The document discusses expedited drug approval classifications including Fast Track, Accelerated Approval, Priority Review, and Breakthrough Therapy. It notes drugs approved under these classifications may have less data available at launch and incomplete manufacturing processes. It provides 9 approaches for managing expedited approvals, including open communication with the FDA, acknowledging limited data with plans to acquire missing data post-approval, and including a post-approval product lifecycle management plan to support deferred activities.

1. Expedited Approval Drugs
9 Approaches for Managing Regulatory Approval and Validation

2. Expedited Drug Approval Classifications
• Fast Track
• Accelerated Approval
• Priority Review
• Breakthrough Therapy

3. Fast Track Designation
• Drug must be intended to treat a serious condition
• May address an unmet medical need
• Fast Track designation request can be submitted at any time during drug development process
• Supporting data can be clinical or nonclinical
• Earlier and more frequent communication with the FDA during development
• Rolling review of application
• Fast Track designation may be withdrawn if drug no longer meets qualifying criteria

4. Accelerated Approval Designation
• Drug must treat a serious condition
• Provide significant improvement in safety or effectiveness when compared to drugs currently on
the market
• May use surrogate endpoints to demonstrate clinical benefit
• Approval is granted on conditional basis – post-approval trials are necessary
• Earlier and more frequent communication with the FDA during development
• Application is submitted in one package
• Drug is subjected to expedited withdraw

5. Priority Review
• Drug must treat a serious condition
• Provide significant improvement in safety or effectiveness when
compared to drugs currently on the market
• Drug review process is shortened to 6 months

6. Breakthrough Therapy
• Drug must treat a serious condition
• Provide significant improvement in safety or effectiveness when compared to drugs currently on
the market
• Supporting data must be clinical
• Intensive FDA guidance and involvement throughout development process involving senior FDA
officials
• Rolling review of application
• Although clinical data is required, an all hands on deck approach is taken to get the drug to
market

7. Often Dual Designations
• A drug often qualifies for two designations. For example, both
Breakthrough Therapy and Accelerated Approval designations are
granted to qualifying drugs

8. Traditional Prescription Drug Development
• On average, 12-year development timeline*
• Including expenditures and opportunity costs, an average of ~$2.6 billion to
bring a drug to market*
*Tufts Center for the Study of Drug Development (CSDD) report

9. Expedited Approval Drugs
• Expedited drug development timelines vary
• Chemistry, Manufacturing and Controls (CMC) data often needs to be developed in about
half the time of the traditional development process
• Patient safety and product supply cannot be compromised
• Analytical methods creation and product and process characterization must be started
earlier in the development process
• Some CMC activities may be incomplete at launch

10. 9 Approaches for Managing Expedited
Approval
#1
Open and transparent communication with the FDA throughout the
entire approval and post-market process. The pharmaceutical company
mindset of not wanting to learn certain information for fear of needing
to revalidate based on those discoveries has no place in this new
reality. New information will be learned pre- and post-launch, and
amendments will need to be filed.

11. 9 Approaches for Managing Expedited
Approval
#2
Additional stability data amendments will likely need to be filed during
the review process and in some cases post-market. This approach is
required given that less data will be available at submission due to
compressed timeframes.

12. 9 Approaches for Managing Expedited
Approval
#3
Launch commercial process with limited experience and optimize
post-approval–the classic three runs is not the guiding force within this
construct. The level of flexibility regulators will extend is determined
for each specific product. Factors taken into consideration include:
riskiness of product characteristics, seriousness of the condition and
medical need, complexity of manufacturing processes, state of the
innovator’s quality system and merits of the innovator’s risk-based
quality assessment including Critical Quality Attributes (CQA).

13. 9 Approaches for Managing Expedited
Approval
#4
Novel statistical models and approaches will need to be applied in
many cases. Representative samples and assays for these models will
likely need to be acquired from sources, like prior knowledge and use
of comparability protocols. Also, determination of the appropriate use
of stability data from representative pilot scale lots will be required.

14. 9 Approaches for Managing Expedited
Approval
#5
Manufacturers should freely acknowledge where data is limited,
demonstrate that the missing data pose no risk to patient safety or
product supply and outline post-market strategy for acquiring the
missing data. Conversations with the FDA are clearly required for
successful outcomes here.

15. 9 Approaches for Managing Expedited
Approval
#6
Focus on patient safety and reliable supply of quality product at
launch, not process optimization. In addition, begin critical product
attributes and process characterization work much earlier than a
typical pharmaceutical development process. In many cases, consider
broader product quality ranges for non-Critical Quality Attributes until
further manufacturing experience is acquired post-approval.

16. 9 Approaches for Managing Expedited
Approval
#7
Enhance analytical methods and understanding to offset more limited
process understanding and to support future comparability work.
Extremely important, involve commercial Quality Control
representatives in the development assay design.

17. 9 Approaches for Managing Expedited
Approval
#8
Some CMC activities may be incomplete at launch. Incomplete
processes could include: Process Validation, stability studies on
commercial product, manufacturing scale/tech transfer data and
complete control system data.

18. 9 Approaches for Managing Expedited
Approval
#9
A post-approval product lifecycle management plan is a must, and it
needs to be included in the filing to support deferred CMC activities.

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