Drug Product Services

Rochi Pharma has a professional preparation technology platform and a professional team with rich experience, and wholeheartedly provides customers with systematic drug research and development services to meet the needs of customers at different R&D stages. Bacterial preparations, etc. provide contract R&D CRDMO services, and have rich R&D experience in sustained and controlled release drugs, microparticle drugs, and protein and peptide pharmaceutical drugs, and have handed over a number of mature products to customers. In addition, we can also apply for FDA/PMDA/EMEA and DCGI registration at the same time.
Preformulation Study
Pre-Formulation Development:
For a very small amount of active pharmaceutical ingredients or candidate compounds with druggability, Runxi Medicine can provide professional pre-prescription services and mine valuable information to lead compounds into late-stage development. The pre-prescription research team of Runqi Medicine has rich experience in the research and development of various compounds, helping customers to successfully advance the early screening of compounds.
Preclinical evaluation of candidate compounds:
Solubility：
•    urveAcid-base sol
•    Solubility in organic solvents
•    Solubility in compound solutions of different salt forms
•    Solubility in simulated fasting intestinal juices, simulated feeding intestinal juices, and simulated artificial gastric juices
Formulation selection：
1. Carrier screening (compatibility of ingredients, dissolution rate, etc.) 
2. PH adjustment and co-solvent selection
3. Surfactants solubilization and permeation enhancement
4. Nanosuspensions (nanocrystals, nanoparticles and liposomes)
5. Particle size distribution
6. Wet or dry method
7. Residual solvents
8. Microemulsions, microspheres and solid dispersions
9. Drug formulation component-drug packaging materials compatibility analysis<2135
10. Gas phase detection methods
11. Microscopic observation, melting point, Pka, moisture, optical isomers, related substances, etc.
Crystal form research：
Crystal form determination by X- ray diffraction or DSC
1. Crystal form research
2. Crystal melting point, solubility, particle size, etc.
3. Stability of crystal form under influencing factors
4. Crystal transformation of the proposed crystal form
5. Proposed API crystal form for animal testing, clinical trials, or drugs to market
6. Process research of the proposed crystal form
7. Stirring method, standing and stirring
8. Crystallization mode (natural, cooling, and seeding crystallization)
9. Drying process (water content standards, crystal water judgment – TG, DSC, and single crystal culture, drying method, and drying temperature)
10. Preparation process simulation (grinding, wet granulation, tabletting, etc.)
11. Quality standards for the proposed crystal form
12. (melting point, solubility, particle size; IR, x-ray, DSC and TG）
Analytical Method Development：
Rochi Pharma offers comprehensive pharmaceutical analysis services, including methodology development and verification, analytical testing and release, stability study, scale separation, and CMC filing documents. Not only applicable to China CFDA declaration, but also FDA, EMEA and other global filings.
Method development and methodology verification:
1. Various chromatographic techniques (HPLC, UPLC, GC, and IC) and detection techniques (UV, MS, MS/MS, ELSD, FID, fluorescence, etc.) to satisfy different compound types
2. Analytical and detective methods of contents and/or related substances for stability study on API and pharmaceutical preparations (tablets, capsules/liquid capsules, liquid preparations/emulsions, powder preparations, pills/coated pills, injections, topical drugs, solid dispersants, etc.)
3. Other special detection methods, such as dissolution (IR, ER and MR), solvent residue, genotoxic impurities, enantiomeric separation, ion chromatography, microbiological test, etc.
4. Experimental design in method development, progress reports, method verification schemes and verification reports, and drug analysis methods
5. Corresponding solutions for each stage of IND/CTA or NDA/MAA filings
Analytical, testing and release
1. Analytical support for drug R&D and cleaning verification
2. CoA calibrated by reference materials or complete standard reports
3. Detections of compound structure and configuration confirmation
4. Structural identification of impurities or degradation products by LC/MS/MS and various nuclear magnetic resonance spectroscopy
5. Determination of degradation pathway and provision of filing materials
6. Leachable/extractable detections
Stability study:
1. Stability tests supporting global drug registrations; experimental/exploratory stability (pre-experiment); and stability tests of drugs after approval for market.
2. Integrated services includingscheme design, project management, stability sample storage and testing, data trend analysis, drug shelf life evaluation, and NDA/MAA filing document preparationI.
3. Storage conditions: 40°C/75%RH, 30°C/75%RH, 30°C/65%RH, 25°C/60%RH, with proper lighting, or customer-defined storage conditions, including 2-8°C, -20°C, -70°C, 25/40, 30/35, 40/20 and 50/40 (new).
