The document discusses the key sections and guidelines for an effective Pharmaceutical Development Report (PDR) as outlined in ICH Q8 and Q8(R1). The six critical sections of a PDR are: 1) active and inactive ingredients, 2) formulation development and properties, 3) manufacturing process development, 4) container closure system, 5) microbiological attributes, and 6) compatibility with diluents. The PDR provides a comprehensive understanding of the product and manufacturing process for regulatory review and should be updated throughout the product lifecycle.

1. PRODUCT
DEVELOPMENT REPORT
(PDR)
(EFFECTIVE ICH Q8
PHARMACEUTICAL DEVELOPMENT
REPORTS)
-By Atul Bhombe
M.Pharmacy (RA) First yr.
Sanjivani college of pharmacy
education & research

2. Introduction
The International Conference on Harmonization (ICH)
Common Technical Document (CTD) format is the
submission standard for new and abbreviated drug product
applications in the United States, the European Union and
Japan.
One of the significant sections of the CTD is the
Pharmaceutical Development Report (PDR). A complete
PDR is essential to provide a comprehensive
understanding
of the product and process for the FDA application
reviewers and inspectors.
The information in the PDR is-
based upon the documentation generated during the
formulation and process development phase of drug

3. The ICH Q8 and Q8(R1) Pharmaceutical Development
Report guidance documents provide the guidelines for
the
PDR.1,2 As stated in the Q8 guidance, “The
Pharmaceutical
Development section provides an opportunity to present
the knowledge gained through the application of
scientific
approaches and quality risk management to the
development of a product and its manufacturing
process.”
The PDR can, and should, be updated over the lifecycle
of

4. There are six critical sections to PDR development listed
in
the Q8 guidance document. Each section addresses a
specific component or process in the development
process,
including:
1. Components of the drug product (Api , Excipient )
2. Information about the drug product formulation
development, overages, and physiochemical and
biological properties

5. 4. Rationale for the choice of the drug product
container closure
5. Microbiological attributes
6. Compatibility of the drug product with
reconstitution diluents or dilution prior to
administration for labelling information

6. 1. Components of the drug
product
 The components thus include the API(s) and all the
Excipients
 A) Active pharmaceutical ingredient :
The physicochemical and biological properties of the
drug substance that can influence the performance of
the drug product and its manufacturability.” Examples of
physicochemical and biological properties that might
need to be examined include- Solubility , Water
content,Particle size, Crystal properties, Biological
activity, Permeability, melting range.

7. B) Excipients
The characteristics and amounts of excipients that can
influence the performance of the pharmaceutical product
or its manufacturing capability should usually be
discussed relative to the respective function. The ability
of functional excipients, e.g. pH-adjusting agents,
buffers, stabilizers (such as antioxidants and chelating
agents), preservatives and dissolution modifiers (such
as surface active agents), to perform throughout the
intended shelf-life of the FPP should usually be
demonstrated.

8. formulation
development, overages, and
physiochemical and
biological properties
formulation development
A summary of formulations used in clinical safety and efficacy and in
any relevant bioavailability or bioequivalence studies should be
provided. Any changes between the proposed commercial
formulation and those formulations used in pivotal clinical batches
and primary stability batches should be clearly described and the
rationale for the changes provided.
Information from comparative in vitro studies (e.g., dissolution) or
comparative in vivo studies (e.g., bioequivalence) that links clinical
formulations to the proposed commercial formulation described. it
should be summarized and a cross-reference to the studies (with
study numbers) should be provided. Where attempts have been
made to establish an in vitro/in vivo correlation, the results of those
studies and a cross-reference to the studies (with study numbers)
should be provided in the Pharmaceutical Development section. A
successful correlation can assist in the selection of appropriate
dissolution acceptance criteria and can potentially reduce the need
for further bioequivalence studies following changes to the product
or its manufacturing process.

9. Overages:
In general, use of an overage of a drug substance to
compensate for degradation during manufacture or a
product’s shelf life, or to extend shelf life, is discouraged.
overage to compensate for loss during manufacture should
usually be provided in the PD, including the step(s) where the
loss occurs, the reasons for the loss and batch analysis
release data (assay results).

10. Physicochemical and biological properties:
Parameters relevant to the performance of the FPP, such
as pH, ionic strength, dissolution,reconstitution, particle
size distribution, aggregation, polymorphism, rheological
properties, biological activity or potency and/or
immunological activity, should be addressed.
(See also ICH Q6A Specifications: Test Procedures And Acceptance Criteria
For New Drug Substances And New Drug Products: Chemical Substances;
Decision Tree #4 (Part 3) and Decision Tree #7 (Part 1) or ICH Q6B
Specifications: Test Procedures and Acceptance Criteria for
Biotechnology/Biological Products. The discussion should crossreference
any relevant stability data in 3.2.P.8.3.)

11. 3. Describes the manufacturing process
development
The selection, the control, and any improvement of the
manufacturing process described (i.e., intended for
commercial production batches) should be explained. It is
important to consider the critical formulation attributes,
together with the available manufacturing process options, in
order to address the selection of the manufacturing process
and confirm the appropriateness of the components.
The rationale for the selection, controls, appropriateness of co
mponents and equipment, and process design is discussed.
The
critical process parameters, their monitoring and control, are p
resented in this section as well as the justification for the drug
product specifications.

12. As with the formulation, the differences between the man
ufacturing processes used for the pivotal clinical trial bat
ches, the primary stability batches and the commercial
process are discussed. Data should be provided to sho
w the robustness of the process to reliably produce the
quality product

13. 4. Container closure
The suitability of the container-closure system used for the
storage, transportation (shipping) and use of the FPP
should be discussed.
This discussion should consider: The choice of primary
packaging materials should consider, e.g., choice of
materials, protection from moisture and light,
compatibility of the materials of construction with the
dosage form (including sorption to container and
leaching), and safety of materials of construction.
Justification for secondary packaging materials should
be included, when relevant.

14. 5. Microbiological attributes
The selection and effectiveness of preservative systems in
products containing antimicrobial preservative or the
antimicrobial effectiveness of products that are inherently
antimicrobial.
• The selection and effectiveness of preservative systems in
products containing antimicrobial preservative or the
antimicrobial effectiveness of products that are inherently
antimicrobial
• For sterile products, the integrity of the container closure
system as it relates to preventing microbial contamination

15. • This may include testing at the lowest specification for the
preservative(s) and testing simulating patient use to justif
y the efficacy and safety such that the minimum concentr
ation of preservatives is used. The results of the microbial
testing substantiate the qualitative and quantitative prese
rvative requirements.
Although chemical testing for preservative content is the
attribute normally included in the drug product
specification, antimicrobial preservative effectiveness
should be demonstrated during development.

16. 6. Compatibility
The compatibility of the drug product with reconstitution
diluents (e.g., precipitation, stability) should be addressed to
provide appropriate and supportive information for the
labelling.
• This information should cover the recommended in-use shelf
life, at the recommended storage temperature and at the
likely extremes of concentration. Similarly, admixture or
dilution of products prior to administration (e.g.,product
added to large volume infusion containers) might need to be
addressed.

17. References
 ICH Q8 R2 Guideline “ Pharamaceutical Development”
(https://database.ich.org/sites/default/files/Q8_R2_Guidelin
e.pdf)
 WHO Guidelines on submission of documentation for a
multisource (generic) finished pharmaceutical product
for the WHO Prequalification of Medicines Programme:
quality part. In: WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Forty-
sixth report. Geneva, World Health Organization, 2012,
Annex 4 (WHO Technical Report Series, No. 970).
 https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/q8r2-pharmaceutical-development