# Presentation: 241840

## MDCK as a substrate for influenza vaccine production

- Solvay Pharmaceuticals
- Presentation to VRBPAC
- November 16, 2005

**Notes:**
Good morning, ladies and gentlemen. My name is Jeroen Medema, Senior Scientist for Vaccines at Solvay Pharmaceuticals. I would like to thank the Center for Biologics Evaluation and Research for the invitation to present to this Advisory Committee our company’s MDCK-based influenza vaccine project, my life’s work for more than 10 years now. I am delighted to be here today to continue our company’s ongoing dialogue with the FDA on the use of MDCK as a substrate for influenza vaccine production. 

## Agenda

- Background Solvay and influenza
- Background Solvay’s MDCK project
- Safety analysis of MDCK-based vaccine
- Conclusions

**Notes:**
In the next half-hour I hope to do the following things: First, to provide the background of Solvay and its role in influenza vaccines. 
Second, I want to share with you the history of the MDCK cell line, and how Solvay came to choosing it as a basis for vaccine production. 
Finally, and most important to today’s meeting, I will provide a data-based safety analysis of various aspects of the MDCK cell line as well as Solvay’s production process employed to purify the vaccine. I will then use that analysis to provide a final risk assessment of the MDCK cell line as substrate for the production influenza vaccine. 
With that assessment, I would like to share with you why we believe  MDCK, in combination with Solvay’s state-of-the-art production process, is highly suitable and safe for the manufacture of purified, inactivated surface antigen influenza vaccine.
Before I begin with that safety analysis, please allow me a moment to introduce Solvay.

## Solvay Pharmaceuticals

- Division of Solvay Group
- Global – top 40 pharma
- 12,800 employees
- 2004 sales: $2.8 billion
- Major R&D sites
- Marietta, GA
- Dijon and Paris, France
- Hanover, Germany
- Weesp, The Netherlands

**Notes:**
Solvay Pharmaceuticals is the pharmaceutical division of the Solvay group and makes up around a quarter with over 7.5 thousand employees and 1.8 billion euro sales in 2003. It is an international research-based company ranking in the top 40 of pharmaceutical industry. There are three major R&D sites: Marietta Georgia, Weesp The Netherlands and Hanover Germany. 

## Solvay Pharmaceuticals & Influenza

- Egg-based vaccine
- First influenza vaccine in Europe (1950)
- Uninterrupted supply for 55 years
- Total > 250 million doses
- Fourth supplier worldwide; over 50 countries

**Notes:**
With respect to influenza we were the first to introduce an influenza vaccine in Europe over 50 years ago and have been producing egg-based influenza vaccines ever since with a track record of uninterrupted supply. In that period hundreds of millions of vaccines have been used. Currently we are the 4th supplier worldwide and distribute influenza vaccine to over 50 countries.

## Solvay Pharmaceuticals & Influenza

**Solvay Pharmaceuticals & Influenza**

**Countries supplied with Solvay’s egg-based influenza vaccine**

**Influenza vaccine production facilities –****Weesp, The Netherlands**

**US Headquarters****Marietta, GA**

**Notes:**
On this world map is depicted in which countries Solvay has a marketing authorization for its egg-based influenza vaccine. This is produced in facilities in The Netherlands; final bulk vaccine in Weesp and filling and packaging in Olst.

## Why a cell-based vaccine project?

- Eggs are open production system prone to contamination
- Availability of eggs is vulnerable to avian diseases
**	**

**Notes:**
These challenges with the use of eggs were the main reasons to initiate development programs for cell-based vaccine. Moreover, and this may turn out to be the major drawback of the use of eggs: the availability of eggs is not a given during outbreaks of avian disease in poultry when chicken are dying or culled on large scale to control the disease, just as seen know with the unprecedented avian flu outbreak in Asia. 

## Why MDCK?

- Broad susceptibility to influenza viruses
- Substantial experience in influenza research and surveillance
- High virus yields
- Economically feasible
- Favorable ratio of virus to impurities
**	**

**Notes:**
There are many different continuous cell lines that could be used for vaccine production. Solvay chose MDCK due to its broad susceptibility to and good growth characteristics for influenza viruses.  For the same reasons, MDCK has been extensively used for influenza virus research and surveillance is the most commonly used substrate in the worldwide influenza surveillance network. It was considered one of the best characterized epithelial cell lines as early as 1966. MDCK’s superior growth characteristics provide high virus yields, which makes it a feasible economical alternative to eggs when producing influenza vaccines. The high yields moreover allow for greater vaccine purity; it is easier to produce a pure vaccine if one starts with larger amounts of virus.

