SOP ON TECHNOLOGY TRANSFER

The objective of this procedure is to provide a guideline on the transfer of technology from R&D to the manufacturing site and from one manufacturing site to another manufacturing site.
Scope:
This procedure is applicable for the technology transfer of the process, method, knowledge from the development stage to the manufacturer site, or from one manufacturer site to another manufacturing site.

Responsibilities

  • It is the responsibility of sending site cross-functional departments (Quality, R&D, Regulatory, Production, and Engineering) to transfer the manufacturing, packaging, analytical technologies & associated training/knowledge to the receiving site through an approved technology transfer protocol.
  • All the cross-functional departments (Quality, R&D, Regulatory, Production, and Engineering) of the receiving site are responsible to receive the complete technologies and knowledge from sending site and approval on the final tech- transfer report.

Procedure

  1. Transfer of technology is defined as “a logical procedure which controls the transfer of any process together with its documentation and professional expertise between development and manufacturer or between manufacturer sites”. It is a systematic procedure that is followed in order to pass the documented knowledge and experience gained during the development and or commercialization to an appropriate, responsible, and authorized party of both sites.
  2. Transfer of technology shall be documented in a planned approach using trained and knowledgeable personnel working within the quality system, with documentation of data covering all aspects of development, production, and quality control.
  3. Any technology transfer will be managed by a team comprising members from the different departments; R&D, QC, Production, Warehouse, QA, Engineering, etc. who involved in the dispensing of material, manufacturing, packing, analysis. A clear responsibility shall be defined in the technology transfer protocol.
  4. A formal agreement between both parties will be made which specifies clear responsibilities before, during, and after technology transfer.
  5. Transparency between both parties shall be maintained during technology transfer because any lack of transparency may lead to an ineffective transfer of technology.
  6. For the successful technology transfer following general principle and requirement should be met;
  • The project plan shall encompass the quality aspects of the project and the plan should be based on the quality risk management principles to identify all the hazards and their mitigation plan.
  • Technology transfer shall be handled through a change control procedure.
  • A comprehensive technical & regulatory gap assessment between the sending site and receiving site shall be done before technology transfer.
  • During technical and regulatory gap assessment following points shall be considered but not limited to:
  • Equipment equivalence of sending site and receiving site w.r.t. capacity, working principle shall be considered during risk assessment, if both site equipment is different in terms of capacity and working principle then adequate risk mitigation plan shall be proposed like process optimization, critical control parameter identification & process validation with receiving site equipment, batch size determination based on the equipment capacity, etc.
  • Manufacturing formula, method of manufacture, bulk specification, and finished goods specification should be freeze and approved before the transfer of technology.
  • Area classification of both the sending site and receiving site shall be verified for its equivalence. Classification of both sites where a product manufactured should be the same and qualified against a predefined standard and raw material and product requirements like relative humidity, temperature, non-viable and viable counts, differential pressure, etc.
  • Water quality (raw water, purified water, water for injection, pure steam) of sending site and receiving site shall be assessed for its equivalence. Water is the main source of microbial proliferation so the microbial limit should not be more than finished goods specification of the product and the water system should be qualified against pre-defined specification before its use.
  • The availability of all other critical utilities shall be ensured before technology transfer. All the critical utilities and its capacities like pressure, purity, piping, and design should match with the sending site critical utilities used in the manufacturing/ packaging of the respective products.
  1. Apart from all technical details personnel knowledge transfer is also required to make technology transfer successful so all the SME (Subject Matter Expert) of sending site is responsible to provide the technical/operational/analytical training to the receiving site respective area personnel.
  2. In the case of new product development and transfer to the manufacturing site from the R&D analytical method to be developed by R&D and suitability of that method shall be verified at the manufacturing site quality control laboratory. In case of technology transfer from one manufacturing site to another manufacturing site responsible person of sending site quality control shall be transferred method at receiving site and trained to all the personnel. Analytical method transfer activity shall be done through approved technology transfer protocol and method transfer report shall be approved by both parties (sending site and receiving site) then only analytical method transfer will be treated as confirmed
  3. If the method is available in pharmacopeia then the pharmacopeia method shall be followed.
  4. Technology transfer shall be performed through an approved protocol which consists following but not limited to; Objective: A clear objective in the protocol is required which state that this technology transfer protocol is applicable for the technology transfer of “Product, Dose” from “sending site with complete address” to “receiving site with complete address- facility”
  • Scope
  • Key personnel and their responsibilities (Both sending site and receiving site)
  • A comparison of material, method, and equipment with details of the action plan if any difference observed
  • The transfer stages with documented evidence that each stage critical stage has been satisfactorily accomplished before the next commences.
  • Identification of critical control points
  • Experimental design and acceptance criteria for the analytical method
  • The project plan for trial batches (optimization batches), qualification batches, and process validation batches.
  • Training and skill development
  • Protocol approval
  1. Technology transfer protocol and associated other protocols like feasibility trial protocol, process optimization, process validation, packaging validation, analytical method transfer, or method validation protocol shall be executed jointly by sending site and receiving site respective personnel to understand the process and to gain process-based knowledge.
  2. A final technology transfer summary report with a conclusion shall be prepared and finally agreed and approved by sending the site and receiving site stakeholders.
  3. Any changes during technology transfer shall be handled through a change control procedure followed by risk assessment.

