WHO Guidelines for Transfer of

Technology

5

WHO Guidelines for Transfer of Technology 61

iii. It involves the transfer of documentation and the ability of demonstration of the

receiving unit (RU) to perform every elements of the transferred technology.

iv. It also demonstrates the ability of RU to perform each aspect of the transferred

technology to satisfy all the parties and related regulatory bodies.

v. Transfer of technology requires:

a. Documented and planned approach

b. Trained and knowledgeable staff

c. Proper operating quality system

d. Documentation of all phases (development, production, quality control)

Three units are involved in the transfer of technology (Fig. 5.1):

1. Sending unit (from where a designated product, process or method is expected to

be transferred)

2. Receiving unit (to where the designated products, process or method is expected to

be transferred)

3. Unit managing the process (mediated the process and it may or may not be a separate

entity).

Principles to be followed for successful technology transfer (as per WHO)

i. The project plan should have quality aspects of the project. The project plan should

be based on the quality risk management principles. Quality risk management is

a systematic process for assessment, control, communication and review of risks

to the quality of the product, process and method across its life cycle.

ii. The RU and SU should have similar capabilities. The facilities and equipment

provided by RU and SU should be operated according to similar operating

principles.

iii. The analysis of technical gaps between RU and SU which includes technical risk

assessment and regulatory gaps should be done as needed. It makes technology

transfer smoother and easier.

iv. There should be the availability of adequately trained staff at RU. Training can

also be given to the staff to make them familiar with upcoming changes.

v. Regulatory conditions of the countries of both RU and SU must be thoroughly

studied and taken into account while the transfer of technology. The regulatory

condition of the respective countries must be interpreted consistently throughout

the procedure.

 

PRACTICE QUESTIONS

Long Answer Type Questions

1. What is technology transfer? Explain the reasons and benefit of technology transfer

in pharmaceutical industry.

2. Explain the types and methods of technology transfer.

Short Answer Type Questions

1. What is technology and technology development?

2. What is technology transfer? Establish the statement that technology transfer is a

cyclic process.

3. Explain in detail the technology transfer in pharmaceutical industry.

4. Describe the steps in transfer of technology.

5. Explain the type of technology transfer.

Objective Type Questions

1. The systematic use of scientific, economical, technical and commercial knowledge

to meet specific set of goals and requirements is known as:

a. Processing b. Development

c. Technology and development d. None of the above

2. Technology transfer includes transfer of:

a. Documents b. Knowledge

c. Experience d. All of the above

58 Industrial Pharmacy II

3. Master formula card, master formula, specifications, development report parts

of:

a. CTD b. Technology transfer report

c. Technology transfer dossier d. DMF

4. Generally there are 4 steps involved in TOT, such as research phase, development

phase, documentation and

a. Production phase b. Non-clinical study

c. Clinical study d. None of the above

5. The involvement of contractor is in which of the following method for TT:

a. Buy-back contract b. Turnkey agreement

c. Licensing d. Support contract

6. In which type of method for TT owner/developer of technology grant permission

to another party with full rights and for even:

a. Licensing-in b. Joint venture

c. Licensing-out d. Support contract

7. In franchising:

a. Developer makes absorber its partner

b. Developer shares its trademark and business model with absorber

c. Developer shares its profit with absorber

d. All of the above

8. The alliance between two big companies that shares specific skills in order to

develop new technology is known as:

a. Franchising b. Strategic alliance

c. Turnkey agreement d. Licensing

9. In which of the following method of TT the dependency on contractor is very

high:

 

a. Buy-back contract

b. Original equipment manufacture

c. Turnkey agreement

d. Support contract

10. Which of the following is not a good reason for technology transfer?

a. Lack of financial resources

b. Lack of manufacturing resources

c. Inferior technology

d. Lack of marketing staff

11. Validation and production aim is to:

a. Verify if the process is able to consistently manufacture the product

b. Monitor scale-up

c. Select staff

d. All of the above

12 Arrange the following in accordance with their occurrence during technology

transfer process:

Technology assessment, economical negotiations, document verification, data

collection, MoU, signature of legal rights based on negotiations.

Technology Development and Transfer 59

13. Match the following:

Content Belongs to

a. Development of technology i. Development phase

by R&D department

b. Validation ii. Documentation

c. Technology transfer to production iii. Research phase

d. Preparation of technology transfer dossier iv. Production phase

ANSWERS

1. c 2. d 3. c 4. a 5. b 6. a 7. b 8. b

9. c 10. c 11. a

12. Data collection, technology assessment, documents verifications, economical

negotiations, transfer of all legal rights based on negotiations MoU signature.

