The document discusses the process of technology transfer in the pharmaceutical industry, which refers to the progression of a drug from discovery to commercialization through development, clinical trials, and manufacturing. It covers the various facets, constituents, and steps of technology transfer including development, documentation, validation, and optimization required to successfully transfer a technology from research to production. Proper planning and documentation of every step of the technology transfer process is important to ensure quality and regulatory compliance.

1. TECHNOLOGY
TRANSFER PROCESS IN
PHARMACEUTICAL
INDUSTRIES

2. CONTENTS
 INTRODUCTION/ WHAT IS TECHNOLOGY TRANSFER?
 FACETS OF TECHNOLOGY TRANSFER
 CONSTITUENTS OF TECHNOLOGY TRANSFER
 TECHNOLOGY TRANSFER FROM VARIOUS SECTORS
 TECHNOLOGY TRANSFER PROCESS FLOW CHART
 GUIDELINES/ IMPORTANCE OF TECHNOLOGY TRANSFER
 WHY/ REASONS OF TECHNOLOGY TRANSFER AND WHEN IT WILL BE DONE?
 FACTORS AND BARRIERS INFLUENCING ON TECHNOLOGY TRANSFER APPROCHES TO
OVERCOME THE BARRIERS
 TECHNOLOGY TRANSFER PROCESS AND ITS STEPS AND PROCEDURE
 TECHNOLOGY TRANSFER TEAM & RESPONSIBILITY
 TECHNOLOGY TRANSFER DOCUMENATION
 TECHNOLOGY TRANSFER CHECKLIST
 TECHNOLOGY TRANSFER DOCUMENATION
 PROBLEMS IN TECHNOLOGY TRANSFER
 TECHNOLOGY TRANSFER OF TEST METHODS
 EXAMPLE OF TECHNOLOGY TRANSFER PROBLEMS IN TABLETS MANUFACTURING

3. INTRODUCTION / WHAT IS TECHNOLOGY TRANSFER?
 Transfer of technology is defined as “a logical procedure that
controls the transfer of any process together with its
documentation and professional expertise between
development and manufacture or between manufacture
sites”
 Technology transfer is both integral and critical to the drug
discovery and development process for new medicinal
products

4.  Technology Transfer is helpful to develop dosage forms in various ways as it
provides efficiency in process, maintains quality of product, helps to achieve
standardized process which facilitates cost effective production. It is the process
by which an original innovator of technology makes its technology available to
commercial partner that will exploit the technology. Technology transfer is both
integral and critical to drug discovery and development for new medicinal
products.
 In pharmaceutical industry, “Technology Transfer” refers to the processes of
successful progress from drug discovery to product development, clinical trials
and ultimately full-scale commercialization.
 “Technology transfer” refers to the processes that are needed for successful
progress from drug discovery to product development to clinical trials to full- scale
commercialization or it is the process by which a developer of technology makes
its technology available to commercial partner that will exploit the technology.
 Technology transfer is important for such research to materialize on a larger scale
for commercialization especially in the case of developing product. Technology
transfer includes not only the patentable aspects of production but also includes
the business processes, such as knowledge and skills.

5. Technology Transfer Process
Regulatory
Submission
Drug Discovery
&
Development
Phases
Lead Candidate
Compounds Drug Nominated First time to man

6. Facets of technology transfer
The transfer of technology could happen in any of following
ways:
1. Government labs to private sector firms.
2. Between private sector firms of same country.
3. Between private sector firms of different country.
4. From academia to private sector firms.
5. Academia, government and industry collaborations

7. Proper
Research
Paper Work
Pricing
Publicity
Partnership
People’s
Acceptance
CONSTITUENTS OF TECHNOLOGY TRANSFER

8. Proper Research – By proper research we mean firstly that in which the result
are reproducible and issues such as scale up, stability etc. and other practical
now has been addressed, also that in which problem were taken up in first
place
Proper work- This refer to institutional and guidelines regarding IP Protection
licensing modalities etc. which must be in place beforehand. In the absence of
these, decision get delayed, lack of fairness in decision e.g. case of X institute,
which came up with good technology but since no guidance were there, kept
running around for two years and then gave up.
Pricing – most difficult and critical area of Transfer of technology.
Too high price can put off buyer, leaving the technology unsold.
Too price a result in revenue loss.
There are basically two model regarding pricing
1)Price charged for a technology should depend upon market force i.e.
impact of the technology irrespective of amount spent on developing it.
2)Price charged should include all expenses involved in developing it.

