supac & pms

Scale Up, Scale Up, Post Approval Changes Post Approval Changes (SUPAC)(SUPAC)& & Post Marketing SurveillancePost Marketing Surveillance

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IntroductionIntroduction

►Approval of ANDA is the start of generic drug product historyApproval of ANDA is the start of generic drug product history►Changes are made frequently to chemistry & mfg controls Changes are made frequently to chemistry & mfg controls

after approval throughout the life term of productafter approval throughout the life term of product►Mfr may bring change in drug formulation, batch size, Mfr may bring change in drug formulation, batch size,

process, equipment, mfg site may affects the identity, process, equipment, mfg site may affects the identity, strength, quality, purity and potency of finished productstrength, quality, purity and potency of finished product

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►Changes to approved ANDA may be doneChanges to approved ANDA may be doneRevised market forecast- change batch sizeRevised market forecast- change batch sizeQualification of new API sourceQualification of new API sourceOptimization of mfg processOptimization of mfg processUpgrade of container/ closureUpgrade of container/ closureEnhancement of analytical method and specsEnhancement of analytical method and specs

►Change made may have varied adverse effects Change made may have varied adverse effects depending on the type or dosage form or productdepending on the type or dosage form or product

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►Eg: Change in container/ closures (solid/parenterals), Eg: Change in container/ closures (solid/parenterals), conc. of inactives (imm rel/ sust rel) – impacts BEconc. of inactives (imm rel/ sust rel) – impacts BE

►Frequent & numerous changes may render the Frequent & numerous changes may render the product substantially different than the one approved product substantially different than the one approved in original ANDAin original ANDA

►Supportive data to be submitted – comparison with Supportive data to be submitted – comparison with original exhibit batch/ bio batchoriginal exhibit batch/ bio batch

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BackgroundBackground

► Food & Drug Administration Modernization Act (FDAMA) – Nov 21, Food & Drug Administration Modernization Act (FDAMA) – Nov 21, 1997 for “further defining the statutory requirements for marketing 1997 for “further defining the statutory requirements for marketing approved drugs in US”approved drugs in US”

► Post FDAMA, FDA issued Guidance for Industry: Changes to an Post FDAMA, FDA issued Guidance for Industry: Changes to an Approved NDA or ANDA – P. Ind to assess & report mfg changesApproved NDA or ANDA – P. Ind to assess & report mfg changes

► FDAMA rewrite of 21 CFR 341.70FDAMA rewrite of 21 CFR 341.70► 4 reporting categories4 reporting categories

►Prior approval supplement: Major changes, need FDA approvalPrior approval supplement: Major changes, need FDA approval►Supplement – changes being effected (30 days) – Moderate changesSupplement – changes being effected (30 days) – Moderate changes►Supplement – changes being effected (0 days) – Moderate changesSupplement – changes being effected (0 days) – Moderate changes►Annual report – Minor changes, immediately implemented, filed in next Annual report – Minor changes, immediately implemented, filed in next

periodic reportperiodic report

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SUPACSUPAC► Prior to FDAMA, basis of revision of FD&C Guidance for Industry: Scale up & Prior to FDAMA, basis of revision of FD&C Guidance for Industry: Scale up &

post approval changes (SUPAC)post approval changes (SUPAC)► Provided the clear, definitive language regarding regulatory notification process Provided the clear, definitive language regarding regulatory notification process

and requirements for post approval changes, reduced regulatory burden on and requirements for post approval changes, reduced regulatory burden on industryindustry

► Classified in to levels, provided requirements for each levelClassified in to levels, provided requirements for each level► SUPAC expanded 21 CFR 314.70 and defined in much detail the types of SUPAC expanded 21 CFR 314.70 and defined in much detail the types of

changes and reporting category required. changes and reporting category required.