4. Constant temperature and humidity boxes (IQ/OQ/PQ certified) for stability study; multi-channel power supply; real-time temperature and humidity monitoring (dual system); and an automatic alarm system.
CMC Filings
1. Our specialized application team, who possess a rich experience and a sound track record after many successful applications in China and other countries around the world.
2. The documents can be provided based on CTD templates or forms required by clients in order to meet local requirements.
3. Our CMC filing can be integrated with preclinical toxicology research, clinical research, and drug administration services to provide more comprehensive experiences
Preparation Development：
According to the form characteristics, physical and chemical properties and stability of drugs, we conduct process research to preliminarily determine the preparation process of laboratory samples, and set corresponding process control indicators. We have equipment and instruments commonly used in preparation process and quality research, for preparations including tablets, injections, capsules, granules, ointments, creams, sprays, gels, syrups, tinctures, oral liquid preparations, etc., as well as GMP-based pilot-scale test workshop for oral solid preparations. Besides, we are also capable of developing new technologies such as sustained-release preparations, nano preparations and fat emulsions.
Development of innovative drugs and corresponding strategies:
1. Suspensions (micro-suspensions and nano-suspensions)
2. Bottled active pharmaceutical ingredients
3. Micro-filling of active pharmaceutical ingredients
4. Dry mixing and potting
5. Liquid capsule filling
6. Spray drying
7. Dry/wet granulating and capsule filling/tableting
8. Direct tableting
9. Pouch filling
Development of generic drugs and corresponding strategies:
1. Election and analysisRLDs
2. Analytical method development
3. Key ingredient selection
4. Comparison with RLD quality index comparison to determine formulation
5. Optimization of production process parameters based on QbD
6. Packaging materials and container selection
7. Process scale-up and technology transfer
8. Analytical methods verification
9. Quality standards verification
10. Product stability investigation
Technical support for preparation
1. Micronization by airflow grinding
2. Granulating after nano suspension or micro suspension
3. Preparation of solid dispersion by spray drying
4. Hot melt extrusion
5. Liquid capsule filling
New technology for preparation
1. Development of single-layer or double-layer sustained-release tablets
2. Skeleton and coating technology
3. Filled capsules with sustained- or delayed-release pellets
4. Sustained-r or delayed-release pellets, granules, and tablets filled with hollow capsules to enable slow release in vivo.
5. Microsphere preparation
6. Dissolves or disperses the drug in a polymer material, and then employs the solvent evaporation method to obtain skeleton-type tiny spherical subjects with a diameter of 1-25 μm (which has a sustained-release effect).
7. Microcapsule preparation
8. Uses natural or synthetic polymer materials to wrap the drug into a warehouse-like structure, and then uses a carrier with slow-release properties to faciliate a sustained release from the capsule.
9. Liposome
10.Encapsulate the drug in vesicles composed of lipid bilayers by film dispersion and reversed-phase evaporation.
Product lifecycle management - preparation development support
Extend market lifecycle by giving late-stage new compounds or product attributes to  compounds available in market
Improve safety
•    Increase effectiveness or become available for new indications
•    Improve patient compliance and convenience of use
•    Feature rapid-acting effects, taste masking, new route of administration, etc.
•    Enable controlled or sustained release with reduced administration frequency
Extend market exclusivity
1. Preparation innovation to enable product differentiation and enhance product performance
2. Further development of new product
3. Potential market for new patent protection
Preparation Quality Research：
With 20 years of working experience, our CMC experts are familiar with various ICH and NMPA regulations and guidelines, and have helped clients complete their preformulation and pharmaceutical preparations studies to provide reliable data for the filing materials. We have successfully assisted our clients in completing the filing of Class 1.1, Class 3.1 and Class 6 new drugs at NMPA.
Method Development
1. Related substances are impurities in drugs except the main components. They may be raw materials, intermediates, reagents, decomposition products, by-products, polymers and isomers brought in during the synthesis of APIs, and degradation products produced during storage, transportation and use. As the content of related substances is generally small, it is very important to choose a detection method featuring good specificity, high sensitivity and great reproducibility.
2. For drugs beyond standards, the methods of related substances shall be developed according to drug properties, product characteristics, FDA, pharmacopoeias of various countries, relevant materials, and optimized to meet the requirements of ICH and pharmacopoeias of various countries for related substances.
3. For drugs within national standards, it is not acceptable to refer to existing national standards mechanically. The principle shall be “follow the category not the standard”, i.e., in the research of drugs within existing national standards, the safety and effectiveness of the developing products should be consistent with those of the products available on the market, and specific standards shall be set for specific categories.
Verification of analytical method:
Analytical methods shall be verified based on the characteristics of drugs and compounds.
