William Gregory

Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition)


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      Images208 — Medication Guides for Prescription Drug Products

      Images310.501 — Patient package inserts for oral contraceptives

      Images310.515 — Patient package inserts for estrogens

      Images312 — Investigational New Drug (IND) Application

      Images312.32 — IND safety reports

      Images312.33 — Annual reports

      Images312.88 — Safeguards for patient safety

      Images314 — Applications for FDA Approval to market a New Drug (NDAs)

      Images314.80 — Post-marketing reporting of adverse drug experiences

      Images314.81 — Other post-marketing reports

      Images314.97 — Supplements and other changes to an approved abbreviated application (ANDA)

      Images314.98 — Post-marketing reports

      Images314.520 — Approval with restrictions to assure safety use

      Images314.540 — Post-marketing safety reporting

      Images314.630 — Post-marketing safety reporting

      Images601 — Biological Licenses

      Images601.12 — Changes to an approved application

      Images601.32 — General factors relevant to safety and effectiveness

      Images601.35 — Evaluation of safety

      Images601.93 — Post-marketing safety reporting

      Images610 — General Biological Products Standards

      Images610.11 — General safety

      In addition, other key documents such as FDA instructions for field staff, E2B ICSR submission information, ICH documents, and others are available.

      The CBER website contains less information regarding product safety than the CDER site because the regulatory responsibility for approval and post-marketing evaluation of many CBER products was transferred to CDER in 2003. The products remaining in CBER include cellular products (e.g., pancreatic islet cells for transplantation, whole cells, cell fragments, or other components intended for use as preventative or therapeutic vaccines); allergenic extracts used for diagnosing and treating allergic diseases and allergen patch tests; antitoxins; antivenins/antivenoms; venoms; blood; blood components; plasma-derived products (e.g., albumin, immunoglobulins, clotting factors, fibrin sealants, proteinase inhibitors), including recombinant and transgenic versions of plasma derivatives (e.g., clotting factors); blood substitutes; plasma volume expanders; human or animal polyclonal antibody preparations, including radio-labeled or conjugated forms; certain fibrinolytics, such as plasma-derived plasmin; and red cell reagents.

      More extensive information on this subject can be found at the CBER website. In regard to safety, there is information covering recalls, shortages, biological product deviation reporting (i.e., errors and accidents in manufacturing), AE reporting, and specific information about safety issues on various products, such as flu vaccines, HIV test kits, tissue products, and blood products. As noted, most AEs are reported via MedWatch using the 3500-voluntary reporting form. One exception is vaccine AEs (e.g., Adverse Events Following Immunization (AEFI)). These are reported to the Vaccine Adverse Event Reporting System (VAERS), which is sponsored by the FDA and the CDC. As with drugs, the goal is to collect and analyze safety signals and vaccine AEs. In particular, compared with drug products, vaccines are given to large numbers of children (FDA notes on its website that more than 10 million vaccinations are given yearly to children younger than 1 year old). As with all other products, the full safety picture is not known at the time of vaccine approval. Most of the VAERS reports are mild and include fever and injection site reactions, but some 15% are more severe AEs.

      The VAERS website has sections for consumer and healthcare professional reporting of AEs online, by fax, or by mail.

      The VAERS database, unlike the drug database, FAERS, has a system called CDC WONDER for obtaining data and producing tables, maps, charts, and various extracts regarding the incidence of vaccine AEs. For example, one can produce a report grouped by symptoms or medical problems (e.g., gastroenteritis) and various other criteria, such as age, gender, manufacturer, US location, date vaccinated, onset interval, seriousness, and outcome. The data are immediately available and are largely up to date. Data downloads are also available. This is a very useful tool. However, many discrepancies have been introduced by the application of SMQs to add an extrapolated diagnosis to the database when a diagnosis was not provided by the reporter. SMQs were not designed or tested for this and, e.g., sometimes age-inappropriate diagnoses are added. Use caution.

      See also Chapter 41.

      This is the center that deals with medical devices and radiologic agents. There are three sections in the CDRH website that are worth examining.

      The first is the Medical Device Safety section, which covers alerts and notices, recalls, and emergencies. There is a large section on Medical Device Reporting (MDR) of adverse events from manufacturers, importers, and user facilities (e.g., hospitals, nursing homes). Consumer and healthcare professionals report via MedWatch (as with biologics and drugs) using either the 3500- or 3500B-voluntary reporting form. With the introduction of electronic reporting, eMDR was launched and mandatory reports must be sent to eMDR according to CDRH technical specifications.

      The second is the Device Advice: Regulations & Guidance section. This is a very useful section that explains the regulations on marketing, standards, guidance, compliance, and post-market requirements. Note that the entire process of approval, marketing, and safety for devices is markedly different from the processes for drugs and biologics.

      The