9. Publicity – It is important to identify and then approach buyer i.e. adopt
targeted Publicity and not blanket publicity. Specific journal, website, letters to
manufacturer, personal selective visit etc. are some common approach which
help in locating buyer
Partnership – this means working along with industry. Industry takes it up,
manufacturer and makes available to society. Partnership are important to
ensure your technology is successfully adopted simply conveying the details
may not be sufficient.
People’s Acceptance – It is no use trying to develop a technology which
people will not accept e.g. due to religious reason/social concern etc.
genetically modified food, irradiated vegetables processed beef in India,
improved capsule made of non- vegetarian material.
LIST OF INSTITUTE IN INDIA ASSISSTING IN TECHNOLOGY TRANSFER
Asia pacific Centre for Transfer of technology ( APCTT)
Technology Bureau for small enterprises ( TBSE)
National Research & Development corporation
Foundation for Innovation and Technology Transfer

10. TECHNOLOGY TRANSFER FROM VARIOUS SECTORS
IDEA

11. TECHNOLOGY TRANSFER PROCESS FLOW CHART
Innovation
Research &
Development
Assessment
Information
and
Assessment
Investment
Collaboration
Commercialization
promotion

12. GUIDELINES/ IMPORTANCE OF TECHNOLOGY TRANSFER
To elucidate necessary information to transfer technology from R&D to actual
manufacturing by sorting out various information obtained during R&D.
Demonstration of necessary information to technology transfer from research and
development to actual manufacturing.
To elucidate necessary information to transfer technology of existing products between
various manufacturing places.
To exemplify specific procedures and points of concern for smooth technology transfer.
For the smooth manufacturing of commercialized products.
This is applicable to the technology transfer through R&D and production of drug
(chemically synthesized drug substances and drug products) and the technology
transfer related to post- marketing changes in manufacturing places.
The ultimate goal for successful technology transfer is to have documented evidence
that the manufacturing process for drug substance and drug products are robust and
effective in producing the drug and drug products complying with the registered
specifications and Good Manufacturing Practice requirement.
General impact of the technology transfer program. i. Improvement of the research
pertinence and its promotion in foreign countries. ii. Contribution with the creation and
consolidation of research groups and centers for technology development, involving the
training of young research students. iii. Promote interdisciplinary projects to be
developed in the region of interest.

13. Why/ Reasons of technology transfer?
Many reasons exist why a company would like to transfer its technology to other
parties:
1) Due to lack of manufacturing capacity, the developer of the technology may only
have manufacturing equipment that suitable for lab and small scale operations and
must partner with another organization to do large scale manufacturing.
2) Due to lack of resources to launch product commercially. The original inventor of
technology may only have resources to conduct early-stage research and Phase-I
and II clinical trials.
3) Due to lack of marketing distribution and distribution capability. The developer of
the technology may have fully developed the technology and even have obtained
regulatory approvals and product registrations, but it may not have the marketing
and distribution channels and must collaborate with another organization that has
the capability.
4) Forming alliances with partners that can progress the development of the
technology to take it to market.
5) Forming alliances with partners with manufacturing capability.
6)Forming alliances with partners with marketing and distribution capability.
7)Exploitation in a different field of application.

14. WHEN TECHNOLOGY TRANSFER IS DONE ?
• Idea to Discovery Lab
• Discovery Lab to Development Lab
• Development Lab to Pilot Plant
• Kilo Lab to Pilot Plant
• Pilot Plant to Semi-works (other pilot plant)
• Pilot Plant to Manufacturing
• Manufacturing to Manufacturing
Various stages of formulation development were as follows
• Preformulation studies.
• Bench scale - (1/1000th of X)
• Lab scale – (1/100th of X)
• Scale up- (1/10th of X or 0.1M whichever is maximum)
• Commercial (X) Where X is the final commercial scale batch size.

15. FACTORS INFLUENCING TECHNOLOGY TRANSFER
Drivers for Technology Transfer –
(A) Good business and manufacturing practices – The company’s success
is primarily the result of its adoption of good business and manufacturing
practices, particularly in the areas of product identification and formulation
technology.
• Potential for competitive pricing – Balance cost to remain competitive by
having higher private sector prices and very low public sector prices.
• Strategic planning – Create an enabling environment for vertical integration,
with prospects for higher capacity utilization and eventual lowering of
production costs.
• Strong economy and environment – For technology transfer to be
successful there needs to be supportive business and scientific environment in
the recipient country, and that environment should include skilled workers,
economic and political stability, supportive regulatory environment, market size
and potential and a well developed national infrastructure of natural resources
and transport.
• Transparent and efficient regulation – Pharmaceuticals are necessarily a
high regulated industry, the regulatory function must be efficient and
transparent for technology transfer to be economically viable.

