Utilizing FDA Standard Terminology

Statutory Pathways for New Products Substantial Equivalence Reports §905(j) Does not raise different questions of public health Premarket Tobacco Product Application §910 Appropriate for protection of public health Modified Risk Tobacco Product Application §911 Benefits the health of the population as a whole

Statutory Requirements on Product Related Health Information Family Smoking Prevention Control Act: FSPTCA §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

Statutory Requirements on Product Related Health Information Family Smoking Prevention Control Act: §911 d) (5) Filling: “all documents …related to the effect of new product on tobacco-related diseases and health related conditions…” (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”

Statutory Requirements on Product Related Health Information Family Smoking Prevention Control Act: §909 Records and Reports on Tobacco Products 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”

Statutory Requirements on Product Related Health Information Consumer Complaints (APE) (call centers) Product quality investigation Trending Market actions Consistent adverse events classification Development and maintenance of safety database infrastructure Clinical Research/ Consumer research Facilitate the identification and investigation of product quality issues Supplier issues Manufacturing issues Product Design issues Distribution issues

Medical Dictionary for Regulatory Activities MedDRA Medical Dictionary for Regulatory Activities Clinically validated international medical terminology used by regulatory authorities and the regulated biopharmaceutical industry through the entire regulatory process, from pre-marketing to post-marketing; and for data entry, retrieval, evaluation and presentation. IND>NDA>Post market CDISC (Clinical Data Interchange Standards Consortium) is an industry Standards Organization.  The Analysis Data Model (ADaM) is a set of guidelines (within CDISC) and examples for analysis datasets used to generate the statistical results for submission to a regulatory authority such as FDA. MedDRA is a terminology used and supported by the CDISC standards.

Structure Overview MedDRA (version 19.0) SOC System Organ Class 27 HLGT High Level Group Term 335 HLT High Level Term 1,732 PT Preferred Term This slide represents the MedDRA levels. The top level is the System Organ Class, known as SOC. There are 26 SOCs in MedDRA 6.0 and their number has been constant since the beginning. MedDRA SOCs correspond to the main anatomical/functional body systems – Cardiac Disorder SOC, Endocrine disorder SOC, Gastrointestinal disorder SOC, etc. Among the 26, there is also a ‘General disorder’ SOC, an ‘Infections’ SOC, ‘Investigations’ SOC, ‘Congenital disorders’ SOC, ‘Neoplasms’ SOC, and a ‘Social circumstances’ SOC. A SOC consists of at least one, but usually more, High level Group Terms, HLGTs, which represent the second level of MedDRA terminology.There are 332 HLGTs in MedDRA 6.0. For example, Immune System Disorders SOC consists of Allergic conditions HLGT, Autoimmune disorders HLGT, Immunodeficiency syndromes HLGT, and Immune disorders NEC HLGT. A HLGT consists of at least one, but usually more, High Level Terms, known as HLTs. There are 1,682 HLTs in MedDRA 6.0. For example, Allergic conditions HLGT consists of Allergies to foods, additives, drugs, chemicals HLT, Anaphylactic responses HLT, Angioedemas HLT, Allergic conditions NEC HLT, Urticarias HLT, and Atopic disorders HLT. Both the HLGTs and HLTs are broad groupings of terminology. They are not used directly for coding, but for understanding the meaning of a term from lower levels of terminology. However, HLGTs and HLTs are used directly for data retrieval and data presentation. An HLT consists of at least one, but usually more, Preferred terms, known as PTs. MedDRA 6.0 contains 16,102 PTs. A Preferred term is a single distinct medical concept. It can represent anything in MedDRA – sign, symptom, lab result, indication, history term. It must be unique – there is no overlap at the PT level. A Preferred term consists of at least one but usually more Low Level Terms, known as LLTs. There are 49,721 current LLTs in MedDRA 6.0 (and 8,839 non-current LLTs, to be explained later). A Preferred term is described and defined by its Low level terms. This implies that a LLT belongs to one and only one PT. Low level terms are mainly synonyms of the PT and dialectic and lexicant variants of the PT. An LLT most closely resembles the original reporter’s words. In some cases, an LLT may represent more clinical information than its corresponding PT, but this information is generally not considered crucial by the regulatory authorities. Thus, regulatory authorities are exchanging information at the PT level. However, pharmaceutical companies are coding at the LLT level. MedDRA reporting to the Food and Drug Administration in the USA and the Ministry of Health Labor and Welfare in Japan is done at the PT level. However, the European authority, EMEA requires reporting of both the LLT and its corresponding PT term. Each MedDRA term, on every level, consists of a text string and a unique8-digit numeric identifier. SMQ Standard MedDRA Queries 21,920 LLT Low Level Term 75,818 9 9

Hierarchy SOC-HLGT-HLT-PT SOC Blood and lymphatic disorders HLGT White blood cell disorders HLT Neutropenias PT Agranulocytosis PT Febrile neutropenia PT Neutropenia PT Idiopathic neutropenia…

ADVANTAGES PROACTIVE approach with data WHY? Record data accurately Preserve specificity and meaning In uniform and consistent manner To ensure comprehensive Data Retrieval Presentation Organization Statistical analysis Communication of data PROACTIVE approach with data

Samina Qureshi, M.D. Vice President of PSI Healthscience and Pharmaceutical Division PSI INTERNATIONAL Inc. 4000 Legato Road, Fairfax, VA 22033 squreshi@psiint.com 703-909-9308 CONTACT INFORMATION