CN110346269A - A kind of biological agent exploitation solution rapidly and efficiently - Google Patents
A kind of biological agent exploitation solution rapidly and efficiently Download PDFInfo
- Publication number
- CN110346269A CN110346269A CN201910409794.XA CN201910409794A CN110346269A CN 110346269 A CN110346269 A CN 110346269A CN 201910409794 A CN201910409794 A CN 201910409794A CN 110346269 A CN110346269 A CN 110346269A
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- China
- Prior art keywords
- biological agent
- preparation
- efficiently
- stability
- solution
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N17/00—Investigating resistance of materials to the weather, to corrosion, or to light
- G01N17/002—Test chambers
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N17/00—Investigating resistance of materials to the weather, to corrosion, or to light
- G01N17/004—Investigating resistance of materials to the weather, to corrosion, or to light to light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
Abstract
The invention discloses a kind of biological agents rapidly and efficiently to develop solution, its key points of the technical solution are that the steps include: that (1) earlier formulations are assessed；(2) the systemic preparation prescription with development technology cooperation screens；(3) targetedly preparation process developmental research system.The present invention intervenes ahead of time and the linking of systematic technique is exactly indirectly to improve development efficiency and success rate.
Description
Technical field
The present invention relates to a kind of exploitations of biological agent, open more specifically, it is related to the biological agent of one kind rapidly and efficiently
Send out solution.
Background technique
The either international or country all shows flourishing situation in recent years for the development of bio-pharmaceutical, 2 years especially nearly
The listing successively of domestic several biological new drugs and similar medicine, the exploitation of Chinese biological drug is it may be said that entered a harvest
Stage.But along with drug evaluation examination & approval and the reform of supervisory system in terms of supervision, Chinese drug initiative environment but occurs
Huge variation, development rate and quality to bio-pharmaceutical preparation are proposed new requirement.
Self-service R & D Enterprises or platform exploitation enterprise are generally inadequate to the attention degree of bio-pharmaceutical formulation development, most
It is just to start to carry out prescription screening after process upstream confirmation, the process of preparation process exploitation is generally also not system and imperfect
, and often have found that problem returns to carry out the exploitation of preparation in clinical stage or production process, finally will
The risk of product is brought into always into clinical or commercialized product.
Summary of the invention
In view of the deficiencies of the prior art, the present invention intends to provide one kind to improve development efficiency and success rate
Biological agent rapidly and efficiently develop solution.
To achieve the above object, the present invention provides the following technical scheme that a kind of biological agent rapidly and efficiently develops solution
Certainly method the steps include:
(1) earlier formulations are assessed；
(2) the systemic preparation prescription with development technology cooperation screens；
(3) targetedly preparation process developmental research system.
The present invention is further arranged to: according to step (1), building up early stage stability and preparation around thermostabilization analysis system
Prescription primary dcreening operation platform.
The present invention is further arranged to: the preparation prescription primary dcreening operation platform includes integrated biological agent thermal stability
The corollary equipment of research equipment and comprehensive stability chamber.
The present invention is further arranged to: biological agent stability study platform includes full fluorescence Spectra, dynamic optical and static light.
The present invention is further arranged to: step (1) further includes the screening of pH range and high-temperature stability, predicts product prescription
And the difficulty of process exploitation, consider whether selection lyophilized technique.
The present invention is further arranged to: according to step (2), carry out more round preparation prescriptions screening based on DOE,.
The present invention is further arranged to: screening conditions include buffer, pH, protective agent and surfactant.
The present invention is further arranged to: being tested by influence factor and is investigated product under the conditions of different prescription buffers and pH
Stability, structural defence agent, and root are screened by degradation pathway of sample under the conditions ofs illumination, oxidation, high temperature, difference pH etc.
According to the type and concentration of the suitable osmotic pressure regulator of the different selections of administration route, while during recipe development gradually
Suitable pharmaceutic adjuvant is introduced and selected, provides selection gist for the preparation process amplification in later period.
The present invention is further arranged to: according to step (3), being selected suitable technological parameter, is being guaranteed stable product quality
In the case where complete each technique unit.
The present invention is further arranged to: each technique unit includes preparation method, feeding sequence, content control, filtering side
Method mixes parameter, density, loading amount, freeze-drying curve, technique duration.
