Sic Evaluation, Management, and Closure
Figure 2 represents a typical flow for the change notification and evaluation for a pharmaceutical or biotech manufacturer. For any process, there are specifics that may differ from company to company (e.g., a process managed centrally versus at each location, responsible department, level of process automation). These differences, notwithstanding each manufacturer’s SIC management process, will typically include the following steps:
Step 1: The pharma client receives the change notification from the supplier per the SIC agreement, or other governing document, and an initial evaluation is performed. This evaluation usually involves a search of the enterprise resource planning (ERP) system and production documentation (e.g., specifications, standard operating procedures [SOPs], test methods) to determine where/how the supplier’s materials or services are used. If it is determined that the material or service is not employed by the manufacturer, in some cases the SIC can be closed, and the supplier notified if required, without further action required.
Step 2: The change is evaluated by the appropriate users and subject-matter experts to determine impact. If necessary, additional data or input may be requested from the supplier to support evaluation of the change. This change evaluation may be performed by multiple sites or user groups, for example, in the case where a change impacts multiple operating sites of a large company.
Step 3: The change is managed via approved change-control procedures, which define the specific elements of the change that need to be addressed. This process is typically risk-based, and defines the evaluations and outcomes that need to be managed, as well as the specific deliverables required to establish that the change has been implemented. These deliverables may include, but are not limited to:
• Receipt of additional information from the supplier
• Execution of qualification studies or review of supplier validation summaries
• SOP/specification updates
• Material qualification
• Supplier audit or questionnaire
• Regulatory filings.
Step 4: Following completion of the defined deliverables, the SIC is closed. If required, notification to the supplier may be performed.
Additional Concerns for Critical Suppliers
For materials or services with a high potential to affect product quality and/or patient safety, a more formal and detailed contract may be required to delineate the responsibilities of each party with regard to control of the quality aspects of the supplier-purchaser relationship. These critical suppliers are typically required to enter into a formal quality agreement. Suppliers subject to quality agreements may include contract manufacturers, manufacturers of APIs, custom or critical raw materials (e.g., animal-derived) or final product contact containers/closures, or manufacturers whose materials and services are referenced in regulatory filings.
In addition to requirements for change notification, a formal quality agreement will typically define the requirements for quality management of other important aspects of the supplier-purchaser relationship, for example:
• Right to audit
• Responsibilities for regulatory inspections, filings, and communication
• Management of documentation and records
• Timing and mechanism for reporting of deviations and out-of-specification (OOS) results
• Qualification requirements for methods and/or manufacturing operations
• Process/timing for handling, archive, and destruction, or records
• Mechanisms for escalation or resolution of quality issues.
The change reporting requirements for critical suppliers are almost always more stringent than those for standard materials. Given the potential impact of the suppliers’ goods/services on product quality, timelines for change notification are typically extended so that drug manufacturers can perform in-depth evaluation/qualification of the changes, which may include evaluation of multiple lots/batches of material, formal technical evaluation, and site audit among others. In some cases (e.g., for APIs and pharmaceutical excipients), specific industry guidance (1) may be included as a standard reference for change reporting.
Conclusion
Pharmaceutical manufacturers and the suppliers that they rely on operate in a world of continuous improvement, and any improvement will result in change. The objective of continuous improvement must be balanced with the recognition that all changes; even those that may seem innocuous require resources to evaluate, plan, and implement. By establishing a good understanding of the needs of each partner, fostered by communication and a clear understanding of expectations, suppliers and drug manufacturers can ensure that their collaborations improve the product while avoiding unnecessary product or supply risks to the patients who depend on them.
Reference
1. The International Pharmaceutical Excipients Council of the Americas, Significant Change Guide for Bulk Pharmaceutical Excipients, Revision 2, March 2009.