16. Opportunities for contingency supply – Multinational pharmaceutical
companies are inclined to transfer technology to local manufacturers with
the potential to receive when they foresee an inability to meet time scales
and volume demand from large procurers.
• Access to new machinery, training, know-how and business partnership –
This makes the prospect of technology transfer very desirable to local
pharmaceutical manufacturers since the technology, equipment, etc. could
be applied profitably beyond the initial purpose.
(B) Barriers of Technology Transfer
• Lack of efficiency – Automation of production processes to improve
efficiency and lower costs.
• Low market share – Local producers face significant challenges in
meeting International Quality Standards and capturing a critical market
share. Greater market share would increase profitability.
• Cost of prequalification – There is benefit in meeting International
Standards since it opens up the opportunity for trading across the entire
world.
• Labour issues – The pharmaceutical sector demands relatively skilled
labour. High labour turns over and absenteeism owing to unattractive
conditions of service is negative contributor

17. Approaches to overcome barriers in technology transfer
1. Commercializing publicly funded technologies: The basic pattern envisioned is to give institutions
receiving public research funds the right to obtain and exploit patents on inventions developed in the
course of research.
2. Research tool patents and freedom to operate for the public sector: Patents sometimes make it difficult
for public researchers to carry out their research or to make the products of that research available. It is
intensified by the tendency of some publicly funded research laboratories to avoid use of a patented
technology without permission even in nations where no relevant patent is in force.
3. Web access and scientific publication: Limited access to scientific journals led to enormous problems for
developing nations scientists.
4. National security issues and restrictions on exports of particular technology: International controls
designed to protect national security and to prevent the proliferation of important technologies also restrict
the flow of technologies.
5. Inadequate funding in important areas and possible treaties: There are areas of research of importance
to the developing world that are being funded inadequately.
6. Co-operative research agreements: Global support for public sector research might be encouraged is
through co-operative research agreements designed to meet specific goals. It would seem more feasible
to focus efforts on technologies of significant social benefit to the developing nations.
7. Possible treaty on scientific access: There has also been a proposal for an international treaty on
access to knowledge and technology negotiated on the basis of the type of reciprocity found in normal
international trade negotiations. The concept is mean to be non- zero sum in the sense that, like free trade
in goods, free trade in scientific ideas benefits all, and such arrangements could be made bilaterally as
well as multilaterally.

18. Technology Transfer Process
Technology transfer is both integral and critical to the drug discovery and development process for new medicinal products. The
decision to transfer products between manufacturing sites is frequently driven by economics.
Key stages of the process include data collection, data review, regulatory impact with particular emphasis on any change
approvals, analytical validation, pilot or full-scale process batch, stability set down (if required).
Technology Transfer Flow chart.
Technology
Transfer

19. REPRESENTATION OF TECHNOLOGY TRANSFER PROCESS

20. TECHNOLOGY TRANSFER PROCESS
The processes are classified into the three categories.
• Research Phase
– Quality by design
• Development Phase
– Research for Factory Production
– Consistency between Quality & Specification
– Assurance of consistency through development & manufacturing
– Technology Transfer from R&D to Production
• Production Phase
– Validation & Production
– Feed back from Production & Technology Transfer of Marketed Products

21. Process Development

22. STEPS IN TECHNOLOGY TRANSFER PROCESS
During development of a formulation, it is important to understand the procedure of operations used, critical
and non-critical parameters of each operation, production environment, equipment and excipients availability
should be taken into account during the early phases of development of formulation so that successful scale up
can be carried out.
(A) Development of technology by R&D. (Research Phase)
(a)Design of procedure and selection of excipients by R&D
(b) Identification of specifications and quality by R&D
(B) Technology transfer from R&D to production (Development Phase)
(a) Master Formula Card (MFC)
(b) Master Packing Card
(c) Master Formula
(d) Specifications and Standard Test Procedures (STP’S)
(C) Optimization and Production (Production Phase)
(a) Validation Studies
(b) Scale up for production
(D) Technology Transfer Documentation
(a) Development Report
(b) Technology Transfer Plan (c) Report
(E) Exhibit

23. TECHNOLOGY TRANSFER PROCESS Cont...
(A) Development of technology by R&D. (Research Phase)
(a) Design of procedure and selection of excipients by
R&D– Selection of materials and design of procedures is
developed by R&D on the basis of innovator product
characteristics.
(b) Identification of specifications and quality by R&D–
Quality of product should meet the specifications of an
innovator product.