The present invention has an advantage that the intervention of the preparation assessment of (1) early stage, active material can be found ahead of time in patent medicine mistake
Problem in science in journey, targetedly proposes solution.Albumen is done at the initial stage (such as colony screening stage) of project development
To dosage form, start the earlier evaluations of preparation life cycle, the thermal stability of albumen, dissolubility, aggregation properties, dosage form are selected
Select, process exploitation difficulty etc. is evaluated, provide reference and direction to subsequent formulation development；
(2) the systematic preparation prescription of upstream and downstream technique cooperation and process exploitation scheme, combined process Development characteristics have
Effect promotes the exploitation of preparation process.Bio-pharmaceutical exploitation early stage, the preparation process and qualitative attribute of albumen also optimization and
It, may be also poor from final technique and qualitative attribute for the bulk samples of formulation development and its corresponding technique during change
It is systematic that different preparation researches is carried out in the different development phases away from far, the actual features of our combined process exploitations
Content；
The stability of bio-pharmaceutical preparation is each by albumen qualitative attribute itself, condition of storage, chemistry, physics and microorganism etc.
The influence of kind factor, rapidly and efficiently biological agent exploitation solution is made by active material to biology first is that solving biological agent for this
Stability problem in agent conversion process supports drug in the correlative study of clinical development；Second is that smoothly by early stage
Preparation blank is converted to biological agent batch production, solves amplification, transfer, verifying and stabilization in preparation process development process
Property problem, it is final to realize efficiently high-quality drug development process, the drug of high quality is delivered into sufferer early and is used.
Detailed description of the invention
Fig. 1 is that pharmaceutical grade protein is resistant to factor flow chart in preparation technical process of the invention.
Specific embodiment
A kind of biological agent rapidly and efficiently of the present embodiment develops solution, the steps include:
(1) earlier formulations are assessed
It is stable that biological agent exploitation solution rapidly and efficiently will build up early stage around thermostabilization analysis system (Uncle)
Property and preparation prescription primary dcreening operation platform, our preparation prescription Screening Platform has been provided with integrated biological agent thermostabilization at present
The corollary equipments such as Journal of Sex Research equipment (UNcle) and comprehensive stability chamber, as integrated biological agent stability study
Platform incorporates full fluorescence Spectra, dynamic optical and static light, using minute quantity sample, can carry out up to 12 kinds of application studies,
The flux screening of primary achievable 48 samples, provides high throughput protein stability anticipation (Tm, Tagg etc.) and early stage high pass
The possibility of volume preparation prescription primary dcreening operation.We can also carry out the screening of pH range and high-temperature stability, predict product prescription and technique
The difficulty of exploitation considers whether selection lyophilized technique.
The assessment of table 1.UNcle thermal stability system earlier formulations
(2) the systemic preparation prescription with development technology cooperation screens
As the propulsion of process exploitation is carried out on the basis of earlier formulations are assessed and are understood product based on the more of DOE
Round preparation prescription screens (buffer, pH, protective agent and surfactant etc.), is tested by influence factor and investigates product not
With the stability under the conditions of prescription buffer and pH, pass through degradation of sample under the conditions ofs illumination, oxidation, high temperature, difference pH etc.
Approach screens structural defence agent (such as amino acids, carbohydrate, surfactant), and is suitable for according to the different selections of administration route
Osmotic pressure regulator type and concentration, while being gradually introducing and selecting suitable medicinal auxiliary during recipe development
Material provides selection gist for the preparation process amplification in later period.The research contents and technique in different prescription screening stages require such as table 2
It is shown.
2. prescription screening research contents of table and technique requirement
(3) targetedly preparation technical process is developed
Preparation process exploitation is to complete the technical process of preparation formulation and packaged form, is pharmaceutical grade protein by active material
Be developed into an indispensable ring for the product for clinical use, preparation process in addition to pharmaceutical grade protein dosage form to be assigned and
Also need to maintain the fixation character and germ-free condition of preparation outside packaged form, it is ensured that the safety and consistency of medication product, still
Some treatment processes of preparation technical process itself can also bring challenges to pharmaceutical grade protein, with the liquid of cillin bottle packaged form
For preparation, the influence factor and process that albumen needs to be resistant in technical process are as shown in Figure 1.
The exploitation of preparation technical process is exactly influenced for the possibility of technical process, is selected suitable technological parameter, is being protected
Card stable product quality in the case where complete each technique unit (including preparation method, feeding sequence, content control, filtering side
Method, mixing parameter, density, loading amount, freeze-drying curve, technique duration etc.).This set of preparation process Development System that we establish is contained
Bio-pharmaceutical preparation process early stage foundation is covered to enlarged experiment scale, preparation technical process research platform has been provided with can be accurate
Filling apparatus, process exploitation type freeze dryer of semi-automatic packing etc. tentatively build up the development platform of liquid preparation and lyophilized preparation,
Preparation pilot plant assemble two canning lines, one be the filling freezing-dry line of cillin bottle, one be preliminary filling needle/clamped bottle line；It can expire
The production of packaging material form and different size in the difference such as sufficient cillin bottle (water needle and freeze-dried powder), preliminary filling needle, clamped bottle.Same
The preparation process developed on platform can realize that process exploitation to the seamless branches and linking of scale up test scale preparation, greatly contracts
The development time of short project improves the efficiency and the quality of production of formulation development.
