Download Pre-Approval-Inspection

Pre-Approval-Inspection
Preparing for Pre-approval Inspection
• Pre-approval inspection is a critical requirement to
acquire commercial manufacturing license for a new
drug or a new manufacturing facility. If you fail to meet
the standards during pre-approval inspection, it may
lead you to legal difficulties and, worse, unanticipated
delay in marketing of those products that can cost you
millions of dollars.
• FDA approves a New Drug Application (NDA), an
Abbreviated New Drug Application (ANDA) or Biological
Licensing Application (BLA) only if the methods,
facilities and procedures used at every step from raw
materials to distribution of drugs are adequate to
preserve the identity, quality, purity and strength of the
drug.
• Types of Pre-approval Inspection
• The pre-approval inspections are of two types – priority and discretionary.
Food and Drug Administration has established criteria to decide whether
the inspection of your firm should be considered a priority or discretionary
one.
• If your firm has applied for the first time to FDA or EMA (European
Medicines Agency) or your final product contains a New Molecular Entity
(NME) or the product is manufactured by a completely different
manufacturing process then FDA makes it a priority to carry out inspection
at your site.
• Certain situations can lead to discretionary inspection. These include:
• Filing of multiple applications within a short period of time involving a
single manufacturing facility
• The investigator found significant deficiencies during previous preapproval inspection or your company has a history of non-compliance.
• Inspection Team and Schedule
• The investigation team for PAI should normally
consist of a district investigator and an analytical
chemist. Sometimes, a microbiologist may also
accompany depending upon requirements.
Generally it is scheduled at the earliest
opportunity possible for the district investigator.
Inspection must be completed within 45 days (for
domestic site) or 60 days (foreign site) of
application.
• Performing a Pre-Approval-Inspection
Readiness Assessment
• To have a successful outcome from the actual
pre-approval inspection, you should conduct a
mock PAI to assess the readiness of your
facility. It should focus on the following three
things:
• Readiness for commercial manufacturing
• Data integrity
• Conformance to application
• During actual PAI, one or more of the above listed objectives will be
addressed. The degree of coverage should depend on whether the new
profile classes are related to already inspected profile classes. A profile is
said to be ‘related’ when the production process or dosage form is similar
to that of a previously inspected product/process at the establishment.
• If the findings of pre-PAI reveal anything that may withhold the actual PAI
approval, you should fix the discrepancy at the earliest to avoid delays in
licensing. These issues may include:
• Substantial problems with data integrity. The data or other conditions
related to submission batch may be misrepresented.
• Grave cGMP concerns that may compel the FDA to question the
formulation or processing.
• Absence of manufacturing and control instructions, SOP, VMP or lack of
data to support those instructions.
• What if You Fail the Pre-approval Inspection?
• Failing the PAI gives investigator an impression that the method of
analysis and the way you claim to manufacture is not up to the
cGMP standards. Though you’ll be given a chance to fix the issues,
failing pre-approval inspections can lead to one or more of the
following problems.
• Increased Frequency of Inspections
• FDA may schedule re-inspection at occasional intervals to verify the
revised procedures, methods, and new supporting data. They will
check everything all over again to ensure that you have made the
required changes. Once they collect data during pre-approval
inspection, they compare it with the information you have provided
in the application.
• Application Integrity Policy
• The FDA inspectors may consider any repeated or severe
discrepancies as a potential attempt of fraud. If you have made
even simple errors in recording and calculating data, you have made
it unreliable for FDA. It can invoke the Application Integrity Policy
forcing you to carry out your own internal audits and fix all the
inconsistencies.
• Delay in Product Launch
• If inspectors witness faulty cGMP, VMP or any other discrepancy in
the manufacturing facility or processes, they will not approve your
NDA or ANDA.
• Since the reports are regularly published, you can’t hide your
failures from the public. So failing the pre-approval inspection can
hamper your reputation, consumers’ trust and stock prices.