24. TECHNOLOGY TRANSFER PROCESS Cont...
B) Technology transfer from R&D to production (Development Phase)
R&D provides technology transfer dossier (TTD) document to
product development laboratory, which contains all information of
formulation and drug product as follows
(a)Master Formula Card (MFC) – Includes product name along with
its strength, generic name, MFC number, page number, effective
date, shelf life and market.
(b)Master Packing Card – Gives information about packaging type,
material used for packaging, stability profile and shelf life of
packaging.
(c)Master Formula – Describes formulation order and manufacturing
instructions. (Process order and environment conditions)
(d)Specifications and Standard Test Procedures (STP’S) – Helps
to know active ingredients and excipients profile, in-process
parameters, product release specifications and finished product
details.

25. TECHNOLOGY TRANSFER PROCESS Cont...
(C) Optimization and Production (Production Phase)
(a)Validation Studies – Production is implemented after validation studies
that can verify that process is able to stabilize the product based on
transferred manufacturing formula. Manufacturing department accepting
technology is responsible for validation and the R&D department
transferring technology should take responsibility for validation such as
performance qualification, cleaning and process validation.
(b) Scale up for production – Involves the transfer of technology during
small scale development of the product and processes. It is essential to
consider the production environment and system during development of
process. Operators should concentrate on keeping their segment of the
production process running smoothly.

26. TECHNOLOGY TRANSFER PROCESS Cont...
(D) Technology Transfer Documentation Generally interpreted as document indicating contents of
technology transfer for transferring and transferred parties. Each step from R&D to production should be
documented, task assignments and responsibilities should be clarified and acceptance criteria for completion
of technology transfer concerning individual technology to be transferred. It is duty of Quality Assurance
department to check and approve the documentation for all processes of technology transfer.
(a) Development Report– The R&D report is a file of technical development, and R&D department is in-
charge of its documentation. This report is an important file to indicate rationale for the quality design of drug
substances and its specifications and test methods. The development report is not prerequisite for the
application for approval; it can be used at the pre approval an inspection as valid document for quality design
of new drug. The development report contains
(1) Data of pharmaceutical development of new drug substances and drug products at stages from early
development phase to final application of approval.
(2) Information of raw materials and components.
(3) Design of manufacturing methods.
(4) Change in histories of important processes and control parameters.
(5) Specifications and test methods of drug substances.
(6) Validity of specification range of important tests such as contents impurities and dissolution.
(7) Verifications of results.

27. TECHNOLOGY TRANSFER PROCESS Cont...
(b) Technology Transfer Plan –
The technology transfer plan is to describe items and contents of technology to be transferred
and detailed procedures of individual transfer and transfer schedule, establish judgment
criteria for the completion of the transfer. The transferring party should prepare the plan before
the implementation of the transfer and reach an agreement on its contents with the transferred
party.
(c) Report –
Completion of technology transfer is to be made once data are taken accordingly to the
technology plan and are evaluated to confirm that the predetermined judgment criteria are
met. Both transferring and transferred parties should document the technology transfer report.
(E) Exhibit
After taking scale up batches of the product, manufacturing of exhibit batches takes place. In
case of exhibit, batch sizes are increased along with equipments and their processes. This is
done for filling purpose in regulatory agencies.

28. TECHNOLOGY TRANSFER PROCEDURE
1. Procedure for Manufacturing and Packaging:
• After the completion of three validation/commercial batches, R&D shall prepare the
technology transfer dossier (TTD), which shall be reviewed by Head- Production, Head-
QC, Head- Engineering and approved by Head-QA.
• The dossier shall contain the details of unitary formula, process flow chart, raw
material and packing material specifications, in-process and finished product
specifications, master formula card, safety parameters, critical process steps, critical
process parameters and their specifications and measured response, process validation
protocol, process validation report, stability data, deviation and change controls, product
development report.
• After successful transfer of technology (manufacturing process), manufacturing of the
respective product is the responsibility of production department. If any problem arises,
QA shall investigate and refer to R&D through investigation report in the form of Inter
Office Communication (IOC).
• Any deviation in the process shall be supported by deviation/change control form as
applicable.
• For third party and loan license products, respective organization will provide the TTD
to QA and manufacturing process shall be demonstrated to production personnel on
minimum of two or three batches.

