FDA is evaluating the root cause of benzene contamination in certain drugs and alerting drug manufacturers to the risk of benzene contamination from drug components and other potential risk factors.
Drug manufacturers are required to ensure the safety and quality of their drugs. As FDA works to better understand the potential sources of benzene in drugs, FDA reminds manufacturers of drugs marketed under approved applications and manufacturers of other drugs, including over-the-counter monograph drug products, of their obligation to ensure their products conform to appropriate quality specifications.
Pharmaceutical quality is the foundation that allows patients and consumers to have confidence in the safety and effectiveness of their medications. CDER established the Office of Pharmaceutical Quality (OPQ) to ensure a uniform drug quality program across all sites of manufacture, whether domestic or foreign, and across all human drug product areas – new drugs and biologics, generics, biosimilars, over-the-counter drugs and certain compounded drugs.
The resources below offer information on pharmaceutical quality topics for manufacturers and applicants.
Quality Information for Applicants: Chemistry, Manufacturing, and Controls (NDA, ANDA, BLA, and IND applications)
The following resources should be helpful to applicants and manufacturers who are required to have an approved application before marketing or conducting a clinical trial. They provide information relevant to various application types. Much of the technical and scientific information will also be helpful for manufacturers of non-application drugs, such as OTC monograph products:
- Investigational New Drug Application regulations (21 CFR 312)
- Applications for FDA Approval to Market a New Drug (21 CFR 314)
- Biological Products: General and Licensing (21 CFR 600 and 601)
- CGMP Regulations
- Developing and Manufacturing Drugs Including Biologics
- Quality Related Guidances go to Search for FDA Guidance Documents and filter by
- FDA Organization - Center for Drug Evaluation and Research and
- Chemistry, Manufacturing, and Controls (CMC)
- Current Good Manufacturing Practice (CGMP)
- Drug Master Files (DMFs)
- Inactive Ingredient Database
- Elemental Impurities
- Expiration Dates - Questions and Answers
- Report a Product Quality Issue
The following resources provide additional details for specific types of applications:
- Questions and Answers on Quality-Related Controlled Correspondence
- Investigational New Drug (IND) Applications for Clinical Investigations: CMC Information
- Current Good Manufacturing Practices for Phase I Investigational Drugs
- Generic Drugs: Information for Industry
Advancing Product Quality
FDA is engaged in efforts to encourage innovations in manufacturing processes and technology and to foster a quality management system.
- Emerging Technology Program: FDA meets early with companies developing technologies that may offer significant improvements to pharmaceutical quality and provides recommendations to help support technology development and implementation and anticipated applications. The Emerging Technology Team has considered a wide range of new technologies such as continuous manufacturing, 3D printing, Process Analytical Technology, distributed manufacturing, and artificial intelligence.
- CDER’s Framework for Regulatory Advanced Manufacturing Evaluation (FRAME) Initiative: CDER is preparing a regulatory framework to support the adoption of advanced manufacturing technologies that could bring benefits to patients. Based on engagements through the Emerging Technology Program and elsewhere, the FRAME initiative prioritized four technologies: End-to-End Continuous Manufacturing, Distributed Manufacturing, Point-of-Care Manufacturing, and the use of Artificial Intelligence in manufacturing.
- International Collaboration: FDA engages foreign regulatory counterparts to coordinate on ways to advance product quality. For example, we work with the International Council on Harmonisation (ICH) to develop harmonized quality standards and facilitate implementation by industry. FDA is a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S), which is an international organization dedicated to harmonizing inspection practices and related policies. FDA has also engaged in initiatives such as the Mutual Recognition Agreement to utilize inspectional observations from capable regulatory authorities, reduce duplicative efforts, and focus resources and inspections on facilities that pose the greatest risk. In addition, the FDA is promoting engagement with global regulators under the International Coalition of Medicines Regulatory Authorities (ICMRA) forum, which is comprised of 28 regulatory authorities from around the globe.
- ConOps: In June 2017, CDER and ORA established a Concept of Operations (ConOps) to integrate facility evaluations and inspections for human drugs. See our Q&A page for additional details about how this collaboration will improve consistency, efficiency, and transparency for facility evaluations, and inspections, and regulatory actions.
- Quality management maturity (QMM): To increase transparency and incentivize investment in mature quality management practices, CDER is developing a framework to objectively rate the QMM of pharmaceutical manufacturing sites. CDER’s QMM webpage explains the importance of QMM and provides information on OPQ’s white paper, upcoming workshops, and quality metrics, which are an important element of QMM.
- Quality metrics: FDA requires all drug manufacturers to monitor quality and drive continuous improvement. FDA’s quality metrics webpage provides background on the FDA’s efforts to initiate a voluntary reporting program that can provide key metrics to the FDA.
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