RAPTIM RESEARCH PVT. LTD.

RAPID - AS TIME MATTERS

https://www.raptimresearch.com/

https://www.linkedin.com/company/raptim-research-pvt.-ltd

VISION

“ To achieve the fastest path to regulatory, scientific

and clinical approvals of drugs, biologics and medical

devices while maintaining the highest ethical and

scientific standards”

OVERVIEW❖ Established in Year 2005.

❖ Headquartered in Mumbai, India.

❖ State of the art infrastructure: Clinical bed strength of ~300 (170 - Mumbai & 125-Ahmedabad) supported by 26 LCMS/MS, 3HPLC, 2 ICP

❖ In-house statistics team

❖ Expert in IVRT and IVPT studies for Topical products

❖ BCS biowaiver studies for Class I and III drugs

❖ Fully Compliant with ICH GCP, US FDA, WHO, UK MHRA, HPRA, BfArM, NPRA,TGA (Australia) and ISP Chile – GCP/ GLP Compliance.

❖ 1500 + BA/BE studies completed.

❖ 500+ studies submitted to FDA (US).

REGULATORY INSPECTION & APPROVALS

US FDA

NABL

Product Approvals

WHODCGI

CHILE

MHRA

Authority No. of Inspections Latest done on

USFDA 14 Sep, 9 – 19, 2019

UK MHRA 01 Sep, 2018

WHO 01 Oct, 2017

GERMANY 01 Mar, 2019

CHILE ISP 01 May, 2015

INDIAN Regulatory 08 Oct, 2019

NABL 03 Apr, 2017

NPRA 01 Oct,2019

CORE TEAM of EXPERTSDr. Rajen ShahDirector

Bachelor of Pharmacy and PhD from University of Maryland, US. More than 14 years of research experience with Novartis in US and Basel. 22 years of Regulatory and CRO experience in India.

Mr. Viraj ShahDirector

Masters in Business Administration from USA. 25+ years of experience in Global Finance and Management in USA & UK. 15+ years of experience in CRO industry.

Dr. Milind BagulHead - Bioanalytical

Masters in Pharmacy and PhD in Pharmaceutical Sciences, more than 15 years of experience with Biopharmaceutical Studies. Broad experience in developing methods and working in regulated environment.

Mrs. Usha RamakrishnanQuality Assurance

Bachelor of Pharmacy and Diploma in Industrial and Analytical Chemistry. 30 yrs of experience in Quality Assurance in Pharma and CRO industry. Strong experience of several regulatory inspections. including US and EU.

Dr. Hardik Dave Head - Clinic

Clinical Investigators with more than 20 years of experience in conducting Bioequivalence and Clinical Studies.

SERVICES PORTFOLIO

Patient PK & PD End Point Studies

Central Bioanalytical Services

BA/BE Studies

IVRT/IVPT Studies

Inhalation Studies

Clinical Trials

(Phase-II–IV)

Complex Bioanalysis (Vitamins , hormones

etc.)

Elemental Bioanalysis

CACO-2 Bio-waiver Studies

Dermatology Studies

Infrastructure-CLINIC

• 170 (Mumbai) + 125 (Ahmedabad) Bed Capacity with Dining and Recreation Facilities

• Separate Housing for Male and Female Subjects

• Well equipped Emergency care unit (ECU)

• Dedicated Sample Collection and Processing Area

• Staging Area for human subjects

• 250 + trained staff members with experiences in BA/BE studies for various regulatory submissions including but not limited to US-FDA, MHRA and EMA

Infrastructure-ANALYTICAL

HPLC Systems(3)

LC/M S/MS Systems(26)

Inductive Coupled Plasma (ICP)

Spectrometer (2)

pH Meter SPE Manifold Nitrogen Evaporator

Centrifuges Ultrasonicator Vortex Mixers

Diffusion Cell Apparatus

UPS and Generator Power Back up

Micro Balance

CAPABILITIES/EXPERTISESERVICE PORTFOLIO

Clinical Development Services

- eCRF’s for studies

- Phase II- IV trials

- PK / PD Studies in patients

- Project Planning and Setup

- Study Design and Protocol Writing

- Regulatory Approvals

- Design & Development of CRF / eCRF

- Project Management

- Site/Investigator Identification and Selection

- Site Monitoring

- Site Management

- Quality Assurance/Audit Services

PK / PD studies

- Bioequivalence / Bioavailability

- PK / PD studies in Healthy subjects

- Special / Patient Population studies.

- Food effect / Drug – Drug Interaction studies.

- Proof of Concept studies.

