Post Approval Activities Flashcards
Life Cycle Management
1.Monitor and assure safety, quality and efficacy of the product
2.Track continuous improvement efforts that provide a competitive advantage
3.Distribute safe and effective products
Quality
Monitor safety, quality and efficacy of the product
Ensure correct and accurate information is provided for Regulatory Agency review
Manufacturing
Partner with Quality to generate data to support implementation of a change
Manufacture product in accordance with the approved processes
Technical Experts (R&D/Manufacturing/Quality)
Determine data requirements to demonstrate no adverse product impact
Generate data that confirms no adverse product impact
Regulatory
Interpret regulatory guidance
Develop filing strategies based on description of proposed change
Prepare regulatory submission
Communicate with Regulatory Agencies
Clinical and Medical
1Continue to collect data from additional studies according to requirements
2Monitor, evaluate and report Adverse Drug Experiences
3Evaluate Risk and Benefit of the drugs
Postmarketing (Phase 4) requirements and commitments
1.Supplements and other changes to an approved application
2.Postmarketing reporting of an Adverse Drug Experience
3.NDA Annual reports
4.NDA Field Alert Reports
4.Biologic Product Deviation Reports
Additional Clinical studies
postmarketing phase4
1.Part of the approval of a NDA
2.To verify and describe clinical benefits for drugs and biologics approved under the accelerated approval regulations (21 CFR 314.510 & 601.41)
3.Deferred pediatric studies (21CFR 314.55 & 601.27) where studies are required under Pediatric Research Equity Act (PREA)
Change to a product, production process, quality, controls, equipment, or facilities is to be reported
(21 CFR 314.70)
This is Supplement because changes for
Specification
Composition and Components
Manufacturing sites
Manufacturing process
Container closure system
Labeling
Types of submissions:
- Prior Approval Supplement (PAS) - major change (only one needs approval)
- Change being Effected in 30 days (CBE-30) - moderate change
- Change being Effected (CBE) - moderate change
- Annual Report (AR) – minor change
Prior Approval Supplement type
-Changes in the qualitative or quantitative formulation, including inactive ingredients
-New analytical method
-Elimination of a test or analytical method
-Elimination of a test from the stability protocol
-Change in acceptance criteria of the stability protocol
-Change to the labeling based on postmarketing study results
-Transfer of the manufacture of a finished drug product sterilized by terminal processes to a newly constructed facility at a different manufacturing site
-Establishing a new procedure for reprocessing a batch of drug substance or drug product that fails to meet the approved specification
-A change to a new container closure system if the new container closure system does not provide the same or better protective properties than the approved container closure system
CBE 30 (Change being effected)
-Changes in the size or shape of a container for a sterile drug substance
-Replacement of equipment with equipment of different design that does not affect the process methodology or process operating parameters
-Filtration process changes that provide for a change from single to dual sterilizing filters in series, or for repeated filtration of a bulk
-Changes in the size or shape of a container for a sterile drug substance
CBE changes
-Addition of a precaution arising out of a postmarketing study
-Change in the labeling to add or strengthen a contraindication, warning, precaution or adverse reaction
-A move to a different manufacturing site for the manufacture or processing of the final intermediate
Annual Reportable Changes
-Editorial labeling change
-Changes in the layout of the
package or container label that
are consistent with FDA
regulations (e.g., 21 CFR part
201) without a change in the
content of the labeling
-Foreign language versions of
the labeling if no change is
made to the content of the
approved labeling and a certified
translation is included.
-Extension of expiration date based on real time data in accordance with an approved stability protocol
-A change in the number of units (e.g., tablets, capsules) or labeled amount (e.g., grams) of nonsterile solid dosage form in a multiple-unit container
-A change in the order of addition of ingredients for solution dosage forms or solutions used in unit operations (e.g., granulation solutions)
Europe (EMEA) Change Requirements
-Any change to the documentation must be submitted as a variation
-No impact on information contained in the original file – generally no reporting requirement
EMEA Types of Submissions
Type IA/IB Variation
Type II Variation
Line Extension applications
Changes requiring new applications
Site Master File changes
There is no annual reportable change category
Canada Change Requirements
Level 1
Supplemental New Drug Submission (similar to US)
6 to 8 month review timeline per the “book”
Level 2
Notifiable Change = 90 day review and approval with a 15-30 day screening period before the clock starts
Level 3
-Notice of Change (i.e. annual reportable)
Level 4
-Letter of Notification (i.e. FYI letter)
Japan Ministry of Health, Labour and Welfare (JMHLW) Changes
Partial Change Application (PCA)
Changes that impact product quality and safety
Only one PCA per product can be reviewed at a time
12 + month review timeline
30-Day Notification
Changes to information in Foreign Manufacturing
Authorization file
JMHLW must be notified within 30 days of change
implementation
Australia and New Zealand
Australia: Category 3 Changes
New Zealand: Variations
All changes that impact product quality and safety
45 calendar day review
Questions will stop the review clock
Rest of the World Changes
Change needs to be approved in the country of origin first
Submission may require additional documentation to meet local requirements
No timelines established
Some geographies require immediate switch over to product manufactured using the change (i.e. no transition period)
Adverse Drug Experience CFR for NDA and BLA
21 CFR 314.80 reporting for drugs with an approved NDA
21 CFR 600.80 reporting for biologics with an approved BLA
US regulations are consistent with ICH and CIOMS (The Council for International Organizations of Medical Sciences)
Adverse Drug Experience that need to be reported list different situations
Any adverse event associated with the use of a drug in humans, whether or not considered drug related
An adverse event occurring in the course of the use of a drug product in professional practice
An adverse event occurring from drug overdose whether accidental or intentional
An adverse event occurring from drug abuse
An adverse event occurring from drug withdrawal
Any failure of expected pharmacological action
Adverse Drug Experience Reporting Requirements 15 Day alert requirements
Serious & unexpected
15 calendar days
MedWatch form 3500A
Follow-up reports - 15 calendar days
Form 3500A or CIOMS for foreign
Form for 15 day Adverse event report
Form 3500A or CIOMS for foreign
