Key Points of Transfer of Technology (TOT) in Pharmaceutical Industry

 

ABSTRACT

The objective of this article is to study how technology is transferred in pharmaceutical industry. The article attempts to discuss about the technology transfer process, importance of technology transfer, goals of technology transfer, robust technology transfer by QBD approach, steps involved in technology transfer in the pharmaceutical industry and understand the aspects related with technology transfer.

Keywords: technology transfer, pharmaceutical industry, goals, robust transfer by QBD, steps involved.

INTRODUCTION [1]

A proper technology transfer (TT) is both essential and important to drug discovery and development for new medicinal products. It is also required to upgrade drug quality planned during research development and to final product during manufacturing as well as to guarantee that stable quality is transferred.

Technology transfer (TT) is defined as “the transfer of the manufacturing process for a new pharmaceutical Drug Substance (DS) and Drug Product (DP), respectively, from the transferring site (in this case R&D) to the receiving site or designated commercial manufacturing site.” This includes all the associated knowledge, information, and skills to be able to manufacture the DS and DP at the receiving site.

This process is important for to elucidate necessary information for technology transfer from R & D (Research &Development) to PDL (product development laboratory). This article gives a brief description about the importance, objective, Factors, steps in technology transfer, various cases and barriers by which technology transfer takes place.

According to WHO, 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”.

IMPORTANCE OF TRANSFER OF TECHNOLOGY(TOT) [2]

• Demonstration of necessary information to technology transfer from R&D to actual manufacturing.
• Demonstration of necessary information to technology transfer of existing product between various manufacturing sites.
• For the smooth manufacturing of commercialized products.

GOALS OF TRANSFER OF TECHNOLOGY(TOT) [3]

• Is a valuable step in the developmental life cycle leading to successful commercial manufacturing.
• To take all the gathered knowledge and use it as the basis for the manufacturing control strategy, the approach to process qualification and on-going continuous improvement.
• The transition of the product/process/analytical method knowledge between development and manufacturing sites.
• To ensure variability of process and parameters are controlled and sufficient in the face of the rigors of a commercial production environment.
• To verify parameters established during development are still within the determined design space and/or adjusted at scale-up.

ROBUST TRANSFER OF TECHNOLOGY(TOT) BY QBD APPROACH [4]

• Form a diverse/skilled and collaborative development team.
• Review process flow diagram for key inputs/outputs that could impact quality (QRM)
• Uni/multi variant experiments should have been completed to study relationships and gain information on potential sources of variability. (Need to know where quality could be impacted)
• Make sure you understand your measurement capability (i.e., repeatability, precision)
• Critical Process Parameters (CPPs), Critical Quality Attributes (CQAs) and other important parameters are identified.
• Design space should be defined and understood consisting of a set of input ranges (CPPs) that provide high probability that CQAs will meet specification.
• A control strategy needs to be in place to assure focus on critical points.

STEPS IN TRANSFER OF TECHNOLOGY(TOT) PROCESS: [5,6]

Technology transfer is not a single way process. The development of new formulation goes through many stages. During development of a formulation, it is important to understand procedure of operations used, critical and noncritical parameters of each operation, production environment, equipment and excipient availability, which should be taken into account during the early phases of development of formulation, so that successful scale up can be carried out. Appropriate care during technology transfer is important to enhance drug quality as developed by research and development in final formulation as well as to assure quality for predetermined period of time.

1.Research phase

 Development of technology by research and development

2. Development phase

 Technology transfer from research and development to production

3. Production phase

Optimization and Production 

RESEARCH PHASE [7]

Quality Design:

For drug substance the quality design is to determine starting materials and their reaction paths and basic specification of the drug. 

DEVELOPMENT PHASE [8]

Research for factory production:

To establish appropriate quality control method and manufacturing method, after detecting variability factors to secure stable quality in the scale up (validation) that is performed to realize factory production of drug designed based on result from small scale experiments.

Consistency between Quality and Specification:

The consistency between quality and specification is to ensure in the products specification that the quality predetermined in the quality design is assured as the manufacture quality, and the product satisfies the quality of design.

