REPRESENTATIVE CASE STUDIES
API
Crystallization
Situation : When I joined the company, they were ready to file a patent for salts of a drug developed at a well-known CRO. However, all the salts were amorphous.
Dr. Joshi's contribution : I requested an opportunity to crystallize the salts before filing the patent. I worked in the lab myself and was able to crystallize the salts.
Results : Filed the patent for the crystalline salts of the drug.
Polymorphism and salt selection
Situation : The final form of one of the two drugs was a free acid. The other drug was neutral, but no formal polymorph study was conducted.
Dr. Joshi's Contribution : For the free acid, I recommended to produce salts and patent them to prevent competitors making the same in the future. I received many quotes and the quote from an Indian company was nearly half compared to the quote from a reputed US company. I visited the company in India to ensure quality and timely delivery. For the other project, I worked with the CRO to come up with a suitable polymorphism study protocol and negotiated the price.
Results : We gave contract to both the projects.
PREFORMULATION
Situation : A medium sized company did not have a preformulation group
Dr. Joshi's Contribution : I started the preformulation group by hiring personnel and purchasing necessary instruments. I created a structure for the group and created awareness about the activities of the preformulation group. Also, I set up a Caco-2 cell culture lab. Worked on the preformulation activities of many projects and supported formulators. Showed one of the compounds to be BCS-I and wrote a section in the NDA for the same.
Results : The preformulation group became functional in a short time.
DRUG PRODUCT
Improvement of Bioavailability
Situation : A water-soluble compound had poor permeability. I was assigned to develop an oral dosage form.
Dr. Joshi' Contribution : It was a difficult task. I worked with a CRO and determined the effect of various excipients on the permeability of the drug in Caco-2 cell model. Based on the data, few excipients were selected and a softgel dosage form was developed.
Results : The bioavailability of the softgel capsules dosage form increased 25 times.
Process Improvement
Situation : Drug (25% drug loading) with poor flow and tendency to stick to SS walls resulting in high blend sample RSD. Formulation had Cabosil. Blend was roller compacted to form granules.
Dr. Joshi's Contribution : Separated Cabosil from the common blend and mixed with only drug. Recommended to change the process. During roller compaction, noticed heating up of the blend causing softening of PEG3350 resulted in clogging. Recommended to install a chiller.
Results : Improved flow of drug during blending and prevented sticking to the wall. Due to decreased temperature during roller compaction, clogging during roller compaction was eliminated.
Spray-dried Formulation
Situation : Drug (neutral) had no aqueous solubility and very poor permeability. Solid dispersion formulation showed better absorption, but limited dose (20 mg/capsule). Needed to increase the dose. The scientist had indicated an amorphous drug formation by complexing with a polymer.
Dr. Joshi's contribution : Worked with a CRO and supervised at micro-level to scale up the process to 2-kg keeping the complex amorphous. Complex had poor flow property and low bulk density. Decided to develop a roller compaction process. Developed the dissolution medium by studying the rate of precipitation of drug in media containing different surfactants.
Results : Produced 1 g tablets with 200 mg drug loading with satisfactory in vitro dissolution profile and good in vivo animal PK profile.
Oral Spray Formulation
Situation: A client wanted to develop an Oral Spray Formulation of a bitter compound. Because the oral spray solutions can have a limited spray volume, the drug solubility was a concern too.
Dr. Joshi's contribution: Attempted several methods for taste masking. Complexation with a compound decreased the bitterness significantly and an addition of sweetner made the formulation palatable. The solubility was improved by cosolvents.
Results: We could develop the formulation meeting client's requirements.
Oily suspension in hard gelatin capsule formulation
Situation : Assigned a task of developing a generic version of the dosage form.
Dr. Joshi's contribution : As a Team Leader of the project, worked with members from different departments. Worked with analytical chemist to determine the particle size of the brand product. Developed a process to produce matching particle size of the suspended API in the generic formulation. Scaled up the process with the help of manufacturing staff.
Results : Passed the bioequivalence study and obtained ANDA.
Cytotoxic drug product
Situation : Assigned a task of developing a generic version of a capsule formulation containing cytotoxic drug. The drug was known to cause severe birth defects. Very few people opted to work on the project. Drug was air-borne even within double gowning.
