.

1. Product Development &
Technology Transfer
 Development of technology by R & D
 Technology transfer from R & D to
production, Optimization and
Production, Qualitative and
quantitative technology models.
 Documentation in technology transfer:
Development report, technology
transfer plan and Exhibit.

3. Trevor M. Jones, CHAPTER 1:Preformulation Studies , in Pharmaceutical Formulation: The Science
and Technology of Dosage Forms, 2018, pp. 1-41 DOI: 10.1039/9781782620402-00001
eISBN: 978-1-78262-040-2
From Book Series: Drug Discovery

5. Technology Transfer Plans and Reports
 Technology transfer plans and reports are used by a research and development
organization in order to document their official ‘‘transfer’’ of a newly developed or
recently upgraded product/process from the developmental area and facilities to an
operations unit and site, usually located in separate buildings, or at an entirely
separate and different manufacturing sites. While the format and content has not
been formally prescribed by FDA, companies generally include the following
information[12] in these documents:
 Definition of responsibilities for key departments; documentation review, approval,
and storage requirements.
 Summary of developmental activities completed.
 Summary of scale-up activities; summary of formulation, synthesis, process, and
analytical method changes; establishment of impurity specifications; establishment
of critical process parameters; identification of validation plans and activities.


6. Technology Transfer Plans and
Reports
 Definition of component, container/closure, and product attributes.
 Analytical methods development and validation summary.
 Descriptions, specifications, design parameters and requirements of facilities,
and major equipment and utility systems.
 Definition of the manufacturing process.
 Stability and expiry dating information.
 Change control.
 Reprocessing.
 Cleaning processes, including methods development and validation of the
processes and methods.
 Summary of Regulatory Affairs activities, including regulatory commitments,
key data and information to be summarized in regulatory filings.

8. Key aspects of Technology Transfer
 Whether a tablet, a transdermal patch, a topical
ointment, or an injectable, the transformation of a
pharmaceutical prototype into a successful product
requires the cooperation of many individuals
 Integration of personnel process & machine &
materials

9. Key aspects of Technology Transfer
 The success of development efforts is measured by the ease
of technology transfer and scale-up to largescale
manufacturing.
 Small-scale studies in the laboratory need to incorporate
influencing factors of largescale manufacturing.
 The intent is to develop a process that is safe, effective,
efficient, and sufficiently robust where the manufacturing
technology can be transferred to routine large-scale
commercial production.
 Product-design objects are efficacy, stability, safety, and
ease of use

10. Key aspects of Technology Transfer
 The scope and extent of the validation studies expand
as batch sizes increase with the progression from
development to commercial manufacturing.
 Knowledge of manufacturing capacities and
capabilities, appropriate and adequate processing
conditions for a robust process, coupled with careful
control of starting material and processing conditions
are necessary for successful technology transfer in
achieving the predefined processing conditions and
predicted finished product qualities.

11. Key aspects of Technology Transfer
 Processing at larger batch sizes provides an
opportunity to verify the suitability of the processing
parameters identified during development and focus
on assessing the distribution of behavior and
uniformity of finished product qualities at a larger
scale.

12. Key aspects of Technology Transfer
 A complete and comprehensive development report is an
invaluable resource for technology transfer. This document
preserves the body of knowledge and experience gained during
product design and process development activities.
 Information including characteristics of the API, formulation,
and finished product outlined in the preceding sections are part
of a comprehensive development report.
 As well, the knowledge and experience in initial scale-up for
processing clinical material is also valuable.
 The expected behavior, finished product attributes, and any
difficulties that arise in scaling-up provide useful insight as
larger batch sizes are integrated into routine manufacturing.
 Obtaining consistent desired properties of the drug product are
the final assessment of a successful scale-up and technology
transfer.

