With the increased pressures of cost control for manufacturers of FDA-regulated products and the rapid expansion of globalization of the supply chain, the expectations of manufacturers and sponsors to control activities and materials provided by their suppliers has been magnified. It is the responsibility of each organization to ensure that their suppliers provide services and materials that are fit for purpose throughout the product lifecycle, from product development through commercial distribution. Regulatory agencies and industry expectations are focusing on supplier management through risk-based quality controls and open communication between the procuring organization and supplier. In fact, the FDA and other international regulatory agencies specify that the contracting organization is ultimately responsible for the quality of purchased material and that the contract facilities are considered an extension of the manufacturer’s own facility.
Supplier Management is best defined through a Supplier Quality Management Lifecycle Model with the following recommended steps for developing and managing the program:
1. Develop User Requirements for materials and services to be outsourced – It is recommended that a risk assessment is performed on all outsourced materials and services for the level of risk that failures could have on the quality, safety and efficacy of the final drug or device product. Suppliers of low-risk, non-critical materials would have less stringent supplier criteria and qualification processes than high-risk, critical materials.
2. Supplier Selection, including due diligence – Confirmation testing of materials and components is performed during the supplier selection process. The confirmation testing will evaluate if a sample a) meets the defined specifications and b) the certificate of analysis provided with the sample is confirmed through independent testing verification. The level of testing is typically dependent on the assessment of risk (e.g. possibly confirm identification testing only for low-risk materials, full CoA confirmation testing for high-risk materials).
Other considerations for supplier selection can include the ability of potential suppliers to assure supply continuity, capacity, pricing, logistics, etc. An initial evaluation of the potential supplier’s regulatory and quality compliance history should also be evaluated (e.g. history of regulatory injunction (Warning Letters, Consent Decrees), recalls, quality culture, etc).
3. Quality Assessment – Once the short-list of suppliers is determined, a formal assessment of the supplier quality systems is performed to determine if there is sufficient evidence of control over the manufacture, testing, release and distribution of the material. It is recommended that supplier questionnaires are sent to suppliers of low-risk, non-critical material/services for a self-assessment of conformance to GMP and quality principles. On-site audits should always be performed for suppliers of higher-risk and critical materials/services. Satisfactory outcomes of quality assessments of high-risk, critical materials/services must be confirmed prior to use in the manufacturing process.
4. Quality Agreement – Suppliers of high-risk, critical materials/services must formalize the responsibilities, communication expectations, and processes relative to quality tasks to assure the manufacture and supply of safe materials/services. A Quality Agreement is based on the quality procedures in place at both the supplier and procuring organization. The Quality Agreement also creates mutual understanding of the quality & regulatory requirements relevant to the material service supplied.
5. Ongoing Monitoring and Control – Once the supply chain is fulfilled, the supplier and procuring organization must continue to openly communicate issues, discrepancies, proposed changes, trends, and suggestions for continuous improvements. Key Performance Indicators are monitored and communicated (e.g. investigations, complaints, OOS results, rejected batches, etc) on a routine basis. All proposed changes that have the potential to impact product quality (identity, strength, purity, bioavailability, regulatory filings) must be evaluated by a cross-functional team from both supplier and procuring organization.
The performance of critical, high-risk material should be confirmed on a routine basis. This typically consists of a quality review and confirmation testing of the critical quality attributes. Results of the performance evaluation will determine the frequency and detail of future performance reviews and audits.