PRODUCT LIFE

CYCLE MANAGEMENT

PRESENTED BY :- PRESENTED TO :-
PRINCE KUMAR DR. (MRS.) SANJU NANDA
M PHARMACY III SEM. PROF. IN PHARMACEUTICS
2033 SUBMITTED BY: SUBMITTED TO:
POOJA RATHEE PROF. SANJU NANDA
M.PHARMACY 2ND SEM. PHARMACEUTICS
1859
CONTENTS:
 Lifecycle management
 FDA Inspection and Enforcement
 Establishment Inspection Report (EIR)
 Recalls
 Warning letters
 Seizures and Injunctions
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LIFE CYCLE MANAGEMENT:

 Life cycle management is an integrated

and flexible approach to business
management that draws on the principles
of life cycle thinking to help businesses of
all kinds - manufacturers, retailers,
financial, professional - understand their
environmental impacts and where they
occur within the lifecycle of their operation,
from raw materials through to end-of-life.

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FDA Inspections:

 FDA developed BIMO (Bioresearch Monitoring

Program) to ensure:
 The protection of the rights, safety, and welfare
of human research subjects
 The quality and integrity of data submitted to the
Agency
 BIMO Program involves site visits to clinical
investigators, IRBs, nonclinical (animal)
laboratories, and bioequivalence analytical
laboratories

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 FDA conducts inspections of clinical investigators:
 Routinely to verify data that has been submitted to the Agency
 As a result of a complaint to the Agency about the conduct of the
study at the site
 In response to sponsor concerns or termination of the clinical site
 At the request of an FDA review division
 Related to certain classes of investigational products that FDA
has identified as products of special interest in its current work
plan

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Types of Inspections:

 Routine inspection:
 Triggered by a New Drug Application (NDA) or
Pre- Market Application (PMA) submission
 Routine inspections account for over 80% of the
inspections performed each year
 Clinical Investigators who enroll the most
subjects in the NDA’s pivotal trial are the most
likely to be inspected.

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 For Cause Inspection:
 Conducting a large volume of clinical trials
 Conducting clinical studies outside of one’s field of
specialization
 Reporting significantly better efficacy, fewer adverse
effects, or different laboratory results than other
investigators studying the same drug

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Inspections by Center:

 Center for Biologics Evaluation and Research (CBER)

 Center for Drug Evaluation and Research (CDER)
 Center for Devices and Radiological Health (CDRH)
 Center for Food Safety and Applied Nutrition (CFSAN)
 Center for Veterinary Medicine (CVM)

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Inspections by entity:

Clinical Investigators
IRBs
Sponsors/Monitors
Good Laboratory Practice

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 The inspector will record the following
information:
 Dates of IRB approvals (original,
continuing review, etc.)
 When the first subject was screened
 When the first subject was consented
 Firstadministration of the
investigational product
 Last follow-up for any study subject

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After the Inspection

 The FDA inspector will hold an exit interview at the

conclusion of the audit to discuss findings and
deficiencies
 Study staff should document the interview,
specifically noting observations, comments, and
commitments
 Any deficiencies will be noted on the FDA form 483
and given to the PI
 PI can respond to the 483 verbally during the
exit interview and/or in writing

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Post-Inspection

 After the inspection, the inspector will write an

Establishment Inspection Report (EIR) and submit
it to FDA headquarters
 After the report has been evaluated you will receive
one of three letters:
 No action indicated (NAI): No objectionable
conditions or practices were found during the
inspection, or the significance of the
objectionable conditions does not justify further
FDA action

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 Voluntary Action Indicated (VAI): Objectionable
conditions were found and documented, but the FDA
is not prepared to take or recommend further
regulatory action because the objectionable
conditions are few and do not seriously impact subject
safety or data integrity
 Official ActionIndicated (OAI): Regulatory violations
uncovered during the inspection are repeated or
deliberate and/or involve submission of false
information to FDA or to the sponsor
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 OAI may result in:
 Warning letter (WL)
 Violations can be corrected through specific action(s) by the
investigator and adherence to the corrective action plan has
a high probability of preventing similar or other violations in
the future
 Notice of Initiation of Disqualification Proceedings and
Opportunity to Explain (NIDPOE)
 Repeatedly or deliberately failed to comply with the
requirements for conducting clinical trials
 Repeatedly or deliberately submitted false information to FDA
or to the sponsor 15
Case study:

 Drug firm Lupin said that it has received an

Establishment Inspection Report (EIR) on April 2, 2018
from the US health regulator for its Pithampur ,Unit 1
manufacturing facility in Madhya Pradesh.
 USFDA gives EIR on closure of inspection of an
establishment that is subject of an FDA.
 In November last, Lupin had received warning letter from
USFDA for its manufacturing facilities in Goa and
Pithampur.