13. a (iii), b (iv), c (i), d (ii).

60 Industrial Pharmacy II

WHO GUIDELINES FOR TECHNOLOGY TRANSFER

WHO guidelines for technology transfer are mentioned in Annexure 7 of WHO

technical report series No 961, 2011 as “WHO guidelines on transfer of technology in

pharmaceutical manufacturing”.

 

Technology Development and Transfer 57

6. Turnkey agreement: In this method, generally contractor is responsible for all the

procedure related to the transfer of technology like design, financing, equipment

supply, etc. The involvement of a single contractor is both harmful and useful. On

one hand, involvement of a single contractor ensures fixed price, efficient technology,

full responsibility while on the other hand any mistake or careless on contractor's

part may lead to project suspension.

7. Foreign company acquisition: This method is now in the trend where big companies

acquire start-ups by which all the technology-related to the start-ups automatically

transfers to the company. It makes the reach of the company to the mind of young

developers more convenient.

8. Buy-back contract: In this method, the foreign company (mainly of developed

countries) supplies industrial high tech equipment to the developing countries in

exchange for the profits gained from the sale of a product from those equipment. It

helps developing countries in establishing high-tech infrastructure and helps foreign

companies in reaching a new market.

9. Original equipment manufacturer: In this method local firms start producing as

per foreign company specifications. Foreign companies also transfer technology

and equipment to local companies. Even the training of staff of a local company is

also conducted by a foreign company. In return, a local company has to supply all

its goods to a foreign company at a fixed price. The foreign company sell these

goods in the market through its own channels and on its own price.

 

4.4.3 Methods of Technology Transfer

There are several methods of technology transfer. But certain things should be kept in

mind while choosing a technology transfer method like future strategy, type of

technology, resources availability, intellectual property rights, etc. The explanation of

various technology transfer methods is given below:

1. Licensing: In this type the owner/developer of the technology grants permission

to another company (receiver/absorber) in the form of license to use the technology

for certain purposes and for certain period of time.

Licensing is of two types:

a. Licensing in: Where the absorber has full rights for technology forever.

b. Licensing out: A developer may allocate rights to any other party other than

absorber at any point of time.

The main advantage of this method is low-cost involvement. However, the

purchase of license requires certain requirements to be fulfilled on the side of the

absorber of technology like sufficient knowledge, skill and expertise staff, and a

well maintained and suitable manufacturing base.

2. Support contract: In this type of technology transfer, the developer of technology is

involved in each and every phase of implementing technology which ensures closer

co-operation between both the parties and ensure transfer efficiency as well.

3. Joint venture: A particular business is executed by both the parties within an

agreement. The business may include mutual assets, management, loss bearing,

profit sharing, marketing, servicing, etc. This method ensures long-term co-operation

between both parties. Low cost and motivation of all participants in the successful

transfer of technology are also the main advantages of choosing this method.

However, the difference between the vision and objectives of both parties may create

hurdles in achieving the desired goal.

4. Franchising: In this method, the developer shares its trademark and business model

with the absorber. The absorber can use the technology as per the developer's

specifications. The developer can also share its expertise and knowledge in running

the business model. However, in this method, the absorber dependency on the

developer is more as compared to other methods.

5. Strategic alliance: This method generally occurs between two big companies that

share specific skills in order to develop new technology. For example, joint labs,

research programmes, production of new products, etc. However, complexities due

to different culture in the companies may create problems in execution.

 

ii. Lack of resources related to marketing and distribution capabilities: Developer of

technology may have all other capacity related to manufacturing, regulatory,

quality control but lack behind on the part of marketing and distribution. Then

developer may feel the need of associating with other organisation for using the

proper channel of marketing and distribution.

iii. Lack of resources for commercial launch of product: Developer of technology may

have capabilities for supporting the technology at early stages only but not for

later stages which involve huge capital investment.

iv. Lack of resources for conducting clinical trials: As clinical trials are the most important

and essential part of the drug approval process. It is very important to conduct a

clinical trial and get approval from the regulatory authority before launching a

new drug in the market. The developer may lack resources (related to finances,

facilities, premises, skilled staff, etc) to conduct clinical trials.

v. Lack of resources for the exploitation of technology: There may be cases like (a) each

partner among the developer and receiver have half of the technology and

association in between them can make them capable in reaching a fruitful result.

(b) Each partner has half of the solution, e.g. developer of technology only have

knowledge about diagnostics application of technology whereas other party has

knowledge about the technology’s therapeutic use.

