Q How can FDA-regulated industries best manage their suppliers? What does FDA expect?
A. A robust system for the continual management of FDA-industry suppliers is necessary to assure the safety, identity, strength,
quality, and purity of drug products. FDA's long history offers many examples of serious impact to consumers, patients, and
marketed products, resulting from inadequate management of suppliers. These quality issues can range from uncontrolled supplier
changes that result in material not meeting intended specifications, to non-conforming product or components that pose serious
health hazards. Comprehensive, far-reaching, and continuous supplier oversight will minimize the risk of such incidents and
ensure sustainable quality and cGMP compliance.
FDA's Guidance for Industry, Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations, and the International Conference on Harmonization (ICH) Q10 Pharmaceutical Quality System documents provide guidance related to the control of outsourced operations (1, 2). In addition to providing general supplier
management direction to the industry, these guidance documents point to FDA's expectations with respect to ongoing monitoring
of key suppliers. Essentially, FDA considers suppliers an extension of the sponsor, insofar as ensuring goods and services
meet pre-established specifications, such that finished product integrity can always be maintained.
Procedures related to the qualification of suppliers, and in some cases quality agreements, are essential components of a
meaningful supplier-management program. These procedures must be sufficiently detailed to ensure adequate control of the materials
and supply chain. The initial qualification of a supplier will typically consist of an onsite assessment of the supplier,
along with characterization and qualification of the supply. Once qualified, the quality agreement provides the basis from
which on-going supplier management is achieved.
The supplier quality agreement will provide details related to periodic audits, re-evaluation, even probation conditions of
the supplier. It should also require that any subsequent outsourcing decisions, or changes that the supplier intends to initiate,
are brought to the attention of the sponsor, for their ultimate review and approval. Although FDA has never stated this specifically,
the extent of oversight provided to suppliers should be commensurate with the risk posed by that material, component, or service.
FDA's stated emphasis on risk assessment and mitigation is consistent with this perspective.
The Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012, Section 703, requires that excipient manufacturers
be identified in the drug listing (3). Section 711 requires oversight of materials used to manufacture drugs and drug products.
FDA expects that meaningful quality agreements will be secured and that periodic audits will be conducted, as needed, to ensure
sustainable compliance against the cGMPs and the Sponsor's quality agreement. The frequency of these audits should be based
on the compliance history of the supplier, and as stated above, the criticality of the supply. At the very least, crucial
suppliers, such as API and container/closure suppliers, must be thoroughly evaluated with onsite assessments and frequent
surveillance audits. Ongoing surveillance audits can be relaxed if, and only if, the supplier has not breached the quality
agreement and does not pose a risk. FDA observations typically associated with supplier management include the lack of quality
agreements, particularly for crucial suppliers, the lack of or inadequate supplier audits, and the lack of adequate follow-up
to supplier issues.
1. FDA, Guidance for Industry Quality Systems Approach to Pharmaceutical CGMP Regulations (September 2006).
2. ICH, Q10, Guidance for Industry Q10 Pharmaceutical Quality System (ICH, April 2009).
3. Food and Drug Administration Safety and Innovation Act, Public Law 112–144 (July 9, 2012).