HOW TO FULFILL STATUTORY REQUIREMENTS ON PRODUCT RELATED HEALTH INFORMATION Samina Qureshi, M.D. PSI INTERNATIONAL Inc.

Tobacco Control Act The Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act), signed into law on June 22, 2009, gives FDA authority to regulate the manufacture, distribution, and marketing of tobacco products The three Statutory Pathways for new products are: Substantial Equivalence Reports, Premarket Tobacco Product Application (PMTA) and Modified Risk Tobacco Product Application (MRTP)

Tobacco Control Act The Act explicitly addresses the requirement of reporting product related health information in all three types of applications. Substantial Equivalence Reports (§905(j))-Does not raise different questions of public health Records and Reports on Tobacco Products Trend Reports – (§909) Premarket Tobacco Product Application (PMTA) (§ 910) Modified Risk Tobacco Product Application (MRTPA) (§ 911)

TCA- §909 Records and Reports on Tobacco Products Trend Reports – (§909) “… to report … information that reasonably suggests that one of its marketed tobacco products may have caused or contributed to a serious unexpected adverse experience associated with the use of the product or any significant increase in the frequency of a serious, expected adverse product experience”

TCA § 910 Premarket Tobacco Product Application (PMTA) (§ 910) (b)(1)(A) Application content: Full reports of all investigations to address the health risks of the product (d)(1)(C) Withdrawal and Temporary Suspension: “(i) has failed to established a system for maintaining records or has repeatedly or deliberately failed to maintain records or to make reports, required by an applicable regulation under section §909

TCA § 911 §911 (d) (5) Filling: “all documents …related to the effect of new product on tobacco-related diseases and health related conditions…” §911 (i)(1) Postmarket Surveillance and Studies: “…to determine impact of the order issuance on consumer perception, behavior and health…” The results …shall be submitted …on an annual basis” The best and most adequate terminology to address this is the Medical Dictionary for Regulatory Activities (MedDRA).

Medical Dictionary for Regulatory Activities- MedDRA MedDRA is in current use by the Pharmaceutical companies in regulatory applications to FDA for : IND BLA NDA FDA guidance has recommended its use in these applications with FDA guidance for Clinical research capture of adverse events and Post market adverse event capture and surveillance

Proactive Approach There are numerous advantages for tobacco product companies to proactively use this terminology in order to become ready to utilize the research data/consumer complaint data and product quality data should it become required as for the other regulatory submissions. Allows for organized and consistent internal methodology for data collection. This is a standardized, medically validated terminology used and supported by the Clinical Data Interchange Standards Consortium-CDISC standards.

Industry Standards for Health Data

Proactive Approach Consumer Complaints (APE) (call centers) Product quality investigation Trending Signal detection Consistent adverse events classification Development and maintenance of safety database infrastructure Clinical Research Facilitate the identification and investigation of product quality issues Supplier issues Manufacturing issues Product Design issues Distribution issues

Advantages Maintain data in FDA compliant data standard format Have clinically significant data to analyze for quality and adverse event issues Utilize the terminology hierarchy for meaningful analysis of aggregate data Data can be utilized to support future regulatory applications for substantial equivalence (SE), PMTA or Modified Risk Tobacco Product Application.

Advantages Currently, FDA reviewers in CDER and CBER review IND’s, NDA’s and BLA’s with data utilizing MedDRA terminology. FDA Center for Tobacco Products (CTP) – staff from CDER & CBER Similarity/Parallels of regulations as in other Centers Substantial Equivalence (similar to CDRH) Post Market surveillance (CDER,CBER, & CDRH) In addition, the recent “Deeming rule” has expanded the FDA authority over increased number of products which can also benefit from data capture in this terminology.

The best and most adequate terminology to address this is the Medical Dictionary for Regulatory Activities (MedDRA). M e d D R A