Technology Development and Transfer 55

4.4.2 Types of Technology Transfer

There are three sectors involved in the development of technology in the pharmaceutical

field. These are:

i. Government labs (funded by the government)

ii. Private sector (manage their R&D sector on their own)

 

iii. Academics (universities, colleges)

1. Technology transfer from the government sector to the private sector: Generally

government sector gets good financial support from the government in the form of

grants. It becomes essential that this technology should reach the mass population.

Technology developed transferred to private sector also improves the government

and private sector associations. It has two advantages:

a. The government labs would get supplementary financial support and inflow of

funds to the institutions funded by the government. It would decrease the

economic burden on governments.

b. The private sector firm would gain the right to technology at a moderately lower

cost. It will make the private sector in a position to make the technology available

to masses.

2. Technology transfer between private sectors of the same country: This is an

important activity due to retention of intellectual capital. This type of technology

transfer may be due to several reasons like incapacity to commercialize the

technology, financial barriers, barriers in the distribution network, and human

resources scarcity, etc. In this case, the developer would get the price of technology

from the absorber that would, in the end, be used to build R&D capacity of the

developer. This tendency would be usually seen when a company is comparatively

small and is in its developmental stage.

3. Between private sector firms of different countries: In this, technology transfer is

from one country to another country. This trend of technology transfer is beneficial

to the developing countries. Before initialising this type of technology transfer, the

economic impact of the transfer of technology on developing countries should be

assessed. The developer would get the incentives, whereas the absorber would get

access to technology new to its country. The absorber can exploit the technology for

economic as well as social well being for people of its country. However, technology

seekers in developing countries face several barriers when tin commercial dealings

with technology holders in developed countries. For example, in the pharmaceutical

sector, the price that has to be given to acquire is huge and companies in developing

countries cannot pay this price to technology developer for acquiring technology.

 

d. Technology transfer from R&D to production: It involves the transfer of technology

from the R&D department to production. A technology transfer dossier

(containing all information about the product, process or method ) is provided

by the R&D department to product development lab (Fig. 4.3 and Table 4.1).

Fig. 4.2: Stages of technology transfer process

Technology Development and Transfer 53

Fig. 4.3: Contents of technology transfer dossier

Table 4.1: Documents to be prepared during the TT process while preparing technology transfer

dossier

Sr. No. Document Description

1. Master formula card It contains product name with strength, generic name,

manufacturing formula number, date, shelf life, packaging

and marketing details with artwork

Ingredient details: Brand name, specifications, vendor label

claim, manufacturing detail in brief

2. Master formula It contains manufacturing instructions and formulation

order

3. Standard test procedures It gives details about qualitative and quantitative parameters

and specifications of active ingredients, excipients and finished products.

Standard test procedure explains the method of conducting

quality tests and specifications specify the limits.

4. Master packaging card It involves the following details about packaging

components.

Packaging type, the material used for packaging, packaging

material stability testing report, the shelf life of packaging

material

5. Development report It is composed of all the documentation generated during

the formulation and process development phase of product

(drug/process/method). There are following six critical

sections in product development reports:

Component of product, manufacturing process

development, The rationale for choosing the container/

closure system, The rationale for selecting a preservative

system, microbial limits and antimicrobial effective tests,

Compatibility of the product with diluents or dilution prior

to administration for labelling information.

All information about product formulation development,

overages and biological as well as physicochemical

properties.

 

6. Packaging development It includes all the rationale for the choice of each packaging

report components

Packaging development procedures, testing limits for

packaging materials and all information about packaging

material formulation development, overages and biological

as well as physicochemical properties.

54 Industrial Pharmacy II

3. Production phase: It involves optimization and production by the following steps:

a. Validation and production: This is to verify if the production department is able to

consistently manufacture the product in accordance with the manufacturing

formula and with more degree of stability. Validation includes performance

qualification, process validation and cleaning validation.

b. Scale-up production: Scale-up is a step between lab-scale production and

commercial-scale production. It is done to target the problems which industry or

manufacturer can face while shifting the production from lab-scale to commercialscale. So, in scale-up production, a unit (which is larger than lab-scale but smaller

than commercial-scale) is set up. Each and every step related to the product is

performed at this stage. Before setting scale-up different parameters like flexibility,

cost, innovation, dependability, product quality are also considered which should

be optimum for successful technology transfer.

c. Selection of method: The best method for batch fabrication is selected on the basis

of data provided by R&D and feedback from scale-up production.

4. Documentation: Each and every step of the product cycle should be adequately

documented. Quality assurance department will check and approve the

documentation for each step.

