Post on 16-Nov-2020
Module 14 | Slide 1 of 31 2013
Basic Principles of GMPBasic Principles of GMP
Transfer
Of
Technology
Part 2
Annex 7. TRS 961, 2011
Module 14 | Slide 2 of 31 2013
Transfer of TechnologyTransfer of Technology
Production:
Processing, packaging and cleaning
Module 14 | Slide 3 of 31 2013
Transfer of TechnologyTransfer of Technology
Production - Processing, packaging and cleaning
Principles:
� RU able to accommodate the intended production
capacity
� Single-batch manufacture, continuous production or
campaigns.
� Identify technical expertise, site technology and site
capabilities of RU 5.1 – 5.3
Module 14 | Slide 4 of 31 2013
Transfer of TechnologyTransfer of Technology
Processing
Starting materials
� Same specifications / relevant functional characteristics – SU and
RU
� Ensure properties the same where these may influence the
process or product
5.5
Module 14 | Slide 5 of 31 2013
Transfer of TechnologyTransfer of Technology
Active pharmaceutical ingredients (API)
� open (applicant’s) part of APIMF/DMF or equivalent information
� manufacturer and associated supply chain
� step of the API to be transferred
� flow chart of synthesis pathway, outlining the process, including
entry points for raw materials, critical steps, process controls and
intermediates
� Information on physical form e.g. photomicrographs, polymorphic
and solvate forms
– solubility profile; pH in solution …/25.6
Module 14 | Slide 6 of 31 2013
Transfer of TechnologyTransfer of Technology
� intrinsic dissolution rate
� particle size and distribution
� bulk physical properties (e.g. bulk and tap density)
� water content
� microbiological considerations (including sterility, bacterial
endotoxins and bioburden)
� specifications and justification for release and end-of-life limits
� summary of stability studies and retest date …/3
5.6
Module 14 | Slide 7 of 31 2013
Transfer of TechnologyTransfer of Technology
� observed synthetic impurities
� information on degradants
� potency factor
� storage and or handling (e.g. sensitivity to heat, light or moisture)
5.6
Module 14 | Slide 8 of 31 2013
Transfer of TechnologyTransfer of Technology
Excipients
� manufacturer and associated supply chain
� description of functionality
� definitive form (particularly for solid and inhaled dosage forms)
� solubility profile (particularly for inhaled and transdermal dosage
forms)
� partition coefficient, including the method of determination (for
transdermal dosage forms)
� dissolution rate
5.7
Module 14 | Slide 9 of 31 2013
Transfer of TechnologyTransfer of Technology
� particle size and distribution
� bulk physical properties; compaction properties (for solid dosage
forms)
� melting point range (for semi-solid or topical dosage forms)
� pH range (for parenteral, semi-solid or topical, liquid and
transdermal dosage forms)
� microbiological considerations
� specifications and justification for release and end-of-life limits;
� storage and or handling5.7
Module 14 | Slide 10 of 31 2013
Transfer of TechnologyTransfer of Technology
� ionic strength (for parenteral dosage forms)
� specific density or gravity (for parenteral, semi-solid or topical,
liquid and transdermal dosage forms)
� viscosity and or viscoelasticity (for parenteral, semi-solid or
topical, liquid and transdermal dosage forms)
� osmolarity (for parenteral dosage forms)
� water content (for solid and inhaled dosage forms)
� moisture content range (for parenteral, semisolid or topical, liquid
and transdermal dosage forms) 5.7
Module 14 | Slide 11 of 31 2013
Transfer of TechnologyTransfer of Technology
Provide detailed characterization of the product
� Qualitative and quantitative composition
� Physical description
� Method of manufacture
� In-process controls
� Control method and specifications
5.8
Module 14 | Slide 12 of 31 2013
Transfer of TechnologyTransfer of Technology
Provide detailed characterization of the product
� Packaging components and configurations
� Safety and handling considerations
� History of process development – helps with further development
and or process optimization after successful transfer
5.8
Module 14 | Slide 13 of 31 2013
Transfer of TechnologyTransfer of Technology
Development information
� Clinical development
– route and form selection,
– technology selection, equipment, clinical tests, and product
composition;
– Scale-up activities
– process optimization,
– statistical optimization of critical process parameters,
– critical quality attributes
– Pilot report and pilot-scale development activities5.9
Module 14 | Slide 14 of 31 2013
Transfer of TechnologyTransfer of Technology
Development information (2)
� Full-scale development activities
– number and disposition of batches manufactured
– deviation and change control
� Change history and reasons
� Investigations of problems and the outcomes of the
investigations5.9
Module 14 | Slide 15 of 31 2013
Transfer of TechnologyTransfer of Technology
Current processing and testing information to be
provided by the SU
� Health, safety and environmental issues
� Detailed description of facility requirements and equipment
� Information on starting materials, applicable MSDS
� Storage requirements for raw materials and finished products
� Description of manufacturing steps and analytical methods
– narrative and process maps or flow charts, and or master batch
records, in-process hold times and conditions, order and method of
raw material addition and bulk transfers between processing steps
5.10 – 5.11
Module 14 | Slide 16 of 31 2013
Transfer of TechnologyTransfer of Technology
Current processing and testing information to be