## Solvay Pharmaceuticals’ MDCK-based influenza vaccine project

- More than 10 years experience
- Microcarrier, serum-free
- Preclinical and clinical development program
- License granted in The Netherlands
- Commercial scale facility
- License to be updated to commercial scale product, followed by worldwide licensing, including US

**Notes:**
We initiated programs to develop cell-based influenza vaccine in 1990 and therefore have 15 years of experience with this technology. In the 1990s, we performed a preclinical and clinical development program for an inactivated, subunit vaccine based on MDCK produced on pilot scale and based on that program were granted a marketing authorization in 2001 in The Netherlands. This registration in one EU member state was the first step in a EU-wide mutual recognition procedure. We are now in the final stages of validation of a new commercial scale facility for production of the MDCK-based vaccine. With product coming from that facility we will update the current marketing authorization in The Netherlands and pursue licensing in the European Union via mutual recognition.

With this introduction on Solvay and its MDCK-based influenza vaccine project I now like to turn to to the most important part for today’s meeting, the assessment to confirm the safety of Solvay’s MDCK cell line as influenza vaccine substrate. [click]

## Solvay Pharmaceuticals’ MDCK-based vaccine facility

**Solvay Pharmaceuticals, Weesp, The Netherlands**

## Identify and quantify potential risks of cell line
Quantify elimination of these potential risks by downstream processing (DSP)
Quantify potential risks of cell substrate remaining for the vaccine recipient

CBER’s Defined-Risks Approach
Lewis AM Jr, Krause P, Peden K. Dev Biol. 2001, vol 106, pp 513-535

- Quantify elimination of these potential risks by downstream processing (DSP)
- Quantify potential risks of cell substrate remaining for the vaccine recipient
- CBER’s Defined-Risks Approach
- Lewis AM Jr, Krause P, Peden K. Dev Biol. 2001, vol 106, pp 513-535

**MDCK safety assessment**

**Notes:**
For this safety assessment, we followed CBER’s “Defined-Risks Approach to the Regulatory Assessment of the Use of Neoplastic Cells as Substrate for Viral Vaccine Manufacture” as published by Drs. Lewis, Krause and Peden. This framework of a "defined-risks" assessment is intended to examine, and wherever possible, to quantify the potential risk of "transmitting" potential concerns with a CCL to the vaccine recipient.  This safety assessment contains of four steps:
First, an identification of all potential risks associated with the use of MDCK as substrate for vaccine manufacture
Secondly, a quantification of these potential risks, in this case determination of the tumorigenic potential of MDCK cells and  cellular components.
Thirdly, the capacity of the vaccine purification process to eliminate cells and cellular components needs to be quantified as well.
Finally, by combining 2 and 3 we can calculate the likelihood of exposure of a vaccine recipient to any tumorigenic component of the cell substrate.

## Cell line characterization
Downstream processing
Final product safety

- Downstream processing
- Final product safety

**MDCK safety assessment**

**Notes:**
We performed this risk assessment for Solvay’s MDCK cell line and vaccine. When characterizing the cell line, we identified potential risks and concerns with MDCK. We assessed the capacity of the vaccine purification process – the downstream processing or DSP – to eliminate these risks and we examined the safety of the resulting product. I would like to go through this in detail to demonstrate that by following CBER’s defined-risks approach we believe MDCK is shown a safe substrate for influenza vaccine production. 

## MDCK safety assessment

- Cell line characterization
- Passage history
- Adventitious agents
- Tumorigenicity

**Notes:**
The cell line characterization consisted of tracking the passage history of the cell lineage we use, a genetic analysis to confirm the integrity and stability of the cell line, testing for presence of adventitious agents and examination of its tumorigenicity. 

## 1a. Cell characterization - History

**No introduction of **
**Bovine Spongiform Encephalopathy-like agents**

**1958: Isolation from dog kidney**

**1964: Deposition at American Type Culture Collection (ATCC)**

**1991: Preparation of ATCC working stock**

**1992: Preparation of Master Cell Bank and Working Cell Bank**

**Notes:**
The MDCK cell line was derived from the kidney of a female cocker spaniel by Drs. Madin and Darby of the University of California in 1958. They deposited it at the American Type Culture Collection – the ATCC - in 1964, which subsequently stored it frozen for almost 30 years prior to preparing a larger stock in 1991. 
It is important to note that this line of MDCK was not manipulated during these 30 years, which means that most manipulations date back to before the era of particularly bovine spongiform encephalopathy. This takes away concerns of contamination with such agents. 
Solvay acquired “MDCK CCL-34” at passage 52 from the ATCC deposit in 1992. These were further propagated under serum-free conditions to prepare a Master Cell Bank and Working Cell Bank.

