidst increased customer expectations and heightened regulatory requirements, medical device manufacturers must be able to meet the demands of an increasingly competitive marketplace. Many medical device manufacturers partner with contract manufacturers and suppliers to help produce safe, reliable and high-quality products.

Selecting the right partner can help ensure the success of a drug product, and medical device manufacturers should perform a comparative analysis of the options available. Start by performing an audit of the potential contract manufacturer’s quality management processes. To begin, request a copy of the organization’s quality manual. Compare quality manuals from three to six firms; pinpoint differences and determine how each potential partner’s approach aligns with the manufacturer’s own quality processes. Such an analysis can be completed quickly with minimal expense, and will narrow the list considerably.

Prior to entering into a partnership, conduct a site audit to further compare the contract manufacturer’s ability to meet specific needs. Site audits can help medical device manufacturers review each supplier’s ability to meet specific needs and establish the firm as an approved, certified and qualified supplier.

In conjunction with a site audit and a thorough comparative analysis, medical device manufacturers should evaluate a firm’s quality management system, risk management tolerance, technical fit/manufacturing core competency, design control capability and root cause analysis tools. These factors can help medical device manufacturers identify potential risks associated with outsourced manufacturing and support an informed partnership decision.

Tip 1: Measure the strength of a quality management system against regulatory standards
and verify company-wide implementation

In order to ensure product safety and efficacy, medical device manufacturers must comply with quality system regulations as defined by the standards set by the countries in which their products are sold. In the United States, medical device manufacturers and partners must develop a quality management system that meets the standards outlined in the FDA Code of Federal Regulations Title 21 Part 820 Quality System Regulation (QSR). In Europe and several other countries, medical device manufacturers must ensure compliance with requirements outlined in the International Organization for Standardization (ISO) 13485.

A comparative analysis can determine how suppliers plan to meet predetermined FDA QSR and ISO requirements. Many firms do not define key processes needed for the quality management system, as well as the sequence, interaction and associated control strategy. Failure to meet this requirement can have implications on the quality culture of the organization and effectiveness of the management team.

During evaluation, review how the contract manufacturer has elected to meet the ISO 13485 requirement in section 4.1 (a) to “identify the processes needed for the quality management system and their application throughout the organization” and in section 4.1 (b) to “determine the sequence and interaction of these processes.” Comparative analysis will determine whether the firm has failed to meet this requirement or invested the time to define these processes.

It is important to confirm that all employees have been trained and understand the firm’s quality policies and objectives. Review the content of the contract manufacturer’s quality policy and quality objectives with the management team. Request the team provide documented and objective evidence that verifies the quality policy and objectives have been implemented and are well understood across the organization. The strength of an organization’s quality management system can be an early indicator of things to come. A new partnership between a medical device manufacturer and a firm whose approach aligns with its own quality management system will be much stronger than one that does not.

Tip 2: Select a partner whose risk management program aligns with the manufacturer’s approach

Contract manufacturers must establish rules for when to use a particular risk management tool. The requirement in ISO 13485 section 7.1 (d) notes, “the organization shall establish documented requirements for risk management throughout product realization.” This section also indicates “… ISO 14971 [for] guidance related to risk management.”

Risk management shortcomings may require greater oversight, and more rigorous review and approval of issues. As such, it is important to determine the potential firm’s comfort level of residual risk and strength of an organization’s risk management rules. Questions to ask include:

  • When should a preliminary hazard analysis be performed?
  • When should a design Failure Mode and Effects Analysis be generated?
  • What are the rules of engagement for risk priority numbers in terms of when risk mitigation activity is appropriate?
  • Does the firm provide a documented evaluation (based on frequency and severity) that establishes a defendable rationale regarding when issues will be investigated and/or escalated to the corrective and preventive action (CAPA) system?
  • Is risk management applied throughout the entire product lifecycle?

One contract manufacturer may be more risk tolerant than another. If the potential firm’s comfort level of residual risk varies greatly, it will be more accepting and comfortable of higher risk priority number outcomes than the device company’s system allows without the need for mitigation, reduction or the elimination of the source(s) of the risk.

When seeking a medical device contract manufacturer, look for evidence of the best practices outlined previously, and consider how the firm has applied risk management into important quality management system audits, including internal audits, complaints, CAPA process, nonconforming product and change management. Select a partner whose program and assessment align well with the manufacturer’s risk management approach.