By using above-mentioned technical proposal, a set of formulation development system rapidly and efficiently is established, by rising for formulation development
Point mentions the initial stage (such as colony screening stage) of project development, and the protein sample of early stage is accomplished dosage form, based on to albumen
The understanding of drug usually " product know-how ", carries out the earlier evaluations of preparation life cycle using minimal amount of protein sample, after giving
Continuous process exploitation provides reference and direction.With the propulsion of drug development process, carry out the DOE formulation development process that is based on, it is overall
Upper shortening formulation development process, it is ensured that accumulate more stability datas before entering next stage development.Protein drug
Development time be it is very long and valuable, ahead of time intervention and systematic technique linking be exactly indirectly improve development efficiency and at
Power.
The above is only a preferred embodiment of the present invention, protection scope of the present invention is not limited merely to above-mentioned implementation
Example, all technical solutions belonged under thinking of the present invention all belong to the scope of protection of the present invention.It should be pointed out that for the art
Those of ordinary skill for, several improvements and modifications without departing from the principles of the present invention, these improvements and modifications
It should be regarded as protection scope of the present invention.
Claims (10)
1. a kind of biological agent rapidly and efficiently develops solution, it is characterised in that: the steps include:
(1) earlier formulations are assessed；
(2) the systemic preparation prescription with development technology cooperation screens；
(3) targetedly preparation process developmental research system.
2. a kind of biological agent rapidly and efficiently according to claim 1 develops solution, it is characterised in that: according to step
Suddenly (1) builds up early stage stability and preparation prescription primary dcreening operation platform around thermostabilization analysis system.
3. a kind of biological agent rapidly and efficiently according to claim 2 develops solution, it is characterised in that: described
Preparation prescription primary dcreening operation platform includes the mating of integrated biological agent THERMAL STABILITY equipment and comprehensive stability chamber
Equipment.
4. a kind of biological agent rapidly and efficiently according to claim 2 develops solution, it is characterised in that: biology system
Agent stability study platform includes full fluorescence Spectra, dynamic optical and static light.
5. a kind of biological agent rapidly and efficiently according to claim 2 develops solution, it is characterised in that: step
(1) further include pH range and high-temperature stability screening, predict the difficulty of product prescription and process exploitation, consider whether that selection is frozen
Dry technique.
6. a kind of biological agent rapidly and efficiently according to claim 2 develops solution, it is characterised in that: according to step
Suddenly (2) carry out more round preparation prescriptions screening based on DOE,.
7. a kind of biological agent rapidly and efficiently according to claim 6 develops solution, it is characterised in that: screening item
Part includes buffer, pH, protective agent and surfactant.
8. a kind of biological agent rapidly and efficiently according to claim 7 develops solution, it is characterised in that: pass through shadow
It rings Factor Experiment and investigates stability of product under the conditions of different prescription buffers and pH, by sample in illumination, oxidation, height
Degradation pathway under the conditions of temperature, difference pH etc. screens structural defence agent, and the infiltration suitable according to the different selections of administration route
The type and concentration of regulator are pressed, while being gradually introducing during recipe development and selecting suitable pharmaceutic adjuvant, after being
The preparation process amplification of phase provides selection gist.
9. a kind of biological agent rapidly and efficiently according to claim 1 develops solution, it is characterised in that: according to step
Suddenly (3) select suitable technological parameter, complete each technique unit in the case where guaranteeing stable product quality.
10. a kind of biological agent rapidly and efficiently according to claim 9 develops solution, it is characterised in that: each
Technique unit include preparation method, feeding sequence, content control, filter method, mix parameter, density, loading amount, freeze-drying curve,
Technique duration.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910409794.XA CN110346269A (en) | 2019-05-16 | 2019-05-16 | A kind of biological agent exploitation solution rapidly and efficiently |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910409794.XA CN110346269A (en) | 2019-05-16 | 2019-05-16 | A kind of biological agent exploitation solution rapidly and efficiently |
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| Publication Number | Publication Date |
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| CN110346269A true CN110346269A (en) | 2019-10-18 |
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| CN201910409794.XA Pending CN110346269A (en) | 2019-05-16 | 2019-05-16 | A kind of biological agent exploitation solution rapidly and efficiently |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113963756A (en) * | 2021-05-18 | 2022-01-21 | 杭州剂泰医药科技有限责任公司 | Platform for developing prescription of pharmaceutical preparation and application |
-
2019
- 2019-05-16 CN CN201910409794.XA patent/CN110346269A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113963756A (en) * | 2021-05-18 | 2022-01-21 | 杭州剂泰医药科技有限责任公司 | Platform for developing prescription of pharmaceutical preparation and application |
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| PB01 | Publication | ||
| PB01 | Publication | ||
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Application publication date: 20191018 |