4.4.1 Reasons for Technology Transfer

There are several reasons for technology transfer. Some reasons that facilitate developer

as well as receiver unit for technology transfer process are as follows:

i. Lack of resources for manufacturing capacity: The developer of technology may have

the capacity for small-scale production/operation or for laboratory-scale

production and want to associate with other organisation for large-scale

production.

 

4

Technology Development and Transfer 51

Fig. 4.1: Cyclic nature of technology transfer

is mainly between primary/source/developer unit to the secondary units for

commercial use of technology. It involves various negotiations related to finances

or rights of secondary and developer units. It is a cyclic process as shown in

Fig. 4.1.

4.4 TECHNOLOGY TRANSFER IN PHARMACEUTICAL SCIENCES

Technology transfer ensures the transfer of knowledge, techniques and experience

required for manufacturing of quality drug product. It is a carrier which carries quality

drug product from its laboratory-scale production to commercial-scale production.

For the economic growth, a product or service should be exposed to the market

place.

A single department is not involved in carrying out technology transfer. It is a

combined task which involves research and development (R&D), quality assurance

(QA) and quality control (QC), administrative staff, supporting staff, etc. of developer

as well as secondary unit. As we know that technology transfer is a systematic process

which involves various stages. These are shown in Fig. 4.2.

 

Technology transfer is a multidisciplinary approach which involves skilled staff

and individuals from different departments. A successful and productive technology

transfer requires the support and effort of different departments.

52 Industrial Pharmacy II

Basically there are four steps involved in transfer of technology:

1. Research phase 2. Development phase

3. Production phase 4. Documentation

1. Research phase: It involves the development of technology by the R&D department.

R&D department performs functions such as (a) procedure designing, (b) selection

of excipients.

R&D performs these functions by conducting different capability studies and

stability studies of the innovator product (the first approved product created

containing specific active ingredients for a particular use) and of the product which

is to be manufactured.

2. Development phase

a. Research for factory production: It is required to establish an appropriate quality

control method as well as a manufacturing method to manufacture the quality

product. It is done after detecting variability factors in the scale-up (which is set

up to establish factory design from results of small-scale production).

b. Consistency between quality and specification: After establishing an appropriate

quality control method and manufacturing method as mentioned above, it is

essential to confirm that the specification sufficiently specifies the product quality.

Associations between upper and lower limits of manufacturing as well as of upper

and lower of control limits of the product specification should be fully understood.

The consistency between the product quality and specifications should be

maintained to ensure in the product’s specification such that (a) the quality

predetermined in the quality design is assured as the manufacture quality,

(b) the product satisfies the quality of design.

c. Assurance of consistency through development and manufacturing: It is the

responsibility of “in charge” of the development of developers party to fully

understand the kind of technical information required by the receiver party in

charge of manufacturing and should establish a correct evaluation method to

establish the quality of design of drug to be manufactured.

 

4. Technology Development and Transfer

5. WHO Guidelines for Transfer of Technology

6. Regulation of Transfer of Technology

Summary

2

Technology Development and

Transfer

50 Industrial Pharmacy II

4.1 TECHNOLOGY

If we go with the dictionary meaning then technology can be defined as the application

of scientific knowledge for practical purposes, mainly in industry. Technology is

originated from the Greek words tekne and logia. Tekne means art and craft. Teknologia

together means systematic treatment. In the early 17th century, this word was

originated.

In pharmaceutical sciences generally, technology also refers as pharmaceutical

technology which involves scientific aspects that are important and critical in the

development as well as manufacturing of new drugs, dispensing methods,

manufacturing of medical devices, etc.

Types of Technology

i. Emerging technology: The technology which is currently undergoing bench-scale

testing, and a small version is tested in the lab.

ii. Innovative technology: The technology which is field-tested but lacks a long

history of full-scale use.

iii. Established technology: The technology which is under full-scale use and results

are fully documented.

4.2 TECHNOLOGY DEVELOPMENT

It is the systematic use of scientific, economic, technical and commercial knowledge to

meet a specific set of goals and requirement. Technology can be developed by using

several fields (such as science, commerce, social sciences, etc). It is a systematic process

which will progress step by step from the stage of procurement of technological skills

to utilisation of such skills for achieving a goal.