In the following areas the change is likelyIn the following areas the change is likely► Components and composition of the drug productComponents and composition of the drug product► Manufacturing site changeManufacturing site change► Scale-up of the drug productScale-up of the drug product► Manufacturing equipmentManufacturing equipment► PackagingPackaging

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SUPACSUPAC

►Describes 3 levels of changesDescribes 3 levels of changes►Recommends chemistry, manufacturing and controls tests, in Recommends chemistry, manufacturing and controls tests, in

vitro dissolution tests, and bioequivalence tests for each levelvitro dissolution tests, and bioequivalence tests for each level

Level & DefinitionLevel & Definition►1 - Changes that are unlikely to have any detectable impact 1 - Changes that are unlikely to have any detectable impact

on formulation quality and performanceon formulation quality and performance►2 - Changes that could have a significant impact on 2 - Changes that could have a significant impact on

formulation quality and performanceformulation quality and performance►3 - Changes that are likely to have a significant impact on 3 - Changes that are likely to have a significant impact on

formulation quality and performanceformulation quality and performance

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►Components/ CompositionComponents/ Composition►Site changesSite changes►Change in batch sizeChange in batch size►Manufacturing Manufacturing ►SpecificationsSpecifications►PackagingPackaging

Current Requirements For Post-approval ChangesCurrent Requirements For Post-approval Changes

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Current Requirements For Post-approval ChangesCurrent Requirements For Post-approval ChangesComponents/ CompositionComponents/ Composition

►Changes to the qualitative/ quantitative composition of the formulation are considered major changes

►These changes must be considered carefully before implementation. Such changes require a “Prior Approval Supplement” unless otherwise exempted by regulation or guidance documents.

►Current guidance for industry, Changes to an Approved ANDA or NDA, does not address components/ composition in detail

►SUPAC guidance remains in effect for defining components and composition changes and the reporting category

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►Addition or deletion of an ingredient can have an adverse effect on the dissolution profile of the finished product and on the in vivo bioequivalence to the RLD

►Addition or deletion of an ingredient must be filed as a Prior Approval Supplement

►Exceptions – colors (removed/ reduced)►Some cases – less stringent reporting

Current Requirements For Post-approval ChangesCurrent Requirements For Post-approval ChangesComponents/ CompositionComponents/ Composition

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►The sponsor of an ANDA - include in its application the site of manufacture, where the drug product will be produced, tested, packaged, and/or labeled. A change in any of these sites can adversely affect the identity, strength, quality, purity, or potency of the finished product

►Any site change under SUPAC-IR calls for the new site to be in compliance with good manufacturing practice (cGMP) regulations

►A stand-alone packaging operation site change, utilizing container (s)/ closure (s) in the approved application, may be submitted as a “Change Being Effected Supplement”

►Facility should also have a current and satisfactory cGMP compliance profile with FDA

Current Requirements For Post-approval ChangesCurrent Requirements For Post-approval ChangesSite ChangesSite Changes

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►If the facility has not received a satisfactory cGMP Inspection If the facility has not received a satisfactory cGMP Inspection within the previous two years for the type of packaging within the previous two years for the type of packaging operation involved, a “Prior Approval Supplement” with the operation involved, a “Prior Approval Supplement” with the same commitment for stability is recommendedsame commitment for stability is recommended

►Supplement should also contain a commitment to place the Supplement should also contain a commitment to place the first production batch of the product on long-term stability first production batch of the product on long-term stability studies using the approved protocol in the application and to studies using the approved protocol in the application and to submit the resulting data in annual reportssubmit the resulting data in annual reports

►Same for the analytical testing laboratorySame for the analytical testing laboratory

Current Requirements For Post-approval ChangesCurrent Requirements For Post-approval ChangesSite ChangesSite Changes

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►Change in batch size from pivotal/ pilot scale bio-batch to larger or smaller production batches tends to change the operating parameters. Therefore, all the parameters, such as mixing time, speed, etc., are adjusted according to the equipment (large or small) used in the process.

►This requires proper validation of the batches before submission of additional information in the application.

►Any change in the production batch for which the operating parameter falls within the range established for the ANDA batch and validation batches will be regarded as a level1change.

