us fda: request for quality metrics · where will the quality metrics come from? annual product...
TRANSCRIPT
US FDA: Request for Quality Metrics
Presented by Eoin Hanley
4 July, 2016
Slide 2 © PharmOut 2015
What we will cover in this session
Why we use quality metrics
Why the US FDA want to look at quality metrics
What the US FDA intend to look
Proposed Optional Metrics
Slide 3 © PharmOut 2015
Guidance in draft
• Draft issued in last week of July
• Comments & suggestions within 60 days
• Based on their mission to protect and promote public health
Metrics:
1. Objective
2. Subject to inspection under section 704 of FD&C Act
3. Valuable in assessing the overall state of quality of product/process/PQS etc
4. Avoid any undue reporting burden
Slide 4 © PharmOut 2015
Quality Metrics
Why do “we” use Quality Metrics?
Slide 5 © PharmOut 2015
Why do “we” use quality metrics?
Monitor Quality Control Systems
Process Validation &
lifecycle
Pharmaceutical Quality Systems
Monitor production processes
Indicators for Continuous
Improvement
Slide 6 © PharmOut 2015
Why do the US FDA want to look quality metrics?
• Help develop compliance and inspection policies & practices
• Risk–based inspection scheduling
• Ability to predict/mitigate future drug shortages
• Support its understanding of the inherent risks
• Resources & help direct the inspections
• Encourage state-of-the-art, innovative PQS
• They have the authority to request records and information by law
Highly controlled manufacturing processes have the potential to be inspected less often
Slide 7 © PharmOut 2015
Risk-based schedule of inspections
• The compliance history
• The record, history and nature of recalls
• The inherent risk of the drug manufacturing processes
• Inspection frequency and history
• Inspections by foreign governments/agencies
• Any other criteria deemed necessary
The risks posed by establishments are based on:
Slide 8 © PharmOut 2015
What data do the US FDA want?
• Manufacture, preparation propagation, compounding or processing of a finished dosage forms of covered drug products or APIs used in the manufacture of covered drug products
• Request would not apply to medical gasses, PET, blood & blood components for transfusion, vaccines, cell & gene therapy products, allergenic extracts, human cells, non-recombinant versions of plasma derived products etc.
• Also encouraged to submit quality metrics data for certain foreign establishments
Slide 9 © PharmOut 2015
What data do the US FDA want?
• The requests for data would include (but are not limited to:
• Contract laboratories
• Contract sterilisers
• Contract packagers
• Or engaged in manufacture, preparation, propagation, compounding or processing etc
• At this time, does not include excipient or container/ closure manufacturers
• One Report for each Finished Dosage Form and one for each API of a covered drug product with metrics
• Quality Control Unit best positioned to compile Reports
As a Contract Giver, you do not delegate your
regulatory responsibilities!
Slide 10 © PharmOut 2015
Quality Metrics
What quality metrics do your vendors supply you with?
Slide 11 © PharmOut 2015
What will the US FDA do with the data?
Recognise the value of quality metrics
Use the data in context with other sources of quality data
Not intended to be all-inclusive set of quality metrics that the US FDA consider useful for assessment
Failure to produce records and information within a reasonable timeframe/refusal to permit access to a record will mean that drugs from the facility may be deemed adulterated
Slide 12 © PharmOut 2015
Where will the quality metrics come from?
• Records associated with a Process Validation Lifecycle and PQS Assessment
• Understand the sources of variation
• Detect the presence and degree of variation
• Understand the impact of variation on process/product
• Control the variation in a manner commensurate with the risk to process/product
• Throughout the lifecycle-including changes
• Evaluation of the state of control
Slide 13 © PharmOut 2015
Where will the quality metrics come from?
Annual Product Reviews/PQRs
Process trends and quality of incoming materials, in-process materials and FPs
Statistically trended by trained personnel
Verification that quality attributes are being controlled
Review a representative number of batches
Facility, systems and equipment status periodically assessed
Continuous/real-time metrics
Slide 14 © PharmOut 2015
What the US FDA intend to look at
• Evaluate whether data reported is consistent with their understanding
• Evaluate how best to interpret and use the metrics:
• Compare metrics for different products?