Dr. Joshi's Contribution : As a Team Leader of the project, created segregated areas for product development, analysis and quality control testing. Scaled up a semi-robotic process so that manufacturing staff was not exposed to dust in the key steps.
Results : Passed the bioequivalence study and obtained ANDA.
PROJECT MANAGEMENT
Situation : I was assigned the project manager role for the first NDA product of the company.
Dr. Joshi's Contribution : I acted as a project manager and also as a formulator. I was instrumental in initiating project team meetings and especially, initiate dialogue between the product development and clinical group. I was also responsible for supervising clinical batch manufacturing. Contributed to NDA writing.
Results : The CMC section was completed diligently and the NDA for the lyophilized product was filed. The NDA was approved and the product is currently in the market.
MARKETING
Market Analysis, Case 1
Situation : My employer purchased rights for a product, which is currently being marketed in Europe and Japan. The racemic form is marketed in the US, in which only the L form is active. The marketing VP left the company and there was no one in the marketing group (small companies often have 1-2 people departments).
Dr. Joshi's Contribution : Because I have completed my MBA and I have a passion for marketing, I took the responsibility upon myself and completed the market analysis of European and Japanese markets (I was the project leader). I also analyzed the market for the dl (racemic) form, which is being marketed in the US. We were developing lyophilized injectable, ready-to-use injectable and tablet products for the l-form. From my analysis, I observed that the tablet dosage form would be the most profitable.
Results : We accelerated the development of the tablet dosage form. We filed NDA's for the lyophilized and for the tablet dosage forms.
Market Analysis, Case 2
Situation: A company wants to enter Indian Pharmaceutical API market. It is a foreign company without much exposure to India.
Dr. Joshi's Contribution : Dr. Joshi acted as the Technical Expert in the team. He analyzed technical information on several API manufacturers and recommended potential target companies.
Results : A complete report was written recommending few possible target API manufacturers. The client was very satisfied with the outcome of Phase I analysis.
MANUFACTURING AND PACKAGING
Packaging supervisor
Situation : I was the first production employee in a major pharmaceutical company at their new location. I was in-charge of the packaging line to fill ointments in tubes. It was a brand new line.
Dr. Joshi's Contribution : I had about 15-20 people on the line. I had to train the technician on the IWKA filling machine and packagers to inspect and package tubes. I had to increase the output of the line.
Results : The line was up and running. In 6 months, the output increased to 60,000 tubes per day. It was a great achievement considering a lot of machine breakdowns in the early days.
Package development
Situation: I was developing a 360° liquid spray product. We were working on a bag-in-a-bottle packaging. The drug solution leaked in few bottles.
Dr. Joshi's contribution: I worked with the bottle manufacturing company and understood the package. I ran my own experiments including Instron, torque-tester etc.
Results: Based on the results, we decided to discontinue working on the bag-in-a-bottle approach. We evaluated two other packaging configurations and manufactured stability batches.
Airpockets in the cream
Situation: A cream product with a spray nozzle faced a problem of excessive air-pockets
Dr. Joshi's contribution: I understood the design of the packaging configuration and found the root cause of the air-pocket issue. I conducted several product evacuation studies. Based on the experience, proposed a solution.
Results: Manufactured new trial and validation batches and analyzed samples. The air-pockets reduced significantly and passed our specifications.
REGULATORY AFFAIRS
A. Report writing for IND, ANDA and NDA filings including – Formulation development, Preformulation, Product Stability, API process development, Analytical method transfer, Manufacturing development, Preregistration batches, and Validation of manufacturing process.
B. eCTD format of NDA filing – mainly CMC section
We can also provide support in – Develop well-structured and rational regulatory strategies, GRAS certification, preparation of Medical device filings, Activities needed for clinical trials including, contract and agreement preparation, clinical trial supplies, Laboratory testing during clinical trials, preparation of reports needed for modules 4 and 5.
QUALITY ASSURANCE
Develop SOP’s, Write change controls and Investigation reports
Completed Technical audits of companies involved in parenteral manufacturing and recommended as CMOs.
Tara Innovations LLC 