► If it falls outside the validation ranges, the change would be permitted under SUPAC-IR as a level 2 change.

►Regardless, SUPAC-IR does not address scale-down below 100,000 units

Current Requirements For Post-approval ChangesCurrent Requirements For Post-approval ChangesChange in Batch SizeChange in Batch Size

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Current Requirements For Post-approval ChangesCurrent Requirements For Post-approval ChangesManufacturingManufacturing

►This includes any change made in equipment and the process used in manufacturing a drug product

1. EQUIPMENT CHANGE► Any change in Any change in manufacturing equipment other thanmanufacturing equipment other than that used in the that used in the

approved application requires appropriate validation studies to approved application requires appropriate validation studies to demonstrate that the new equipment is similardemonstrate that the new equipment is similar to the original equipment. to the original equipment.

► Equipment within the Equipment within the same class and subclasssame class and subclass would be considered to would be considered to have the have the same design and operating principlesame design and operating principle under SUPAC-IR. under SUPAC-IR.

Eg: Change in diff mfr of V-cone blender – acceptable

►Change from one class of equipment to another would be considered a would be considered a change in design and operating principle and change in design and operating principle and would be considered would be considered differentdifferent under SUPAC-IR. under SUPAC-IR.

Eg: V-cone blender to ribbon blender

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►A guidance for industry, A guidance for industry, SUPAC-IR/MR: Immediate Release SUPAC-IR/MR: Immediate Release and Modified Solid Oral Dosage Forms Manufacturing and Modified Solid Oral Dosage Forms Manufacturing Equipment AddendumEquipment Addendum, 1999 (3), explains in detail about , 1999 (3), explains in detail about various changes in equipment and the regulatory requirementvarious changes in equipment and the regulatory requirement

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The two different levels of change and regulatory requirements on change

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PROCESS CHANGEPROCESS CHANGE►Change in manufacturing process or technology – may have Change in manufacturing process or technology – may have

adverse effects on the identity, strength, quality, purity, or potency adverse effects on the identity, strength, quality, purity, or potency of a drug product. of a drug product.

►The safety or effectiveness of the product depends on the The safety or effectiveness of the product depends on the type of type of the manufacturing processthe manufacturing process and the changes being instituted for the and the changes being instituted for the drug substance or drug product. drug substance or drug product.

►Any Any fundamental change in the manufacturing processfundamental change in the manufacturing process, e.g., dry to , e.g., dry to wet granulation or change from one type of drying process to wet granulation or change from one type of drying process to another (e.g., oven tray, fluid bed) is considered a another (e.g., oven tray, fluid bed) is considered a major changemajor change, , whereas whereas change in mixing time, operating speedchange in mixing time, operating speed, etc., within an , etc., within an approved range is considered a approved range is considered a minor changeminor change

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The guidance defines 3 levels of in-process changesThe guidance defines 3 levels of in-process changes

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►Specifications are the Specifications are the standards a drug product must meet to standards a drug product must meet to ensure conformance to predetermined criteria for consistency, ensure conformance to predetermined criteria for consistency, reproducibility, and qualityreproducibility, and quality. .

►Such changes generally Such changes generally requirerequire a “Prior Approval a “Prior Approval Supplement” unless the specification is tightening or Supplement” unless the specification is tightening or otherwise exemptedotherwise exempted by regulation guidance documents by regulation guidance documents

Current Requirements For Post-approval ChangesCurrent Requirements For Post-approval ChangesSpecificationsSpecifications

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►Prior approvalPrior approval is required on the is required on the following major changesfollowing major changes in in specification except as provided in the SUPAC-IR guidancespecification except as provided in the SUPAC-IR guidance Relaxing an acceptance criterionRelaxing an acceptance criterion Deleting any part of a specificationDeleting any part of a specification Changing or establishing a new regulatory analytical procedure that does not Changing or establishing a new regulatory analytical procedure that does not

provide the same or increased assurance of the identity, strength, quality, purity, provide the same or increased assurance of the identity, strength, quality, purity, or potency of the material being tested as the analytical procedure described in the or potency of the material being tested as the analytical procedure described in the approved applicationapproved application