29. TECHNOLOGY TRANSFER PROCEDURE Cont....
2. Procedure for Analytical Method Transfer: A) For Drug Product:
• Analytical method transfer shall be initiated by analytical department for all the validated methods.
• Analytical department analyst along with quality control analyst has to perform analysis as per the analytical
method transfer protocol.
• The transfer activity shall be established on the optimization batch or process batch with the final formula.
• Analytical method transfer activity shall be initiated with analytical method transfer protocol prepared by AR&D,
reviewed by DQA/QC and finally approved by QA.
• The analytical method transfer protocol shall explain the transfer activities of the drug product and also the
parameters that shall be transferred are Assay, Dissolution, Related substances, Content uniformity and
Residual solvents.
• In case of multiple strengths, analytical method transfer shall be performed for lower strength.
• All chromatograms, record of results and other information have to be interlinked and records have to be
maintained.
• A report has to made with summarized results and conclusions and the same shall be reviewed by Head-DQA
and Head-QC, approved by Head-QA.
• The analytical method transfer process is considered to be completed upon the certification by analytical
department, quality control & quality assurance that the method under consideration meets the acceptance
criteria.
• Finally analytical method transfer report shall be prepared.

30. TECHNOLOGY TRANSFER PROCEDURE Cont....
2. Procedure for Analytical Method Transfer:
B) For Drug Substances:
i) Non Pharmacopoeial Methods: The vendor has to transfer the analytical methods to QC. In case, if
the analytical method transfer activity was not performed by the vendor the same shall be prepared by
AR&D as per the STP.
ii) Pharmacopoeial Methods: The vendor has to transfer the analytical methods to QC. If the methods
are same as per respective pharmacopoeia, the method suitability shall be performed by AR&D.
Suitability of the analytical method shall verified by performing the specificity (RRT verification) and
precision study (Triplicate) and the same shall be reviewed by DQA and communicated to QC.
• Analytical method transfer protocol and report shall be prepared. • The analytical method transfer
protocol shall explain the transfer activities of the drug substance and also the parameters that shall
transferred are assay, residual solvents and related substances.
• All chromatograms, record of results and other information have to be interlinked and records have to
be maintained.
• A drug substance analytical method transfer report has to be made with summarized results with
conclusions as per drug product method transfer report.
• The limits and parameters described for drug product/drug substance are indicative, but shall altered
based on customer’s requirements and nature of drug product/drug substances to be followed as per
respective analytical method transfer protocol.
• Documentation for analytical method transfer activity shall be done by analytical R&D department.

31. TECHNOLOGY TRANSFER TEAM
The technology transfer team consists of
– R&D Process Technologist
– QA Representative
– Production Representative
– Engineering Representative
– QC Representative

32. Constitution of technology transfer team and their responsibilities
Technology Transfer Team member Responsibilities
Process Technologist a) Central focus for transfer activities.
b) Collates documentation from donor site
c) Performs initial assessment of transferred project for Feasibility,
Compatibility with site capabilities and Establishes resource requirements.
QA Representative a) Reviews documentation to determine compliance with
marketing authorization (MA).
b) Reviews analytical methods with QC to determine capability,
equipment training requirements.
c) Initiates conversion of donor site documentation into local systems or format.
d) Initiates or confirms regulatory requirements, e.g., change to manufacturing
license; variations to MA if process changes needed, etc.
Production Representative a) Reviews process instructions (with process technologist) to confirm
capacity and capability.
b) Considers any safety implications, e.g., solvents; toxic; sanitizing materials.
c) Considers impact on local standard operating procedures (SOPs).
d) Considers training requirements of supervisors or operators.

33. Constitution of technology transfer team and their responsibilities Cont...
Technology Transfer Team member Responsibilities
Engineering Representative a) Reviews (with production representative) equipment
requirement.
b) Initiates required engineering modifications, change or
part purchase.
c) Reviews preventative maintenance and calibration impact,
e.g., use of more aggressive ingredients; more
temperature sensitive process, and modifies accordingly.
QC Representative a) Reviews analytical requirement.
b) Availability with instruments.
c) Responsible for analytical method transfer for drug
substance and drug product.