1.Method verification for enantiomer
2.Method verification for related substances
3.Method verification for content uniformity
4.Method verification for content determination
5.Method verification for microorganism
6.Method verification for dissolution determination
7.Bacterial endotoxin test for drugs
8.Determination of impurity content
9.Verification contents include: specificity, linear range, accuracy, precision, detection limit, quantitative limit, durability, system adaptability, etc. The specific verification contents shall be subject to the requirements of pharmacopoeias.
Stability Study:
Verification of analytical methods provides scientific basis for the determination of production, packaging, storage, transportation conditions and validity period of pharmaceutical products by investigating the laws of the changes of the properties of APIs and preparations with time under the influence of temperature, humidity and light, so as to ensure the safety and effectiveness of clinical medication. Stability study is one of the main contents of drug quality control research. It is closely related to drug quality research and the establishment of quality standards. The research on preparation stability is featured by phases and links all steps in drug R&D.
1.Different placement conditions for stability study based on different forms
2.Different investigation items based on different forms
3.Different packaging materials based on different forms
4.Investigation of physicochemical properties and stability of drugs based on time change
5.Scheme design of stability study, project management, storage and detection of samples for stability study, data trend analysis, and evaluation of drug shelf life
Content of stability study:
1.Stability of global drug registration; experimental/exploratory stability (pre-experiment); and stability of drugs after approval for market
2.Comprehensive services such as scheme design, project management, stability sample storage and testing, data trend analysis, drug shelf life evaluation and NDA/MAA filing document preparation
3.Storage: 40°C/75%RH, 30°C/75%RH, 30°C/65%RH, 25°C/60%RH, with proper lighting, or the storage conditions specified by the customer, including 2-8°C, -20°C, -70°C, 25/40, 30/35, 40/20 and 50/40 (new)
4.Qualified constant temperature and humidity box (IQ/OQ/PQ certified) for stability study; multi-channel power supply; Real-time temperature and humidity monitoring (dual system); and automatic alarm system;
5.Three batches (filing batches) of pilot-scale stability test
Investigation of influence factors with packages of one batch of samples removed;
Investigation of influence factors during production with packages of one batch of samples remained;
Acceleration test of three batches of samples;
Intermediate condition test of three batches of samples;
Long-term test of three batches of samples
Detection of microorganism:
1. Antibacterial test of drugs
2.Sterility test of sterilized preparation
3.Microbial limit test of non-sterilized preparations
Laboratory-scale Preparation and Pilot-scale Preparation
Equipped with Tofflon's freeze dryers, Thermo Fisher Scientific's hot melt extruder and Yamato's spray dryers, Rochi Pharma is capable of laboratory-scale test for oral administration, injection, external use and various preparations.
Service:
Based on the concept of Quality by Design (QbD), the laboratory-scale test aims to conduct design of experiment (DOE) and research targeting at medium/high risks, after the early determination of quality target product profile (QTPP) and critical quality attributes (CQA) and preliminary risk assessment based on CQA. With understanding and control strategy based on the critical material attributes (CMA) and critical process parameters (CPP), the formulation process can be determined and the risks can be lowered.
If the samples for laboratory-scale tests are approved for batch tests, facilities for pilot-scale tests, such as rotary tablet presses and hopper mixers, are recommended to avoid scale-up failure caused by facilities featuring different principles (such as the difference of dwell time between the single punch tablet press and the rotary tablet press).
We verify our understanding of formulation process by preparing samples for laboratory-scale tests to determine whether the CQA of products of such formulation process can be guaranteed.
During laboratory-scale tests, we not only focus on the quality of finished products, but also establish draft quality standards for intermediates. We also pay attention to the mixing uniformity, particle fluidity, and the possibility of delamination during tableting or filling.
In the meantime, for 1~3 months, we will conduct influencing factor & acceleration tests based on samples for laboratory-scale tests to explore the stability of such samples, so as to provide reference for the improvement of formulation process, the development of quality standard draft and the stability of subsequent pilot-scale test samples.

Pilot-scale Preparation Testing：
For oral solid preparations, we can conduct laboratory-scale production and preliminary stability study. After the determination of the formulation process, the preliminary stability of samples and the proposed inner packaging materials, we will prepare relevant documents and materials for pilot-scale tests.
Preparation of documents for pilot-scale tests
1.Scheme of pilot-scale tests
2.Records for batch production & packaging
3.Draft quality standard for finished products
4.Draft quality standard for intermediates
Preparation-making for pilot-scale tests：
1.Collection of APIs
2.Procurement of ingredients and packaging materials
3.Determination or customization of tableting, capsule filling and aluminum-plastic molds
The preparation of documents and materials shall be made during the pre-stability period of laboratory-scale test to meet the requirements of the new drug project for the schedule and time limit.
