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14 October 2018 Tablets & Capsules PIC/S is an internationally recognized cooperative arrangement between 49 regulatory authorities, including the FDA, and its goal is to harmonize inspection proce- dures worldwide and develop common standards in the field of good manufacturing practices. After observing an audit of a country's drug inspec- torate, the FDA conducts an independent and compre- hensive assessment. This assessment includes a review of the country's conflict-of-interest policies, specific legisla- tion related to GMP, samples of inspection reports, inspector training records, inventory of drug manufactur- ing facilities, surveillance programs, and numerous stan- dard operating procedures. The FDA evaluates pharmaceutical inspectors' creden- tials as part of the capability assessment of each EU coun- try and believes it is important for the authorities to employ trained and qualified inspectors with the skills and knowledge to identify manufacturing practices that may lead to patient harm. The annex also includes main- tenance provisions to ensure that each capable country continues to meet FDA requirements. Both the FDA and the EU reserve the right to inspect at any time and in any country. However, this is expected to be the exception rather than the rule since, following posi- tive capability assessments, the FDA will recognize the EU inspectorates as capable and recognize their drug manufac- turing facility inspections as meeting FDA requirements. Other FDA activities for monitoring the nation's drug product supply chain MedWatch reporting program. Since the early 1970s, the FDA has operated a voluntary program specifically directed to healthcare professionals for the reporting of observed or suspected defects and problems associated with finished drug products in the pharmaceutical supply chain, though the name of the program has changed over the years. From 1988 to 1993, the program was called the Drug Quality Reporting System (DQRS), and the form used for reporting was DQRS Form 3318. In June 1993, the FDA introduced the MedWatch reporting program to simplify reporting to the FDA by consolidating several FDA reporting programs involving drugs, biologics, devices, and medical foods through a single reporting form (FDA 3500/3500A) (Attachment Part VI B) and a toll-free telephone/fax number. The MedWatch program plays a vital role in the post-market- ing phase of regulating all pharmaceutical products and has a twofold purpose: 1) to rapidly identify significant health hazards associated with the manufacturing and packaging of pharmaceuticals, and 2) to establish a cen- tral reporting system for capturing and identifying drug-quality problem areas or trends that may require regulatory action. Although the MedWatch form replaced the DQRS Form 3318, it did not replace the DQRS system or the offices in the FDA's Center for Drug Evaluation and Research (CDER) that are responsible for evaluating and processing drug quality problems reported to FDA. FDA Form 3500 is used for voluntary reporting by both healthcare professionals and consumers and is the subject of the DQRS program. NDA field alert reports (FARs). The new drug appli- cation (NDA) and abbreviated new drug application (ANDA) field alert reporting requirements—21 CFR 314.81(b)(1)(i) and (ii)—became effective on May 23, 1985 [2]. The regulation requires holders of NDAs and ANDAs to "submit certain information about distributed drug products" to the jurisdictional FDA district offices within three working days. The three-working-day period begins when the applicant becomes aware of a reported problem through either a complaint or internal testing. It does not begin the day the applicant confirms or invalidates a problem. FARs may be reported via tele- phone or other means of rapid communication with a prompt written follow-up. The FAR and its mailing cover should be plainly marked: "NDA-Field Alert Report." Form FDA 3331 (References Part VI A) provides a stan- dardized form for applicants to report. FARs, in contrast to the "post marketing reporting of adverse drug experiences" covered by 21 CFR 314.80, contain a variety of drug-quality issues and are of interest to both field and CDER offices. Quality defect problems reported in FARs involve vio- lative issues and concerns that pose a potential health hazard to the public. These problems include, but are not limited to, matters concerning dissolution failures, impu- rity levels, mislabeling, and sub- or super-potency of dis- tributed drug products and articles. If the applicant holder can invalidate the problem (for example, by demonstrating that the problem was due to an analytical laboratory error) within three working days, a FAR is not required. For guidance on investigating out-of-specifica- tion test results, see "Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production" [3]. If the applicant holder determines that further investiga- tion is required, or if a corrective action is initiated (such as a formulation revision or labeling change), a FAR must be submitted. Criteria for when a FAR must be submitted by the NDA/ANDA holder include but are not limited to: • any incident that causes the drug product or its labeling to be mistaken for or applied to another article; • bacterial contamination; • significant chemical, physical, or other changes; • product deterioration; and • failure of one or more distributed batches of drug products to meet the specification established in the application. Foreign NDA/ANDA holders must follow the same FAR reporting criteria required for domestic sites for drug products manufactured overseas according to the specifi- cations of an NDA/ANDA and/or distributed in foreign markets. Per 21 CFR 314.50(a)(5), foreign application holders are required to have a US office or agent who is responsible for reporting to the FDA [4]. The US agent