13. Key aspects of Technology Transfer
 Formula
 handling and safety considerations
 Raw materials
 Manufacturing equipment
 Manufacturing precautions
 Manufacturing procedures
 Packaging
 Process validation
 Specifications for raw materials, packaging components, and in-
process and finished product
 Validated analytical methods
 Regulatory considerations
 Rework procedures
 Transportation

14. Activities leading to Technology
transfer
 Product development (PD) is the first step to TT
 Objective of PD is to develop product that meets with QTTP & CQA so
as to obtain product that is safe, stable & is complying with efficacy
requirement.
 PD activity includes conduct of experimental trials resulting in
understanding of input variables and process variables.
 In order to develop product with consistent quality, ICH guidelines are
followed

15. ICH guidelines for product life
cycles management
ICH Q8 Pharmaceutical Development
ICH Q9 Quality Risk Management
ICH Q10 Pharmaceutical Quality System

16. Product development strategy
 PD starts with identifying a suitable dosage form on
the basis of :
 properties (physical, chemical & biological) of the drug
substance
 Patient need
 Market need
 Regulatory & IPR consideration
 After QTPP & CQA are identified, the next step is to
identify CMAs composition variables, CPPs

17. Raw material selection
 Raw materials include API, excipients, packaging
material
 The properties of API – polymorphic form, particle
size, surface area, impurity profile
 Depending on the desired CQA of drug product, risk
assessment of CMA of APIs is done.
 Quality attributes of APIs should be within the
specified acceptance limit set as per the official
compendial limits

18. API selection
 Raw materials include API, excipients, packaging material
 The properties of API – polymorphic form, particle size,
surface area, impurity profile
 Depending on the desired CQA of drug product, risk
assessment of CMA of APIs is done.
 Quality attributes of APIs should be within the specified
acceptance limit set as per the official compendial limits
 Follow the ICH guidelines or in-house specifications
 Initial risk assessment of CMA of API on CQA done

21. API selection
 It is preferable to select at least 3 sources of API for qualification
based on their compliance
 API supplier should provide OPEN PART OF DMF information
about - ROS, impurities, degradants, analytical data, stability
data
 3 lots of API of product batch are obtained from the supplier and
evaluated for the compliance
 PD is done in RD atleast with 2 sources
 It is better to register the product with 2 sources of API so that
during commercial phase reliability & continuity of supply chain
is mainitained

22. Project Case study:
Sr.
No.
Parameter Observation
1. Manufactured for Company ABC
2. Country USA
3. Strength 40 mg Drug A, 25 mg Drug B
4. Dosage form Tablet
5. Description
Pink, oval, film-coated tablets, approximately 15*7
mm
6. Composition
Hydroxypropyl Cellulose, Hypromellose, Lactose,
Low substituted Hydroxypropyl Cellulose, MCC,
Red Iron Oxide, Talc, Titanium Dioxide, Yellow
Iron Oxide
7. Shape Oval shaped
8. Average weight (Coated) 432.60 mg
23-05-2023 22
Analysis of Innovator’s Product

23. 23-05-2023 23
Sr.
No.
Parameter Observation
9. Thickness of tablet 4.70-4.75 mm
10. Length of tablet 15.20 mm
11. Breadth of tablet 7.20 mm
12. Hardness 16.0-22.0 kP
13. Disintegration time 3 min 15 seconds
14.
Dissolution Medium:
0.05M pH6.8 phosphate buffer,
Volume: 900 mL, Apparatus: USP
Type II, Speed: 50 rpm
Time (min)
% Drug dissolved
Drug A Drug B
5 56 80
10 69 94
15 71 98
20 74 100
30 77 102
45 79 103
60 80 103
15. Tablet scoring Unscored
16. Storage Store at 20-25˚C
17. Pack Bottles of 30’s
18.
Related substance
Active moiety of Drug A: NMT 1.0% ND
Drug A related Compound-A: NMT 0.5% ND
Benzothiadiazine Related Compound-A: NMT 0.5% 0.16

24. 23-05-2023 24
Sr.
No
Excipients Function
Tentatively
% w/w used
1. Hydroxypropylcellulose Binder/Film, coating
polymer
2-5 %
2. Hypromellose Binder/Film coating
polymer
1-3 %
3. Microcrystalline Cellulose Diluent 4-8 %
4. Low-substituted Hydroxypropyl
Cellulose
Binder & Disintegrant 4-15 %
Sr.
No
Excipients Function
Tentatively
% w/w used
5. Talc Glident 1-2 %
6. Lactose Diluent 80-90 %
7. Magnesium Stearate Lubricant 2-10%
9. Red Iron Oxide Colourant
2-3 %
10. Titanium Dioxide Opacifier
11. Yellow Iron Oxide Colour
Innovator’s Product Composition- function and tentative quantity