►A A 30 days Changes Being Effected Supplement30 days Changes Being Effected Supplement needs to be needs to be filed filed in case of moderate changesin case of moderate changes in specifications, e.g., in specifications, e.g., Change in regulatory analytical procedures other than editorial or identified as Change in regulatory analytical procedures other than editorial or identified as

major major A change in analytical procedure or deletion of a test for raw materials used in A change in analytical procedure or deletion of a test for raw materials used in

drug substance mandrug substance man

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►The following include The following include changeschanges in specifications that are in specifications that are considered to considered to have minimal potentialhave minimal potential for an adverse effect on for an adverse effect on the identity, strength, quality, purity, or potency of a product as the identity, strength, quality, purity, or potency of a product as they may relate to the safety or effectiveness of the product, they may relate to the safety or effectiveness of the product, and therefore and therefore can be submitted in an annual reportcan be submitted in an annual report:: Change in specification made to comply with an official compendiumChange in specification made to comply with an official compendium Change in analytical procedure for testing raw material, drug substance or drug Change in analytical procedure for testing raw material, drug substance or drug

product that provides the same or increased assurance of identity, strength, product that provides the same or increased assurance of identity, strength, purity, or potency of the material being tested as the analytical procedure purity, or potency of the material being tested as the analytical procedure described in the approved applicationdescribed in the approved application

Tightening of acceptance criteriaTightening of acceptance criteria

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Current Requirements For Post-approval ChangesCurrent Requirements For Post-approval ChangesPackagingPackaging

►A A container/closure systemcontainer/closure system for a solid oral dosage form tends for a solid oral dosage form tends to be to be low risk and will have little impactlow risk and will have little impact on the shelf life of the on the shelf life of the finished product. Therefore, under the new guidance for finished product. Therefore, under the new guidance for industry, and the stability guidance, the requirements for industry, and the stability guidance, the requirements for packaging changes have been relaxed significantpackaging changes have been relaxed significant

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Comparability ProtocolsComparability Protocols► A comparability protocol is a plan for anticipated future CMC changes. A comparability protocol is a plan for anticipated future CMC changes.

FDA recently published a draft guidance, FDA recently published a draft guidance, ““Comparability Protocols Comparability Protocols Chemistry, Manufacturing, and Controls Information”Chemistry, Manufacturing, and Controls Information”, to provide , to provide recommendations on recommendations on preparing and using comparability protocols for preparing and using comparability protocols for post-approval changespost-approval changes in the in the CMC section of an NDA or ANDACMC section of an NDA or ANDA..

► According to the guidance, According to the guidance, ‘‘A comparability protocol is a ‘‘A comparability protocol is a well defined, well defined, detailed, written plandetailed, written plan for for assessing the effect of specific CMC changesassessing the effect of specific CMC changes in the identity, strength, quality, purity, and potency of a specific drug in the identity, strength, quality, purity, and potency of a specific drug product as these factors relate to the safety and effectiveness of the product as these factors relate to the safety and effectiveness of the product. A comparability protocol product. A comparability protocol describesdescribes the the changes that are changes that are covered under the protocolcovered under the protocol and and specifies the tests and studiesspecifies the tests and studies that will that will be performed, including be performed, including analytical proceduresanalytical procedures that will be used, and that will be used, and acceptance criteriaacceptance criteria that will be achieved to demonstrate that that will be achieved to demonstrate that specified specified CMC changes do not adversely affect the productCMC changes do not adversely affect the product.’’.’’

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Comparability ProtocolsComparability Protocols

► A comparability protocol may be A comparability protocol may be submitted with an ANDA or NDAsubmitted with an ANDA or NDA application or as a application or as a Prior Approval Supplement (post-approval).Prior Approval Supplement (post-approval).

