A key regulation regarding CMOs is 21 CFR 200.10 Contract Facilities, which states that FDA considers the CMO as an extension of the client (1). As such, the client
may be considered in violation of the regulation if the CMO is in violation. The FDA Safety and Innovation Act (FDASIA) update,
approved by Congress and signed by the President in 2012, includes Enhancing the Safety and Quality of the Drug Supply Chain
(FDASIA § 711), which states "'current good manufacturing practices' for the purposes of subsection (a)(2)(B), include the
implementation of oversight and controls over the manufacture of drugs to ensure quality, including managing the risk of and
establishing the safety of raw materials, materials used." (2).
This may be interpreted as requiring firms to have "Modern Pharmaceutical Quality Systems," not just strength, identity, safety,
purity, and quality (SISPQ) compliance. BioPharma quality systems are evolving to truer "Quality" systems, not just regulatory
requirements. With the newer systems, risk-based approaches are used. More efficient and simple systems are built that remove
wasted efforts, allowing us to focus on the more important issues. It is comforting to know that FDA and industry have similar
expectations and goals: to assure safe and effective drugs reach the patients who need them.
ICH Q10, Modern Pharma-ceutical Quality Systems, a tripartite guidance document approved by FDA, the European Medicines Agency (EMA) and the Pharmaceuticals and Medical
Devices Agency (PMDA) of Japan, states in Section II.F (d) OR 1.7, "The pharmaceutical quality system should include appropriate
processes, resources, and responsibilities to provide assurance of the quality of outsourced activities and purchased materials
as described in section II.G (2.7)" (3).
Section II.G or 2.7, Management of Outsourced Activities and Purchased Materials, states: "The pharmaceutical quality system,
including the management responsibilities described in this section, extends to the control and review of any outsourced activities
and quality of purchased materials. The pharmaceutical company is ultimately responsible to ensure processes are in place
to assure the control of outsourced activities and quality of purchased materials. These processes should include quality
risk management and include:
- Assessing prior to outsourcing operations or selecting material suppliers, the suitability and competence of the other party
to carry out the activity or provide the material using a defined supply chain (e.g. audits, material evaluations, qualification).
- Defining the responsibilities and communication processes for quality-related activities of the involved parties. For outsourced
activities, this should be included in a written agreement between the contract giver and contract acceptor.
- Monitoring and review of the performance of the contract acceptor or the quality of the material from the provider, and the
identification and implementation of any essential improvements.
- Monitoring incoming ingredients and materials to ensure they are from approved sources using the agreed supply chain" (3).
These references are not meant to be all inclusive, but they show the increasing concern that regulators throughout the world
have about the relationship between a client and a CMO.