• Compare same product at different sites?
• A facility trended over time?
• All facilities/subset making the same dosage form or same drug against each other?
• Manufacturing complexity? i.e. biologicals
• The US FDA do not intend to publicly disclose quality metric data submissions
Slide 15 © PharmOut 2015
What the US FDA intend to calculate
= 1 – x, where x = the # of specification-related rejected lots in a timeframe ÷ # of lots attempted in the same timeframe
= # of complaints received for the product ÷ the total # of lots of the product released in the same timeframe
Lot Acceptance Rate
Product Quality Complaint Rate
Slide 16 © PharmOut 2015
What the US FDA intend to calculate
= the # of OOS test results for the FP invalidated ÷ the total # of OOS ÷ the total # of tests performed in the same timeframe
= # of APR/PQRs completed within 30 days of annual due date ÷ # of products produced at the facility
Invalidated OOS Rate
APR or PQR on Time Rate
Slide 17 © PharmOut 2015
Additional request for public comment
Opportunity to submit additional optional metrics as evidence of robustness and a commitment to quality?
May merit a reduction in inspection frequency?
Measures of quality culture? Senior Management engagement?
3 Optional Metrics proposed (next few slides) but US FDA also request alternative approaches
Slide 18 © PharmOut 2015
Proposed Optional Metric 1
• CAPA Effectiveness
• Strong indicator of a robust quality culture
• Continual Improvement-prevent the initial occurrence or recurrence of an undesirable situation
• Weak systems: personnel re-training
• Strong systems: re-design/re-development of the process
What % of your corrective actions involved re-training of personnel (i.e. a root cause of the deviation is lack of adequate training)?
Slide 19 © PharmOut 2015
Proposed Optional Metric 2
• Process Capability/Performance
• Statistical Process Control-understand variability
• Statistician/person with adequate training
• Data Collection Plan
• Methods & Procedures
• Knowledge during scale-up & manufacturing
• Control Strategy
• Evaluate process stability/capability
• Must be appropriate/meaningful
• Science and risk-based QRM
Slide 20 © PharmOut 2015
Proposed Optional Metric 3
A “YES” or “NO” value of whether there is a process capability or performance index for each CQA as part of the APR/PQR
A “YES” or “NO” value of whether there is a policy of requiring a CAPA at some lower process capability or performance index
If a “YES” to the above question – what is the process capability or performance index that triggers a CAPA?
If “NO” to the above question – please do not respond.
Slide 21 © PharmOut 2015
What the US FDA want to see
# of lots attempted of the product
# of specification-related rejectedlots of the product, rejected during or after manufacturing
# of attempted lots pending disposition for more than 30 days
# of OOS results for the product including stability testing
# of lot release & stability tests conducted for the product
# of OOS results for lot release & stability tests for the product which are invalidated due to lab error
Slide 22 © PharmOut 2015
What the US FDA want to see
# of product quality complaintsreceived for the product
# of lots attempted which are released for distribution or for the next stage of manufacturing
If the associated APRs or PQRs were completed within 30 days of annual due date for the product
The number of APRs or PQRs required for the product
Slide 23 © PharmOut 2015
How to report quality data
• Submit data for a 1 year period after the Agency request
• Reports to be submitted within 60 days of the end date of the reporting period
• Data segregated in the report on a quarterly basis
• Appendix A describes the information that would be submitted through the Electronic Submissions Gateway
• US FDA also want additional information on:
• When to make additional requests for data
• Alternative approaches to data collection i.e. alignment with current APR/PQR timeframes
• Text fields for data explanation
Slide 24 © PharmOut 2015
Other quality metrics?
Can you suggest other quality metrics that might be useful?
Slide 25 © PharmOut 2015
Section recap?
Risk-based Inspections
Drug Shortages
Opportunity to provide feedback
Slide 26 © PharmOut 2015
Thank you for your time.Questions?
Eoin Hanley
Technical Manager
www.pharmout.net