34. TECHNOLOGY TRANSFER DOCUMENATION
1. Organization for Technology Transfer
2. Research and Development Report
3. Product Specification File
4. Technology Transfer Plan
5. Technology Transfer Report
6. Verification of Results of Technology Transfer

35. TECHNOLOGY TRANSFER CHECKLIST
It consists of
• Production master formula
• Manufacturing instructions
• Dispensing instructions
• Analytical methods
• Previous process validation
• Previous analytical validation
• Cleaning instructions and previous cleaning validation
• Stability reports
• Excipients specifications and source
• Active specifications and source
• Primary packaging material specifications and source
• Packaging instructions
• Process deviations file, Analytical deviations file
• Reject and rework file
• Specimen manufacturing batch record.

36. PROBLEMS IN TECHNOLOGY TRANSFER
1. Problems during the technology justification and selection stage.
i. Wrong selection of technology based on misjudgment when preparing a business case for a
technology transfer project.
ii. Cost of buying, installing, operating and maintaining the technology is also high.
iii. The technology selected is also complex for easy understanding and assimilation of the transferee.
iv. The technology needs extensive adaptation to suit local conditions.
2. Problems during the planning stage.
i. Transferor (seller) underestimates the problems in transferring the technology to a developing country setting.
ii. Transferor does not fully understand transferee needs.
iii. Transferee managers are not involved in the planning which is carried out only by the transferor.
iv. Too much attention is paid to the hardware to be purchased and not enough attention is paid to
skills and information acquisition.
v. Overestimation of the technological capabilities of the transferee by the transferor thereby leading to unrealistic
expectations on how well the transferee can meet target dates.
vi. Poor market demand forecasting by the transferee of the outputs to be produced by using the transferred technology.
vii. The objectives of the transferor and transferee are not compatible.
viii. Mechanisms chosen for implementing the transfer are not appropriate.

37. PROBLEMS IN TECHNOLOGY TRANSFER Cont...
3. Problems during negotiations.
i. Differences in negotiation approaches and strategies.
ii. Lack of trust between the transferor and transferee.
iii. Goal incompatibility during negotiations.
iv. Inability to reach agreements on pricing, product and marketing strategies.
v. Both parties try to achieve results in an unrealistically short period of time.
4. Problems during technology transfer implementation.
i. Shortage of experienced technology transfer managers.
ii. Lack of trust in transferor developed systems by the transferee.
iii. Inability to achieve quality targets.
iv. Delay in obtaining supplementary materials, from the local environment, needed for quick implementation.
v. High cost and poor quality of locally available materials needed to implement the technology transferred.
vi. Inadequate tracking of the technology during implementation.
vii. Cost overrun due to poor implementation.

38. Success of Technology Transfer
Its depends on
• Communication
– Open communication between all team members
– Direct communication between technical members
– Effective and timely communication with regulators
• Sending and Receiving Unit
– Technology transfer is not a “one way street”
– The sending unit and receiving unit must be equally
involved in the process to ensure success
• Team work at all time

39. Technology Transfer of Test Methods
Test methods subject to technology transfer include the
following
• Test methods for drug substances
• Test methods for drug products
• Test methods for raw materials and components
• Test methods for in-process tests
• Test methods for drug residue tests
• Test methods for environmental tests

40. Technology Transfer Plan
• For technology transfer of test methods, it is required to clarify
validation range and acceptance criteria of conformity of
technology transfer regarding individual test methods to be
transferred.
• The validation range (e.g. full validations, reproducibility, etc.)
should be judged on the basis of results of evaluation of
technologies, facilities and equipments of transferred party, and
the range may be influenced by information to be contained in
the technology transfer documentation.
• To compare test results, samples (including dose range,
number of batches, etc.), specific test methods and evaluation
methods to be used in the transferring and transferred parties
should be specified.