## 1a. Cell characterization - Passage history

- passages used for vaccine manufacture

** ****0: Isolation from dog kidney**

**49: Deposition at American Type Culture Collection (ATCC)**

**52: Preparation of ATCC working stock**

**97: Preparation of Extended Cell Bank**

**56: Preparation of Master Cell Bank**

**57: Preparation of Working Cell Bank**

- passages used for safety assessment

**Notes:**
In terms of passage level, the history of MDCK looks like this: MDCK was deposited at ATCC at passage 49, ATCC conducted three passages to prepare a larger working stock, Solvay acquired this passage 52 and this was banked as a Master Cell Bank at passage 56 and as a Working Cell Bank at passage 57. Vials of this Working Cell Bank will be used for large scale vaccine production to a maximum of passage 80. Cells from the Working Cell Bank were propagated for another 40 passages to prepare an Extended Cell Bank at passage 97, significantly higher than will be used for vaccine production. The Extended Cell Bank was used to study the integrity and stability of MDCK throughout production. Once the different cell banks were prepared, the testing program to fully characterize them was conducted. 

## 1b. Cell characterization - Adventitious agents

- Mycoplasmas
- Bacterial and fungal sterility
*In vitro* co-cultivation in detector cell lines
*In vivo* testing in various species
- Electron microscopy
- Retrovirus testing

**No adventitious agents found**
**in Solvay’s MDCK**

**Notes:**
In the context of extraneous agents, I would like to emphasize that one of the advantages of MDCK over eggs is the possibility to comprehensively test for absence of adventitious agents. This is not possible for each individual egg. As you can see from this list, the testing program for Solvay’s MDCK indeed is comprehensive. It was done in accordance with regulatory guidance. All tests were negative, demonstrating no evidence for presence of any adventitious agent whatsoever. 

## Specific testing for naturally-occurringcanine viruses
Specific testing for viruses to which MDCKis susceptible

- Specific testing for viruses to which MDCKis susceptible

**1b. Cell characterization - Adventitious agents**

**No adventitious agents found**
**in Solvay’s MDCK**

**Notes:**
In the context of extraneous agents, I would like to emphasize that one of the advantages of MDCK over eggs is the possibility to comprehensively test for absence of adventitious agents. This is not possible for each individual egg. As you can see from this list, the testing program for Solvay’s MDCK indeed is comprehensive. It was done in accordance with regulatory guidance. All tests were negative, demonstrating no evidence for presence of any adventitious agent whatsoever. 

## 1c. Cell characterization – Tumorigenicity

- Phenotypic characteristic; tumor formation in animal models
- Concern of exposure of vaccine recipient to
- Intact cells
- Cellular components
- Residual cellular DNA
- Unlikely in vaccine recipient due toallograft rejection

**Notes:**
Then we turn to the final part of characterization of the MDCK cell line, its tumorigenicity. The term tumorigenicity sounds alarming, so let me explain what it actually is: it’s the capacity of a cell to grow in culture and to form tumors in animal test models, so under artificial conditions. It is thus important to note that tumorigenicity risks are associated with the growth characteristics of the cell, not of the vaccine. Therefore, the main concern when using a tumorigenic cell line for vaccine production is the exposure of the vaccine recipient to any potential tumorigenic component of the cell line that was not adequately removed during downstream processing.

## Tumorigenic potential of intact cells 
4 week and 6 month study in adult immune-deficient nude mice
Tumorigenic potential of cell lysates 
6 month study in adult and newborn nude mice, newborn rats and newborn hamsters 
Oncogenic potential of DNA 
6 month study in adult and newborn nude mice, newborn rats and newborn hamsters

- 4 week and 6 month study in adult immune-deficient nude mice
- Tumorigenic potential of cell lysates
- 6 month study in adult and newborn nude mice, newborn rats and newborn hamsters
- Oncogenic potential of DNA
- 6 month study in adult and newborn nude mice, newborn rats and newborn hamsters

