Pharmaceutical API and Dosage Form Development

Proprietary Cytostatic Dosage Form (Value Added Generic)

Being a billion turnover cytostatic drug with the API patent expiration in 2010, docetaxel was for years in the centre of interest of the generic community. Numerous patent hurdles in the complicated API synthesis were solved by only a few companies.

The same issue was to be solved regarding the formulation the ever-greening patents intended to prolong the originator market exclusivity effectively till 2014. Several solutions were devised by generic companies, all of these changing the composition in a way that clinical trials (bio-equivalence and beyond) were required to approve the formulation.

A proprietary, out-of-the-box solution was invented by us in I.Q.A., the formulation being "essentially similar" to the originator one. The product received Marketing Authorisation in the RMS in May 2010, with 25 EU countries as CMS. In addition, the formulation is significanly simpler to be manufactured than the originator product, has better stability and can be more easily handled during the application. The product was out-licensed to major pharmaceutical companies.

Xenia and Michal are co-authors of the key formulation patent. Michal was a project manager to the research and supervised the technology development and transfer as a CSO.

Dex-ibuprofen Proprietary Dosage Forms (Value Added Generics)

Dex-ibuprofen is the active enantiomer of the well established pain killer ibuprofen. The first drug based on dex-ibuprofen was launched in Austria in 1994 by Gebro. The product achieved between 5-10% market share in EU and up to 40% market share in Austria and ca 60% in Korea. Data exclusivity and patents already expired and it is a freedom to operate for the launch of the novel composition based drug.

Dex-ibuprofen is difficult to formulate in solid dosage forms (nicely crystalline compound with nelting point of 50deg C) and (as ibuprofen) possesses very unpleasant taste, making it difficult to formulate into palatable liquid dosage form (e.g. syrup). We have solved both obstacles and  we have developed two proprietary dosage forms based on dex-ibuprofen, i.e. easy to produce, rapid dissolution tablets, and a taste masked syrup. Due to the extremely difficult market, these projects are still waiting for a strategic investors to bring them to the market.

Xenia and Michal are authors of the patents, Michal was a project manager to the research and supervised the tablet technology development and transfer as a CSO.

Drug Development

Fast and Budget Track to Phase II Clinical Trials (NME, Anti-HIV and Cytostatics)

The customer, a computer aided drug desinn centre of undisclosed multinational company was developing new molecular entities with expected anti-HIV activity and a novel path mechanism of action. The internal development facilities were not able tp follow wth the fast pace of the drug design group.

To speed up the development, the customer hired small pharmaceutical development company to provide turn-key solution and bring the compounds as fast as possible to Phase I clinical trial. The chemical sythesis, toxicology, ADME/toxicokinetics and safety pharmacology studies were fully outsourced. In parallel, the Clinical Trial Application and Dossier were developed. This resulted in Phase I study being finished within 24 month after the NME were synthesized for the first time.

Xenia and Michal were important palyers in the team, Xenia's responsibility being the regulatory issues, Michal was a project manager and ADME and toxicokinetic studies GLP study manager.

Same approach was applied for the new cytostatic drug in the hand of the small US based biotech.

GXP management and implementation

GMP Implementation in China Based Follow-up Biologics Manufacturer

A biogeneric development project was run for a customer, a major multinational generics company. While the Chinese producer possessed good technical equipment and know how, their GMP was initially far inferior to the GMP standards acceptable for the EU and US market.

The site was developed during repeated visits connected with the specific know how transfer on the product manufacturing and standardization.

The site was successfully audited by the team of auditors of the customer in 2007.

Michal was a project manager, with the major impact on the producer improvement process in years 2004-2007.

GMP and DMF Support to Brazil Based API Manufacturer

The international generic company with headquarters in the Czech Republic run a generic development project with the high potent API producer in Brazil. Due to low GMP based experience the API manufacturer was not able to produce the Drug Master File.

Xenia mediated the close cooperation efforts and performed on site training of the manufacturer's staff. The cooperation lead to a the full success with the product on the market.

Xenia, as a QA specialist, was a key member of the problem solving team, working on both sites.

GMP Implementation and QP Activity for the Batch Release for EU from India

A CEE drug distributor, located in the Czech Republichad the duty to build up the batch release function after Czech republic entered the EU in 2004. The products were imported form India.

The project was prepared and run in the last quarter of 2003. In March 2004, the distributor was the first certified batch release organization in the Czech Republic. The project covered also numerous audits at the manufacturing places in India and interaction with the site quality management system.

Xenia participated in this project as the contracted Qualified Person and Project Leader. Xenia performed as QP for the distributor during 2004-2007 and she made about 1000 batches releases without any claims from the market or regulatory authorities.

Business Projects

Fully Functional Drug Development Company from 6-Staffed Spin-Off

I.Q.A., a.s. started in 2000 as a 6 people spin-off with the aim to grow from small size service laboratory to a company, developing its own portfolio of value added generic drugs.

The Company has grown to a middle size company with 50 employees, solid development portfolio and IP,  and 2 mil EUR turn-over coming mainly from the milestone payments on development projects. The Company was the first life science company in CEE to win venture financing. The Company achieved substantial success in added value generics development, resulting in licensing out patents and connected rights to the leading generic pharmaceutical companies in Europe and the USA. A control stake of shares was sold to Luxembourg based financial group in 2008 in an unsolicited bid.

Xenia and Michal were co-founders and principals of I.Q.A. Xenia served as a CEO and a GMP Qualified Person and Michal as a CSO and Project Manager from 2000 to 2008.

Re-building Analytical Laboratories of a Pharmaceutical Research unit after Major Spin-off.

In 1997, a pharmaceutical research institute suffered sudden lack of work force and management capacity in Analytical Chemistry laboratories after major spin off of the analytical department (21 persons from about 50 staff).

A fast recovery was needed within several month to keep the development projects running. The institute hired Michal to accomplish the task. Michal was appointed Head of the Analytical Department with the goal to recover all the activities. He successfully managed to recover the Department without any major setbacks tp the institute's projects.

Michal then continued in this position until 2000.

Agilent Instruments and Laboratory Materials Distributorship.

The business was build in Slovakia for several speciality chemicals vendors as Fluka, Aldrich and Labscan during 1991 -1997, and it grew up to become Hewlett-Packard Analytical Instruments (now Agilent Technologies) dealer in 1994.  During 1995 o 1997, the company increased the Hewlett Packard instruments from 7 to 25 % of market share. The company has been awarded as the most successful company in the Europe/Middle East Area ofr Hewlett Packard in 1996. The company was sold in 1997 to international dealership chain and is today operating as Hermes Lab Slovakia..

Xenia and Michal were owners and managers of the Company from 1991 to 1997.