41. Technical information to be described in or attached to the technology transfer plan
Information of Raw Materials
 Summary including physical and chemical properties and stability
• Name and structural formula
• Stability data
 Specifications and test methods
• Specific test methods and specifications
• Change history of specifications and test methods and its rationale
• Results of analytical validation
 List of reference standards (Test results should be attached.)
 Information of toxicity and stability for laboratory use
 List of subject samples for comparative evaluation and their test results

42. Information of Drug Substances
Summary including physicochemical properties and
stability
• Name and structural formula
• Elucidation of chemical structure
• Possible isomers
• Physical and chemical properties (including physicochemical
properties)
• Stability data (including severe test data)

43. Batch records
• Chemical synthesis methods of subject batches
• Analytical data of batches
• Impurity profile of representative batch

44. Specifications and test methods
• Specific test methods and specifications (including items
related to efficacy such as particle size distribution,
polymorphism, crystallinity, and hygroscopicity)
• Change history of specifications and test methods and their
rationales
• Results of analytical method validation

45. Information of Drug Products
 Summary including formula and stability
• Elucidation of dissolution profile
• Stability data (including severe test data)
• Storage conditions and expiry date (if established)
 Analytical data of batches
 Specifications and test methods
• Specific test methods and specifications (including items related to
efficacy such as particle size distribution and hygroscopicity)
• Change history of specifications and test methods and its rationale
• Results of analytical method validation
 List of reference standards (Test results should be attached.)

46. Information on Implementation of Technology Transfer
 Persons in charge of planning, checking and settlement of technology transfer
 Test methods (test method number
 Objectives
 Persons in charge of transferring and transferred parties
 Training plan (including explanation of test methods and demonstration)
 Plan of comparative evaluation study
• Samples: Lot No. (including rationale for the number of lots), storage condition during test,
and handling after the completion of the test (disposal or return to the transferred party, etc.)
• Test period
• Number of repeated tests
• Handling of data (Handling method)
• Retest and handling of outlier
• Acceptance criteria
• Storage of raw data (storage department, storage place, and duration

47. Items Concerning Manufacturing Methods
• Information on manufacturing methods (synthetic routes and
purification methods)
• Information on operating conditions (control parameters and
acceptable range)
• Information on important processes and parameters
(identification of processes and parameters which will affect
quality)
• Information on in-process control
• Information on reprocess and rework (places and methods)

48. Items Concerning Facilities and Equipments
• Information on equipment cleaning (cleaning methods,
cleaning solvents, and sampling methods)
• Information on facilities (selection of materials, capacity,
and equipment types, and necessity of special
equipments.

49. Items Concerning Test Methods and Specifications
• Information on specifications and test methods of drug
substances, intermediates, and raw materials (physical
and chemical, microbiological, endotoxin and
physicochemical properties, etc.)
• Validations for test methods of drug substances and
intermediates

50. Problem in tablets are either related to imperfections in
any one or more of the following during transfer of
technology
 I. Tableting Process
 II. Excipient
 III. Machine

51. PROCESS RELATED PROBLEMS :
• CAPPING: It is due to air-entrapment in the granular
material.
• LAMINATION: It is due to air-entrapment in the granular
material.
• CRACKING: It is due to rapid expansion of tablets when
deep concave punches are used.

52. EXCIPIENT RELATED PROBLEMS :
• CHIPPING: It is due to very dry granules.
• STICKING: It is due to excess moisture present in the
granules.
• PICKING: It is due to the improper drying of the granules.
• BINDING: It is due to the excessive binder present in the
granules.

53. MACHINE RELATED PROBLEMS :
• DOUBLE IMPRESSION: It is due to free rotation of the
punches, which have some engraving on the punch faces.

54. CAPPING:
Capping happened when the upper or lower segment of the
tablet separates horizontally, either partially or completely
from the main body of a tablet and comes off as a cap, during
ejection from the tablet press, or during subsequent handling.
Reason: Capping is usually due to the air– entrapment in a
compact during compression, and subsequent expansion of
tablet on ejection of a tablet from a die.

55. CAPPING RELATED TO ‘FORMULATION’ (GRANULATION)
Sr.No. CAUSES REMEDIES
1. Large amount of fines in the granulation Remove some or all fines through 100 to 200 mesh
screen
2. Too dry or very low moisture content Moisten the granules suitably. Add hygroscopic substance
(leading to loss of proper binding action). e.g.: sorbitol, methyl- cellulose or PEG- 4000.
3. Not thoroughly dried granules. Dry the granules properly.
4. Insufficient amount of binder or Increasing the mount of binder OR Adding dry binder such
gelatinized improper binder. as pre- gelatinized starch, gum acacia, powdered sorbitol,
PVP, hydrophilic silica or powdered sugar.
5. Insufficient or improper lubricant. Increase the amount of lubricant or change the type of
lubricant.
6. Granular mass too cold to compress firm. Compress at room temperature.