**1c. Cell characterization***** *****– Tumorigenicity**

## Intact cells: 6 month study in 4 week nude mice 

**1c. Cell characterization***** *****– Tumorigenicity**

## Intact cells: 6 month study in 4 week nude mice 

|  | Nodule atinjection site | Tumor at injection site
(MDCK adeno-carcinoma) | Tumor in spleen
(hystiocytic tumor) | Tumor in lung
(adenoma) |
| --- | --- | --- | --- | --- |
| Negative control | 0/26 | - | - | - |
| 101 MDCK, p98 | 0/26 | - | 1* | - |
| 103 MDCK, p98  | 0/26 | - | - | - |
| 105 MDCK, p98 | 18/26 | 6 | - | - |
| 107 MDCK, p98 | 30/30 | 16 | - | 1 |
| 107 MDCK, p56 (ATCC) | 23/26 | - | - | 1 |

**1c. Cell characterization***** *****– Tumorigenicity**

- * Non-MDCK

## Lysate of 107 cells: 6 month oncogenicity study

|  | Test group | N | Nodules at injection site  | Tumors in other tissues |
| --- | --- | --- | --- | --- |
| 4w + 0-4d nude mice | cell lysate | 68 | 0 | 0 |
|  | neg. controls | 50 | 0 | 0 |
| 0-7d hamsters | cell lysate | 98 | 0 | 0 |
|  | neg. controls | 54 | 0 | 0 |
| 0-7d rats | cell lysate | 91 | 0 | 0 |
|  | neg. controls | 58 | 0 | 0 |

**1c. Cell characterization***** *****– Tumorigenicity**

## 0.1mg MDCK-DNA: 6 month oncogenicity study

|  | Test group | N | Nodules at injection site  | Tumors in other tissues |
| --- | --- | --- | --- | --- |
| 4w + 0-4d nude mice | 0.1mg DNA | 48 | 0 | 2 |
|  | neg. controls | 48 | 0 | 0 |
| 0-7d hamsters | 0.1mg DNA | 64 | 0 | 0 |
|  | neg. controls | 48 | 0 | 0 |
| 0-7d rats | 0.1mg DNA | 69 | 0 | 0 |
|  | neg. controls | 39 | 0 | 0 |

**1c. Cell characterization***** *****– Tumorigenicity**

## Characterization of tumors in DNA study
Histopathology
One mouse: histiocytic tumor in liver
One mouse: lymphoma in thoracic cavity
Spontaneous tumors not unexpected in immune-deficient nude mice

- Histopathology
- One mouse: histiocytic tumor in liver
- One mouse: lymphoma in thoracic cavity
- Spontaneous tumors not unexpected in immune-deficient nude mice

**1c. Cell characterization***** *****– Tumorigenicity**

## Follow-up studies with MDCK cell DNA
Larger study in nude mice
Fetal and neonatal safety study in rats

- Larger study in nude mice
- Fetal and neonatal safety study in rats

**1c. Cell characterization***** *****– Tumorigenicity**

## Moderate tumorigenic potential in immune-deficient animals shown at dose levels ≥105 
Majority of nodules partially regress; complete regression in 5/25 at 105 and in 4/28 at 107 
Increases with passage level and/or adaptation to serum-free growth
Histopathology at passage 98 is in agreement with the literature for MDCK cells

- Majority of nodules partially regress; complete regression in 5/25 at 10**5** and in 4/28 at 10**7**
- Increases with passage level and/or adaptation to serum-free growth
- Histopathology at passage 98 is in agreement with the literature for MDCK cells

**1c. Cell characterization***** *****–****Tumorigenicity summary**

**Notes:**
In the majority of the animals, nodules showed complete or partial regression during the six-month observation period. Compared to the ATCC parent MDCK lineage, Solvay's MDCK cell line showed slower regression, which is likely the consequence of selection of a cell lineage with favorable growth characteristics in a serum free medium.  Importantly, the nodules do not show progressive growth. 
We have characterized the species origin of these nodules and they appear to contain canine cells in well organized epithelial structures, all signs of MDCK cells transplanted into an environment where they are allowed to grow. 

## Tumorigenic potential not observed inimmune-competent animals
Lysates of 107 MDCK cells not tumorigenic
0.1 mg MDCK-DNA not considered oncogenic; confirmative studies initiated

- Lysates of 10**7** MDCK cells not tumorigenic
- 0.1 mg MDCK-DNA not considered oncogenic; confirmative studies initiated

**1c. Cell characterization***** *****–****Tumorigenicity summary**

**Notes:**
In the majority of the animals, nodules showed complete or partial regression during the six-month observation period. Compared to the ATCC parent MDCK lineage, Solvay's MDCK cell line showed slower regression, which is likely the consequence of selection of a cell lineage with favorable growth characteristics in a serum free medium.  Importantly, the nodules do not show progressive growth. 
We have characterized the species origin of these nodules and they appear to contain canine cells in well organized epithelial structures, all signs of MDCK cells transplanted into an environment where they are allowed to grow. 