The sample production for pilot-scale test includes：

1.Pretreatment of raw materials (mechanical crushing, airflow crushing, etc.)
2.Mixing - box-type mixing or high shear mixing
3.Granulating - wet granulating, dry granulating and fluidized bed granulating
4.Drying - fluidized bed drying and oven drying
5.Sieving -fast sieving equipment
6.Tableting - high-speed tablet press
7.Capsule filling - capsule filling machine, available for granules, powders or pellets at the same time
8.Coating - efficient coating machine with digital display of key parameters
9.Packaging - aluminum-plastic packaging and bottle packaging
The documents for pilot-scale test shall be released after being drafted and taken into effect, and implemented under a sound management system.
As a transition between laboratory-scale batches and clinical batches, pilot-scale batches shall be produced based on the risk control strategy in process research and the production experience of multiple drug varieties. As the equipment basically corresponds to GMP-based workshop, seamless connection with later GMP-based batches and the successful production of clinical samples can be both guaranteed.
Samples for pilot-scale tests are mainly used for the verification of analytical methods and the research on stability.
GMP-based Clinical Sample Production & Packaging：
In order to better meet the clients' demand for one-stop service in preparation R&D, we have established a GMP-compliant workshop for oral solid preparations capable of crushing, weighing, mixing, granulating, drying, sieving, tableting, capsule filling, coating and packaging of raw materials while improving the level of pharmaceutical production and quality management system. In that way, we cannot only carry out the R&D, inspection and stability study of generic drugs for clients, but also promise the R&D, production, packaging, inspection and stability study of innovative drugs in clinical phases I and II to enable our CDMO services.
Service：
Our services regarding GMP-based clinical sample production and packaging mainly include the following. These items can be provided in modules or as a whole.
1.Raw material crushing (micronizing)
2.Weighing - each precision balance under the weighing cover system
3.Mixing - box-type mixing or high shear mixing
4.Granulating - wet granulating, dry granulating and fluidized bed granulating
5.Drying - fluidized bed drying and oven drying
6.Sieving -fast sieving equipment
7.Tableting - high-speed tablet press with digital display of key parameters
8.Capsule filling - capsule filling machine with digital display of key parameters, available for granules, powders or pellets at the same time
9.Coating - efficient coating machine with digital display of key parameters.
10.Packaging - aluminum-plastic packaging and bottle packaging
The advantage of our production and packaging plant lies in its GMP-compliant management, stable and reliable product quality, traceable quality conditions, complete functions and flexible production, especially suitable for the preparation of samples for phase I clinical research.
Our clinical production packaging can provide product label selection for single-blind and double-blind clinical trials, and different types of clinical production packaging services that meet the current GMP standards according to clients’ requirements.
Consistency Evaluation:
In the quality consistency evaluation of generic drugs, Rochi Pharma has successfully completed a number of quality consistency evaluations. With rich experience in generic drug R&D, we can provide you with more professional consistency evaluation services.
The quality consistency evaluation of generic drugs focuses primarily on the re-evaluation of the quality of the oral solid preparations of generic drugs (including tablets, capsules, and granules) approved before the promulgation and implementation of the Drug Registration Administrative Measures in 2007. The evaluation mainly investigates the consistency of pharmaceutical quality and efficacy.
Our Generic Drug Quality Consistency Evaluation Service Platform is available for the
Comprehensive comparison of the quality of reference preparations and generic drugs
1.Discovery of determination conditions for the four dissolution curves, the dissolution curves of reference preparations and generic drugs, and the comparison of those dissolution curves;
2.Determination of methods for related substances and isomers, and as well as the determination of related substances, contents, and isomers in reference preparations and generic drugs;
3.Research on crystal forms of API used in reference preparations and generic drugs;
4.Stability study (including influencing factors, accelerating influences, and long-term influences).
Formulation process re-development
1.Further research on the quality of the original preparation;
2.Full research on  API properties;
3.Optimization of the formulation  process to ensure the durability of said process through step-by-step pilot-scale testing;
4.Pilot-scale testing /production technology transfer;
5.Quality research
BE tests with animals:
We have animal laboratories and testing centers in compliance with GLP certification. As such, we are able to conduct BE testing with animal subjects such as beagles  or crab-eating macaques, providing data support for preparation optimization and reducing clinical BE risks.

Report templates and SOPs
1.Completion of analysis based on clients requirements;
2.Accurate and compliant documents;
3.High-quality raw data that is traceable, of high integrity and NMPA compliant.
Regulatory and application:
1. Data processing of regulatory data
2. Arrangement and translation of regulatory materials
3. Regulatory application