- End-to End Service: Protocol to Report

- Project Management

- Final submission Report (eCTDCDISC / ICH E3)

Clinical Data Management

- Data Management Plan (DMP)

- Database Design & Development

- Double-Data Entry

- Query Management

- Medical Coding, SAE Data Reconciliation

- Edit, Validation and Design check programming

- Data Validation & Cleaning

- Quality Control and Data Quality Audits

- Database Lock and Export to SAS

- Project Data Archival and Storage

Biostatistics & Medical Writing

- Sample Size and Power Calculation

- Medical writing and literature search

- Providing Statistical Inputs during Protocol Designing

- Randomization

- Statistical Analysis Plan (SAP)

- SAS Programming and Validation

- Statistical Report

FORMULATION/THERAPEUTIC AREAS

Therapeutic Areas

• Antibiotic/ Antimicrobial

• Antidepressant, Antiepileptic,

Antiretroviral

• Hormonal

• Hypoglycemic agents

• Lipid lowering agents

• Muscle relaxants, NSAIDs

• Controlled substances – Narcotics

• Oral contraceptive

• Psychotropic agents

Formulations

• Oral Solids –Capsules, Tablets, Soft gels,

Granules, ODT, ODP

• Modified Release

• Liquid Orals

• Parenterals

• Transdermal patches

• Topical Gel, Cream, Lotion

• Inhalers –MDI/MDI

• Nasal Sprays

• Suppository

KEY STUDIES/PRODUCTS

PARTIAL LIST of complex STUDIES conducted

• Thalidomide

• Mesalamine Suppository

• Nuvaring – female ring contraceptive

• Phytonadione

• Fulvestrant

• Octreotide acetate Inj. Suspension (depot)

• Ergocalciferol and Calcitriol

• Everolimus

• Salmeterol + fluticasone(LLOQ 1 pg/ml

• Metaxalone

• Selexipag

• Fluphenazine

PARTIAL LIST of CONTROLLED Products conducted

• Morphine

• Buprenorphine

• Buprenorphine + Naloxone

• Methylphenidate

• Dexmethylphenidate

• Oxycodone

• Guaifenesin + pseudoephedrine

• Cetirizine + pseudoephedrine and

other such combinations

OPTHAL STUDY Experience

• Ophthalmic PK studies with estimation

of drug in human aqueous humor-

- Method available for Dexamethasone in

human aqueous humor for Tobradex PK

end point study .

Feasibility done

- Prednisolone Suspension Drop in

aqueous humor.

- Loteprednol Suspension Drop in

aqueous humor

LIST OF ANTIRETROVIRAL DRUGS STUDIES

- Sofosbuvir 400mg Tablet

- Ledipasvir + Sofosbuvir Tablets 90mg/400mg

- Tenofovir Alafenamide Tablet 25 mg

- Tenofovir Alafenamide Fumarate 25mg + Lamivudine 300 mg + Dolutegravir 50mg Tablets

- Tenofovir Alafenamide Fumarate 25mg + Emtricitabine200 mg + Dolutegravir 50mg Tablets

- Tenofovir Disoproxil Fumarate 300mg + Lamivudine 300 mg + Dolutegravir 50mg Tablets

- Tenofovir Disoproxil Fumarate 300mg + Emtricitabine200 mg + Dolutegravir 50mg Tablets

- Sofosbuvir and Velpatasvir tablets 400mg/100mg

- Tenofovir disoproxil fumarate 300mg + Lamivudine 300mg + Efavirenz tablets 600mg

Emtricitabine And Tenofovir Alafenamide Tablets 200 mg/25 mg.

KEY STUDIES/PRODUCTS

BIOLOGICS EXPERIENCE• Bio-analytical Methods developed for quantification of

Teriparatide , Insulin glargine with metabolite M1 and

M2 from human plasma

• Working on other large molecules like Octreotide,

Adalimumab

Teriparatide Method details:

- Method developed on LC/MS/MS API 6500+

- LLOQ 2.5 pg/mL

- Chromatographically endogenous PTH is well separated

from synthetic PTH

- Signal to Noise at 2.5 pg/mL is 8.80 which is well above

the acceptance

- Reproducibility at 2.5 pg/mL is found within 15% (n=3)

• At Raptim, we have conducted study on 3 healthy subjects

using Forteo (Teriparatide) Injection

• PK parameters are

Chromatogram of Blank Sample

Chromatogram of LLOQ (2.5 pg/mL)

2.5pg/mL

Cmax(pg/mL)

AUC0-t AUC0-inf Tmax

Mean 136.49 101.194 110.336 0.25

% CV 41.2 39.7 37.5 57.7

Conclusion from Study:

-Dose of 40 mcg is safe for PK study.

-From the Cmax data LLOQ of 5.0pg/mL is sufficient but our method with LLOQ of 2.5pg/mL is found reproducible during the study.

-We can do studies on Large molecules and Biologics at Raptim

In-vitro BE Studies Experience

• Conducting In vitro equilibrium and kinetic binding studies

- Colesevelam Tablets and Colesevelam Suspension

- Sevelamer Tablet and Sevelamer Suspension

- Sucralfate suspension

• In-vitro solubility and permeability studies for biowaiver request based on BiopharmaceuticsClassification System (BCS).

- Established Caco-2 permeability method using 20 model drugs.