► The benefit of the comparability protocol is that an The benefit of the comparability protocol is that an FDA request for FDA request for additional information to support a changeadditional information to support a change is is less likelyless likely when the change when the change is covered under an approved protocol. is covered under an approved protocol.

► Thus, the sponsor Thus, the sponsor couldcould implementimplement a CMC post approval change as a CMC post approval change as described in the comparability protocol. This would described in the comparability protocol. This would allow the sponsor to allow the sponsor to place the product in distribution soonerplace the product in distribution sooner

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Post Marketing SurveillancePost Marketing Surveillance► Once the FDA approves a generic drug product, Once the FDA approves a generic drug product, manufacturers are manufacturers are

responsibleresponsible for conducting post-marketing surveillance. for conducting post-marketing surveillance. ► Post-marketing reporting requirements for an approved ANDA are set forth Post-marketing reporting requirements for an approved ANDA are set forth

in the in the US Federal Code of Regulations, 21 CFR 314.80 (5) and 314.98US Federal Code of Regulations, 21 CFR 314.80 (5) and 314.98 ..► The main component of this requirement is the The main component of this requirement is the reporting of adverse drug reporting of adverse drug

experiences (ADEs).experiences (ADEs). ► According to 21 CFR 314.80(a), an adverse drug experience is defined as According to 21 CFR 314.80(a), an adverse drug experience is defined as

‘‘‘‘any adverse event associated with the use of a drug in humans, whether any adverse event associated with the use of a drug in humans, whether or not considered drug relatedor not considered drug related’’’’

► The The definition continuesdefinition continues by stating that adverse events include those that by stating that adverse events include those that occur in the occur in the course of the usecourse of the use of a drug product in professional practice, of a drug product in professional practice, occur from drug overdose (accidental or intentional), abuse, or withdrawal, occur from drug overdose (accidental or intentional), abuse, or withdrawal, or involve failure of expected pharmacological action.or involve failure of expected pharmacological action.

► According to the definition, it is According to the definition, it is irrelevantirrelevant whether or not an event is whether or not an event is considered drug related.considered drug related.

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► The fact that an adverse event The fact that an adverse event occurred while a person was using a drug occurred while a person was using a drug productproduct is is reason enough to considerreason enough to consider it an ADE. it an ADE.

► It is important to examine It is important to examine who is involvedwho is involved in the in the process of ADE reportingprocess of ADE reporting. . ► Generally, there are Generally, there are three membersthree members that take part in this process: that take part in this process: ► A reporter, a manufacturer, and the FDA. Essentially A reporter, a manufacturer, and the FDA. Essentially anyone can anyone can

reportreport an ADE. an ADE.► The reporter can be a patient, doctor, pharmacist, nurse, or anyone else aware The reporter can be a patient, doctor, pharmacist, nurse, or anyone else aware

of such an event. This person can report it to either the manufacturer of the of such an event. This person can report it to either the manufacturer of the drug product or directly to the FDA. drug product or directly to the FDA.

► If the manufacturer receives the report first, the If the manufacturer receives the report first, the manufacturer is responsible for manufacturer is responsible for investigating the ADE and reporting it to the FDAinvestigating the ADE and reporting it to the FDA. If the FDA is notified directly . If the FDA is notified directly by the reporter, the by the reporter, the agency informs the manufactureragency informs the manufacturer so that the ADE can be so that the ADE can be investigatedinvestigated..

Post Marketing SurveillancePost Marketing Surveillance

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► Part of investigating an ADE Part of investigating an ADE may include, but is not limited tomay include, but is not limited to, contacting , contacting the patient’s physician, the prescriber (if different from the physician), the patient’s physician, the prescriber (if different from the physician), and the pharmacy that filled the prescription. Other investigations and the pharmacy that filled the prescription. Other investigations include performing all required testing of the include performing all required testing of the retain sample from the lot retain sample from the lot of the product that was used by the patientof the product that was used by the patient..

► Of course, there are many times when the Of course, there are many times when the lot number is not knownlot number is not known and and therefore, this therefore, this testing cannot be conductedtesting cannot be conducted. .