provided by the SU
� Identification and justification of control strategy
– critical performance aspects
– process control points
– product quality attributes
– statistical process control (SPC) charts
� Validation plans and reports
� PQR; stability information; environmental conditions 5.11
Module 14 | Slide 17 of 31 2013
Transfer of TechnologyTransfer of Technology
� Location of all equipment considered
– process maps or flow charts
� Flows of personnel and material
� Impact of introducing a new product
� Modification of existing equipment documented in the transfer
project plan
� RU compare own with that of SU - including qualification
� Gap analysis
� Must be able to reproduce the process (volumes and batch sizes)
5.11
Module 14 | Slide 18 of 31 2013
Transfer of TechnologyTransfer of Technology
During transfer process
� Identify and understand any differences in facilities, systems and
capabilities
Actions may include:
� comparison and assessment of suitability and qualification of
facility and equipment;
� description of manufacturing process and flow of personnel and of
materials5.12
Module 14 | Slide 19 of 31 2013
Transfer of TechnologyTransfer of Technology
Actions may include (2):
� determination of critical steps in manufacture
– also hold times, endpoints, sampling points and sampling
techniques
� writing and approval of SOPs
� evaluation of stability information
– Generate site-specific stability data
� compliance with regulatory requirements for any changes made,
e.g. in terms of batch size 5.12
Module 14 | Slide 20 of 31 2013
Transfer of TechnologyTransfer of Technology
Packaging
Same procedure/principles as those of the production and include:
� specifications for a suitable container or closure system
� additional information on design, packing, processing or labelling
requirements
� tamper-evident and anti-counterfeiting measures
� specifications for QC testing – also drawings, artwork and material
(e.g. glass, card) 5.13 – 5.15
Module 14 | Slide 21 of 31 2013
Transfer of TechnologyTransfer of Technology
� Based on the information provided, the RU should perform a suitability study for initial qualification of the packaging components.
� Other considerations in packaging:
– to provide adequate protection (preventing degradation of the
medicine due to environmental influences)
– Should be safe (absence of undesirable substances released
into the product)
– Compatibility (absence of interaction possibly affecting
medicine quality)
– Performance (functionality in terms of drug delivery)5.16
Module 14 | Slide 22 of 31 2013
Transfer of TechnologyTransfer of Technology
Cleaning
Module 14 | Slide 23 of 31 2013
Transfer of TechnologyTransfer of Technology
Cleaning - Key messages
� Prevention of contamination and cross contamination essential
� Manufacturing process, operator exposure, environmental effects
� Limits for product residues
� Rationale for limit selection
� Site SOPs developed and validated based on e.g.:
– potency, toxicity, solubility, corrosiveness, temperature sensitivity,
manufacturing equipment design and configuration, cleaning agent
and product residue 5.17 – 5.18
Module 14 | Slide 24 of 31 2013
Transfer of TechnologyTransfer of Technology
Adequate cleaning procedures are essential
� Cleaning procedures and their validation are site-specific
� Know:
– information on solubility of active ingredients, excipients and
vehicles
– minimum therapeutic doses of active ingredients
– therapeutic category and toxicological assessment
– existing cleaning procedures
5.18
Module 14 | Slide 25 of 31 2013
Transfer of TechnologyTransfer of Technology
Adequate cleaning procedures
� SU to provide
– cleaning validation reports
– chemical and microbiological
– Information on cleaning agents used
– Efficacy
– Not interfere with analytical testing for residues of APIs
– Information on recovery studies to validate the sampling
methodology5.18
Module 14 | Slide 26 of 31 2013
Transfer of TechnologyTransfer of Technology
Documentation
� Wide range of documents needed to support transfer
� Documented evidence for successful transfer
� Technology transfer summary report:
– the scope of the transfer,
– the critical parameters as obtained in the SU and RU
(tabulated)
– final conclusions
� Discrepancies and actions taken listed8.1 – 8.2
Module 14 | Slide 27 of 31 2013
Transfer of TechnologyTransfer of Technology
Examples
Key Task Document from SU Transfer document
Equipment selection
and transfer
List of equipment,
systems, makes and
models, qualification
Drawings, manuals
Side by side
comparison
Gap analysis
Qualification
Module 14 | Slide 28 of 31 2013
Transfer of TechnologyTransfer of Technology
Examples
Key Task Document from SU Transfer document
Process transfer: Production
and packaging
Reference batches
Development reports
Specifications
Validation
DMF
BMRs
BPRs
Stability
Deviations
PQR
History of development
Experiences
Provisional BMD
Provisional BPD
Process validation
Module 14 | Slide 29 of 31 2013
Transfer of TechnologyTransfer of Technology
Examples
Key Task Document from SU Transfer document
Cleaning SOPs and Validation SOPs
Cleaning validation
protocol and report
Module 14 | Slide 30 of 31 2013
Transfer of TechnologyTransfer of Technology
Summary
� SU and RU - responsibilities
� Regulatory requirements
� Transfer: Organized and managed
� Premises, Equipment, Materials, Documentation, Personnel
� Data and information – protocols and reports
� Production and Quality control
� Include qualification and validation
Module 14 | Slide 31 of 31 2013
Transfer of TechnologyTransfer of Technology
� Case study and/or assessment