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TRIPHASE BROCHURE

"If an experiment does not hold out the possibility of causing one to revise one's views, it is hard to see why it should be done at all."

-Peter Medawar
1960 Nobel Laureate

"If you don't have time to do it right, when will you have time to do it over?"

-John Wooden
Basketball Coach

"It's the little details that are vital.  Little things make big things happen."

-John Wooden
Basketball Coach

"Intellectuals solve problems, geniuses prevent them."

-Albert Einstein

"Strive not to be a success, but rather to be of value."

-Albert Einstein

"The whole of science is nothing more than a refinement of everyday thinking."

-Albert Einstein

"Whoever is careless with the truth in small matters can not be trusted with important matters."

-Albert Einstein

"I start where the last man left off."

-Thomas A. Edison

"Hard work doesn't guarantee success, but improves its chances."

-Thomas A. Edison

"Success is dependent on effort"

-Sophocles (496-406)

"Show me a thoroughly satisfied man and I will show you a failure."

-Thomas A. Edison

"The three great essentials to achieve anything are hard work, stick-to-itiveness, and common sense."

-Thomas A. Edison

"What you are will show in what you do."

-Thomas A. Edison

"Opportunity is missed by most people because it is dressed in overalls and looks like work."

-Thomas A. Edison

"When one door closes, another opens; but we often look so long and so regretfully upon the closed door that we do not see the one that has opened for us."

-Alexander Graham Bell

"He who asks a question is a fool for five minutes; he who does not ask a question remains a fool forever."

-Chinese Proverb

"Let me tell you the secret that had led to my goals; my strength lies solely in my tenacity."

-Louis Pasteur

"Nobody is right all the time and even a broken clock is right two times a day."

-Bill Clinton on need to work together to solve problems DNC 2012

"Good science doesn't happen when people are keeping their heads down.  You need a raucous, rowdy discussion"

- Anonymous

"The great tragedy of Science is the slaying of a beautiful hypothesis by an ugly fact."

Thomas H. Huxley, "Biogenesis and Abiogenisis"

"Many consultants can 'turn the crank' but only few know 'when to crank, which crank to turn, which direction to crank, or how many turns."

- Anonymous

 

 

 

 


The following case studies exemplify how we have worked with clients on past projects and helped them solve problems and get their development back on track.


CASE #1:

Sterile Injectable Diagnostic Agent (Phase 1-3)


Background

This project spanned a 1 year period and we managed every aspect of the the CMC activities included preparing the final Module 3 for the IND filing.  The client came to us with an FDA clinical hold letter due to insufficient characterization data to progress to Phase 1b studies.  The goal was to get this compound back into the clinical and progress to Phase 2-3 for a partner buy-out.  Additionally, while the Technetium-complexed ligand (active drug ingredient) was stable in water, the active ingredient ligand had only a 30 minute half life in water. Additionally ligand (API) storage conditions must be at -78 oC to maintain stability of API.

Activities

  • Identified Synthesis CRO and developed a route to active ligand to make sufficient material and suitably characterized the ligand which was a complex mixture of 4 equilibrating isomers

  • Identified and liaisoned with an academic expert in technetium 99m development to obtain LC-MS on the putative active Tc99m complex claimed in the patent thus proving unambiguouslty structure of active ingredient for FDA.

  • Managed both API and Drug Product activities; initiated RFPs, managed CROs to ensure analytical and manufacturing controls were sufficient to support a Phase 3 clinical trial. 

  • Wrote entire drug substance and product Module 3 summarizing the activities of the last year and provided the CMC amendment along with the proposed clinical Phase 2-3 protocol

Result

A compound that had been on clinical hold for 3 years and through multiple CROs who were unsuccessful was finally brought under control and turned into a well-characterized, well-understood, commerciallizable drug substance and drug product (sterile vial kits) in the span of 1 year.  The CMC filig amendment was submitted along with the Phase 2-03 clinical protocol and the FDA removed the clinical hold and the compound has now completed a successful Phase 3 trial and no more CMC activities are currently required.  The company is currently negotiating large pharma deal.  

