and the Generic Industry Mark Vieder RPh MBA Director, Safety & Medical Writing Biorasi
Disclaimer: This presentation has been prepared by Biorasi, LLC solely for the purpose of sharing information and is a general summary obtained from other references, links or materials.
Topics Discussion of the Proposed Rule Safety Reporting Requirements for Human Drug and Biological Products Status of the Proposed Rule Potential Impact of the Proposed Rule on Industry
Proposed Rule Posted to Federal Register Covering 21CFR Parts 310, 312, 314, 320, 600, 601, 606 Rule to amend FDA Pre-Market & Post Marketing safety reporting regulations.
Proposed Rule What is being amended? Establish worldwide consistency in the submission and collection of safety reports & information. Why? Content Increase quality of safety reports, review critical safety information allowing the protection and promotion of public health.
Proposed Rule These proposed changes are in response to recommended standards by the International Conference on Harmonization (ICH) and the WHO Council for International Organizations of Medical Sciences (CIOMS)
Status of Proposed Rule Posted in March 2003 Current Status Continues to be worked on within the FDA Implementation Date -??????? Note: once the Rule is published a comment period will follow and a year for implementation will begin.
Safety Topics of Potential Impact Many topics are covered in the proposed rule, the potential impact discussion will be on the following: 1. Minimum Data Set Full Data Set 2. Medication Errors 3. MedDRA 4. Periodic Reporting 5. Active Query
Minimum Data Set Full Data Set Currently four (4) elements are needed for a reportable case. An identifiable patient, identifiable reporter, suspect drug or biologic product and an event. Proposed Full Data Set would include completion of all applicable elements of a 3500A/VAERS/CIOMS form and Electronic.
Minimum Data Set Full Data Set What does all applicable elements mean? Contains the four minimum elements plus a concise medical narrative, meaning an accurate summary of the relevant data and information collected. Need to insure complete, accurate data collection. Are there any exceptions to this proposal of full data set? Medication error reports
Medication Errors Definition Any preventable event that may cause or lead to inappropriate medication use or patient harm. Examples of events that may be related to Medication errors could be: professional practice, products, procedures, prescribing, labeling, packaging, nomenclature
Medication Errors The proposed rule identifies actual medication errors and potential medication errors. Actual Medication Error is one that involves an identifiable patient whether the error was prevented prior to administration or after administration and whether an adverse event resulted. Potential Medication Error is one that does not involve an identifiable patient. May be related to product name, labeling or packaging.
Medication Errors Medication errors are increasing on a yearly basis. Within the FDA the Division of Medication Error Prevention and Analysis (DMEPA) monitors safety reports for medication errors. Modification of the minimum data set/full data set is being proposed allowing the greater capture of these medication error reports. Increased pharmacovigilance to interpret the occurrence of medication errors (serious & non)
MedDRA ICH recognized a need for standardized medical terminology to be instituted allowing data retrieval and analysis of safety data to occur faster. Medical Dictionary for Regulatory Activities (MedDRA) was selected as the vehicle to capture safety data in a uniformed manner. Other vehicles were mentioned as possibilities.
MedDRA MedDRA is mandated by the EMA and PMDA and currently accepted by the FDA Subscription required to utilize MedDRA Versioning occurs twice a year Infrastructure costs incurred as well.
Periodic Reports Current reporting of periodics is: 1. Quarterly for three years from approval date 2. Annually thereafter Proposed: ICH recommendations for all Regulatory authorities is for submissions to occur at six (6) months intervals or multiples thereof.
Periodic Reports Proposed: NDA, ANDA and BLA holders of approved drug or biologic products (prior to January 1, 1998) submit a periodic report every 5 yrs. after FDA approval and then at 7.5 and 12.5 year post approval. Proposed: NDA, ANDA and BLA holders of approved drug or biologic products (after January 1, 1998) submit a periodic report semiannually for 2 yrs., annually for the next 3 yrs. and every 5 yrs. thereafter with submissions at 7.5 and 12.5 yrs.
Current Content of periodic adverse drug experience report Narrative summary and analysis of the information contained in the report Analysis of expedited reports submitted to FDA during the reporting interval FDA Form 3500A (VAERS form for vaccines) for each adverse drug experience not submitted to FDA as an expedited report Index consisting of a line listing of the applicant's patient identification number and adverse reaction term(s) History of actions taken since the last report because of adverse drug experiences Pharmacovigilance Proposed revisions to content of periodic adverse drug experience report Excludes nonserious expected SADRs. Includes discussion of increased frequency of serious expected SADRs and lack of efficacy reports. Includes applicant's recommendations for safety-related actions to be taken. Not revised. Revoked requirement.1 Not revised. Not revised. Require submission summary tabulations.2 New section added for location of safety records. New section added for contact information for licensed physician responsible for information in TPSR. 1 Individual case safety reports would be submitted to FDA separately on a semiannual basis. 2 Summary tabulations are currently requested (see the guidance of 1992) but not required for postmarketing periodic adverse drug experience reports.
Active Query Direct verbal contact with a reporter by a Health Care professional (physician, PA, pharmacist, nurse or anyone with health care training). Verbal contact in person, phone or other interactive means. Purpose FDA believes that a HCP would better understand the medical impact of a case and ask appropriate questions acquiring more complete safety information.
Active Query Active query is a process that manufacturers, applicants, sponsors would be required to use in acquiring safety information in an expeditious manner. Seriousness, non-serious, medication error determinations can be made rapidly, minimum elements and full data sets would be gathered.
Summary Proposed Rule while many years in process will in the future become reality. Greater emphasis being placed on Industry by the Regulatory Agencies in the collection of Safety data. Pharmacovigilance/Safety data is driving force allowing needed medicinal products to reach patients. Ultimately Industry needs to be aware of this emphasis and the Impact it potentially will have.
Contact Information Mark Vieder RPh MBA Director, Safety &Medical Writing Biorasi, LLC (786)388-0700 mvieder@biorasi.com