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RECALLS:

 FDA recalls: The recall of a defective or possibly

harmful product by the US Food & Drug
Administration (the FDA).
 The guidelines of FDA categorize all recalls into
one of three classes according to the level of
hazard involved.
 CLASS I
 CLASS II
 CLASS III

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 Class I recalls are for dangerous or defective products that
predictably could cause serious health problems or death.
 Example :- a food found to contain botulinal toxin, a label mix-up
on a lifesaving drug, or a defective artificial heart valve.
 Class II recalls are for products that might cause a temporary health
problem, or pose only a slight threat of a serious nature.
 Example:- drug that is under- strength, but that is not used to
treat life-threatening situations.
 Class III recalls are for products that are unlikely to cause any
adverse health reaction, but that violates FDA regulations.
 Example:-bottles of aspirin that contains 90 tablets instead of the
100 stated on the label.
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 The FDA develops a strategy for each individual recall that sets forth
how extensively it will check on a company's performance in
recalling the product in question.
 For a Class I and II recall, for example, the FDA would check to
make sure that each defective product has been recalled or
reconditioned.
 For Class III recall the FDA may decide that it only needs to spot
check to make sure the product is off the market.

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WARNING LETTERS:

 An FDA warning letter is an official

message from the United States Food and
Drug Administration (FDA) that it has found
that a manufacturer or other organization
has violated some rule in a regulated
activity.

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 ..a correspondence that notifies regulated industry about violations that FDA
has documented during its inspections or investigations.
 Typically, a Warning Letter notifies a responsible individual or firm that the
Agency considers one or more products, practices, processes, or other
activities to be in violation of the Federal Food, Drug, and Cosmetic Act (the
Act), its implementing regulations and other federal statutes.
 Warning Letters should only be issued for violations of regulatory
significance, i.e., those that may actually lead to an enforcement action if
the documented violations are not promptly and adequately corrected.
 A Warning Letter is one of the Agency’s principal means of achieving prompt
voluntary compliance with the Act.

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 A Warning Letter is informal and advisory.
It communicates the agency's position on a
matter, but it does not commit FDA to
taking enforcement action. For these
reasons, FDA does not consider Warning
Letters to be final agency action on which
it can be sued.

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What happens when the FDA investigator
arrives at the site?
 The FDA investigator will:
 Ask to see the top management
 Present credentials (identification as an authorized FDA
investigator)
 Issue FDA-482 “Notice of Inspection” (explains FDA’s
legal authority to inspect)

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Situations where the agency will
take enforcement action without
necessarily issuing a Warning
Letter include:
 A history of repeated or continual conduct of violation.
 The violation is intentional or flagrant;
 The violation presents a reasonable possibility of injury or death;
 The violations, under Title 18 U.S.C. 1001, are intentional and willful acts
that once having occurred cannot be retracted.

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Warning letter close-out letter

After the FDA completes an evaluation of

corrective actions via a follow-up
inspection, it may issue a so-called
warning letter close-out letter if the FDA’s
evaluation shows that the firm has taken
corrective action to address the violations
contained in the warning letter. This
procedure applies to warning letters issued
on or after September 1, 2009.

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REFERENCES:

 https://en.wikipedia.org/wiki/FDA_warning_letter
 http://www.sustainability.vic.gov.au/Business/Efficient-
business-operations/Lifecycle-management
 https://www.fda.gov/ICECI/ComplianceManuals/Regula
toryProceduresManual/ucm176733.htm#SUB6-1-1
 https://www.fda.gov/ICECI/ComplianceManuals/Regula
toryProceduresManual/ucm176733.htm#SUB6-1-2

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