How The FDASIA Can Affect Your Supply Chain

By Dr. Guo, VP of pharmaceutical and quality services, AMRI

The supply chain for active ingredients and drug products in the pharmaceutical industry is becoming more complex as globalization in the world economy continues. Globalization provides benefits for costeffective solutions, enhanced security, and stability for the supply chain. On the other hand, companies therefore need a more sophisticated approach to manage their global supply chain. After all, suppliers in individual countries operate under their own regulatory, environmental, and cultural norms and requirements.

Key info About The FDASIA
As part of the U.S. effort to modernize regulation for the 21st century, the U.S. FDA Safety and Innovation Act (FDASIA) was enacted in July 2012. This act reauthorized/ authorized user fees for various submissions to ensure that the FDA is adequately funded for its mission. Another part of this act covers the supply chain.

First, the FDASIA introduced the “riskbased inspection” concept for drug establishments, which shall be inspected according to known safety risks, based on risk factors such as:

a) compliance history of the establishment
b) the record, history, and nature of recalls linked to the establishment
c) the inherent risk of the drug manufactured, prepared, propagated, compounded, or processed at the establishment
d) the inspection frequency and history of the establishment
e) whether the establishment has been inspected by a foreign government.

Second, the FDASIA clarified the term cGMP (current good manufacturing practice), defined specifically to 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 in the manufacturing of drugs, and finished drug products.’’

Risk-based Management of the Globalized Supply Chain
Risk-based management of the supply chain is increasingly important considering the increased complexity of the globalized supply chain and the FDA’s expectation that market authorization sponsors manage the risk to and establish the safety of drugs — including all materials used in manufacturing. This is equally important for pharmaceutical companies or contract manufacturers.

Risk factors considered in the FDASIA provide a good basis for a company to establish a risk-based management program. This program should cover the life cycle of the supply chain — from selection, inspection, and qualification to ongoing quality monitoring and requalification or disqualification as appropriate.

For this risk-based program, it is important to first research and evaluate a supplier’s history. This analysis should review the supplier’s registration and inspection history, including establishment inspection reports, agency databases for objectionable actions including recalls, and product lists (especially for known sensitizers, sex hormones, or animal-originated materials). Second, it’s important to evaluate the inherent risk of a drug or intermediate manufactured, prepared, propagated, compounded, or processed at the establishment. The inherent risk increases from GMP starting material, to GMP intermediates, to GMP active pharmaceutical ingredients, to GMP oral drug products, and to GMP injectable drug products. The suppliers for each type of material or product shall be risk-assessed and managed as appropriate. For example, although a GMP starting-material supplier may have less inherent risk in comparison to a GMP injectable-drug product supplier, the risk assessment is still important for such a supplier. Otherwise, a contaminated starting material could carry such risk all the way to the drug product. Often, starting materials are supplied by a chemical or other company instead of a GMP establishment, and quality systems can sometimes be weak.

With a comprehensive risk assessment of multiple factors, companies should develop supplier qualification standard operating procedures. A supplier qualification and inspection plan should also be evaluated periodically to reflect the dynamic nature of the globalized supply chain and industry best practices.

The FDA clearly expects that market authorization sponsors shall be responsible for the quality of the entire supply chain starting from raw materials. Establishing, following, and continuously updating a risk-based assessment process is highly recommended.