The document outlines the process of Product Lifecycle Management (PLM) in pharmaceuticals, detailing its four phases: conception, design, realization, and service. It also describes the regulatory framework for submitting major, moderate, and minor changes to drug products as per FDA guidelines, including Prior Approval Supplements and Scale-up and Post-Approval Changes (SUPAC). Additionally, it discusses reporting requirements and necessary assessments to ensure compliance and safety in the manufacturing and distribution of pharmaceutical products.

1. Guided By…
Prof.(Dr.) Sanju Nanda
Professor of Pharmaceutics
Presented By…
Garima Saini
M.Pharm. (SEM-II)

2. Product lifecycle
management(PLM)

3. INTRODUCTION
oprocess of managing the entire lifecycle of a
product from its conception, through design
and manufacture, to service and disposal.

4. PHASES OF PRODUCT LIFECYCLE
oPHASE 1: CONCEIVE [IMAGINE, SPECIFY, PLAN, INNOVATE]
The first stage is the definition of the product requirements based on customer, company, market and
regulatory bodies’ viewpoints.
oPHASE 2: DESIGN [DESCRIBE, DEFINE, DEVELOP, TEST, ANALYZE AND VALIDATE]
This is where the detailed design and development of the products form starts, progressing to
prototype testing, through pilot release to full product launch.
oPHASE 3: REALIZE [MANUFACTURE, MAKE, BUILD, PROCURE, PRODUCE, SELL AND DELIVER]
Once the design of the product’s components is complete the method of manufacturing is defined.
This includes CAD tasks such as tool design;
oPHASE 4: SERVICE [USE, OPERATE, MAINTAIN, SUPPORT, SUSTAIN, PHASE-OUT, RETIRE, RECYCLE
AND DISPOSAL]
The final phase of the lifecycle involves managing of in service information. Providing customers and
service engineers with support information for repair and maintenance, as well as waste
management/recycling information

5. Prior Approval Supplement(PAS)
A major change requires the submission of a supplement and approval by FDA prior to
distribution of drug product This type of supplement is called, a Prior Approval Supplement.
Filing with the FDA to approval of a major change may lead to adverse effect on:
1. Identity
2. Strength
3. Quality
4. Purity
5. Potency
These factors may relate to the safety or effectiveness of the drug product.

6. Section 506A of the FD&C Act (which was added by section 116 of the Food and Drug Administration
Modernization Act of 1997) provides requirements for making and reporting manufacturing changes to an
approved application and for distributing a drug product made with such changes
 Major Change: A change that has a substantial potential to have an adverse effect on the identity,
strength, quality, purity, or potency of a drug product as these factors may relate to the safety or
effectiveness of the drug product. A major change requires the submission of PAS and approval by FDA
before distribution of the drug product made using the change.
 Moderate Change: A change that has a moderate potential to have an adverse effect on the identity,
strength, quality, purity, or potency of a drug product as these factors may relate to the safety or
effectiveness of the drug product. Depending on the nature of the change, one of the following two
types of supplements must be submitted to FDA for a moderate change
 Minor Change: A change that has minimal potential to have an adverse effect on the identity, strength,
quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of
the drug product. The applicant must describe minor changes in its next annual report

7. Scale-Up and Post- Approval
Changes(SUPAC)
The scale-up process and the changes made after approval in the composition, manufacturing
process, manufacturing equipment , and change of site have become known as Scale – Up and
Post approval Changes or SUPAC.
The FDA has issued various guidance for SUPAC changes designed as:
1. Supac-IR (immediate release solid oral dosage form)
2. Supac-MR (for modified release solid oral dosage form)
3. Supac-SS (for non-sterile semisolid dosage form including creams, ointments, gels and lotions)

8. Level of Changes
• Level 1: Those changes that are unlikely to have any detectable impact on formulation quality
and performance.
Example: • Changes in the color, flavors
Changes in the excipient express as the percentage (w/w) of total formulation, less than or equal
to the following range.
• Level 2: Changes are those that could have significant impact on the formulation quality and
performance.
Example: • Changes in the technical grade of excipient (Avicel PH102 vs. Avicel PH200)
Changes expressed as percent (w/w of total formulation)
• Level 3: Changes are those that are likely to have significant impact on formulation quality and
performance.

9. Changes Being Effected in 30 Days (CBE-
30 supplement)
• CBE-30 supplement involves certain moderate changes that require the submission of the
supplement to FDA at least 30 days before the distribution of the drug product made using the
change.
• There are two types of moderate change. One type of moderate change requires the
submission of a supplement to FDA at least 30 days before the distribution of the drug product.
• This type of supplement is called, and should be clearly labeled, a Supplement - Changes
Being Effected in 30 Days
• If, after review, FDA disapproves supplement it may order the manufacturer to cease
distribution of the drug products made using the disapproved change.

10. Annual report
The applicant must describe minor changes in its Annual Report
In annual reports, the list should be included in the summary section.
Assessment of the Effects of the Change The holder of an approved application under section
505 of the Act must assess the effects of the change before distributing a drug product.

11. POST-MARKETING
REPORTING
REQUIREMENTS
Reporting requirements
• A timetable of completion
• Periodic reports on the status of the study, including whether
any difficulties in completing the study
• Periodic report on the status of the clinical trial
Reporting requirements
• NDA—Field alert report
• distributed drug products
• articles to the FDA district office (within 3 working days of
receipt by the applicant)
• report and its mailing cover should be plainly marked: “NDA—
Field Alert Report.”
• any incident
• bacteriological contamination
Required for all
studies and
clinical trials

12. Post approval labeling change
• Current Level of Reviewed CBE-0 Supplements for Safety-Related Labeling Changes Submitted
by NDA Holders
• Current Level of CBE-0 Supplements for Safety-Related Labeling Changes for Drugs
• Current Level of CBER - reviewed CBE-0 Supplements for Safety-Related Labeling Changes
Submitted by NDA Holders
• Current Level of CBE-0 Supplements for Safety-Related Labeling Changes Submitted by BLA
Holders
• Current Level of PAS Submissions for Changes to the Highlights of Drug Labeling

13. REFERENCES
• https://www.pharmatutor.org/articles/product-life-cycle-management-in-pharmaceuticals-review
• https://altegra.se/english/what-is-plm/
• https://www.ipqpubs.com/wp-content/uploads/2014/08/ANDA_PAS.pdf
• https://www.fda.gov/regulatory-information/search-fda-guidance-documents/supac-ir-immediate-
release-solid-oral-dosage-forms-scale-and-post-approval-changes-chemistry