► Once an investigation is complete, the Once an investigation is complete, the manufacturer is responsible for manufacturer is responsible for submitting the information in a report to the FDAsubmitting the information in a report to the FDA..

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► There is certain information that must be known, though, There is certain information that must be known, though, before a report is before a report is submitted to the FDAsubmitted to the FDA. .

► Among this information are four elements: an identifiable patient, an Among this information are four elements: an identifiable patient, an identifiable reporter, a suspect drug/biological product, and an adverse identifiable reporter, a suspect drug/biological product, and an adverse event or fatal outcome. event or fatal outcome.

► If If any ofany of these basic elements these basic elements remain unknownremain unknown after being actively sought after being actively sought by the applicant/ manufacturer, a by the applicant/ manufacturer, a report on the incident should not be report on the incident should not be submitted to the FDAsubmitted to the FDA, because reports without this information make , because reports without this information make interpretation of their significance difficult, if not impossible.interpretation of their significance difficult, if not impossible.

► In these cases, the In these cases, the applicant/ manufacturer should track the stepsapplicant/ manufacturer should track the steps taken to taken to acquire the additional information in their safety files for the product. acquire the additional information in their safety files for the product.

► To facilitate the reporting process, FDA created the To facilitate the reporting process, FDA created the MedWatch programMedWatch program

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► MedWatch is the FDA Medical Products Reporting Program. MedWatch is the FDA Medical Products Reporting Program. ► It was originally designed to It was originally designed to emphasize the responsibility of healthcare emphasize the responsibility of healthcare

providers to identify and report ADEsproviders to identify and report ADEs. . ► Through the MedWatch program, healthcare professionals can report Through the MedWatch program, healthcare professionals can report

ADEs with the use of ADEs with the use of FDA Form 3500 (MedWatch Form).FDA Form 3500 (MedWatch Form). ► However, this reporting is However, this reporting is done on a voluntary basisdone on a voluntary basis. Currently, . Currently, there are there are

no regulationsno regulations that require healthcare professionals to report adverse drug that require healthcare professionals to report adverse drug experiences to the FDA or the manufacturer.experiences to the FDA or the manufacturer.

► In contrast, a manufacturer aware of an ADE is required by law to report it In contrast, a manufacturer aware of an ADE is required by law to report it to the FDA (provided the four elements noted earlier are known).to the FDA (provided the four elements noted earlier are known).

► The The FDA/ MedWatch Form 3500AFDA/ MedWatch Form 3500A is used for is used for mandatory reporting by mandatory reporting by manufacturersmanufacturers..

► At the bottom of the form At the bottom of the form ‘‘Submission of report does not constitute an ‘‘Submission of report does not constitute an admission that the product caused or contributed to the event.’’admission that the product caused or contributed to the event.’’

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► After an adverse event is reported to a manufacturer, two classifications After an adverse event is reported to a manufacturer, two classifications must be made. must be made.

► First, the adverse event must be First, the adverse event must be categorized as either serious or non-categorized as either serious or non-seriousserious. .

► Second, it must be determined whether the ADE is Second, it must be determined whether the ADE is expected or expected or unexpectedunexpected. Again, . Again, these terms are defined in 21 CFR 314.80these terms are defined in 21 CFR 314.80 ..

► A serious adverse drug experience is ‘‘any A serious adverse drug experience is ‘‘any ADE occurring at any doseADE occurring at any dose that that results in any of the following outcomes: death, a life-threatening adverse results in any of the following outcomes: death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.’’congenital anomaly/birth defect.’’

► A A non-serious ADEnon-serious ADE is one that is one that does not result in any outcomedoes not result in any outcome listed in the listed in the definition of a serious ADE.definition of a serious ADE.