4.3 TECHNOLOGY TRANSFER

Technology transfer is a collaborative process which involves the transfer of all types

of documents, knowledge, experience related to all aspects of technology. It also

involves the transfer of legal rights (intellectual property rights). Technology transfer

50

Technology Development and

Transfer

 

Summary 47

Nowadays the pharmaceutical industry used these platforms to develop new

technology, new drug, new process, etc. Platform technologies are proving to be a

valuable tool in improving efficacy and quality in drug development. A platform is

considered as the most systematic method which helps in taking maximum advantage

from prior knowledge of the product to generate a new molecule. Such platforms

always have a scope of improvement. The data of new molecule which is developed

through the platform can be added to the platform and hence results in an increase in

the robustness of the platform.

Examples of Platform Technologies Used in the Pharmaceutical Industry

i. Immunotherapy platform for treating a range of cancers

ii. Platform technology for targeted drug delivery to the lower gastrointestinal tract

iii. Tumour-targeting technology

iv. Platform technology for speeding discovery and development of marine-inspired

therapeutics

v. Platform technology for developing DNA-based vaccines for infectious disease

vi. Platform technology for developing therapeutic antibodies

vii. Bio-molecular platform to design multiple DNA–RNA-based therapies for

diseases.

 

1. Material handling system

2. Blending

3. Granulation

4. Binders

5. Drying

6. Particle size reduction

7. Compression

8. Tablet coating

PILOT-PLANT SCALE-UP CONSIDERATIONS FOR ORAL LIQUIDS

Oral liquids can be defined as homogenous liquid preparations, mainly contains an

emulsion, a suspension or a solution having one or more active ingredients in an

appropriate base, i.e. liquid. They are for oral administration. These preparations are

used either as such or after dilution. The main substances added in these preparations

are: Emulsifying agents, suspending agents, sweetening agents, flavouring agents,

stabilizing agents, thickening agents, etc. during pilot-plant scale-up each and every

material and equipment is tested in the same amount and with same characteristics as

to be used at large-scale production. This is a pourable dosage form which displays

Newtonian or Pseudoplastic flow behaviour. This dosage form remains conforms to

its container.

Steps in Liquid Manufacturing Process

a. Planning of material requirements

b. Liquid preparation

c. Filling and packing

d. Quality assurance

Summary 45

PILOT-PLANT SCALE-UP CONSIDERATIONS FOR SEMISOLIDS

Semisolid dosage forms are composed of mainly two phases, i.e. oil and water. One of

the phases is the continuous or external phase and the other one is dispersed or internal

phase. The active pharmaceutical ingredient is mainly dissolved in one phase and if it

is insoluble in one or both phases then a third phase is introduced. This is known as a

three-phase system.

Various factors affect the physical property of the semisolid dosage form. Some of

them are as follows:

i. Size of dispersed particle

ii. The interfacial tension between the phases

iii. The partition coefficient of an active ingredient in between the phases

iv. Rheology of product

v. The viscosity of both phases

vi. Nature of the third phase (if introduced)

The all factors mentioned above determined the release as well as other characteristics

of drugs.

 

DOCUMENTATION

The documentation is the essential part of pilot-plant scale-up process because of the

following reasons:

i. Act as a source of data for large-scale production

ii. Helps in the transfer of technology at pilot-plant scale-up stage only

iii. Helps in analysing the problems that can be there at the commercial stage

iv. Provides an efficient way of sharing knowledge

v. Supports the maintenance and enhancement of the system

vi. Facilitates internal communication between departments

vii. Helps in review procedure at any time and at any scale of production of the

concerned product

viii. Good documentation helps personnel by giving them sorted documents. They

only have to deal with the content relevant to them which saves time and increase

the efficiency level

ix. Provides a clear description of the responsibilities of different departments/

personnel

x. Provides data related to other activities like any updates, amendments, circulars,

notices, etc during scale-up or pilot-plant study

xi. Helps in identification of changes and reason for those changes during the process

xii. Helps in consulting previous historic versions where relevant

SUPAC GUIDELINES

The batch size of the product under development process at laboratory-scale is very

small. It increases gradually as development process develops. This is known as scaleup. During the scale-up of the product, the product gets market approval from

regulatory authorities. But there may be some changes in the product after the approval.

These are known as SUPAC, i.e. Scale-up Post Approval Changes. These changes are

46 Industrial Pharmacy II

related to composition, manufacturing process, manufacturing equipment and

manufacturing sites. These changes have to be approved before implementation. So,

to guide the industries regarding SUPAC, USFDA issues various guidance documents

such as:

i. SUPAC-IR (immediate release solid oral dosage form)

ii. SUPAC-MR (for modifies release solid oral dosage form)

iii. SUPAC-SS (for non-sterile semisolid dosage forms)

3.1 PURPOSE OF GUIDANCE

1. The guidance provides recommendations to sponsors of:

i. New drug applications (NDAs)