## MDCK safety assessment

- 1.	Cell line characterization
- Downstream processing (DSP)
- Elimination of intact cells
- Elimination of cellular DNA

**Notes:**
Genetic analysis such as chromosome staining, isoenzyme analysis and karyology showed no chromosome damage and that both the Master and Extended Cell Banks are of canine origin and do not contain a Y-chromosome, all consistent with the original MDCK isolate from a female cocker spaniel. This demonstrates that Solvay’s MDCK is genetically stable up to passage level – or age – higher than applied for production. With the genetic integrity and stability being established, we developed the production process for the MDCK-based subunit vaccine 

## MDCK-based vaccine production

**MDCK-based vaccine production**

**Notes:**
With the genetic integrity and stability being established, we developed the production process for the MDCK-based subunit vaccine. This process was largely based on the production process for our egg-based subunit vaccine, but obviously using MDCK cells cultured to large scale from the Working Cell Bank rather than eggs. This is a multi-stage process and there is a lot of information is this flow scheme. Important to point out here is that we designed and added several specific steps throughout the DSP – seen here with the dotted red circles - to efficiently remove substrate proteins and DNA. This further enhances purity and safety of the resulting final product and is important for the safety assessment of MDCK. Therefore I will come back to this scheme several times later to explain these details.

## 2a. DSP - Elimination of intact cells

**2a. DSP - Elimination of intact cells**

**Notes:**
With the genetic integrity and stability being established, we developed the production process for the MDCK-based subunit vaccine. This process was largely based on the production process for our egg-based subunit vaccine, but obviously using MDCK cells cultured to large scale from the Working Cell Bank rather than eggs. This is a multi-stage process and there is a lot of information is this flow scheme. Important to point out here is that we designed and added several specific steps throughout the DSP – seen here with the dotted red circles - to efficiently remove substrate proteins and DNA. This further enhances purity and safety of the resulting final product and is important for the safety assessment of MDCK. Therefore I will come back to this scheme several times later to explain these details.

## 2a. DSP - Elimination of intact cells

| Intact cells 
10 log clearance factor |
| --- |

|  | Pilot scale | Production scale |
| --- | --- | --- |
| Homogenization | - | Validation ongoing |
| Centrifugation | 3.6 |  |
| Detergent treatment | ≥3.6 |  |
| Ultracentrifugation | ≥3.6 |  |
| 0.22μ filtration x3 | ≥3.6 |  |
| Total | ≥ 21.4 |  |

**Notes:**
With the genetic integrity and stability being established, we developed the production process for the MDCK-based subunit vaccine. This process was largely based on the production process for our egg-based subunit vaccine, but obviously using MDCK cells cultured to large scale from the Working Cell Bank rather than eggs. This is a multi-stage process and there is a lot of information is this flow scheme. Important to point out here is that we designed and added several specific steps throughout the DSP – seen here with the dotted red circles - to efficiently remove substrate proteins and DNA. This further enhances purity and safety of the resulting final product and is important for the safety assessment of MDCK. Therefore I will come back to this scheme several times later to explain these details.

## 2b. DSP - Elimination of DNA

**2b. DSP - Elimination of DNA**

- Benzonase

- Benzonase

**Notes:**
With the genetic integrity and stability being established, we developed the production process for the MDCK-based subunit vaccine. This process was largely based on the production process for our egg-based subunit vaccine, but obviously using MDCK cells cultured to large scale from the Working Cell Bank rather than eggs. This is a multi-stage process and there is a lot of information is this flow scheme. Important to point out here is that we designed and added several specific steps throughout the DSP – seen here with the dotted red circles - to efficiently remove substrate proteins and DNA. This further enhances purity and safety of the resulting final product and is important for the safety assessment of MDCK. Therefore I will come back to this scheme several times later to explain these details.