- Studies conducted for Buspirone, Capacitabine, Imatinib, Dexamphetamine and Ramelteon

- Feasibility done for Ramelteone, Levorphanol, Temozolomide, Pimavanserin Tartrate ,Cyclophosphamide, Varenicline and Ethinyl Estradiol, Tipiracil, Imatinib, Brivaracetam

In vitro Naso-Gastric tube studies• Conducted in vitro comparative recovery study using naso-gastric feeding tubes with Mycophenolate

mofetil oral suspension, 200 mg/mL

Material Size (French)Number of

tubes% Recovery

PVC 8 2 110.33

PVC 10 2 110.86

PVC 12 2 113.22

Method is optimized and soon be validated. Apart from Mycophenolate Mofetil, we are working on formulations like Lansoprazole, pantoprazole and Rivaroxaban for NG tube studies

Permetro technique-Tool to identify the prototype before proceeding for pilot and pivotal BE studies

- This In-vitro technique involves dissolution followed by permeation of drug through simulated GI

membrane.

- Similar in-vitro work is plan for Sublingual and other routes of administration

- Current work involves Dissolution study, Permetro study and PK studies with Test, reference and

altered formulation. Discrimination ability of in-vitro method will be established

- Data from three methods will be correlated

- Will have correlation data by Aug end.

DERMATOLOGY

• Tape Stripping

• Dermal Microdialysis

• Bioequivalence: Clinical End point / PK studies

• In vitro Skin Permeation and Mass Balance Studies

DERMATOLOGY - Experience

Tape Stripping Dermal Micro dialysisPharmacokinetic

Studies- Systemically Acting Formulations

In Vitro Release Testing (IVRT) Studies

In Vitro Permeation (IVPT) Studies

• Miconazole nitrate

gel, cream and

ointment

• Tacrolimus gel

• Betamethasone gel

• Adapalene gel

• Clindamycin gel

• Diclofenac gel

• Heparin Solution

• Tretinoin gel

• BuprenorphinePatches

• Nicotine Patches

• Rotigotine Patches

• Fentanyl TransdermalPatches

• OxybutyninTransdermal Patches / gel

• Acyclovir Ointment

• Lidocaine Ointment

• Diclofenac gel

• Nystatin Cream

• Triamecinolone Cream

• Nystatin + TriamecinoloneOintment and Cream

• Cyclosporine OpthalmicEmulsion

• Acyclovir Cream

• Doxepine Cream

• Dapsone gel

• Adapalene and

Clindamycin gel

• Tacrolimus gel

• Pencyclovir

INHALATION STUDIES• Negative pressure area is designed for dosing of inhalational products to ensure there is

no inter-subject unaccounted dosing via aerial contamination.

• For MDI and DPI study, subjects are trained with placebo using special training devicecalled Vitalograph prior to dosing (one day before dosing).

• Well experienced team for frequent blood sample collection for every 2 min, 5 minsamples after dosing

• Developed and validated highly sensitive single method for Salmeterol+ Fluticasonecombination with LLOQ of 1 pg/ml.

Studies conducted

• PK and PD – pilot/pivotal studies of Salmeterol+ Fluticasone Dry- powder Inhaler (DPI)and Metered-dose Inhaler (MDI)

• Pilot and pivotal studies for Budesonide Dry-powder Inhalation (DPI)

• Pilot and pivotal studies of Salbutamol Metered-dose Inhaler (MDI)

• Pilot study of Glycopyrrolate Dry-powder Inhalation (DPI)

• Upcoming projects - Beclomethasone MDI, Ipratropium Bromide MDI, LevalbuterolHFA Aerosol

PATIENT STUDIES

Clinical Operation

Site & Project Management

Medical Writing

Biostatistics

Safety reporting

PATIENT STUDY Experience – Completed Product Indication

Felbamate 600 mg Tablet Refractory Epilepsy Patients

Doxorubicin Hydrochloride Liposome Injection 2mg/mLMetastatic breast cancer/advanced ovarian carcinoma patients

Clozapine Tablets 100 mg Schizophrenic Patients

Diclofenac Gel 1 % Patients with Osteoarthritis of the Knee

Fixed dose combination Microsphere Adapelene 0.1% & Benzoyl Peroxide 2.5% gel

Patients with Acne Vulgaris

Imatinib Mesylate Tablets 400mg Chronic Myeloid Leukemia and Gastrointestinal Stromal Tumors

Budesonide Dry Powder Inhaler Patients with Mild to Moderate Asthma

PATIENT STUDY Experience – Ongoing

Product Indication

Clindamycin Phosphate Topical Gel Eq. 1% Acne vulgaris

Sunitinib Malate 50mg Capsule Oncology

Hydrocortisone Acetate Suppositories, 25 mgSafety and efficacy study

Gastroenterology

Diclofenac Gel 1 % Osteoarthritis of the Knee

Scientific writing for Publication Retrospective studyPaclitaxel protein-bound particles for Inj. suspension -100 mg/vial

Patients with breast metastatic cancer

India office

Dr. Rajen Shah

Director

rajen@raptimresearch.com

Tel.: +91-22-2778 1889 / 87 Ext. 133 / 118

e-mail: contact@raptimresearch.com

US Office

Mr. Viraj Shah

Director – Raptim Research Pvt. Ltd.

Tel.: +1 609-333-9660

(Mob.): +1 609-933-0003

E-mail : shahviraj@raptimreseach.com

Thank You

https://www.linkedin.com/company/raptim-research-pvt.-ltd

https://www.raptimresearch.com/