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Post Marketing SurveillancePost Marketing Surveillance► In regards to the expected and unexpected designation, the In regards to the expected and unexpected designation, the labeling of labeling of

the product is used to determine the type of ADEthe product is used to determine the type of ADE. . ► If the If the product labeling listsproduct labeling lists a particular adverse event, it is considered a particular adverse event, it is considered

expected.expected. If not, it is considered unexpectedIf not, it is considered unexpected. . ► This classification of ADEs is This classification of ADEs is not always clearnot always clear..► Unexpected ADEs also include events that may be Unexpected ADEs also include events that may be symptomatically and symptomatically and

pathophysiologically relatedpathophysiologically related to an event to an event listedlisted in the labeling, but in the labeling, but differdiffer from the event because of from the event because of greater severity or specificitygreater severity or specificity..

► Eg: Marketed pdt label – Visual disturbances; reported that complete Eg: Marketed pdt label – Visual disturbances; reported that complete loss of vision. Now this is severe than what is expected, hence classified loss of vision. Now this is severe than what is expected, hence classified as unexpected ADE. as unexpected ADE.

► As discussed earlier, it is not an admission of guilt or even agreement As discussed earlier, it is not an admission of guilt or even agreement that the product caused the event.that the product caused the event.

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► It is It is important to correctly classify an ADEimportant to correctly classify an ADE as either serious or non-serious as either serious or non-serious and either expected or unexpected. and either expected or unexpected.

► The The classification of the ADEclassification of the ADE will determine the will determine the type of reporttype of report that is that is submitted to the FDA. submitted to the FDA.

► ADEs that are considered both ADEs that are considered both serious and unexpectedserious and unexpected must be submitted must be submitted to the FDA in an expedited manner and are known as to the FDA in an expedited manner and are known as 15-Day Alert 15-Day Alert ReportsReports. .

► Manufacturers must submit these reports to the FDA as soon as possible, Manufacturers must submit these reports to the FDA as soon as possible, but in no case later than but in no case later than 15 calendar days15 calendar days of the initial receipt of the of the initial receipt of the information.information.

► All other ADEsAll other ADEs (those that are (those that are serious and expected, non-serious and serious and expected, non-serious and expected, or non-serious and unexpectedexpected, or non-serious and unexpected) should be reported to the FDA ) should be reported to the FDA as as Periodic ReportsPeriodic Reports..

► Periodic Reports must be submitted at Periodic Reports must be submitted at quarterly intervals for three yearsquarterly intervals for three years from the from the date of FDA approval of the product, and then annuallydate of FDA approval of the product, and then annually ..

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► During the investigation and submission of the ADE report to the FDA, During the investigation and submission of the ADE report to the FDA, patient privacy should be maintainedpatient privacy should be maintained. .

► The manufacturer should not identify patients by name or address in the The manufacturer should not identify patients by name or address in the reports. Instead, the manufacturer should assign a reports. Instead, the manufacturer should assign a unique codeunique code (e.g., (e.g., patient’s initials or a tracking number) to each report. patient’s initials or a tracking number) to each report.

► In addition, names of patients, healthcare professionals, hospitals, and In addition, names of patients, healthcare professionals, hospitals, and geographical identifiers in adverse drug experience geographical identifiers in adverse drug experience reports are not reports are not releasable to the publicreleasable to the public under FDA’s public information regulations. under FDA’s public information regulations.

► The ADE reporting system is efficient and straightforward, but its The ADE reporting system is efficient and straightforward, but its complex.complex.

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► Main goal of the requirement is to Main goal of the requirement is to identify new or previously identify new or previously unrecognized adverse eventsunrecognized adverse events that are that are caused by drug productscaused by drug products..

► This often results in the This often results in the addition of safety informationaddition of safety information to a product’s to a product’s labeling, but can also lead to labeling, but can also lead to more severe actions like product recalls or more severe actions like product recalls or withdrawalswithdrawals. .

► In any case, the objective is to In any case, the objective is to expand the informationexpand the information available to the available to the medical community and the public regarding a product’s adverse event medical community and the public regarding a product’s adverse event profile and therefore profile and therefore increase public safetyincrease public safety..

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Any queries…….Any queries…….

• SUPAC & PMSSUPAC & PMS

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