 Assurance of consistency through development and manufacturing:

For stable production of consistent products, it is fundamental to fully refer to information of products of the past maintained by the manufacturer when research for factory production is implemented.

 Technology Transfer from R&D to Production:

 R&D provides technology transfer dossier (TTD) document to process development laboratory, which contains all information of formulation and drug product as given below:

• Master formula card (MFC)
• Master packaging card
• Master formula
• Specifications and standard test procedure (STPs)

PRODUCTION PHASE [9,10]

Validation and Production:

 Production is implemented after various validation studies verify that it is able to stable product based on transferred manufacturing formula. While the manufacturing facility accepting technology is responsible for validation, the research and development department transferring technology should take responsibility for validation such as performance qualification, cleaning validation, and process validation unique to subject drugs.

Scale up for production:

Scale up involves the transfer of technology during small scale development of the product and processes. Effective technology transfer helps to provide process efficiency and maintain product quality.

Considerations of different parameters for scale-up:

Before starting scale-up, we also considered different parameters that should be optimum for successful technology transfer. These were flexibility, cost, dependability, innovation, and product quality.

Selection of method:

The method for batch testing was selected based on data given from research and development.

CONCLUSION

Effective technology transfer is critical to success in pharmaceutical industry. In pharmaceutical industry technology transfer can be defined as the transfer of scientific information, a capability or a technological basis associated with a drug or a pharmaceutical procedure from a donor side (knowledge center) to a receptor side (drug manufacturing plant) implying a positive experience learned and realized by both sides and complying all the regulatory requirements in terms of Efficacy, Quality and Safety. The three primary considerations to be addressed during an effective technology transfer are the plan, the persons involved, and the process. Technology transfer is a complex issue and should be deal with using holistic approach.

ACKNOWLEDGEMENT

The authors are grateful to Mr. Gaurav Tripathi, Works Manager, Mr. Sanjay Chauhan, Sr. Manager, Supply Chain, and Ms. Monika Tomar, Manager-R&D, Sigachi Industries Private Limited, Telangana, India for support.

FUNDING

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CONFLICT OF INTEREST

The author declares that he does not have any financial and personal relationships with other people or any other organizations that could inappropriately influence this research work.

QUERY

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REFERENCES

1. Pharma Solutions by Dr. Ajay “Tablet processing: Formulation challenges and its solution”
2. Pharma Solutions by Dr. Ajay “Impurities in pharmaceutical products How, Why, Characterize and Acceptance criteria”.
3. Pharma Solutions by Dr. Ajay “Bilayer Tablets An Emerging Trend”
4. Pharma Solutions by Dr. Ajay “Building a Quality by Quality by Design (QbD) and Quality Culture”
5. Pharma Solutions by Dr. Ajay “Strategies and Key challenges for Safe Parenteral preparation”
6. Pharma Solutions by Dr. Ajay “Fundamental aspect of super disintegrants: A concise review”
7. Pharma Solutions by Dr. Ajay “Lyophilized injection A modern approach of injectable dosage form”
8. Pharma Solutions by Dr. Ajay “Magnesium stearate: Formulation challenges for oral solid dosage form”
9. Pharma Solutions by Dr. Ajay “Oral disintegrating tablets (ODTs) A new trend in drug delivery”.
10. Pharma Solutions by Dr. Ajay “Superdisintegrants : A Review”
11. Photo courtesy: Google

ABBREVIATIONS

TOT: Transfer of Technology, TT: Technology Transfer, DS: Drug Substance, DP: Drug Product, R&D: Research &Development, PDL: Product development laboratory. WHO: World Health Organization, TTD: Technology Transfer Dossier, CPPs: Critical Process Parameters, CQAs: Critical Quality Attributes, MFC: Master Formula Card, PE: Pre Exhibit, EB: Exhibit Batch, BPR: Batch Packaging Record, BMR: Batch Manufacturing Record, STP: Standard Test Procedure. 

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