Tip 3: Reduce the risk of future quality issues by using past performance to evaluate manufacturing capability

Manufacturers of medical devices and combination products often seek and select contract manufacturers based on a given organization’s manufacturing capabilities. During a comparative analysis, several factors can help indicate a firm’s technical fit and manufacturing capability core competency.

Determine if producing a particular product is a core competency for the contract manufacturer. Find out if the firm has a robust equipment calibration, qualification, process validation, preventive maintenance and statistical process control systems in place. Ask if the contract manufacturer is able to perform manual, semi-automated and/or fully automated assembly processes, final acceptance activities, drug handling, final packaging and labeling.

Ensure that the firm’s technical staff possesses the necessary qualifications, training and experience to be successful with the task at hand, and confirm that facility and infrastructure align with the product’s overall contamination control strategy.

More often than not, past performance acts as a strong predictor of future performance. Find out if the contract manufacturer has produced product with similar features and characteristics and a history of successfully producing projected volumes. In conjunction with a comparative analysis, this information will help make an educated decision and reduce the risk of poor quality.

Tip 4: Evaluate the strength and post-market surveillance activities of a potential contract manufacturer’s design control system

Medical device manufacturers must satisfy several design control requirements to remain compliant. Evaluate the answers to the following questions to help reduce risk and determine the strength of a potential contract manufacturer’s design control system:

  • Has the firm established, and does it maintain a compliant design control system that could be leveraged to design and develop components, sub-assemblies, medical devices, pharmaceutical primary packaging components, combination product constituents and combination products?
  • If a design control system has been established, does the system end with product launch?
  • Does the system include post-market surveillance activities designed to provide input to management review to drive continuous improvement as the product and process is “monitored and measured” in accordance with ISO 13485 section 8.2.3 and 8.2.4?

Tip 5: Assess the root cause analysis tools used to determine how organizations respond to problems and drive continued improvement

The true measure of control associated with sustainable manufacturing is long-term supply “on time in full” and “right the first time” without disruption. Knowing how the contract manufacturer will respond when problems arise is crucial to sustaining an effective manufacturing operation.

Problems offer an opportunity to reveal a contract manufacturer’s ability to demonstrate specific root cause analysis tools. Under the Tech Group’s risk assessment system, an investigation can be performed at any time, though Level 1 (low occurrence, low risk) issues do not require investigation. Level 2 issues require a documented justification if an investigation is not performed. If not escalated into the CAPA system, Level 3 (high occurrence, high risk) issues require investigation and a documented justification.

Contract manufacturers should know how to respond when problems arise, and an effective firm will deploy resources based on risk from a quick evaluation that defines the frequency and severity of a given event. When evaluating a potential contract manufacturer, review the critical quality systems to determine strengths or weaknesses associated with the firm’s ability to recognize problems, determine root causes, effectively contain the issues, apply corrections and implement corrective and preventive actions that drive significant continuous improvement.

Tip 6: Measure the partnership’s success with a robust quality agreement

A robust quality agreement should identify specific roles and responsibilities of each organization, as well as guidance and rules of engagement associated with the critical quality systems. It should be implemented prior to forming a partnership or in the early stages of development.

The quality agreement must define formal governance expectations for the working team, management team and management with executive responsibility. These meetings will help drive continuous improvements and accountability to a predetermined and agreed upon scorecard that measures the success of the partnership.

These factors, along with comparative analysis and site audits, will greatly affect the contract manufacturer selection process by uncovering issues prior to entering a contractual partnership. It is important to know specifically what constitutes a great fit in a strategic contract manufacturing partnership. Contract manufacturers are not “one size fits all,” and device manufacturers must invest time and dedication in the selection process. By doing so, the reward is an exponential return on the initial investment that will lead to the long-term successes associated with a successful and effective partnership.

Published in the February 2013 issue of Pharmaceutical Manufacturing magazine



ABOUT THE AUTHOR
Leigh Toole is Director of Quality at The Tech Group, a subsidiary of West Pharmaceutical Services Inc. To learn more about contract manufacturing quality and other issues, read West’s blog at http://westpharma.wordpress.com.

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