CASE #2:

Capsule Formulation Development (Phase 2)

Background

Client was developing 'powder in capsule" and capsules failed stability after 8 months.  Capsules were falling apart.

Activities

  • Identified source of capsule failure.  After developing an investigative strategy, and performing the suggested experiments, it was discovered that API lot associated with failed capsules was amorphous and hygroscopic.  Water was leached from gelatin capsules leading to cracking and failure.

  • API was re-crystallized to obtain crystalline material to match previous batches (less hygroscopic).  

  • Specifications were put in place to control physical form

  • New capsules were identified that are hydroxycellulose based and more resistant to dehydration

  • CMC amendment filed

Result

New capsules are successfully being used and new API specs and capsules ensure reproducible and stable capsule batches.

CASE #3:

Pre-Formulation Salt Selection (Pre-IND)

Background

A pre-IND lead compound was identified and was found to be superior in all respects to other leads yet remained undevelopable as it presented itself as an oil.  The client did not want to develop as an oral gelatin solution formulation and wanted to explore salt formation to generate a stable solid API that could be tabletted.  A Fortune 20 API CRO worked to obtain a solid salt form unsuccessfully and eventually gave up on this task stating it to be not possible.  The client came to us with the problem.  

Activities

  • Worked with CROs and suggested a list of solvents to try for crystallization they had not yet implemented.  The result was that one of the suggested solvents by TRIPHASE led to a crystalline compound.  The so called "magic solvent' is still being used to manufacture kilo quantities of this drug.  A patent was issued for protection of this process and TRIPHASE will share in the authorship.

Result

A lead compound that was previously abandoned due to physical property issues was brought back into life.  A patent is pending on this compound on the process developed by TRIPHASE principals and the result is now a druggable lead has been identified.  This success was 100% attributable to TRIPHASE identifying the appropriate solvents to achieve success where CROs had failed.

CASE #4:

Clinical Hold (Genotoxic Agent Issues)


Background

Client came to us on clinical hold.  The following reasons were cited in the letter from the FDA:

  • Synthesis reagent was alkylating agent and potential genotoxic agent.  Either this reagent must be removed or suitable analytical tecnigue must be developed and levels must be shown to below allowable limits.

  • Drug product showed stability issues and 2 impurities at 0.2% indicated potential "structure alert' as genotoxics.

Activities

  • Developed and validated a suitable compliant analytical method to test for levels of genotoxic agent reagent AND levels were shown to be within allowable limits for a 1 month clinical trial (120 ppm).

  • It was observed that the HCl portion of the molecule reacted with the molecule which led to the potential genotoxic agents which were also "uncontrolled".  A "free-base' form of drug was therefore developed to avoid stability issues associated with hydrochloride salt.  

  • The potential genotoxic degradants were Isolated and tested in AMES test and confirmed not mutagenic.

Result

An amended CMC was submitted for drug substance and drug product including new methods and data.  The compound removed from clinical hold and studies are progressing forward.

CLICK HERE TO READ OUR WHITE PAPER ON GENOTOXIC AGENTS...

CASE #5:

Sterile Injectable Drug (ANDA/DMF)

Background

Patent expiration was pending on a marketed diagnostic product.  Active ingredient supply chain was dominated by several large players.  The goal was to develop a process and manufacture the active ingredient and drug product vials and obtain an approvable ANDA.  

Activities

  • A new synthesis was developed in the lab and demonstrated on a multi gram scale.  RFPs were preapred and small-scale API manufacture was identified and registration stability batches were manufactured

  • Drug product kits were designed based on marketed cardiolite kits and 3 registration stability batches were produced.

  • Wrote DMF Type II and the ANDA was submitted 

Result:

The ANDA was approved for the product.

 
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