Life science i technical bulletin ISSUE N°19 /APRIL 2009
A REGULATORY EMPHASIS ON SUPPLIER COMPLIANCE
Angela Moy, Director - Global Quality Assurance (GMP/GLP), SGS Life Science Services
The recent heparin contamination inadequacies in its supplier qualification test results at appropriate intervals. An investigations have cast a spotlight efforts. Although an audit was previously established supplier qualification program performed on the crude material supplier would provide adequate evidence that the on suppliers to the Pharmaceutical who was designated as “unacceptable”, supplier can consistently provide reliable industry. As a result, the FDA is no corrective actions were taken with and safe materials. Suppliers should increasingly vigilant in inspecting the crude supplier with respect to the be monitored and regularly scrutinized overseas manufacturing facilities processed material. However, the firm to assure ongoing reliability. It is the accepted and subsequently used crude manufacturer’s responsibility to ensure and in enforcing the manufacturers’ materials from the supplier. The firm that their suppliers are suitable and responsibilities to ensure their had also failed to establish appropriate qualified. supplier’s compliance. specifications for the incoming crude materials. In order to be proactive, drug In April 2008, FDA issued a warning manufacturers must have a compliant letter to an Active Pharmaceutical Under the CGMP at CFR Part 211.84, supplier audit program. The program Ingredient (API) manufacturing facility the regulation permits a manufacturer should be based on the quality systems in China. The firm had failed to have to release a shipment of raw material approach as explained on FDA’s Guidance adequate systems for evaluating the and/or packaging material based on the for Industry issued in September 2006. suppliers of its crude materials and the supplier’s certificate of analysis and a A Quality System approach is one of the crude materials themselves. This firm visual identification of the material or most important GxP requirements. The did not ensure that these materials are component. In order to accept a shipment quality systems of a supplier will change acceptable before use and the warning based on the certificate of analysis, the as the manufacturer grows and as the letter indicated that the firm had received past quality history of the supplier is key company’s products, operations and materials from an unacceptable supplier information for receiving APIs, excipients employees change. Thus, an effective and the materials were used in their API and components. The reliability of a supplier audit program is an ongoing manufacturing process. Subsequently, the supplier needs to be established through monitoring program. firm has acknowledged that there were appropriate validation of the supplier’s
Supplier Audit Requirements The scope of the supplier audit program A supplier audit program should include, Audit Schedules should include the suppliers for API, but not limited to the following: Assignment of responsibilities excipients, packaging materials, software Evaluation of criteria for GxP systems, calibration laboratories Management Review of results and contractors. Audit Objective – to ensure the quality Corrective action policies, schedules and systems of the suppliers will provide due dates monitoring A written supplier audit procedure products that meet the safety, identity, As products and processes become should be in place. The details of the strength, quality and purity of their increasingly complex, evidence from audit procedures will vary depending on products; supplier audits and testing of incoming the manufacturer size and nature of the Audit Scope – includes all functions that materials may no longer be sufficient to manufacturing operations. impact the products or services; provide full assurance that the suppliers’ Life science i technical bulletin 2
operations will consistently produce supplier’s company policies, procedures Audit Criteria quality products/services. During supplier and the full range of products, including audits, a full quality system audit is those products that are not purchased by When designing audit criteria, GMP required to ensure that the established the manufacturer. The audit team should requirements should be used as a quality systems are adequate for notify the suppliers before the audit. baseline for the evaluation. Since the producing quality products and services. Furthermore, the audit team should hold quality system regulation is broad, each The quality system approach inspects if a pre-audit conference to clarify exactly manufacturer shall tailor the criteria to there are any company-wide problems, what the audit will include and what the the manufacturing operations of their and will ensure that the product quality objective(s) of their audit will be. suppliers. Small manufacturers may will consistently meet the specifications need only minimal documentation. This and expectations. Auditors may consist of an audit checklist with appropriate ancillary instructions to assure Audit Schedule Manufacturers can have their own that all aspects of the quality system are experienced auditors perform audits of covered. Manufacturers are responsible for their suppliers. This function can also be deciding the frequency of supplier audits. outsourced to a consultant, corporate or An audit checklist may be a series of The frequency should depend upon other independent auditor. questions, phrases, trigger words, previous audit findings and the quality or any combination of these that will trends of products received from the Individuals(s) responsible for conducting prompt auditors to cover the entire supplier. If an audit reveals no problems, audits should be sufficiently trained. quality system. Checklist should cover then audit intervals could be lengthened. They should have the experience to requirements of the quality system If problems are identified, audits may detect variations and problems in the applicable to the supplier’s products, need to be conducted more often. For a quality system. An auditor is expected services, operations, and other areas of new supplier with many audit findings, a to objectively see the overall quality total quality system. Experienced auditors minimum of an annual audit is required. approach, company culture and any may not want to follow an audit checklist, For an established supplier with good systemic problems. For a manufacturing but rather may follow the quality system quality history, a biennial schedule is site, the auditing team should have or product/process flows during their common for the pharmaceutical industry. a working knowledge in the product audits. For a supplier with excellent quality trends development and validation aspects, the and good quality systems, a triennial manufacturing processes and process Audit Results audit is acceptable by most regulatory controls, the change controls, the agencies. applicable quality assurance principles, A supplier audit program with sufficient and the human relations aspect of depth can detect undesirable variations Audit Planning auditing. and trends in operating procedures. Management, upon becoming aware of The effectiveness of an audit begins with these quality variations, should make the planning. The manufacturer should Communications decisions on using materials from start by defining the purpose and scope unqualified suppliers. Manufacturers of their audits. The lead auditor and the An experience auditor should ask can also work with suppliers to correct audit team should be identified early in questions clearly and listen actively and prevent unsafe, unreliable and the planning process, and the members during the audits. The lead auditor should inconsistent product or services from of this team should possess the skills and present the audit findings opening and getting to the market. Audit results should knowledge of quality system principles. honestly. Any finding should be based be provided to the supplier management Preparing an audit checklist will enable on facts and support by rationale or for their resources allocation for corrective the team to properly cover the audit regulations. actions. requirements, while review of previous audits and their responses will enable the The supplier audit requires a written audit Copies of the current audit reports should audit team to evaluate their audit plans report, and auditors must have sufficient be maintained by the manufacturer. and scope. The background preparation writing skills to effectively communicate FDA has authority to review and copy should also include the review of the findings and recommendations. all records required by the regulations. Life science i technical bulletin 3
Consequently, manufacturers must quality, patient safety and reduce citations ensure that supplier audits have been from regulatory agencies. No company conducted and the results documented. wants its products to be on the news and on the GxP history like the heparin Regulatory agencies are raising the case - neither as a negative example in compliance bar on supplier audits. a case study, nor causing any harm to Manufacturers should implement consumers. a rigorous and proactive supplier audit program, along with proper documentation. This will ensure product
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