25. 23-05-2023 25
Drug product
CQAs
Drug Substance Attributes
Solubilit
y
Related
substance
s
Assay Residual
Solvents
Particle size
distribution
(PSD)
LOD
(Loss on
drying)
Flow
properties
Dissolution High Low Low Low High Low Low
Assay Low Low Low Low Medium Low Medium
Content
uniformity(CU
)
Low Low Low Low Medium Low High
Related
substances
Low Low Low Low Low Low Low
Table 9.8: Initial risk assessment of drug substance attributes- For Drug A

26. 23-05-2023 26
Drug
substance
attribute
Drug
product
Critical
Quality
Attribute
(CQA)
Initial Risk
Assessed
Justification
Solubility Dissolution High
As Drug A exhibited low solubility across the
physiological pH range, its solubility will strongly
impact dissolution. The risk is assessed as High. The
formulation process will be designed to mitigate the
risk.
Justification of risk assessment
Particle Size
Distribution
(PSD)
Dissolution High
As API being a BCS class II drug, PSD can impact
dissolution, so risk identified is high.
Assay Medium
Small particle size of API may impact blend flowability.
In extreme cases, poor flowability may cause an assay
failure. The Risk identified is medium.
CU Medium
PSD has a direct impact on drug substance flowability
and ultimately tablet CU. The Risk identified is medium.

27. 23-05-2023 27
Flow
properties
Dissolutio
n
Low
The flowability of the drug substance is not
related to its solubility. Hence will not impact
dissolution. Therefore, the risk is low.
Assay Medium
Drug A has poor flow properties. In extreme cases,
poor flow may impact assay. The risk is medium.
CU High
The poor flow properties of API may lead to poor
tablet CU. The risk is high.
RS Low
The flowability of the drug substance is not related
to its degradation pathway or solubility. Therefore,
the risk is low.

28. Specification of API
 Quality attributes of API as per ICH Q6A, as per
pharmacopoeia & manufacturer
 CMA s are identified as per the risk assessment
 Specifications for the CMAs are decided on the basis of
experiments conducted during formulation development
using API with varying parameters
 As you proceed with the development activity,
specifications evolve and are fine tuned
 The objective is to minimize the risk of failure in the drug
product during scale up & technology transfer

30. Excipients
 Criteria of excipient selection – type of dosage form ,route
of administration, safety profile, manufacturing process,
regulatory aspects & IPR
 Route of administration: for parenterals excipients to be
sterile & pyrogens free
 Safety profile: Acceptable daily intake, IIG Limits (IID –
USFDA), if used beyond ADI justification required.
Excipient gives safety & toxicity data of excipients especially
for new excipient

31. Excipients
 Regulatory aspects : compendial grade excipients to be
used, in case of co processed excipients (Ludipress ,
Prosolv) – regulatory status in intended market to be
checked
 GRAS status required
 Compatibility : between drug & excipient to be checked.
Selection of excipients should be based on basic
mechanistic understanding of structure of drug molecule,
impurities, degradation pathway, processing conditions

32. Excipients
 Manufacturing process : choice of excipients is driven by type of
mfg process . For example for DC, directly compressible
excipients are used
 RISK ASSESSMENT – based on impact of CMA on CQA done
based on that material attributes and specifications are set and
requirements given to excipient vendor.
 3 lots of excipients of production batch are obtained from the
supplier and evaluated for the compliance
 PD is done in RD at least with 2 sources
 It is better to register the product with 2 sources of excipients so
that during commercial phase reliability & continuity of supply
chain is mainitained

33. Packaging materials
 Primary pkging materials are most relevant from
regulatory perspective as they are in direct contact

35. Analytical Method Development
 Analytical Method Development: method dev &
validation as per ICH Q2A&B
 QbD – QATP
 Accuracy, precision, linearity, robustness, recovery,
repeatability, sensitivity,
 Pharmacopoeal / Inhouse

36. Analytical Method Development
 Method development for API
 Method Development for Drug Product
 Impurities as per ICH Q3A & Q3B
 Dissolution Method development & setting
specifications with/without clinical relevance

37. Prototype Formulation Development
 Preliminary experimental trials with understanding of
 QTPP
 CQAs
 CMAs
 CPPs
 Screening designs – Plackett Burman, Factorial &
Fractional Factorial design
 Charging of R& D batches on short term stability and stress
conditions

38. Pilot Clinical Study
 After satisfactory data of accelerated study of 3 months
of R&D batches – pilot clinical batch is taken
 In case of NDA :