## 2b. DSP - Elimination of DNA

**2b. DSP - Elimination of DNA**

- specification: < 10 nanograms per dose

- _DNA content _
- clearance factor

|  | Pilot scale | Production scale |
| --- | --- | --- |
| DNA digestion 1 | 51 | Validation ongoing (including contentand size) |
| DNA digestion 2 | 88 |  |
| Detergent treatment/Ultracentrifugation | 168 |  |
| Total clearance | 760,000 |  |

**Notes:**
With the genetic integrity and stability being established, we developed the production process for the MDCK-based subunit vaccine. This process was largely based on the production process for our egg-based subunit vaccine, but obviously using MDCK cells cultured to large scale from the Working Cell Bank rather than eggs. This is a multi-stage process and there is a lot of information is this flow scheme. Important to point out here is that we designed and added several specific steps throughout the DSP – seen here with the dotted red circles - to efficiently remove substrate proteins and DNA. This further enhances purity and safety of the resulting final product and is important for the safety assessment of MDCK. Therefore I will come back to this scheme several times later to explain these details.

## 2. DSP - Summary

- Adequate purification and testing warrants vaccine safety
- Solvay is committed to follow the latest scientific insights as well as regulatory guidance

## MDCK safety assessment

- Cell line characterization
- Downstream processing
- Final product safety
- Pre-clinical experience
- Clinical experience

**Notes:**
Genetic analysis such as chromosome staining, isoenzyme analysis and karyology showed no chromosome damage and that both the Master and Extended Cell Banks are of canine origin and do not contain a Y-chromosome, all consistent with the original MDCK isolate from a female cocker spaniel. This demonstrates that Solvay’s MDCK is genetically stable up to passage level – or age – higher than applied for production. With the genetic integrity and stability being established, we developed the production process for the MDCK-based subunit vaccine 

## MDCK-based vaccine – Pre-clinical experience

|  | Species | Route | Dose 
(g HA)  |
| --- | --- | --- | --- |
| Local tolerance | rat, rabbit | s.c. / i.m. / i.v. | 45 |
| Systemic toxicity | rat, rabbit | s.c. | 45, 75, 450 |
| Pyrogenicity | rabbit | i.v. | 45 |
| Mutagenic potential | mouse | s.c. | 45 |
| Active and passive anaphylaxis | guinea pig | s.c. for induction
i.v. for challenge | 45 |

## MDCK-based vaccine – Pre-clinical experience

- Local tolerance
- No local irritation
- Systemic toxicity
- No adverse effects
- Pyrogenicity
- No distinct increase in body temp

- Mutagenicity
- No increase in number of micronuclei
- Anaphylaxis
- No active anaphylaxis
- Passive anaphylaxis favorable to egg-based

## MDCK-based vaccine – Clinical experience

- 14 randomized, double-blind studies
- 1,023 subjects on MDCK-based subunit vaccine
- Population: 18-60, over 60, patients at-risk for complications for influenza, atopic patients and subjects with an egg-allergy
- Major objectives: Show immunogenicnon-inferiority and comparable safety toexisting egg-based subunit influenza vaccine

## MDCK-based vaccine –Clinical experience

- Local and systemic reactogenicity profile is comparable to egg-based vaccine
- Reactions are minor and short-lived
- No unexpected safety findings
- Non-inferior in immunogenicity

**MDCK-based vaccine has comparable safety and immunogenicity profile as egg-based vaccine**

## Conclusions

- Solvay is confident MDCK is a safe substrate for inactivated influenza vaccines
- The use of MDCK will improve reliabilityof influenza vaccine supply, and enhance pandemic preparedness
- Solvay will pursue licensing worldwide, including US

## Participants

- Iris de Bruijn, Ph.D.
- Global Clinical Director, Influenza Vaccines
- Ed Geuns, Pharm.D.
- Director, Regulatory Affairs
- Michael Hare, B.S.
- Manager, Regulatory Affairs
- Alex Kersten, D.V.M.
- Senior Scientist,Pre-Clinical Development

- Jeroen Medema, MSc.
- Senior Scientist, Vaccines
- Peter Finn, MRCVS., FRCPath.
- Consultant
- Michael Williams, B.S.
- Vice President, Viral Products
- 	The Biologics Consulting Group
- Ruth Wolff, Ph.D.
- Director, Therapeutics
- 	The Biologics Consulting Group

## MDCK as a substrate for influenza vaccine production

- Solvay Pharmaceuticals
- Presentation to VRBPAC
- November 16, 2005

**Notes:**
Good morning, ladies and gentlemen. My name is Jeroen Medema, Senior Scientist for Vaccines at Solvay Pharmaceuticals. I would like to thank the Center for Biologics Evaluation and Research for the invitation to present to this Advisory Committee our company’s MDCK-based influenza vaccine project, my life’s work for more than 10 years now. I am delighted to be here today to continue our company’s ongoing dialogue with the FDA on the use of MDCK as a substrate for influenza vaccine production.