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Handling a FDA Inspections

Wednesday, June 10, 2015

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Key points for Handling of a FDA Inspection

The FDA Inspector provides notice (FDA Form 482)

of the inspection prior to the start of the actual

audit. This document has to be signed by the

highest authority in the company. At the initiation

of an audit, it may be advisable to provide the FDA

Inspector with a product overview or overview of

services provided (as in the case of a contract

laboratory).

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Key points for Handling of a FDA Inspection

This often helps the review process. Verify that

someone is recording the minutes of all meetings

with the FDA inspector. Always have a scribe as

well as a host/tour guide with the FDA Inspector.

Prior to the inspection, an internal audit of the data

submitted supporting the application should be

conducted.

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Key points for Handling of a FDA Inspection

A directed facility audit should be conducted by

trained auditors who will mimic what the FDA will

do during the PAI. This can help the company

identify any deficiencies and allow time to take

proper corrective actions. Train personnel on how

to communicate with the FDA before they arrive.

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Run It – Don’t Let It Run You

Here are tips for Handling a FDA Inspection the

right way:

Route all requested documents through a “war

room”. Provide information promptly, but review the

data prior to giving it to the FDA Inspector. Keep

separate copies of any documentation given to the

inspectors. Do not allow the FDA in your “war

room”. Have Subject Matter Experts (SME) available

to answer questions posed by the FDA Inspector.

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Run It – Don’t Let It Run You

Here are tips for Handling a FDA Inspection the right way:

When possible, prepare the SME with likely

questions prior to the conversation between the SME

and the FDA Inspector. Ensure you understand the

question; if necessary, ask for clarification before

answering. If process validation has begun or has

been accomplished, data is likely to be reviewed

during the PAI.

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Run It – Don’t Let It Run You

Here are tips for Handling a FDA Inspection the right way:

The proposed manufacturing process filed in the

chemistry, manufacturing, and controls section

(CMC) of the NDA/ANDA will be reviewed. Generally,

PAIs are combined with routine GMP inspections if

the facility had no GMP inspection during previous

two years.

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Run It – Don’t Let It Run You

Here are tips for Handling a FDA Inspection the right way:

A review of all corrective actions taken by the

company resulting from the FDA’s last inspection

may be reviewed by the inspectors. Samples of the

product will be taken by the FDA Inspector and

tested in the FDA laboratory to ensure that they

meet appropriate standards.

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Run It – Don’t Let It Run You

Here are tips for Handling a FDA Inspection the right way:

If there is a compendial method, often the sample will

be tested against it. A receipt should be given by the

inspector for any samples taken by the FDA. Form 484

is used for this purpose. Collect duplicate samples and

have analysed independent of the FDA analyses.

Continually seek FDA’s input during the audit.

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Run It – Don’t Let It Run You

Here are tips for Handling a FDA Inspection the

right way:

This gives you a chance to make corrections or

clarify misunderstandings. When handling a FDA

inspection and dealing with a FDA representative,

demonstrate knowledge of and confidence in your

quality system. Do not respond arrogantly or

defiantly.

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IMPORTANT FDA INSPECTION NOTE

When handling a FDA inspection, it is good to know

that by law the FDA cannot inspect the following:

sales data, financial data, personnel files (other

than individual qualifications), pricing data, and/or

records of a personal nature (employee evaluations,

addresses, social security numbers, and/or pay

records).

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IMPORTANT FDA INSPECTION NOTE

If these items are requested, it may be an

indication that the inspector doesn’t know or is

testing your knowledge. It could also indicate the

beginning of serious regulatory proceedings by the

government. It is suggested that notice of these

requests be forwarded to legal counsel immediately.

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The FDA’s Quality System Inspection Approach

The FDA utilizes a Quality System Inspection

Technique (QSIT) when performing inspections. This

means that the FDA looks at specific systems and

determines if deficiencies exist within that system.

The key systems are Quality, Facilities and Equipment,

Material Controls, Production, Packaging and

Labelling, and Laboratory Controls.

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The FDA’s Quality System Inspection Approach

Evidence to support a significant and/or trend of

deficiencies within an examined system could

demonstrate failure of that system and may result in

the FDA considering issuance of a Warning Letter or

other regulatory action.

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FDA INSPECTION CLASSIFICATION - (NAI, VAI, OAI) &ESTABLISHMENT INSPECTON REPORT (EIR)

If regulatory non-compliance observed during FDA

inspection, the FDA inspector issues “Form 483”

(Notice of Inspectional Observations) to the facility.

The contents of the 483 comprise inspectional

observations but do not represent a final Agency

determination regarding compliance.

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FDA INSPECTION CLASSIFICATION - (NAI, VAI, OAI) &ESTABLISHMENT INSPECTON REPORT (EIR)

The company which receives a 483 should respond to

the FDA addressing each item within 15 working days.

A response is not compulsory but a good response can

help the company avoid receiving a warning letter, or

stronger enforcement actions including withholding of

product approval or even a plant shutdown.

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FDA INSPECTION CLASSIFICATION - (NAI, VAI, OAI) &ESTABLISHMENT INSPECTON REPORT (EIR)

FDA provides initial classification of the inspection

based on the observations noted during the inspection,

the investigator’s report, and FDA District Office

supervisory personnel review. With the exception of

instances where procedures indicate that the relevant

product centre has the right of final classification,

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FDA INSPECTION CLASSIFICATION - (NAI, VAI, OAI) &ESTABLISHMENT INSPECTON REPORT (EIR)

the final classification of the inspection is made by the

FDA District Office. An inspection classification reflects

the compliance status of the establishment at the time

of the inspection, based on the observations

documented. The conclusions of the inspection are

reported as Official Action Indicated (OAI), Voluntary

Action Indicated (VAI), or No Action Indicated (NAI).

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FDA INSPECTION CLASSIFICATION - (NAI, VAI, OAI) &ESTABLISHMENT INSPECTON REPORT (EIR):

An OAI inspection classification occurs when

significant objectionable conditions or practices were

found and regulatory action is warranted to address

the establishment's lack of compliance with statute(s)

or regulation(s).

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A VAI inspection classification occurs when

objectionable conditions or practices were found that

do not meet the threshold of regulatory significance.

Inspections classified with VAI violations are typically

more technical violations of the FDCA (The United

States Federal Food, Drug, and Cosmetic Act).

FDA INSPECTION CLASSIFICATION - (NAI, VAI, OAI) &ESTABLISHMENT INSPECTON REPORT (EIR):

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An NAI inspection classification occurs when no

objectionable conditions or practices were found

during the inspection or the significance of the

documented objectionable conditions found does not

justify further actions.

FDA INSPECTION CLASSIFICATION - (NAI, VAI, OAI) &ESTABLISHMENT INSPECTON REPORT (EIR):

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If no enforcement action is contemplated, or after

enforcement action is concluded, FDA provides

inspected establishments with a final inspection

report, called an Establishment Inspection Report

(EIR), which includes:

Brief history of prior inspectional findings, including

FDA INSPECTION CLASSIFICATION - (NAI, VAI, OAI) &ESTABLISHMENT INSPECTON REPORT (EIR):

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any action taken by FDA or corrective action taken by

the firm in response to a previous inspection The

investigator’s narrative report Any refusals, voluntary

corrections, or promises made by the firm’s

management Copies of forms the FDA issued to the

firm during the inspection, including the FDA Form

483.

FDA INSPECTION CLASSIFICATION - (NAI, VAI, OAI) &ESTABLISHMENT INSPECTON REPORT (EIR):

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Thank you very much your valuable time!