56. CAPPING RELATED TO ‘MACHINE’ (DIES, PUNCHES AND TABLET PRESS)
Sr.No CAUSES REMEDIES
1. Poorly finished dies Polish dies properly. Investigate other
steels or other materials.
2. Deep concave punches Use flat punches.
or beveled-edge faces of punches.
3. Lower punch remains below Make proper setting of
the face of die during ejection. lower punch during ejection.
4. Incorrect adjustment of Adjust sweep-off blade correctly
sweep- off blade. to facilitate proper ejection.
5. High turret speed. Reduce speed of turret
5. (Increase dwell time).

57. Lamination / Laminating
• Definition: ‘Lamination’ is the separation of a tablet into two
or more distinct horizontal layers.
• Reason: Air–entrapment during compression and
subsequent release on ejection.
• The condition is exaggerated by higher speed of turret.

58. LAMINATION RELATED TO FORMULATION (GRANULATION)
Sr. No CAUSES REMEDIES
1. Oily or waxy materials in granules Modify mixing process.
Add adsorbent or absorbent.
2. Too much of hydrophobic lubricant Use a less amount of lubricant or
e.g.: Magnesium- stearate. change the type of lubricant
LAMINATION RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
Sr. No. CAUSES REMEDIES
1. Rapid relaxation of the peripheral Use tapered dies, i.e. upper part of the die
regions of a tablet, has an outward taper of 3° to 5°.
on ejection from a die.
2. Rapid decompression Use pre-compression step. Reduce turret
speed and reduce the final compression
pressure.

59. CHIPPING
• Definition: ‘Chipping’ is defined as the breaking of tablet
edges, while the tablet leaves the press or during subsequent
handling and coating operations.
• Reason: Incorrect machine settings, specially mis-set
ejection take- off.

60. CHIPPING RELATED TO FORMULATION (GRANULATION)
Sr. No CAUSES REMEDIES
1. Sticking on punch faces Dry the granules properly or increase
lubrication.
2. Too dry granules. Moisten the granules to plasticize.
Add hygroscopic substances.
3. Too much binding causes
chipping at bottom. Optimize binding, or use dry binders.
CHIPPING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
Sr. No CAUSES REMEDIES
1. Groove of die worn at Polish to open end, reverse or replace the die.
compression point.
2. Barreled die (center of the die Polish the die to make it cylindrical
wider than ends)
3. Edge of punch face turned Polish the punch edges
inside/inward
4. Concavity too deep to compress properly. Reduce concavity of punch faces. Use flat punches.

61. MOTTLING
• Definition: ‘Mottling’ is the term used to describe an unequal
distribution of colour on a tablet, with light or dark spots
standing out in an otherwise uniform surface.
• Reason: One cause of mottling may be a coloured drug,
whose colour differs from the colour of excipients used for
granulation of a tablet.

62. CAUSES AND REMEDIES OF MOTTLING:
Sr.No. CAUSES REMEDIES
1. A coloured drug used along with Use appropriate colourants.
colourless or white-coloured
excipients.
2. A dye migrates to the surface of Change the solvent system,
granulation while drying. Change the binder,
Reduce drying temperature and
Use a smaller particle size.
3. Improperly mixed dye, Mix properly and reduce size
especially during if it is of a larger size to prevent
‘Direct Compression’. segregation.
4. Improper mixing of a Incorporate dry colour additive
coloured binder solution. during powder blending step,
then add fine powdered adhesives
such as acacia and tragacanth & mix
well and finally add granulating liquid.

63. Double impression
• Definition: ‘Double Impression’ involves only those punches,
which have a monogram or other engraving on them.
• Reason: At the moment of compression, the tablet receives
the imprint of the punch. Now, on some machines, the lower
punch freely drops and travels uncontrolled for a short distance
before riding up the ejection cam to push the tablet out of the
die, now during this free travel, the punch rotates and at this
point, the punch may make a new impression on the bottom of
the tablet, resulting in ‘Double Impression’.
• If the upper punch is uncontrolled, it can rotate during the
short travel to the final compression stage and create a double
impression.

64. CAUSES AND REMEDIES OF DOUBLE IMPRESSION:
Sr. No. CAUSE REMEDIES
1. Free rotation of either upper punch - Use keying in tooling, i.e. inset a key
or lower punch during ejection of a tablet. alongside of the punch, so that it fits
the punch and prevents punch rotation.
- Newer presses have anti-turning devices,
which prevent punch rotation.

65. THANK YOU