CRITICAL STAGES OF TECHNOLOGY TRANSFER AND THEIR ASSESSMENT:

  • Starting Material Specification and other relevant functional characteristics of the starting material (both API & raw excipients) to be used at the receiving unit that shall be the same. Any properties of the material which can influence the product quality that shall be identified…The following information shall be gathered about the material during any technology transfer but not limited to:
  • Manufacturer details; their approval status, material route of synthesis; flow chart of process control and intermediate which are used in the manufacturing of raw material
  • Any volatile impurities, use of any carcinogenic material during synthesis or any other impurities which can impact the product quality.
  • Solubility profile of a material
  • Particle size and distribution
  • Density, flowability
  • Microbiological susceptibility
  • The shelf life of raw material/stability data
  • Storage requirement, supply chain
  • Potency
  • Process and Product information
  • Sending site shall provide complete details on a product like a method of manufacture (MOM), all in-process control, critical control parameter (CCP), critical quality attribute (CQA), specification, test method, packaging configuration.
  • Sending site shall provide all the details on process development i.e. information on clinical development, information on scale-up, process optimization or stretch, critical process parameter determination, and similarly details on full-scale development also.
  • All the product-related deviations, change control, out of specification, market complaints, and annual product quality review should also be shared with the receiving site to get more details about the process, process changes history, analytical part and post-market surveillance.
  • Packaging material details to be shared with the receiving site with complete details on packaging material specification and their stability in that packaging material. If any development is done initially that also needs to be shared.
  • Stability studies details of the product shall also be shared with the receiving site.
  • Facility, Utilities & Equipment A quality risk assessment to be carried out at receiving site jointly by sending site and receiving site responsible person to assess the gaps between sending site and receiving site facility, utilities, and equipment gaps and to define the risk mitigation action. During risk assessment to consider following but not limited to:
  • Manufacturing flow, material/ man movement flow, related SOP’s, area classification and air filtration, contamination and cross-contamination control, temperature/ RH control. Differential pressure in each area.
  • Equipment drawing, manual, make / model, principle of working, capacity, review of receiving site equipment qualification, the material of construction, critical equipment component, calibration & preventive maintenance program of equipment
  • Utilities qualification and availability of required pressure, temperature, cooling, vacuum, electricity, etc. at point of use
  • Water quality and its qualification; sampling procedure, testing procedure.
  • Analytical 
  • Availability of written and approved analytical method transfer protocol
  • Availability of all chemical and reagent
  • Method specific training to receiving site analyst
  • experimental design, sampling method, and acceptance criteria
  • knowledge about equipment
  • review of method adequacy
  • Trained people
  • Cleaning validation includes the following which should be provided from sending site;
  • Solubility information, therapeutic dose, toxicological data
  • Existing cleaning procedure
  • Validation report which contains details of chemical and microbiological details along with details of cleaning agent used
  • Recovery study
  • At receiving site, site-specific cleaning procedure should be available
  • A cleaning validation protocol should be available.

References:

  1. Annex 7 WHO guideline on transfer of technology in pharmaceutical: WHO Technical Report Series, No. 961, 2011